LilSugar

Interview with Kate Gosselin: Feeding a Family of 10

LilSugar — Mon, 29 Sep 2008 07:00:00 -0700

Parents watch TLC's Jon and Kate Plus 8 in shock and awe. Moms and dads are awed by the way the young couple, Jon and Kate, are raising two sets of multiples and shocked by the fact that all the children - Cara, Mady, Alexis, Hannah, Leah, Aaden, Collin, and Joel - eat! The twins' and sextuplets' diets don't consist of just peanut butter and jelly and buttered pasta; they entertain their pint-sized palates with everything from traditional Korean food to cracked crab and fresh vegetables.

lilsugar recently had the opportunity to ask queen of the Gosselin kitchen, Kate, a few questions about feeding her family of ten, the importance of an organic diet, and her recent partnership with the Grains Foods Foundation to promote brown bag lunches. To see her tips and what she had to say, read more.

lilsugar: Why did you decide to team up with the Grains Foods Foundation?

KG: These days, everyone is looking for ways to cut costs while still managing to eat healthy. With a family of 10, we’re certainly no different. We’ve been brown bagging for years and I’m working with the Grain Foods Foundation to show other families how packing lunches can be an easy and fun way to save money and eat healthy. There’s even a calculator on their website - grainpower.org - that shows how much money and calories you can save when you pack a lunch instead of eating out. It’s amazing!

lilsugar: Does or did incorporating grains into the Gosselin family diet bring down the food bill?

KG: Definitely. Grains like bread, crackers, pretzels, and granola bars have always been a part of our family diet because they are affordable, delicious and nutritious. We go through a loaf of bread at every meal so I usually buy a whole flat of bread at one time!

lilsugar: How important do you think it is to raise children on an organic diet?

KG: More than anything, I think it’s important to raise children on a healthy diet. As I’m sure you’ve seen on the show, I try to find fruits and vegetables from local farm stands but when that isn’t possible, there are always great and healthy options available at the supermarket.

lilsugar: As someone who fed a family of 10 on a budget, what tips would you offer other mothers to cut costs?

KG: Pay attention to the things that are on sale, clip coupons and, above all, avoid buying things that you don't need. Being organized and planning ahead is one of the best ways to stick to a budget. I know it’s not always easy for families to plan ahead but making sandwiches and packing lunches is a relatively simple way to save money and eat healthy. Nutrition has always been important to me personally as a woman, a nurse and especially as a mom.

lilsugar: On Jon and Kate Plus 8, your children seem to eat all of the healthy things you prepare. How have you managed to raise eight adventurous eaters?

KG: I have always prepared healthy meals without other options. I firmly believe that if they are hungry, they will eat what is in front of them. I also do not "over-snack" them. That said, if they do have a snack, it's usually something with grains (pretzels, wheat crackers, etc).

lilsugar: What are your family's favorite meals? Are there any foods your children do not like?

KG: We have a lot of favorites and I believe in exposing kids to a variety of foods from a very young age to avoid those childhood ruts (eating and wanting to eat the same four things for every meal).

lilsugar: You are often filmed packing cereal bags, lunches and picnics prior to outings on your show, do you do that for convenience or to save money?

KG: Both. Packing lunches and snacks ahead of time saves us money and help me make sure my family eats healthy no matter where we are. It ensures I’ll have something nutritious on hand when we’re away from home.

lilsugar: Do you have advice for moms on how to pack lunches that children will actually eat?

KG: Try to make their lunches fun. Include a note in their lunch bag or scribble words of inspiration on a napkin. And if you want to get really creative, use cookie cutters to transform your child’s sandwich into a work of art – or even into their initials. These little surprises are sure to bring a smile to their face.

Another thing I do is aim for variety. For instance, I’ll make them checkerboard sandwiches where I mix up the bread - using one slice of light colored bread and one slice of a darker bread, I simply cut the sandwiches into quarters and flip two of the quarters over to make a checkerboard. This is a great way to start introducing kids to whole grain bread. Kids love fun-looking food, even if it’s good for them!

lilsugar: You are extraordinarily organized. Do you have favorite products to pack food in a certain type of cereal bag, lunch box or drink container, etc.?

KG: I love cute reusable lunch bags and am a huge fan of color coding. With a family of 10, everyone having their own special color makes things much easier! Plus, it fosters a sense of ownership in the kids, which makes it less likely they’ll leave it behind or swap it with another child’s lunch!

lilsugar: You make cool, interactive snacks from edible play-dough to the pudding paint, do you have others?

KG: Those are the latest ones. Anything that is able to be eaten as well as fun (and healthy!) thrills my kids!

lilsugar: What is your family's favorite edible splurge, for example, ice cream for dinner?

KG: Well, ice cream for dinner is great but sometimes we will also have breakfast for dinner (French toast is always a big hit). Think variety with nutrition and it will keep everyone interested!

Check back on lilsugar each morning this week for some of Kate's delilicious kid-friendly sandwich recipes!

High Blood Pressure, a Hidden Killer

FitSugar — Wed, 24 Feb 2010 07:00:11 -0800

With American Heart Month coming to an end, I'd like to urge you to get your blood pressure checked. According to a new report from the Institute of Medicine, hypertension - aka high blood pressure - is becoming a neglected disease. When the doctor slips the Velcro cuff on and off of our arm, it's easy to zone out, but consider this: one in three American adults has hypertension and one in six will die from hypertension-related complications like a stroke or heart disease.

Although the exact cause of high blood pressure is unknown, there are many contributing factors to the condition. Here are a few things you can do to avoid becoming part of the deadly statistic.

Lay off the salt. Ninety percent of American adults consume more than the RDA of sodium of one teaspoon per day. Not entirely shocking when you consider the salt content in most processed or restaurant-made foods is through the roof. To keep your salt intake in check, make an effort to check the sodium content of the foods you buy at the grocery store, ask that your food be prepared with less salt when dining out, and go homemade whenever you can.
Relax. Stress is a contributing factor to high blood pressure. Make sure you have a way to decompress from all of life's little knots that can get tied up in you. Exercise, massage, sex, getting enough sleep, and meditation are great starts to a calmer you.

To find out four other ways you can prevent high blood pressure, read more.

Control your vices. If you're smoking, quit. If you're a drinker, keep it to one drink a day. Smoking and hitting the bottle too often are associated with a wave of health problems - hypertension is just one of them.
Get moving. Research has found that individuals who are overweight are prone to hypertension. But just because you're thin, doesn't mean you're off the hook - sedentary individuals are also are prime candidates for the condition. Whatever your weight, make sure you're physically active.
Eat the right thing. Certain foods like whole grains, potassium-rich foods, and fat-free milk products have all been linked to reducing the risk of hypertension.
Get checked out. As I mentioned in the beginning, it's important to regularly get your blood pressure checked. If you don't have insurance or can't afford a doctor's visit, many supermarkets, fire stations, and pharmacies have blood pressure monitors that you can use for a nominal fee. Normal blood pressure is 120/80 (systolic/diastolic) or less. When both numbers start to go way up, you've got high blood pressure.

Diabetes diet

FitSugar — Wed, 08 Oct 2008 17:35:01 -0700

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Lifestyle Changes Essential for People at Risk for Diabetes

Lifestyle interventions that include weight loss, dietary changes, and increased physical activity can definitely help prevent or delay the progression to diabetes among at-risk people, suggest several recent studies. Weight loss through diet and exercise is especially important for overweight people with pre-diabetes.

Grain Fiber Important for Diabetes Prevention

Eating whole-grain, fiber-rich, cereal foods may help reduce the risk of developing type 2 diabetes, indicates a 2007 study in the Archives of Internal Medicine. In the study, people who consumed the most fiber from grains and cereals had a 33% lower risk of developing diabetes than people with the lowest fiber intakes. The study also found an association between high magnesium intake and reduced diabetes risk. Although fruits and vegetables also contain fiber, they did not appear to affect diabetes risk.

Low-Fat Dairy Products

Incorporating low-fat dairy products (such as yogurt and milk) into a healthy diet may help reduce diabetes risk for women, suggests a study in Diabetes Care.

Beware of Internet Dietary Supplement Scams

In 2006, the FDA alerted consumers not to be misled by dietary supplements advertised on the Internet as treatments or cures for diabetes. These products have not been scientifically studied or approved.

Low-Glycemic Index Diets

Food low on the glycemic index -- such as whole grains, fruits, lentils, and soybeans -- can help promote weight loss and heart health. Illustrating the complexity of this area, a 2006 study in the New England Journal of Medicine indicated that a low-carb, low-glycemic index diet was beneficial while another study in the Archives of Internal Medicine suggested advantages for a high-carb, low-glycemic index diet.

Low-Fat Vegan Diets

A low-fat diet that excludes meat and dairy products may help improve glycemic control and increase insulin sensitivity, suggests a Diabetes Care study. Researchers think that the high fiber content of these diets, in addition to their reduced fat, may be a factor.

Introduction

The two major forms of diabetes are type 1, previously called insulin-dependent diabetes mellitus (IDDM) or juvenile-onset diabetes, and type 2, previously called non-insulin-dependent diabetes mellitus (NIDDM) or maturity-onset diabetes. [See In-Depth Report #9: Diabetes - type 1 and In-Depth Report #60: Diabetes - type 2.]

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to absolute or relative insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It normally works in the following way:

During and immediately after a meal the process of digestion breaks carbohydrates down into sugar molecules (of which glucose is one) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply. (Glucose levels after a meal are called postprandial levels.)
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal insulin rises to its peak level.
Insulin then enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

Click the icon to see an image of the liver.

In type 1 diabetes, the disease process is more severe than with type 2, and onset usually begins in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."

Click the icon to see an image of the pancreas.

Patients with type 1 diabetes need to take insulin. Dietary control in type 1 diabetes is very important and focuses on balancing food intake with insulin intake and energy expenditure from physical exertion. [See In-Depth Report #9: Diabetes - type 1.]

Type 2 diabetes is the most common form of diabetes, accounting for up to 95% of all diabetes cases. About 20 million Americans have type 2 diabetes, and half are unaware they have it. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that the disease may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin, and in the beginning this amount is usually sufficient to overcome such resistance. Patients whose blood glucose levels are higher than normal, but not yet high enough to be classified as diabetes, are considered to have “pre-diabetes.” It is very important that people with pre-diabetes control their weight to stop or delay the progression to diabetes.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

Obesity is common in patients with type 2 diabetes and this condition appears to be related to insulin resistance. The primary dietary goal for overweight type 2 patients is weight loss and maintenance. Studies indicate that when people with type 2 diabetes maintain intensive exercise and diet modification programs, many can minimize or even avoid medications. Weight loss medications or bariatric surgery may be appropriate for some patients. [See In-Depth Report #60: Diabetes - type 2 and In-Depth Report #53: Weight control and diet.]

General Dietary Guidelines

For people who have pre-diabetes, or who are at high risk of developing type 2 diabetes, lifestyle changes of diet and exercise are extremely important. Several studies have shown that lifestyle interventions are very effective in preventing or postponing the progression to diabetes. These interventions are especially important for overweight people -- even moderate weight loss can help reduce diabetes risk.

The American Diabetes Association recommends that people at high risk for type 2 diabetes eat high-fiber (14g fiber for every 1,000 calories) and whole-grain foods. A 2007 study in the Archives of Internal Medicine also suggested that high intake of fiber and magnesium, especially from whole grain cereals and breads, can help reduce type 2 diabetes risk.

For people who have diabetes, the treatment goals for a diabetes diet are:

Achieve near normal blood glucose levels. People with type 1 diabetes and people with type 2 diabetes who are taking insulin or oral medication must coordinate calorie intake with medication or insulin administration, exercise, and other variables to control blood glucose levels. New forms of insulin are now allowing more flexibility in timing meals.
Protect the heart and aim for healthy lipid (cholesterol and triglyceride) levels and control of blood pressure.
Achieve reasonable weight. Overweight patients with type 2 diabetes who are not taking medication should aim for a diet that controls both weight and glucose. A reasonable weight is usually defined as what is achievable and sustainable, rather than one that is culturally defined as desirable or ideal. Children, pregnant women, and people recovering from illness should be sure to maintain adequate calories for health.
Manage or prevent complications of diabetes. People with diabetes, whether type 1 or 2, are at risk for a number of medical complications, including heart and kidney disease. Dietary requirements for diabetes must take these disorders into consideration.
Promote overall health.

Overall Guidelines. Overall Guidelines. There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

For example, a patient with type 2 diabetes who is overweight and insulin-resistant may need to have a different carbohydrate-protein balance than a thin patient with type 1 diabetes in danger of kidney disease. Because regulating diabetes is an individual situation, everyone with this condition should get help from a dietary professional in selecting the best method.

Healthy eating habits along with good control of blood glucose are the basic goals in managing this complex disease, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.
Lose weight if body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

Several different dietary methods are available for controlling blood sugar in type 1 and insulin-dependent type 2 diabetes:

Diabetic Exchange Lists (for maintaining a proper balance of carbohydrates, fats, and proteins throughout the day)
Carbohydrate Counting (for tracking the number of grams of carbohydrates consumed each day)
Glycemic index (for tracking which carbohydrate foods increase blood sugar)

Tests for Glucose Levels. Both low blood sugar (hypoglycemia) and high blood sugar (hyperglycemia) are of concern for patients who take insulin. It is important, therefore, to monitor blood glucose levels carefully. Patients should aim for the following measurements:

Pre-meal glucose levels of 90 - 130 mg/dL
Bedtime levels of 110 - 150 mg/dL

In general, patients who are tightly controlling glucose levels need to take readings four or more times a day. Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend that these patients measure blood levels only once or twice a day. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Tests for Glycosylated Hemoglobin. Another test examines blood levels glycosylated hemoglobin, also known as hemoglobin A1c (HbA1c). Measuring glycosylated hemoglobin is useful for determining the severity of diabetes. The test is not affected by food intake so it can be taken at any time. A home test has been developed that may make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Other Tests. Other tests are needed periodically to determine potential complications of diabetes, such as high blood pressure, unhealthy cholesterol levels, and kidney problems. Such tests may also indicate whether current diet plans are helping the patient and whether changes should be made. Annual urine tests showing even microscopic traces of a protein known as albumin can indicate a future risk for serious kidney disease.

For prevention of long-term complications of diabetes, experts now recommend that all patients with diabetes aim at keeping blood levels as close to normal as possible. Such intensive insulin treatment can increase the risk of hypoglycemia, which occurs when blood sugar is extremely low (below 60 mg/dL). The following tips may help avoid hypoglycemia or prepare for attacks.

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients on therapies that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Food Labels. Every year thousands of new foods are introduced, many of them advertised as nutritionally beneficial. It is important for everyone, most especially people with diabetes, to be able to differentiate advertised claims from truth. The current food labels show the number of calories from fat, the amount of nutrients that are potentially dangerous (fat, cholesterol, sodium, sugars) as well as useful nutrients (fiber, carbohydrates, protein, vitamins).

Labels also show "daily values," the percentage of a daily diet that each of the important nutrients offers in a single serving. Unfortunately, the daily value is based on 2,000 calories, generally much higher than most patients with diabetes should have, and the serving sizes may not be equivalent to those on the Exchange Lists. Most people will need to recalculate the grams and calories listed on food labels to fit their own serving sizes and calorie needs.

Weighing and Measuring. Weighing and measuring food is extremely important in order to get the correct number of daily calories.

Along with measuring cups and spoons, choose a food scale that measures grams. (A gram is very small, about 1/28th of an ounce.)
Food should be weighed and measured after cooking.
After measuring all foods for a week or so, most people can make fairly accurate estimates by eye or by holding food without having to measure everything every time they eat.

Timing. Meals should not be skipped, particularly for those who are on insulin. Skipping meals can upset the balance between food intake and insulin and also can lead to weight gain if the patient eats extra food too often to offset low blood sugar levels.

The timing of meals is particularly important for people taking insulin:

Patients should coordinate insulin administration with calorie intake. In general, they should eat three meals each day at regular intervals. Snacks are often required.
They should try to take an insulin injection 30 minutes before they eat, although this timing could vary, depending on the form. Some experts recommend a fast acting insulin (insulin lispro) at each meal and a longer (basal) insulin at night.

Diabetes can lead to kidney disease and failure. People with early-stage kidney failure need to follow a special diet that slows the build-up of wastes in the bloodstream. The diet restricts protein, potassium, phosphorus, and salt intake. Fat and carbohydrate intake may need to be increased to help maintain weight and muscle tissue.

People who have late-stage kidney disease usually need dialysis. Once patients are on dialysis, they must have more protein in their diet. Patients must still be very careful about restricting salt, potassium, phosphorus, and fluids. Patients on peritoneal dialysis may have fewer restrictions on salt, potassium, and phosphorus than those on hemodialysis.

Major Food Components

Compared to fats and protein, carbohydrates have the greatest impact on blood sugar. Both the amount and type of carbohydrate affect blood glucose. Carbohydrate types are either complex (as in starches) or simple (as in fruits and sugars). One gram of carbohydrates equals four calories. The current general recommendation is that carbohydrates should provide between 40 - 65% of the daily caloric intake. Carbohydrate intake should not fall below 130 grams/day. Most experts do not recommend low-carb diets for diabetes management or weight control.

Vegetables, fruits, whole grains, and beans are good sources of carbohydrates. Whole grain foods provide more nutritional value than pasta, white bread, and white potatoes. Brown rice is a better choice than white rice. Patients should try to consume a minimum of 20 - 35 grams of fiber daily (ideally 50 grams/day), from vegetables, fruits, whole grain cereals, breads, nuts and seeds.

Complex Carbohydrates. Complex carbohydrates found in whole grains and vegetables are preferred over carbohydrates found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Most of these are high in fiber, which is important for health. Whole-grains specifically are extremely important for people with diabetes or at risk for it. [For specific benefits, see Box Whole Grains, Nuts, and Fiber-Rich Foods and Table Some Examples of Healthy Foods.]

Simple Carbohydrates (Sugar). Sugars are generally one of two types:

Sucrose (table sugar). Sucrose has been associated with higher triglycerides and harmful cholesterol levels. A 2002 study suggested that a high level of sugar consumption may also reduce levels of HDL cholesterol, the so-called good cholesterol.
Fructose (sugar found in fruits). Fructose may produce a slower increase in blood sugar than sucrose, which may have some advantages for people with diabetes. Dark-colored fruits are rich in important vitamins and other nutrients, and studies continue to report their benefits for the heart and health in general. Other fruits, such as apples and grapes also have important beneficial food chemicals.

Sugar itself, either as sucrose or fructose, adds calories, increases blood glucose levels quickly, and provides no other nutrients. High levels of sugar consumption -- both fructose and sucrose -- have been associated with higher triglycerides and lower levels of HDL cholesterol, the so-called good cholesterol. The high consumption of sugar is most likely one of the factor in the current obesity epidemic. Soda, other sweetened beverages, and fruit juice in fact may be singled out as major contributors to childhood obesity.

People with diabetes should avoid products listing more than 5 grams of sugar per serving, and some doctors recommend limiting fruit intake. If specific amounts are not listed, patients should avoid products with either sucrose or fructose listed as one of the first four ingredients on the label. [See Box Fat Substitutes and Artificial Sweeteners.]

Of increasing interest to researchers is possible harm from sugar from advanced glycation end-products (called AGEs). These are end-products of the chemical reaction between sugar and protein. This reaction occurs most intensively when cooking at high temperatures -- particularly animal fats. (Steaming or cooking food in water does not produce these chemicals. Low, slow cooking also produces fewer AGEs.) AGEs can also be formed by chemical reactions in the body itself. They may promote factors in the inflammatory response that cause a number of diseases or their complications, including diabetes and other serious conditions (Alzheimer's, atherosclerosis, cataracts, and osteoporosis).

The Carbohydrate Counting System. Some people plan their carbohydrate intake using a system called carbohydrate counting. It is based on two premises:

All carbohydrates (either from sugar or starch) will raise blood sugar to a similar degree. In general, 1 gram of carbohydrates raises blood sugar by 3 points in people who weigh 200 pounds, 4 points for people who weigh 150 pounds, and 5 points for 100 pounds.
Carbohydrates have the greatest impact on blood sugar; fats and protein play only minor roles.

In other words, the amount of carbohydrates eaten (rather than fats or proteins) will determine how high blood sugar levels will rise. There are two options for counting carbohydrates: advanced and simple. Both rely on collaboration with a doctor, dietitian, or both. Once the patient learns how to count carbohydrates and adjust insulin doses to their meals, many find it more flexible, more accurate in predicting blood sugar increases, and easier to plan meals than other systems.

The basic goal is to balance insulin with the amount of carbohydrates eaten in order to control blood glucose levels after a meal. The steps to the plan are as follows:

The patient must first carefully record a number of factors that are used to determine the specific requirements for a meal plan based on carbohydrate grams:

Multiple blood glucose readings (taken several times a day)
The time of meals
Amount in grams of all the carbohydrates eaten
Time, type, and duration of exercise
The time, type, and dose of insulin or oral medications
Other relevant factors, such as menstruation, illness, and stress

The patient works with the dietitian for two or three 45 - 90 minute sessions to plan how many grams of carbohydrates are needed. There are three carbohydrate groups:

Bread/starch
Fruit
Milk

One serving from each group should contain 12 - 15 carbohydrate grams. (Patients can find the amount of carbohydrates in foods from labels on commercial foods and from a number of books and web sites.)

The dietitian creates a meal plan that accommodates the patient's weight and needs, as determined by the patient's record, and makes a special calculation called the carbohydrate to insulin ratio. This ratio determines the number of carbohydrate grams that a patient needs to cover the daily pre-meal insulin needs.

Eventually, patients can learn to precisely adjust their insulin doses to their meals.

Patients who choose this approach must still be aware of protein and fat content in foods. These food groups may add excessive calories and saturated fats. Patients must still follow basic healthy dietary principles.

The Glycemic Index. The glycemic index helps determine which carbohydrate-containing foods raise blood glucose levels more or less quickly after a meal. The index uses a scale of numbers for specific foods that reflect greatest to least delay in producing an increase in blood sugar after a meal. The lower the index number, the better the impact on glucose levels. Some evidence suggests that the benefit of foods with a low glycemic index is due to their ability to increase insulin levels quickly and so remove blood sugar rather than their ability to slow the release of blood sugar itself.

There are currently two indices in use. One uses a scale of 1 - 100 with 100 representing a glucose tablet, which has the most rapid effect on blood sugar [See Table The Glycemic Index of Some Foods]. The other common index uses a scale with 100 representing white bread (so some foods will be above 100).

A major 2003 analysis suggested that choosing foods with a low glycemic index scores may have a small but significant effect on controlling the surge in blood sugar after meals. Many of these foods are also high in fiber and so have heart benefits as well. Substituting low- for high-glycemic index foods may also help prevent weight gain.

One easy way to improve glycemic index is to simply replace starches and sugars with whole grains and legumes (dried peas, beans, and lentils). However, there are many factors that affect the glycemic index of foods, and maintaining a diet with low glycemic load is not straightforward. The following are some considerations:

The numbers attributed to each carbohydrate-rich food cannot be added to equal a certain number. In other words, adding All Bran cereal (index of 49) to a banana (index of 61) does not equal 110.
Adding certain fats to a food (for example butter to potato) can slow down the food's impact on blood sugar. One study reported that when patients ate fatty foods first, their blood glucose levels were significantly lower an hour after the meal than when carbohydrates were eaten first.
Adding foods with organic acids (pickles, yogurt) to meals may reduce the impact of foods with high glycemic scores on blood sugar. (It should be noted that yogurt alone, however, has the same high glycemic index as regular milk.)

No one should use the glycemic index as a complete dietary guide, since it does not provide nutritional guidelines for all foods. It is simply an indication of how the metabolism will respond to certain carbohydrates. Some experts believe it is too complicated to be practical and that simply tracking carbohydrates, eating healthily, and maintaining a healthy weight is sufficient. Nevertheless, a study on children with type 1 diabetes suggested that the glycemic index offered as many choices as the exchange diet, and they did not report feeling any greater limitations. [For additional information on low-glycemic index diets, see "Heart-Healthy Diets" section of this report.]

Fiber is an important component of many complex carbohydrates. It is almost always found only in plants, (particularly vegetables), fruits, whole grains, nuts, and legumes (dried beans, peanuts, and peas). (One exception is chitosan, a dietary fiber made from shellfish skeletons.) Fiber cannot be digested but passes through the intestines, drawing water with it and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, legumes, and fruit and vegetable peels) may help achieve weight loss. Consuming whole grains on a regular basis appears to provide many important benefits, especially for people with type 2 diabetes. Whole grains may even lower the risk for type 2 diabetes in the first place. Of special note, nuts, such as almonds, macadamia, and walnuts may be highly heart protective, independent of their fiber content. However, nuts are high in calories.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly reducing blood pressure as well. Evidence on the heart benefits of beans continues to grow. For example, a 2001 study indicated that eating beans four or more times a week reduced the risk for heart disease by 22%.
Soluble fiber supplements, such as those that contain psyllium or glucomannan, may be beneficial. Psyllium is taken from the husk of a seed grown in India. It is found in laxatives (Metamucil), breakfast cereals (Bran Buds), and other products. In a 2002 study, patients with type 2 diabetes who consumed psyllium (Plantaben) for breakfast for 11 weeks experienced lower total and LDL cholesterol levels. There was no difference in glucose or HbA1c levels. Psyllium can increase sodium so people who increase their levels of soluble fiber should also increase water and fluid intake.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat replacer (derived from oats) as part of a low-calorie diet. At the end of 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from your diet can be harmful to general health. Some fat substitutes include:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand as part of a low-fat diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that their use can allow lower doses of statins (cholesterol -lowering drugs). These products do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does. They can be hydrogenated, however, and can contain some trans-fatty acids.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Simply adding snacks containing olestra do not appear to have any effect on cholesterol or weight loss.) However, it can cause cramping and diarrhea. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The adverse health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-replacers are also available. Although studies to date do not show any significant adverse health effects, their effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners in beverages and foods and reduced their sugar intake weighed less over time than those who ate similar types and amounts of drinks and food containing sugar. However, using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain as long as the total caloric intake is under control. There is some public concern about chemicals used to produce many of these sweeteners and adverse effects in studies using rats. Natural low-calorie sweeteners that may be more acceptable to many people are also available. Low-calorie sweeteners include:

Saccharin (Sugar Twin, Sweet n’Low, Sucaryl, and Featherweight). Saccharin has been used for years but is not used as commonly now. Some studies found that large amounts of saccharin caused bladder cancer in rats. Although the rats were fed huge amounts that do not apply to human diets, some evidence suggests that people who have six or more servings of saccharin per day may have an increased risk.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of neurologic disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a rare genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing hydroxyl atoms with chlorine atoms. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the US since 1988 with no reported adverse effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced calorie sweetener is a novel low-calorie sweetener derived from lactose, which is found in dairy products and other foods. It may be specifically beneficial for people with type 2 diabetes and have additional benefits that aid the intestinal tract.
Alitame (Aclame) is formed from amino acids. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been rigorously tested.

Other artificial sweeteners being investigated include, glycyrrhizin (derived from licorice), and dihycrochalcones (derived from citrus fruits).


Based on 100 = a Glucose Tablet
BREADS
pumpernickel	49
sour dough	54
rye	64
white	69
whole wheat	72
GRAINS
barley	22
sweet corn	58
brown rice	66
white rice	72
BEANS
soy	14
red lentils	27
kidney (dried and boiled, not canned)	29
chickpeas	36
baked	43
DAIRY PRODUCTS
milk	30
ice cream	60
CEREALS
oatmeal	53
All Bran	54
Swiss Muesli	60
Shredded Wheat	70
Corn Flakes	83
Puffed Rice	90
PASTA
spaghetti-protein enriched	28
spaghetti (boiled 5 minutes)	33
spaghetti (boiled 15 minutes)	44
FRUIT
strawberries	32
apple	38
orange	43
orange juice	49
banana	61
POTATOES
sweet	50
yams	54
new	58
mashed	72
instant mashed	86
white	87
SNACKS
potato chips	56
oatmeal cookies	57
corn chips	72
SUGARS
fructose	22
refined sugar	64
honey	91
Note. These numbers are general values, but may vary widely depending on other factors, including if and how they are cooked and foods they are combined with.

Protein intake in diabetes is complicated. Protein recommendations vary among experts and depend on various factors. These factors include whether a patient has type 1, type 2, or pre-diabetes. There are additional guidelines for patients who show signs of kidney damage (nephropathy).

In general, diabetes dietary guidelines recommend that proteins should provide 12 - 20% of total daily calories. This daily amount poses no risk to the kidney in people who do not have kidney disease. Protein is important for strong muscles and bone. Some experts recommend a higher proportion of protein (20 - 30%) for patients with pre- or type 2 diabetes. They think that eating more protein helps people feel more full and thus reduces overall calories. In addition, protein consumption helps the body maintain lean body mass during weight loss.

Because protein causes the kidneys to work harder, patients with diabetic nephropathy need to limit their intake of protein. A typical protein-restricted diet limits protein intake to no more than 10% of total daily calories. Patients with kidney damage also need to limit their intake of phosphorus, a mineral found in dairy products, beans, and nuts. (However, patients on dialysis need to have more protein in their diets.) Potassium and phosphorus restriction is often necessary as well.

One gram of protein contains 4 calories. Protein is commonly recommended as part of a bedtime snack to maintain normal blood sugar levels during the night, although studies are mixed over whether it adds any protective benefits against nighttime hypoglycemia. If it does, only small amounts (14 grams) may be needed to stabilize blood glucose levels.

Good sources of protein include fish, skinless chicken or turkey, nonfat or low-fat dairy products, soy (tofu), and legumes (kidney beans, black beans, chick peas, lentils).

Fish. Fish is probably the best source of protein. Evidence suggests that eating moderate amounts of fish (twice a week) may improve triglycerides and help lower the risks for death from heart disease, dangerous heart rhythms, blood pressure, a tendency for blood clots, and the risk for stroke.

The most healthy fish are oily fish such as salmon, mackerel, or sardines, which are high in omega-3 fatty acids. Three capsules of fish oil (preferably as supplements of DHA-EPA) is about equivalent to eating one serving of fish.

Some studies have reported a higher incidence of heart attack in men who ate fish daily. Such findings may be due to mercury toxicity, which has harmful effects on the heart. High mercury content has been observed in swordfish and shark and, to some extent, in tuna, trout, pike, tilapia, and bass.

Fish oil supplements may also have some adverse effects on LDL levels and glucose control in type 2 diabetes. More research is needed to further define the risk and benefits of fish, but at this time most guidelines recommend eating fish two or three times a week.

Soy. Soy is an excellent food. It is rich in both soluble and insoluble fiber, omega-3 fatty acids, and provides all essential proteins. Soy proteins have more vitamins and minerals than meat or dairy proteins. They also contain polyunsaturated fats, which are better than the saturated fat found in meat. The best sources of soy protein are soy products (tofu, soy milk, soybeans). Soy sauce is not a good source. It contains only a trace amount of soy and is very high in sodium.

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 American Heart Association (AHA) review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still encourages patients to include soy foods as part of an overall heart healthy diet, but does not recommend using isoflavone supplements.

Meat and Poultry. Lean cuts of meat are the best choice for heart health and diabetes control. Saturated fat in meat is the primary danger to the heart. The fat content of meat varies depending on the type and cut. For patients with diabetes, experts recommend choosing skinless chicken or turkey over red meat. (Fish is an even better choice.) A large, long-term 2006 study found that high heme iron intake from red meat increases the risk of developing type 2 diabetes in women. Another 2006 study suggested that replacing red meat with chicken improves kidney function and lipid levels in patients with diabetic nephropathy.

Dairy Products. A 2002 study reported that a high intake of dairy products can lower risk factors related to type 2 diabetes and heart disease (insulin resistance, high blood pressure, obesity, and unhealthy cholesterol). Some researchers suggest the calcium in dairy products may be partially responsible for these benefits. However, because many dairy products are high in saturated fats and calories, doctors recommend that patients choose low-fat and nonfat dairy items. Other studies have indicated that increasing the amount of low-fat diary products in a daily diet may help reduce type 2 diabetes risk, particularly for women.

Some fat is essential for normal body function. Fats can have good or bad effects on health, depending on their chemistry. New research suggests that the type of fat is more important than the total amount of fat when it comes to reducing heart disease.

Current dietary guidelines for diabetes and heart health recommend that total fat be 25 - 35% of total daily calories. Monounsaturated fats (olive oil, canola oil, peanut oil, nuts, avocados) and omega-3 polyunsaturated fats (fish, flaxseed, walnuts) should be the first choice for fats. Omega-6 polyunsaturated fats (corn oil, safflower, oil, sunflower oil, soybean oil) are the second choice. Limit saturated fat to less than 7% of total daily calories. Limit trans-fats (margarine, commercial baked goods, snack and fried foods) to less than 1% of total calories.

All fats, good or bad, are high in calories compared to proteins and carbohydrates. In order to calculate daily fat intake, multiply the number of fat grams eaten by nine (1 fat gram is equal to 9 calories, whether it's oil or fat) and divide by the number of total daily calories desired. One teaspoon of oil, butter, or other fats equals about 5 grams of fat. All fats, no matter what the source, add the same calories. The American Heart Association recommends that fats and oils have less than 2 grams of saturated fat per tablespoon.

Try to replace saturated fats and trans fatty acids with unsaturated fats from plant and fish oils. Omega-3 fatty acids, which are found in fish and plant sources, are a good source of unsaturated fats. Generally, two servings of fish per week provide a healthful amount of omega-3 fatty acids.

The Chemistry of Fats and Cholesterol.

Fatty Acids. All fats and oils found in foods are made up of chains of molecules called fatty acids. There are three major chains: saturated fatty acid (found mostly in animal products) and two unsaturated fatty acids -- monounsaturated and polyunsaturated fatty acids (found in plant products). The oils and fats that people and animals eat are nearly always mixtures of these three chains, but one type of fatty acid usually predominates in specific oils or fats.
Essential Fatty Acids. In addition, there are three chemical subgroups of polyunsaturated fatty acids called essential fatty acids: omega-3 and omega-6 polyunsaturated fatty acids, and omega-9 monounsaturated fatty acids.
Trans Fatty Acids. To complicate matters, there are also trans-fatty acids, which are not natural but are manufactured by adding hydrogen atoms to polyunsaturated fatty acids (called hydrogenation).

Harmful Fats. Reducing consumption of saturated fats and trans-fatty acids is the first essential step in managing cholesterol levels through diet.

Saturated Fats. Saturated fats are found predominantly in animal products, including meat and dairy products. They are strongly associated with higher cholesterol levels, and they may be even more dangerous in women than in men. High-fat meals are associated with sudden surges in triglyceride levels and other lipids along with impaired blood flow in the arteries to the heart. (Tropical oils such as palm, coconut, and cocoa butter are also high in saturated fats.)
Trans Fatty Acids. Trans fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They are particularly dangerous for the heart and may pose a risk for certain cancers. These partially hydrogenated fats are even worse than saturated fats. Studies report that high consumption of these fats reduces HDL and raises LDL cholesterol levels, has harmful effects on the linings of the arteries, and may increase the risk for type 2 diabetes. Hydrogenated fats are used in stick margarine and in many fast foods and baked goods, including most commercially produced white breads. (Liquid margarine is not hydrogenated and is recommended.) The FDA ordered that food labels list the amount of trans fatty acids in food products beginning in January 2006.

Beneficial Fats and Oils. Some fat is essential for health, and fat is essential for healthy development in children. Public attention has mainly focused on the possible benefits or hazards of monounsaturated (MUFA) and polyunsaturated (PUFA) fats.

Polyunsaturated fats are found in safflower, sunflower, corn, and cottonseed oils and fish.
Monounsaturated fats are mostly present in olive, canola, and peanut oils and in most nuts. (Canola is the least saturated of all the fats.) Studies report that replacing carbohydrates with monounsaturated fats improves glucose control after meals and reduces triglycerides in people with type 2 diabetes. Oils are more calorie-dense, however, and such patients should be wary of weight gain.

Researchers are most interested in the smaller fatty-acid building blocks contained in both oils, which may have more specific effects on lipids. Three important fatty acids are the essential fatty acids omega-3, omega-6, and omega-9.

Omega-3 fatty acids are found in fish oil (docosahexaenoic and eicosapentaneoic acids) and plants (alpha-linolenic acid).

Docosahexaenoic (DHA) and Eicosapentaneoic (EPA) Acids. DHA and EPA are found in fish oils, and evidence suggests that they have significant benefits for the heart, including reducing sudden death from heart disease, inflammation, blood clotting factors, blood pressure, and improving triglyceride and HDL levels. Results from a study presented at the 2005 meeting of the American Heart Association suggested that daily EPA supplements plus statin therapy can protect against heart attack, angina, and coronary artery disease. However, although fish and fish oil are good for the heart, patients who have an implantable defibrillator should not take fish oil supplements.

Alpha-linolenic Acid. Alpha-linolenic acid is a plant precursor of DHA, which means the body can convert it to DHA. Sources include canola oil, soybeans, flaxseed, and certain nuts and seeds (walnut, flax, chia and sometimes pumpkin seed). Some, but not all, studies suggest that oils or foods containing these oils may also be heart-protective. Supplements or foods containing these oils may also protest the heart. For example studies have reported heart protection from flaxseed supplements and also from nuts, such as almonds, macadamia, and walnuts. Nuts are high in calories, however.

Omega-6 polyunsaturated fatty acids are found in corn, safflower, soybean, and sunflower oil. PUFA oils containing omega-6 fatty acids constitute most of the oils consumed in the US. Some omega-6 fatty acids are important for health. However, high intake of these fats may be associated with weight gain in the abdomen (the so-called apple shape), a risk factor for heart disease. High consumption is also associated with a higher risk for certain cancer and some chronic diseases.

Omega-9 monounsaturated fatty acids are contained in canola and olive oil, which help protect the heart.

Research suggests that a healthy balance of all these fats may be important and that our current Western diet contains an unhealthy ratio of omega-6 to omega-3 fatty acids (10 to 1). Omega-9 fatty acids may also contain chemicals that block harmful factors found in omega-6 fatty acids. Researchers suggest that the most benefits may be found in mixture of all three fatty acids found in both poly- and monounsaturated oils, but in modest amounts that do not add too many calories.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories. [See Box Fat Substitutes and Artificial Sweeteners.]

The story on cholesterol found in the diet is not entirely straightforward. The body produces cholesterol naturally or obtains it through meals. Animal-based food products contain cholesterol. High amounts occur in meat, dairy products, egg yolks, and shellfish. (Plant foods, such as fruits, nuts, grains, do not contain cholesterol.) The American Heart Association recommends no more than 300 mg of dietary cholesterol per day for the general population and no more than 200 mg daily for those with high cholesterol.

Antioxidant Vitamins. Vitamins C and E are most studied for their health effects because they serve as antioxidants. Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). High intake of foods rich in these vitamins (as well as other food chemicals) have been associated with many health benefits, including prevention of heart problems.

Research on the effects of vitamin supplements on heart disease and diabetes, however, has been mixed. Although some research initially observed favorable effects from vitamin E in preventing blood clots and build-up of plaque on blood vessel walls, most studies found no heart protection from either vitamin E or C supplements. A 2005 Journal of the American Medical Association study found that vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases. In addition, vitamin E had no effect on preventing cancer or heart disease.

Because of the lack of scientific evidence for benefit, the American Diabetes Association does not recommend regular use of vitamin supplements, except for people who have vitamin deficiencies. Researchers, however, are still studying the treatment possibilities of antioxidants. A 2006 study suggested that alpha-lipoic acid, another type of antioxidant, may have promise as a treatment for diabetic peripheral neuropathy, the nerve damage condition that is a common complication of diabetes.

B Vitamins and Folic Acid. Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure.

Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks. Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or who suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid, B6, and B12 vitamins and those who received placebo. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Niacin (vitamin B3) is used for lowering unhealthy cholesterol levels. Although vitamin B3 is available over the counter, it can have significant side effects. A doctor should prescribe niacin in order to ensure its safety and effectiveness.

Patients with type 2 diabetes who take metformin (Glucophage) should be aware that this drug can interfere with vitamin B12 absorption. Calcium supplements may help counteract metformin-associated vitamin B12 deficiency.

Most experts recommend salt restriction in people who have high blood pressure. Some people, however, are much more sensitive to harmful effects from salt than others:

People at Risk for Salt-Sensitivity. About half of people with hypertension have blood pressure that reacts significantly to salt. Such people are known as salt-sensitive. Among those at highest risk for salt sensitivity are African Americans, people with diabetes, and elderly people.
Overweight People. Overweight individuals may absorb and retain sodium differently from people with normal weights. One study reported that high sodium intake was associated with an increased risk of heart disease and all-cause mortality in overweight, but not in normal weight, people. Reducing sodium can also help reduce the risk of stroke in people who are overweight.

Simply eliminating table and cooking salt can be beneficial. Salt substitutes, such as Cardia, (containing mixtures of potassium, sodium, and magnesium) are available, but they are expensive. About 75% of the salt in the typical American diet comes from processed or commercial foods, not from food cooked at home, so the benefits of table-salt substitutes are likely to be very modest. Some sodium is essential to protect the heart, but most experts agree that the amount is significantly less than that found in the average American diet. If people cannot significantly reduce the amount of salt in their diets, adding potassium-rich foods might help to restore a healthy balance.

Calcium. Calcium supplements may be important in older patients with diabetes to help reduce the risk for osteoporosis, particularly if their diets are low in dairy products.

Potassium. Evidence strongly indicates that a potassium-rich diet can help achieve healthy blood pressure levels, and that potassium supplements can lower systolic blood pressure by 1.8 m Hg and diastolic blood pressure by 1 mm Hg. In fact, there is some evidence that a potassium-rich diet can reduce the risk of stroke by 22 - 40%. Current guidelines support the use of potassium supplements or enough dietary potassium to achieve 3,500 mg per day for people with normal or high blood pressure (who have no risk factors for excess potassium levels). This goal is particularly important in people who have high sodium intake. The best source of potassium is from the fruits and vegetables that contain them. Potassium-rich foods include bananas, oranges, pears, prunes, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.

However, patients with diabetic nephropathy (kidney disease) and kidney failure need to restrict dietary potassium, as well as phosphorus. Kidney problems can cause potassium overload and medications commonly used in diabetes, (such as ACE inhibitors or potassium-sparing diuretics), also limit the kidney's ability to excrete potassium. No one should take potassium supplements without consulting a doctor. The best source of potassium is from the fruits and vegetables that contain them.

Magnesium. Magnesium deficiency may have some role in insulin resistance and high blood pressure. Research indicates that magnesium-rich diets may help lower type 2 diabetes risk. Whole grain breads and cereals, nuts (almonds, cashews, soybeans), and certain fruits and vegetables (spinach, avocados, beans) are excellent dietary sources of magnesium. Dietary supplements do not provide any benefit. Persons who live in soft water areas, who use diuretics, or who have other risk factors for magnesium deficiency may require more dietary magnesium than others.

Chromium. Some studies have reported an association between deficiencies in the mineral chromium and a higher risk for type 2 diabetes. Studies on fat rats that were given chromium reported improvement in insulin sensitivity and glucose metabolism. Most studies on type 2 patients, however, reported little or no effect on glucose metabolism and some even reported adverse side effects.

Selenium. Selenium, a trace mineral, does not reduce diabetes risk. In fact, it may increase it. In a 2007 study, researchers found that people who took selenium supplements had more than 1.5 times the risk of developing type 2 diabetes as those who did not take the supplements. The higher the blood level of selenium, the greater the risk. An average healthy diet supplies adequate amounts of selenium and there is no need to take dietary supplements.

Zinc. Many patients with type 2 diabetes are also deficient in zinc; more studies are needed to establish the benefits or risks of taking supplements. Zinc has some toxic side effects, and some studies have associated high zinc intake with prostate cancer.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Patients should always check with their doctors before using any herbal remedies or dietary supplements.

Traditional herbal remedies for diabetes include bitter melon, fenugreek, and Gymnema sylvestre. These herbs may have properties that help lower blood sugar. However, there have been few well-designed studies and there is not enough evidence to recommend them for prevention or treatment of diabetes.

Several recent preliminary studies suggest that cinnamon may help improve blood sugar and lipid levels. One small study found beneficial effects for people with type 2 diabetes who took between 1 - 6 grams (equivalent to 0.25 - 1.25 teaspoons) of cinnamon each day.

Various fraudulent products are often sold on the Internet as “cures” or treatments for diabetes. These dietary supplements have not been studied or approved. In 2006, the FDA and Federal Trade Commission (FTC) launched a crackdown on these scams. The FDA and FTC warn patients with diabetes not to be duped by bogus and unproven remedies.

Water. Many heart risk factors, especially those associated with blood clotting, are elevated with dehydration. In one study, drinking five or more glasses of water a day was significantly associated with a lower risk for fatal heart events than drinking two or fewer glasses a day.

Alcohol. A number of studies have found that light to moderate intake of alcohol may provide protection from heart disease and type 2 diabetes. Some research suggests that alcohol has anti-inflammatory properties that protect arteries from injury. Red wine in particular may have specific benefits for people with type 2 diabetes. It has strong antioxidant effects that benefit the heart. Some evidence also suggests that red wine may improve insulin sensitivity and reduce blood glucose levels and may even protect against type 2 diabetes. The American Diabetes Association recommends limiting alcoholic beverages to 1 drink per day for non-pregnant adult women and 2 drinks per day for adult men.

Tea. Although it contains caffeine, tea, both black and green, is often cited for its health benefits. Green tea is especially is rich in chemicals that offer protection against damaging forms of LDL. In one study, for example, higher intake, particularly by women, was associated with a lower risk for severe coronary artery disease. Black tea has also been associated with heart health. In one study oolong tea, a partially fermented tea, was specifically associated with lower blood sugar levels in patients with type 2 diabetes.

Coffee. Many studies have noted an association between coffee consumption and reduced risk for developing type 2 diabetes. A 2006 study of 29,000 postmenopausal women confirmed this reduced risk. Compared to non-coffee drinkers, women who drank at least 6 cups a day of coffee (either regular or decaf) were 22% less likely to develop type 2 diabetes. Decaffeinated coffee was even more beneficial -- women who drank at least 6 cups a day of decaf were 33% less likely to develop diabetes than women who did not drink coffee. Researchers are still not certain how coffee protects against diabetes. Neither the caffeine in coffee nor the mineral magnesium have a preventive effect. It may be that coffee contains antioxidant properties that protect the pancreas’ insulin-producing cells.

Weight Control for Type 2 Diabetes

The American Diabetes Association recommends that patients aim for a small but consistent weight loss of ½ - 1 pound per week. Most patients should follow a diet that supplies at least 1,000 - 1,200 kcal/day for women and 1,200 - 1,600 kcal/day for men.

Even modest weight loss can reduce the risk factors for heart disease and diabetes. There are many approaches to dieting and many claims for great success with various fad diets. They include calorie restriction, low-fat/high-fiber, or high protein and fat/low carbohydrates. Some evidence suggests that people may respond differently to specific diets depending on whether their weight is overly distributed around the abdomen.

Lifelong changes in eating habits, physical activity, and attitudes about food and weight are essential to weight management. Unfortunately, although many people can lose weight initially, it is very difficult to maintain weight loss. People with type 2 diabetes may have a particularly difficult time. Here are some general suggestions that may be helpful:

Start with realistic goals. When overweight people achieve even modest weight loss they reduce risk factors in the heart. Ideally, overweight patients should strive for 7% weight loss or better, particularly people with type 2 diabetes.
A regular exercise program is essential for maintaining weight loss. If there are no health prohibitions, choose one that is enjoyable. Check with a doctor about any health consideration. [See In-Depth Report #29: Exercise.]
Hunger pangs should not be taken as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat, and track calories carefully. Studies on weight control that depend on self-reporting of food intake frequently reveal that subjects badly misjudge how much they eat (typically underestimating high-calorie foods and overestimating low-calorie foods). In one study, even dietitians underreported their calorie intake by 10%. People who do not carefully note everything they eat tend to take in excessive calories when they believe they are dieting.
For patients who cannot lose weight with diet alone, effective weight-loss medications are now available, including orlistat (Xenical) and sibutramine (Meridia). Orlistat may have particular benefits for patients with type 2 diabetes. This drug may delay or even prevent the onset or progression of diabetes. It may also improve cholesterol levels, regardless of weight loss. A non-prescription form of orlistat, Alli, is now available. Sibutramine is also helpful in weight loss but should not be used by patients with high blood pressure or kidney or liver problems.
Once a person has lost weight, maintenance is required. To maintain a healthy weight, make careful decisions about how many calories you consume in food and how many calories you expend through physical activity. Such thinking will eventually become automatic.
A procedure known as bariatric surgery has been very helpful in producing rapid weight loss and improving insulin and glucose levels in people with diabetes.

Even repeated weight loss failure is no reason to give up. [See In-Depth Report #53: Weight control and diet.]

Calorie restriction has been the cornerstone of obesity treatment. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels.

The standard dietary recommendations for losing weight are:

As a rough rule of thumb, 1 pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds and is mildly active might need only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might need 25 calories per pound (2,025 calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Avoid saturated fats (found in animal products).

Heart-Healthy Diets

In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 - 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish -- such as salmon, mackerel, and sardines -- are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Limit beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

[See In-Depth Report #43: Heart-healthy diet.]

Dietary guidelines from the National Cholesterol Education Program recommend:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains and legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides or low HDL or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (such as Benecol or Take Control). Avoid trans fatty acids found in commercial products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

There are several variations to the Mediterranean diet, but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet's main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season foods with garlic, onions, and herbs.
Use virgin olive oil.

Low-carb diets, such as South Beach, The Zone, and Sugar Busters, rely on a concept called the "glycemic index (GI)," which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include white bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans.

A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women. However, another 2006 study suggested that low-glycemic index diets that are high in carbohydrates can also promote weight loss and reduce body fat.

A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride levels and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels. A 2007 Journal of the American Medical Association study that compared four different diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet helped raise HDL levels, and reduce triglyciderides, but had no effect on LDL levels nor insulin or glucose measurements. Women who followed the Atkins diet also had improved blood pressure compared to patients on the other diets. The Atkins diet resulted in slightly better weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors. Some experts think that the main finding from this study is that even a moderate weight loss can help improve heart health.

Although low-carbohydrate diets may produce good short-term weight loss, they do not appear to help patients maintain weight loss in the long term. The American Diabetes Association does not recommend low-carb diets (less than 130 g of carbohydrates per day) for treatment of overweight and obesity.

Dietary guidelines recommend keeping total fat intake to 25 - 35% of total daily calories, with saturated fat less than 7% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories.

In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated and omega-3 polyunsaturated) and bad fats (saturated and trans fats).

Another 2006 study indicated that low-fat, vegan diets may help improve glycemic control and increase insulin sensitivity. The higher fiber content of these diets, plus lower intake of total and saturated fat, may account for some of these benefits. A vegan diet eliminates all meat and dairy products.

The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure.)
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. In one study people who increased their intake of fruits and vegetables experienced a drop in blood pressure after 6 months. Many of these foods are rich in potassium, fiber, or both, which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein or monounsaturated fats may help reduce heart disease risk factors. [See In-Depth Report #14: High blood pressure.]

Diabetic Exchange Lists

The objective of using diabetic exchange lists is to maintain the proper balance of carbohydrates, proteins, and fats throughout the day. Patients should meet with a dietician or diabetes nutrition expert for help in learning this approach.

In developing a menu, patients must first establish their individual dietary requirements, particularly the optimal number of daily calories and the proportion of carbohydrates, fats, and protein. The exchange lists should then be used to set up menus for each day that fulfill these requirements.

The following are some general rules:

The diabetic exchanges are six different lists of foods grouped according to similar calorie, carbohydrate, protein, and fat content; these are starch/bread, meat, vegetables, fruit, milk, and fat. A person is allowed a certain number of exchange choices from each food list per day.
The amount and type of these exchanges are based on a number of factors, including the daily exercise program, timing of insulin injections, and whether or not an individual needs to lose weight or reduce cholesterol or blood pressure levels.
Foods can be substituted for each other within an exchange list but not between lists even if they have the same calorie count.
In all lists (except in the fruit list) choices can be doubled or tripled to supply a serving of certain foods. (For example 3 starch choices equal 1.5 cups of hot cereal or 3 meat choices equal a 3-ounce hamburger.)
On the exchange lists, some foods are "free." These contain less than 20 calories per serving and can be eaten in any amount spread throughout the day unless a serving size is specified.

The following are the categories on exchange lists:

Starches and Bread. Each exchange under starches and bread contains about 15 grams of carbohydrates, 3 grams of protein, and a trace of fat for a total of 80 calories. A general rule is that a half-cup of cooked cereal, grain, or pasta equals one exchange. One ounce of a bread product is 1 serving.

Meat and Cheese. The exchange groups for meat and cheese are categorized by lean meat and low-fat substitutes, medium-fat meat and substitutes, and high-fat meat and substitutes. Use high-fat exchanges a maximum of 3 times a week. Fat should be removed before cooking. Exchange sizes on the meat list are generally 1 ounce and based on cooked meats (3 ounces of cooked meat equals 4 ounces of raw meat).

Vegetables. Exchanges for vegetables are 1/2 cup cooked, 1 cup raw, and 1/2 cup juice. Each group contains 5 grams of carbohydrates, 2 grams of protein, and 2 - 3 grams of fiber. Vegetables can be fresh or frozen; canned vegetables are less desirable because they are often high in sodium. They should be steamed or cooked in a microwave without added fat.

Fruits and Sugar. Sugars are included within the total carbohydrate count in the exchange lists. Sugars should not be more than 10% of daily carbohydrates. Each exchange contains about 15 grams of carbohydrates for a total of 60 calories.

Milk and Substitutes. The milk and substitutes list is categorized by fat content similar to the meat list. A milk exchange is usually 1 cup or 8 ounces. Those who are on weight-loss or low-cholesterol diets shoudl follow the skim and very low-fat milk lists -- while avoiding the whole milk group. Others should use the whole milk list very sparingly. All people with diabetes should avoid artificially sweetened milks.

Fats. A fat exchange is usually 1 teaspoon, but it may vary. People, of course, should avoid saturated and trans fatty acids and choose polyunsaturated or monounsaturated fats instead.


Calories	1,200	1,500	1,800	2,000	2,200
Starch/Bread	5	8	10	11	13
Meat	4	5	7	8	8
Vegetable	2	3	3	4	4
Fruit	3	3	3	3	3
Milk	2	2	2	2	2
Fat	3	3	3	4	5

Exercise

Sedentary habits, especially watching TV, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercises. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself. (In general, patients with diabetes should aim for a heart rate target of 55 - 85% of their maximum heart rate when exercising.)

Strength Training. Strength training, which increases muscle and reduces fat, may also be helpful for people with diabetes.

Some Precautions for People with Diabetes Who Exercise. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dl or under 100 mg/dl.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.

Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure. [See In-Depth Report #29: Exercise.]

Chronic stress has been associated with the development of insulin resistance, a primary factor in diabetes. Stress can also worsen existing diabetes by impairing the patient's ability to manage the disease effectively. Stress-relieving techniques include meditation, biofeedback, relaxation response, and yoga. One study reported that yoga helped patients with type 2 diabetes reduce their need for oral medications. Studies have also indicated that yoga and Tai Chi (an ancient Chinese exercise involving slow relaxing movements) may lower blood pressure almost as well as moderate-intensity aerobic exercises. [See In-Depth Report #31: Stress.]

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.jdrf.org -- Juvenile Diabetes Research Foundation
www.kidney.org -- National Kidney Foundation
www.joslin.org -- Joslin Diabetes Center
www.eatright.org -- American Dietetic Association
www.nal.usda.gov/fnic -- Food and Nutrition Information Center
www.gourmetconnection.com/diabetic -- Diabetic Gourmet Magazine

References

American Diabetes Association. Nutrition recommendations and interventions for diabetes: A position statement of the American Diabetes Association. Diabetes Care. 2007 Jan;30 Suppl 1:S48-65.

American Heart Association Nutrition Committee; Lichtenstein AH, Appel LJ, Brands M, Carnethon M, Daniels S, et al. Diet and lifestyle recommendations revision 2006: a scientific statement from the American Heart Association Nutrition Committee. Circulation. 2006 Jul 4;114(1):82-96. Epub 2006 Jun 19.

Barnard ND, Cohen J, Jenkins DJ, Turner-McGrievy G, Gloede L, Jaster B, et al. A low-fat vegan diet improves glycemic control and cardiovascular risk factors in a randomized clinical trial in individuals with type 2 diabetes. Diabetes Care. 2006 Aug;29(:1777-83.

Gardner CD, Kiazand A, Alhassan S, Kim S, Stafford RS, Balise RR, et al. Comparison of the Atkins, Zone, Ornish, and LEARN diets for change in weight and related risk factors among overweight premenopausal women: the A TO Z Weight Loss Study: a randomized trial. JAMA. 2007 Mar 7;297(9):969-77.

Gillies CL, Abrams KR, Lambert PC, Cooper NJ, Sutton AJ, Hsu RT, et al. Pharmacological and lifestyle interventions to prevent or delay type 2 diabetes in people with impaired glucose tolerance: systematic review and meta-analysis. BMJ. 2007 Feb 10;334(7588):299. Epub 2007 Jan 19.

Halton TL, Willett WC, Liu S, Manson JE, Albert CM, Rexrode K, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006 Nov 9;355(19):1991-2002.

Lindstrom J, Ilanne-Parikka P, Peltonen M, Aunola S, Eriksson JG, Hemio K, et al. Sustained reduction in the incidence of type 2 diabetes by lifestyle intervention: follow-up of the Finnish Diabetes Prevention Study. Lancet. 2006 Nov 11;368(9548):1673-9.

Liu S, Choi HK, Ford E, Song Y, Klevak A, Buring JE, et al. A prospective study of dairy intake and the risk of type 2 diabetes in women. Diabetes Care. 2006 Jul;29(7):1579-84.

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K, et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

Schulze MB, Schulz M, Heidemann C, Schienkiewitz A, Hoffmann K, Boeing H. Fiber and magnesium intake and incidence of type 2 diabetes: a prospective study and meta-analysis. Arch Intern Med. 2007 May 14;167(9):956-65.

Stranges S, Marshall JR, Natarajan R, Donahue RP, Trevisan M, Combs GF, et al. Effects of long-term selenium supplementation on the incidence of type 2 diabetes: a randomized trial. Ann Intern Med. 2007 Jul 9; [Epub ahead of print]

Ting RZ, Szeto CC, Chan MH, Ma KK, Chow KM. Risk factors of vitamin B(12) deficiency in patients receiving metformin. Arch Intern Med. 2006 Oct 9;166(18):1975-9.

Ziegler D, Ametov A, Barinov A, Dyck PJ, Gurieva I, Low PA, et al. Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial. Diabetes Care. 2006 Nov;29(11):2365-70.

Review Date:
7/20/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

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adam.com

Heart-healthy diet

FitSugar — Wed, 08 Oct 2008 17:35:07 -0700

In This Report

Highlights
Introduction
Dietary Changes
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

General Dietary Guidelines

In 2006, the American Heart Association (AHA) revised its dietary and lifestyle recommendations. The new guidelines specifically recommend limiting daily saturated fat intake to less than 7% and trans fats to less than 1% of total daily calories.
The AHA recommends consuming plenty of deep-colored vegetables and fruits, eating oily fish at least twice a week, and including whole grains in your daily diet.

Fish

Women with existing heart disease may consider taking fish oil supplements, suggests 2007 AHA guidelines. Women should include a variety of low-mercury fish in their diet. Women who are of childbearing age or nursing should avoid high-mercury fish (such as swordfish) and limit tuna consumption to no more than 6 ounces a week.
The benefits of fish outweigh its risks, according to a 2006 Journal of the American Medical Association (JAMA) study. The researchers found that eating fish 1 – 2 times a week may help reduce the risk of heart-related death by 36%.

Diet Plans

Low-carbohydrate diets do not increase heart disease risks for women, indicates a 2006 New England Journal of Medicine study. A 2007 JAMA study found that people lost somewhat more weight on the Atkins diet compared with three other popular diet plans. The Atkins diet also helped raise HDL (“good”) cholesterol levels, reduce triglycerides, and improve blood pressure. Some experts think that the weight loss may have been the main factor for the heart benefits.
However, according to a 2006 study in the Archives of Internal Medicine, diets that are high in carbohydrates but low on the glycemic index may also help promote weight loss, reduce body fat, and improve heart disease risk factors.
The Mediterranean diet is better than a low-fat diet in quickly lowering blood pressure, cholesterol levels, and blood sugar levels, according to a 2006 Annals of Internal Medicine study.

Introduction

Heart-Healthy Goals. The goals of a heart-healthy diet are to eat foods that help obtain or maintain healthy levels of cholesterol and fatty molecules called lipids. You can achieve this by:

Reducing overall cholesterol levels and low-density lipoproteins (LDL), which are harmful to the heart
Increasing high-density lipoproteins (HDL), which are beneficial for the heart
Reducing other harmful lipids (fatty molecules), such as triglycerides and lipoprotein(a)

Any diet should also help keep blood pressure and weight under control.

General Recommendations

In 2006, the American Heart Association (AHA) issued revised diet and lifestyle recommendations. The current guidelines recommend:

Balance calorie intake and physical activity to achieve or maintain a healthy body weight. (Controlling weight, quitting smoking, and exercising regularly are essential companions of any diet program. Try to get at least 30 minutes, and preferably 60 – 90 minutes, of daily exercise.)
Consume a diet rich in a variety of vegetables and fruits. Vegetables and fruits that are deeply colored (spinach, carrots, peaches, berries) are especially recommended as they have the highest micronutrient content.
Choose whole-grain, high-fiber foods. These include fruits, vegetables, and legumes (beans). Good whole grain choices include whole wheat, oats/oatmeal, rye, barley, brown rice, buckwheat, bulgur, millet, and quinoa.
Consume fish, especially oily fish, at least twice a week (about 8 ounces/week). Oily fish such as salmon, mackerel, and sardines are rich in the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). Consumption of these fatty acids is linked to reduced risk of sudden death and death from coronary artery disease.
Limit daily intake of saturated fat (found mostly in animal products) to less than 7% of total calories, trans fat (found in hydrogenated fats, commercially baked products, and many fast foods) to less than 1% of total calories, and cholesterol (found in eggs, dairy products, meat, poultry, fish, shellfish) to less than 300 mg per day. Choose lean meats and vegetable alternatives (such as soy). Select fat-free and low-fat dairy products. Grill, bake, or broil fish, meat, and skinless poultry.
Use little or no salt in your foods. Reducing salt can lower blood pressure and decrease the risk of heart disease and heart failure.
Cut down on beverages and foods that contain added sugars (corn syrups, sucrose, glucose, fructose, maltrose, dextrose, concentrated fruit juice, honey).
If you consume alcohol, do so in moderation. The AHA recommends limiting alcohol to no more than 2 drinks per day for men and 1 drink per day for women.

Women

The AHA guidelines for women are similar to the general dietary recommendations. However, the AHA suggests that women with existing heart disease consider taking omega-3 fatty acid supplements (850 - 1,000 mg/day of EPA and DHA). For women with high triglyceride levels, higher doses (2 - 4 g/day) may be appropriate. The AHA recommends against women taking antioxidant vitamin supplements (C, E, beta-carotene) or folic acid supplements for prevention of heart disease.

In addition, women who are pregnant or breast-feeding should avoid eating fish that is high in mercury content (shark, swordfish, mackerel, and tile fish). Choose fish and shellfish that are lower in mercury content and eat about 12 ounces/week. (The AHA recommends a higher weekly fish amount for women than for men. However, women of childbearing age should limit tuna to 6 ounces a week to reduce the risks for mercury contamination.)

Children

Atherosclerosis, the build-up of plaque in the arteries, begins in childhood. Experts stress the importance of heart-healthy dietary guidelines for children and adolescents to help prevent the development of heart disease later in life. Children should eat foods that are low in saturated fat, trans fat, and cholesterol. These foods include:

Fruits and vegetables
Whole grains
Low-fat and nonfat dairy products
Beans, fish, and lean meats

Cholesterol is a soft, waxy substance that is present in parts of the body including the nervous system, skin, muscle, liver, intestines, and heart. It is made by the body and obtained from animal products in the diet. Cholesterol is manufactured in the liver and is needed for normal body functions, including the production of hormones, bile acid, and vitamin D. Excessive cholesterol in the blood contributes to atherosclerosis and subsequent heart disease. The risk of developing heart disease or atherosclerosis increases as the level of blood cholesterol increases.

[See In-Depth Report #23: Cholesterol; Report #3: Coronary artery disease and angina; Report #14: High blood pressure; Report #53: Weight control and diet.]

All fats, good or bad, are high in calories compared to proteins and carbohydrates. In order to calculate daily fat intake, multiply the number of fat grams eaten by nine (one fat gram is equal to 9 calories, whether it's oil or fat) and divide by the number of total daily calories desired. One teaspoon of oil, butter, or other fats equals about 5 grams of fat. All fats, no matter what source they are from, add the same calories. The American Heart Association recommends that fats and oils have less than 2 grams of saturated fat per tablespoon.

The Chemistry of Fats and Cholesterol.

Fatty Acids. All fats and oils found in foods are made up of chains of molecules called fatty acids. There are three major chains: saturated fatty acid (found mostly in animal products) and two unsaturated fatty acids -- monounsaturated and polyunsaturated fatty acids (found in plant products). The oils and fats that people and animals eat are nearly always mixtures of these three chains, but one type of fatty acid usually predominates in specific oils or fats.
Essential Fatty Acids. In addition, there are three chemical subgroups of polyunsaturated fatty acids called essential fatty acids: omega-3 and omega-6 polyunsaturated fatty acids, and omega-9 monounsaturated fatty acids.
Trans Fatty Acids. Trans fatty acids are manufactured by adding hydrogen atoms to polyunsaturated fatty acids (a process called hydrogenation). This process helps keep foods fresh, or may be performed to produce a solid fat product, such as margarine.

Harmful Fats. Reducing consumption of saturated fats and trans fatty acids is the first essential step in managing cholesterol levels through diet.

Saturated Fats. Saturated fats are found predominantly in animal products, including meat and dairy products. They are strongly associated with higher cholesterol levels, and they may be even more dangerous in women than in men. High-fat meals are associated with sudden surges in triglyceride levels and other lipids along with impaired blood flow in the arteries to the heart. (Tropical oils such as palm, coconut, and cocoa butter are also high in saturated fats.) The American Heart Association recommends limiting saturated fat consumption to less than 7% of total calories per day.

Click the icon to see an image of saturated fats.

Trans Fatty Acids. Trans fatty acids are manufactured fats created during a process called hydrogenation, which is aimed at stabilizing polyunsaturated oils to prevent them from becoming rancid and to keep them solid at room temperature. They are particularly dangerous for the heart and may pose a risk for certain cancers. These partially hydrogenated fats are even worse than saturated fats. Studies report that high consumption of these fats reduces HDL cholesterol levels, has harmful effects on the linings of the arteries, and may increase the risk for type 2 diabetes. Hydrogenated fats are used in stick margarine and in many fast foods and baked goods, including most commercially produced white breads. (Liquid margarine is not hydrogenated and is recommended.) The FDA ordered that food labels list the amount of trans fatty acids in food products beginning in January 2006. The American Heart Association recommends limiting daily consumption of trans fats to less than 1% of total daily calories.

Click the icon to see an image of trans fatty acids.

Polyunsaturated fats are found in safflower, sunflower, corn, and cottonseed oils and fish.
Monounsaturated fats are mostly present in olive, canola, and peanut oils and in most nuts. (Canola is the least saturated of all the fats.) Studies report that replacing carbohydrates with monounsaturated fats improves glucose control after meals and reduces triglycerides in people with type 2 diabetes. Oils are more calorie-dense, however, and such patients should be wary of weight gain.

Researchers are most interested in the smaller fatty-acid building blocks contained in both oils, which may have more specific effects on lipids. Three important fatty acids are the essential fatty acids omega-3, omega-6, and omega-9.

Omega-3 fatty acids are found in fish oil (docosahexaenoic and eicosapentaneoic acids) and plants (alpha-linolenic acid).

Click the icon to see an image of omega-3 fatty acids.

Docosahexaenoic (DHA) and Eicosapentaneoic (EPA) Acids. DHA and EPA are found in fish oils, and evidence suggests that they have significant benefits for the heart, including reducing sudden death from heart disease, inflammation, blood clotting factors, blood pressure, and improving triglyceride and HDL levels. Results from a study presented at the 2005 meeting of the American Heart Association suggested that daily EPA supplements plus statin therapy can protect against heart attack, angina, and coronary artery disease. However, although fish and fish oil are good for the heart, patients who have an implantable defibrillator should not take fish oil supplements. A 2005 study suggested that these supplements may make heart rhythm problems worse in some patients.
Alpha-linolenic Acid. Alpha-linolenic acid is a plant precursor of DHA, which means the body can convert it to DHA. Sources include canola oil, soybeans, flaxseed, and certain nuts and seeds (walnut, flax, chia, and sometimes pumpkin seed). Some, but not all, studies suggest that oils or foods containing alpha-linolenic acid may also be heart-protective. Supplements or foods containing alpha-linolenic acid may also protest the heart. For example studies have reported heart protection from flaxseed supplements and also from nuts, such as almonds, macadamia, and walnuts. Nuts are high in calories, however.

Click the icon to see an image of different types of weight gain.

Omega-9 monounsaturated fatty acids are contained in canola and olive oil, which help protect the heart.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking, deliver some of the desirable qualities of fat, but do not add as many calories.

Plants substances known as sterols, and their derivatives called stanols, reduce cholesterol by blocking its absorption in the intestinal tract. Margarines containing sterols (Benecol, Take Control) are available. Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand as part of a low-fat diet can lower LDL and total cholesterol. In one study, consuming a sterol-based margarine doubled the LDL-lowering effects of a statin (a common cholesterol-lowering drug) compared to a standard margarine. These products do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does. They may be hydrogenated and include some trans fatty acids, however.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it helps improve cholesterol levels and may help overweight people lose weight. Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-replacers are also available. Although studies to date have not shown any significant adverse health effects, their effect on weight control is uncertain, since many of the products containing them may be high in sugar. One study suggested that people who consume foods that contain fat substitutes do not learn to dislike fatty foods, while people who learn to cook using foods naturally lacking or low in fat eventually lose their taste for high-fat diets.

Click the icon to see an image of foods that contain cholesterol.

Carbohydrates are either complex (as in starches) or simple (as in fruits and sugars). One gram of carbohydrates equals four calories. The current general recommendation is that carbohydrates should provide between 50 - 60% of the daily caloric intake. Many studies report that people can protect their heart and circulation by eating plenty of fruits and vegetables.

Complex Carbohydrates. Complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Most complex carbohydrates are high in fiber, which is important for health. Whole grains specifically are extremely important for people with diabetes or at risk for it.

Click the icon to see an image of complex carbohydrates.

Simple Carbohydrates (Sugar). Experts recommend that no more than 10% of daily calories should come from sugar. (Currently, Americans eat nearly half a pound of sugar a day on average, and sugar intake constitutes 25% of a day's calories.) Sugars are usually one of two types:

Click the icon to see an image of simple carbohydrates.

Sucrose. Source of most dietary sugar, found in sugar cane, honey, and corn syrup.
Fructose. Found in fruits and vegetables. Although fructose does not appear to be have any different effects in the body than sucrose, most of the fruits and vegetables that contain it are vital for good health.

High levels of sugar consumption -- whether fructose or sucrose -- have been associated with higher triglycerides and lower levels of HDL cholesterol, the so-called good cholesterol. The high consumption of sugar is most likely one of the factors in the current obesity epidemic. Soda, other sweetened beverages, and fruit juice are major contributors to childhood obesity.

Fiber is an important component of many complex carbohydrates. It is almost always found only in plants. (One exception is chitosan, a dietary fiber made from shellfish skeletons.) Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. High-fiber diets (up to 55 grams a day) can be very helpful. Different fiber types may have specific benefits:

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, legumes, and fruit and vegetable peels) may help achieve weight loss. Consuming whole grains on a regular basis may lower the risk for heart disease and heart failure, improve factors involved with diabetes, and lower the risk for type 2 diabetes. (Wheat bran taken as a supplement has not been associated with any benefits. The whole grain may be needed for good health.) High consumption of nuts (such as almonds, macadamia, and walnuts) may be highly heart protective, independent of their fiber content.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) may help achieve healthy cholesterol levels and possibly reduce blood pressure as well. For example, one study indicated that eating beans four or more times a week reduced the risk for heart disease by 22%. Oat bran has also been highly studied for its benefits on the heart.
Soluble fiber supplements, such as those that contain psyllium or glucomannan, may also be beneficial. Psyllium is taken from the husk of a seed grown in India and is very effective for lowering total and LDL cholesterol. It is found in laxatives (Metamucil), breakfast cereals (Bran Buds, Plantaben), and other products. However, some studies suggest that psyllium increases triglyceride levels in postmenopausal women. Sodium levels may also rise. People who increase intake of soluble fiber should also drink more water.

Click the icon to see an image of soluble and insoluble fiber.

In general, experts recommend that proteins should provide 12 - 20% of daily calories. One gram of protein contains four calories. Protein is important for strong muscles and bones and may have specific benefits on blood pressure. The best sources of protein are fish, poultry, and soy. Restrict intake of red meat or any meat that is not lean.

Fish. Fish is probably the best source of protein. Evidence suggests that eating moderate amounts of fish (twice a week) may improve triglyceride and HDL levels and help lower the risks for death from heart disease, dangerous heart rhythms, blood pressure, a tendency for blood clots, and the risk for stroke.

Click the icon to see an image of stroke.

The most healthy fish are oily fish, such as salmon, mackerel, or sardines, which are high in omega-3 fatty acids. A 2006 Journal of the American Medical Association (JAMA) study suggested that modest consumption of oily fish can reduce the risk of heart-related death by 36% and death from all causes by 17%. On average, three capsules of fish oil (preferably as supplements of DHA-EPA) is about equivalent to eating one serving of fish.

Most guidelines recommend eating fish at least twice a week. Doctors may recommend that people with existing heart disease or high triglyceride levels consume extra quantities or take DHA-EPA supplements.

Women of childbearing age or nursing mothers should avoid fish that contains high amounts of mercury (shark, swordfish, golden bass, king mackerel) and limit intake of tuna to 6 ounces/week. They should, however, try to eat at least 12 ounces/week of a variety of lower mercury-containing fish and shellfish (catfish, salmon, haddock, perch, tilapia, trout, crab, shrimp, scallops). According to the JAMA study, the benefits of fish intake (especially from low-mercury fish) outweigh the potential risks.

For many years, soy was promoted as a food that could help lower cholesterol and improve heart disease risk factors. But an important 2006 American Heart Association (AHA) review of studies found that soy protein and isoflavone supplement pills do not really have any effects on cholesterol or heart disease prevention. The AHA still encourages patients to include soy foods as part of an overall heart healthy diet but does not recommend using isoflavone supplements.

Meat and Poultry. For heart protection, choose lean meat. Saturated fat in meat is the primary danger to the heart. The fat content of meat varies depending on the type and cut. It is best to eat skinless chicken or turkey. However, the leanest cuts of pork (loin and tenderloin), veal, and beef are nearly comparable to chicken in calories and fat as well as their effect on LDL and HDL levels. However, even chicken and lean meat do not improve cholesterol levels and, in terms of heart health, fish is a more desirable choice.

Dairy Products. The best dairy choices are low-fat or fat-free products. A 2006 study indicated that consuming low-fat dairy products can help lower blood pressure. In the study, patients who ate the most low-fat dairy products had lower systolic blood pressure. A 2002 study also reported a lower incidence of factors related to type 2 diabetes and heart disease (insulin resistance, high blood pressure, obesity, and unhealthy cholesterol) with a high intake of dairy products. Some researchers suggest the calcium in dairy products may be partially responsible for these benefits. However, at least with high blood pressure, many studies indicate that the helpful effects of dairy products are not directly related to calcium.


Foods	Important Phytochemicals (Plant chemicals) Contained in the Foods	Vitamins and other valuable food components	Possible Benefits
Apples	Flavonoids	Fiber	May protect against certain cancers (lung), heart disease, asthma, and type 2 diabetes.
Avocados		Vitamin E, vitamin B6, folate	May be heart protective.
Beans	Flavonoids	Folate, iron, potassium and zinc, fiber	Some experts believe beans are the perfect food.
Berries, all kinds of dark colored (especially blueberries)	Ellagic Acid	Vitamin C, minerals	May protect the aging brain. (Many studies recommend blueberries.)
Broccoli (also kale, Brussels sprouts, cauliflower)	Flavonoids, Isothiocyanates	Vitamin C, folate, fiber, and selenium	Anticancer properties. Protects against heart disease and stroke.
Carrots and other bright yellow vegetables	Lutein, Beta carotene	Vitamin A (converted from carotenoids), vitamin C, fiber	Protect heart, eyes, lungs. (Cooking carrots may increase their benefits.)
Fish (particularly oily fish, such as mackerel, salmon, sardines)		Vitamins B3 and B12, essential fatty acids, selenium	Heart and brain protective.
Garlic	Allium (organosulfurs)		Although garlic does not appear to help lower cholesterol levels, it still may protect against heart disease. Possible infection fighter.
Ginger	Zingiberaceae		Cancer fighting properties.
Grains (whole)	Lignans (phytoestrogens)	Vitamin B, selenium (important antioxidant mineral), fiber, folate	May help reduce the ability of cancer cells to invade health tissue.
Grapes and red wine	Flavonoids, resveratrol		Fight heart disease and cancer. May have activity against asthma, and type 2 diabetes.
Nuts (such as almonds, macadamia, and walnuts)		Vitamin E, Vitamin B1, Essential fatty acids, folate, fiber	May lower cholesterol levels, reduce sudden death rates from heart disease, and help prevent stroke and type 2 diabetes.
Onions	Flavonoids, allium (organosulfurs)		May have activity against certain cancers (lung), heart disease, asthma, and type 2 diabetes.
Oranges and orange juice	Monoterpenes	Vitamin C, folate, potassium, fiber	Many health benefits. Increase HDL levels and helps maintain normal blood pressure.
Potatoes (Sweet)		Vitamins A, C, and E	Many health benefits.
Soy: Four ounces of tofu equals about 8 - 13 grams of soy. A soy burger contains about 18 grams of soy.	Isoflavones (phytoestrogens), flavonoids, phytosterol, phytate, saponins		May have effects similar to estrogen, including maintaining bone and benefiting the heart. May protect against prostate cancer and possibly other cancers. Possible protection against mental decline.
Spinach and other dark green leafy vegetables	Zeaxanthin, Beta carotene	Vitamin C, folate, vitamin A (converted from carotenoids)	Protects heart, lungs and brain.
Tomatoes	Lycopene, flavonoids	Vitamin C, biotin, minerals	Protects heart. Studies suggest reductions in prostate and other cancers. Infection fighters.

Antioxidant Vitamins E, C, and A. Vitamins E, C, and A are most studied for their health effects because they serve as antioxidants. Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants ). High intake of foods rich in these vitamins (as well as other food chemicals) have been associated with many health benefits, including prevention of heart problems.

Research on the effects of vitamin supplements on heart disease and diabetes, however, has been mixed. Although some research initially observed favorable effects from vitamin E in preventing blood clots and preventing build-up of plaque on blood vessel walls, most studies found no heart protection from either vitamin E or C supplements. A 2005 Journal of the American Medical Association study found that vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases. Results from the long-term Women’s Health Study, also released in 2005, showed that vitamin E supplements do not protect women from attacks or stroke.

Click the icon to see an image of the benefits of vitamin C.

Antioxidants are chemicals that act as scavengers of particles known as oxygen-free radicals (also sometimes called oxidants). These chemically active particles are by-products of many of the body's normal chemical processes. Their numbers are increased by environmental assaults, such as smoking, chemicals, toxins, and stress. In higher levels, oxidants can be very harmful:

Oxygen-free radicals can damage cell membranes and interact with genetic material, possibly contributing to the development of a number of disorders including diabetes, cancer, heart disease, cataracts, and even the aging process itself.

They can also enhance the dangerous properties of low-density lipoprotein (LDL) cholesterol, a major player in the development of coronary artery disease.

Antioxidant vitamins (A, C, and E), beta carotene, and many phytochemicals can neutralize free radicals and have been studies for possible benefits. It is clear that such vitamins are required to prevent deficiency diseases. In addition, foods rich in antioxidants are important disease fighters. To date, however, there is no strong evidence that antioxidant supplements offer any real protection.

Special Warning on High-Dose Antioxidant Supplements. Some studies suggest that excessive use of antioxidant supplements may interfere with other nutrients or convert into pro-oxidants and become harmful. Some of the findings are as follows:

A 2002 randomized study of postmenopausal women found a higher risk for heart disease in people who took vitamin E and C supplements. A 2005 study found that vitamin E supplements can increase the risk of heart failure, especially for patients with diabetes or vascular diseases.
Of particular concern are studies that have found an increase in lung cancer and overall mortality rate among smokers who took beta carotene supplements. A 2000 study further reported a higher risk for cancer in male smokers who took multivitamins plus A, C, or E. Even more worrisome, in people with existing cancer, high doses of antioxidant vitamins, such as vitamin C or beta carotene, may actually protect cancer cells (just as they do healthy cells).

Click the icon to see an image of a cataract.

Click the icon to see an image of coronary artery disease.

Click the icon to see an image of phytochemicals.

B Vitamins (Folic Acid). Deficiencies in the B vitamins folate (known also as folic acid), B6, and B12 have been associated with a higher risk for heart disease in some studies. Such deficiencies produce higher blood levels of homocysteine, an amino acid that has been associated with a higher risk for heart disease, stroke, and heart failure. Researchers have been studying whether vitamin B supplements can reduce homocysteine levels and, consequently, heart disease risks.

Several major 2006 studies indicated that while B vitamin supplements help lower homocysteine levels, they have no effect on heart disease outcomes. The studies, published in the New England Journal of Medicine, examined patients who had either recently had a heart attack or who suffered from diabetes or heart disease. Results showed a similar number of heart attacks and strokes among patients who took folic acid and B6 and B12 vitamins and those who received placebo. And, the vitamins seemed to increase risks for patients who had undergone stenting. A 2006 Journal of the American Medical Association study also found that folic acid supplements did not help reduce the risk of heart disease or stroke in patients with a history of vascular disease. Some experts think that homocysteine may be a marker for heart disease rather than a cause of it.

Click the icon to see an image of sources of folate.

Click the icon to see an image of sources of B12.

Potassium, Magnesium, and Calcium. Some experts believe that sufficient intake of minerals, particularly potassium, magnesium, and calcium, may be even more beneficial than salt restriction for reducing blood pressure.

Potassium. Evidence strongly indicates that a potassium-rich diet can help achieve healthy blood pressure levels, and that potassium supplements can lower systolic blood pressure by 1.8 m Hg and diastolic blood pressure by 1 mm Hg. Some evidence suggests that a potassium-rich diet can reduce the risk of stroke by 22 - 40%. Expert guidelines now support the use of potassium supplements or enough dietary potassium to achieve 3,500 mg per day for people who have no risk factors for excess potassium levels. (People who take potassium-sparing diuretics should not take potassium supplements.) This goal is particularly important for people who have a high sodium intake. The best source of potassium is from the fruits and vegetables that contain them. Potassium-rich foods include bananas, oranges, pears, prunes, cantaloupes, tomatoes, dried peas and beans, nuts, potatoes, and avocados.
Magnesium. Some studies report that magnesium supplements may cause small but significant reductions in blood pressure. The recommended daily allowance is 320 mg. People who live in soft water areas, who use diuretics, or who have other risk factors for magnesium loss may require more dietary magnesium than others. No major studies have been done on long-term benefits or risks of magnesium supplements.
Calcium. Calcium regulates the tone of the smooth muscles lining blood vessels. Studies have found that people who consume enough dietary calcium on a daily basis have lower blood pressure than those who do not. Hypertension increases calcium loss from the body. The effects of extra calcium on blood pressure, however, are mixed, with some showing higher pressure.

Click the icon to see an image of sources of calcium.

In the past, everyone was advised to consume less than 2,400 mg (about one teaspoon) of sodium (salt) each day. However, in February 2004, a long-awaited report by the Institute of Medicine (IOM) recommended that individuals slash their salt intake in half. The IOM report stressed that no one should consume more than 1,500 mg/day. Because blood pressure tends to rise with age, the Institute also suggested that people over 50 reduce their sodium intake to less than 1,300 mg daily; those over 70 should not eat more than 1,200 mg a day. Reducing sodium may also help protect against heart failure. Unfortunately many people find it very difficult to achieve these goals. Experts disagree on the overall benefits of salt restriction for everyone. Still, the following people should take particular measures to restrict salt:

People at Risk for Salt-Sensitivity. About half of people with hypertension have blood pressure that reacts significantly to salt. Such people are known as salt-sensitive. Among those at highest risk for salt sensitivity are African-Americans, people with diabetes, and elderly people.
Overweight People. Overweight individuals may absorb and retain sodium differently from people with normal weights. One study reported that high sodium intake was associated with an increased risk of heart disease and all-cause mortality in overweight, but not in normal weight, people. Reducing sodium can also help reduce the risk of stroke in people who are overweight.

Water. Many heart risk factors, especially those associated with blood clotting, are increased with dehydration. In one study, drinking five or more glasses of water a day was significantly associated with a lower risk for fatal heart events than drinking two or fewer glasses a day.

Alcohol. A number of studies have found heart protection from moderate alcohol intake (one or two glasses a day). The benefits reported include higher HDL levels, blood clot prevention, and anti-inflammatory properties plus lower rates of heart failure and heart attack. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit.

On the negative side, an estimated 10% of hypertension cases are caused by alcohol abuse. Men with high blood pressure should limit their intake to an average of no more than one or two drinks a day, and women (especially those at risk for breast cancer) and lighter people should only have one drink a day. (A “drink” is equivalent to a 12-ounce bottle of beer, a 4-ounce glass of wine, or a 1.5-ounce shot of hard liquor.) Alcohol may raise a man’s risk for atrial fibrillation according to a study in the Archives of Internal Medicine. Pregnant women, people who can't drink moderately, and people with liver disease should not drink at all. People who are watching their weight should be aware that alcoholic beverages are very high in calories.

Caffeinated Beverages.

Tea. Although it contains caffeine, tea, both black and green, is often cited for its health benefits. Green tea especially is rich in chemicals that may offer protection against damaging forms of LDL. A 2006 study of Japanese adults who drank high amounts of green tea (3 or more cups a day) found that green tea consumption was associated with reduced risk of death from heart disease. Green tea did not, however, appear to offer any protection against cancer.
Coffee. Coffee, like red wine, contains phenol, which helps prevent oxidation of LDL cholesterol. However, unfiltered coffee (Turkish coffee, Scandinavian boiled or French pressed coffee, and espresso) contains an alcohol called cafestol, which may raise cholesterol and triglyceride levels. Filtered coffee does not contain this residue. Coffee drinking is associated with small increases in blood pressure, but the risk it poses is very small in people with normal blood pressure. Moderate coffee consumption (1 - 2 cups a day) poses no heart risks and a 2006 Circulation study found that long-term coffee consumption did not increase the risk for heart disease in most people, even if they consumed large daily amounts.

Dietary Changes

The Atkins diet restricts healthful complex carbohydrates in vegetables and particularly in fruits that are known to protect against heart disease. The Atkins diet also causes excessive calcium excretion in urine, which increases the risk for kidney stones and osteoporosis, and the release of ketones. An overload of ketones leads to ketosis, which can cause nausea, lightheadedness, and bad breath.

Low-carb diets such as South Beach, The Zone, and Sugar Busters rely on a concept called the "glycemic index," or GI, which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans. A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women.

There has been debate about whether Atkins and other low-carbohydrate diets can increase the risk for heart disease, especially as people who follow these diets tend to eat more animal-saturated fat and protein and less fruits and vegetables. A 2006 New England Journal of Medicine study of over 80,000 women found that diets lower in carbohydrates and higher in protein do not increase heart disease risk. In fact, if people select vegetable sources of fat and protein (such as soy and nuts), these diets may even moderately reduce the risk of heart disease.

A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride levels and raise HDL (“good”) cholesterol levels, they also raised overall cholesterol and LDL (“bad”) cholesterol levels. In contrast, a 2007 Journal of the American Medical Association study that compared four different diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet helped raise HDL levels, and reduce triglyciderides (although it had no effect on LDL levels). Women who followed the Atkins diet also had improved blood pressure compared to patients on the other diets. The Atkins diet resulted in better weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors. Some experts think that the main finding from this study is that even moderate weight loss can help improve heart health.

The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated “good” fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and possible benefits for people with type 2 diabetes. Experts think that the main health benefit of olive oil is oleic acid, which is a type of monounsaturated fatty acid. Olive oil also contains polyphenol, which are phytochemicals that contain antioxidant properties. A 2006 study found that virgin olive oil, which comes from the first pressing of olives, contains a higher polyphenol content than refined olive oil, which comes from later pressings.

There are several variations to the Mediterranean diet, but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season foods with garlic, onions, and herbs.
Use virgin olive oil.

Positive Arguments. Even though fats make up about 40% of the calories found in the traditional Mediterranean diet, they are largely unsaturated. Growing evidence continues to support the heart-protective properties of the Mediterranean diet. Research has shown that such a diet reduces the risk for a second heart attack and helps cholesterol-lowering statin drugs work better.

Seniors who combine a Mediterranean diet with healthy lifestyle habits live longer lives, according to a 2004 study in The Journal of the American Medical Associationstudy. Researchers observed the effect of a Mediterranean diet on more than 2,000 elderly people for a period of 10 years, and measured the diet's effects on death rates alone and in combination with three risk factors: smoking, physical activity, and alcohol use. Overall, seniors who followed the Mediterranean diet decreased their risk of death from all causes by 23%. The elimination of each additional risk factor boosted their life expectancy rate even more. For example, non-smoking seniors on the diet who exercised regularly and drank only a moderate amount of alcohol reduced their death rates by 65%.

Negative Arguments. Weight gain due to a high intake of fats and risk for alcohol abuse can be problems with the Mediterranean diet. However, a 2006 study that compared several types of Mediterranean diets to a low-fat diet found that the Mediterranean diets were better at lowering blood pressure, cholesterol levels, and blood sugar levels after only 3 months. And, in research presented at the 2007 American College of Cardiology annual conference, the Mediterranean diet proved just as good as the American Heart Association low-fat diet for preventing recurrence of heart attack, stroke, or other heart events.

Other concerns include reduced iron levels and possible calcium loss resulting from a reduced consumption of dairy products. People on the diet should eat foods rich in iron or vitamin C, which aids in iron absorption. They should also ask their doctor if a calcium supplement may be needed because of a lack of dairy products. People should avoid wine if they have risk factors for complications from alcohol. Such people include women who are pregnant or at risk for breast cancer and anyone prone to alcohol abuse.

A diet that is effective in lowering blood pressure is called Dietary Approaches to Stop Hypertension (DASH).

DASH diet recommendations:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal.)
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include calcium-rich dairy products that are non- or low-fat.)
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. In one study people who increased their intake of fruits and vegetables experienced a drop in blood pressure after 6 months. Many of these foods are rich in potassium, fiber, or both which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.)
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with protein-rich foods from plant sources (nuts, seeds, soy) or monounsaturated fats (canola or olive oil) may help reduce heart disease risk factors.

Dietary guidelines recommend keeping total fat intake to 20 - 30% of total daily calories, with saturated fat less than 10% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories.

The Ornish program is a very demanding regimen:

It excludes all oils and animal products except nonfat yogurt, nonfat milk, and egg whites.
Foods stressed are whole grains, legumes, and fresh fruits and vegetables.
People in the program exercise for 90 minutes at least three times a week.
Stress reduction techniques are used.
People do not smoke or drink more than two ounces of alcohol per day.

Positive Arguments.

Low-fat programs may help keep weight off.
Low-fat diets that are high in fiber, whole grains, legumes, and fresh produce offer health advantages in addition to their effects on cholesterol. These foods are also lower on the glycemic index than high-glycemic foods such as bread, potatoes, and pasta. Lowering the glycemic index (by, for example, cutting down on starchy vegetables and replacing pasta with whole grains) may help increase weight loss and heart benefits for high-carbohydrate diets.
The Ornish program directors have reported a 91% reduction in angina after 1 year and a 72% reduction after 4 years in spite of significant HDL cholesterol reduction. One study reported that the diet reduced LDL levels to recommended levels without the addition of a cholesterol-lowering drug.

Negative Arguments.

In 2006, the largest study-to-date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 – 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated omega-3 polyunsaturated) and bad fats (saturated and trans fats).
The American Heart Association notes that the Ornish program is so difficult to maintain that it will not benefit many people. In a 2007 study comparing various weight loss plans, patients on the Ornish diet lost slightly less weight than those on Atkins. The difficulty of the Ornish diet may have been one factor.
Very low-fat diets may reduce calcium absorption, which may be particularly harmful for women at risk for osteoporosis.
Many people who reduce their fat intake do not consume enough of the basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low fat diets should consume a wide variety of foods and take a multivitamin if appropriate.

Calorie restriction has been the cornerstone of weight-loss programs. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels. At this point, reducing calories and increasing exercise is still the best method for maintaining weight loss and preventing serious conditions, notably diabetes. A 2006 study reported that a low-calorie, but nutritionally balanced, diet can help prevent an aging-associated change in heart function. Patients in the small study took in 1,400 - 2,000 calories a day for an average of 6 years.

The standard dietary recommendations for losing weight are:

As a rough rule of thumb, one pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss.
To determine the daily calories requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year-old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Start with realistic goals. When overweight people achieve even modest weight loss they reduce risk factors in the heart. Ideally, overweight patients should strive for 15% weight loss or better, particularly people with type 2 diabetes.
A regular exercise program is essential for maintaining weight loss. If there are no health prohibitions, choose one that is enjoyable. Check with a doctor about any health consideration. [See In-Depth Report #29:Exercise.]
Hunger pangs should not be taken as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat, and track calories carefully. Studies on weight control that depend on self-reporting of food intake frequently reveal that subjects badly misjudge how much they eat (typically underestimating high-calorie foods and overestimating low-calorie foods). In one study, even dietitians underreported their calorie intake by 10%. People who do not carefully note everything they eat tend to take in excessive calories when they believe they are dieting.
For patients who cannot lose weight with diet alone, effective weight-loss medications are now available, including sibutramine (Meridia) and orlistat (Xenical). Orlistat may have particular benefits for patients with type 2 diabetes. This drug may delay or even prevent the onset or progression of diabetes. It may also improve cholesterol levels, regardless of weight loss. Sibutramine is also helpful in weight loss but should not be used by patients with high blood pressure or kidney or liver problems.
Once a person has lost weight, maintenance is required. To maintain a healthy weight, make careful decisions about how many calories you consume in food and how many calories you expend through physical activity. Such thinking will eventually become automatic.
A procedure known as bariatric surgery has been very helpful in producing rapid weight loss and improving insulin and glucose levels in people with diabetes.

Even repeated weight loss failure is no reason to give up. [See In-Depth Report #53: Weight control and diet.]

Lifestyle Changes

Inactivity is a major risk factor for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol lower their risk for heart disease only when they also follow a regular aerobic exercise program.

Research strongly supports the benefits of exercise on coronary artery disease:

People who maintain an active lifestyle have a 45% lower risk of developing heart disease than do sedentary people. Even moderate exercise reduces the risk of heart attack.
People who lose weight and exercise regularly have a significantly better chance of maintaining weight loss compared to those who do not exercise.
Some studies suggest that for the greatest heart protection, it is not the duration of the exercise that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise.
Burning at least 250 calories a day (the equivalent of about 45 minutes of brisk walking or 25 minutes of jogging) seems to confer the greatest protection against coronary artery disease, particularly by raising HDL (the so-called good cholesterol) levels. (It may take up to a year of sustained exercise for HDL levels to show significant improvement, but in terms of raising HDL levels, more is better.)
Aerobic exercise also appears to open up the blood vessels and, in combination with a healthy diet, may improve blood-clotting factors.
Resistance (weight) training offers a complementary benefit by reducing LDL (the so-called bad cholesterol) levels.
Exercises that train and strengthen the chest muscles may be very important for patients with angina.

[See In-Depth Report #29: Exercise.]

Stress is always highly associated with negative effects on the heart and other parts of the body. A number of techniques are available to help people relax and reduce tension. [See In-Depth Report #31: Stress.]

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.eatright.org -- American Dietetic Association
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology
http://fnic.nal.usda.gov -- Food and Nutrition Information Center

References

Bazzano LA, Reynolds K, Holder KN, He J. Effect of folic acid supplementation on risk of cardiovascular diseases: a meta-analysis of randomized controlled trials. JAMA. 2006 Dec 13;296(22):2720-6.

Bryson CL, Mukamal KJ, Mittleman MA, Fried LP, Hirsch CH, Kitzman DW, et al. The association of alcohol consumption and incident heart failure: the Cardiovascular Health Study. J Am Coll Cardiol. 2006 Jul 18;48(2):305-11.

Covas MI, Nyyssonen K, Poulsen HE, Kaikkonen J, Zunft HJ, Kiesewetter H, et al. The effect of polyphenols in olive oil on heart disease risk factors: a randomized trial. Ann Intern Med. 2006 Sep 5;145(5):333-41.

Djousse L, Pankow JS, Hunt SC, Heiss G, Province MA, Kabagambe EK, et al. Influence of saturated fat and linolenic acid on the association between intake of dairy products and blood pressure. Hypertension. 2006 Aug;48(2):335-41.

Estruch R, Martinez-Gonzalez MA, Corella D, Salas-Salvado J, Ruiz-Gutierrez V, Covas MI, et al. Effects of a Mediterranean-style diet on cardiovascular risk factors: a randomized trial. Ann Intern Med. 2006 Jul 4;145(1):1-11.

Gardner CD, Lawson LD, Block E, Chatterjee LM, Kiazand A, Balise RR, et al. Effect of raw garlic vs commercial garlic supplements on plasma lipid concentrations in adults with moderate hypercholesterolemia: a randomized clinical trial. Arch Intern Med. 2007 Feb 26;167(4):346-53.

Halton TL, Willett WC, Liu S, Manson JE, Albert CM, Rexrode K, et al. Low-carbohydrate-diet score and the risk of coronary heart disease in women. N Engl J Med. 2006 Nov 9;355(19):1991-2002.

Kuriyama S, Shimazu T, Ohmori K, Kikuchi N, Nakaya N, Nishino Y, et al. Green tea consumption and mortality due to cardiovascular disease, cancer, and all causes in Japan: the Ohsaki study. JAMA. 2006 Sep 13;296(10):1255-65.

Lopez-Garcia E, van Dam RM, Willett WC, Rimm EB, Manson JE, Stampfer MJ, et al. Coffee consumption and coronary heart disease in men and women: a prospective cohort study. Circulation. 2006 May 2;113(17):2045-53.

McMillan-Price J, Petocz P, Atkinson F, O'Neill K, Samman S, Steinbeck K,et al. Comparison of 4 diets of varying glycemic load on weight loss and cardiovascular risk reduction in overweight and obese young adults: a randomized controlled trial. Arch Intern Med. 2006 Jul 24;166(14):1466-75.

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Review Date:
4/9/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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Vitamins

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Cholesterol

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In This Report

Highlights
Introduction
Cholesterol's Effect on the...
Cholesterol's Effect on the...
Risk Factors
Symptoms
Diagnosis
Lifestyle Changes
Treatment
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

New Guidelines for Children and Adolescents

In 2007, the American Heart Association (AHA) established new guidelines for assessing and treating high cholesterol in children and adolescents. According to the AHA’s scientific statement:

LDL (“bad") cholesterol goals for children should be 190 mg/dL or less for children without heart disease risk factors and 160 mg/dL or less for children with heart disease risk factors.
Children who are overweight or obese, as well as those with a family history of high cholesterol and heart disease, should get their cholesterol levels checked.
For overweight and obese children with cholesterol imbalances, diet changes and exercise should be tried before drug treatment. For children with cholesterol imbalances who have a family history of cholesterol and heart problems, statins are the best first-line drug therapy.

Herbs and Supplements

Garlic, whether raw or in supplement form, does not help lower LDL in patients with moderately high LDL levels, according to a 2007 Archives of Internal Medicine Study.
Policosanol, a dietary supplement derived from sugar cane, has no effect on cholesterol, indicates a 2006 Journal of the American Medical Association (JAMA) study.

Diet Plans

In a 2007 JAMA comparison study of four diet plans (Atkins, Ornish, Zone, and LEARN), the low-carbohydrate Atkins diet was best at raising HDL (“good cholesterol”) levels and lowering triglyceride levels, but did not affect LDL levels. The low-fat Ornish diet was best at lowering LDL levels.
The Mediterranean diet works better than a low-fat diet in quickly lowering cholesterol as well as blood pressure and blood sugar, suggests a 2006 Annals of Internal Medicine study.

Drug Research

In contrast to research findings released last year, rosuvastatin (Crestor) does not appear to reverse heart disease, according to a 2007 JAMA study. However, the statin drug did help slow the progression of arterial thickening.

Introduction

Lipids are the building blocks of the fats and fatty substances found in animals and plants. They are microscopic layered spheres of oil, which, in animals, are composed mainly of cholesterol, triglycerides, proteins (called lipoproteins), and phospholipids (molecules made up of phosphoric acid, fatty acids, and nitrogen). Lipids do not dissolve in water and are stored in the body to serve as sources of energy.

Cholesterol is a white, powdery substance that is found in all animal cells and in animal-based foods (not in plants). In spite of its bad press, cholesterol is an essential nutrient necessary for many functions, including:

Repairing cell membranes
Manufacturing vitamin D on the skin's surface
Producing hormones, such as estrogen and testosterone
Possibly helping cell connections in the brain that are important for learning and memory

Regardless of these benefits, when cholesterol levels rise in the blood, they can have dangerous consequences, depending on the type of cholesterol. Although the body acquires some cholesterol through diet, about two-thirds is manufactured in the liver, its production stimulated by saturated fat. Saturated fats are found in animal products, meat, and dairy products.

Saturated fats are found predominantly in animal products, such as meat and dairy products, and are strongly associated with higher cholesterol levels. Tropical oils -- such as palm, coconut, and coconut butter -- are also high in saturated fats.

Triglycerides are composed of fatty acid molecules. They are the basic chemicals contained in fats in both animals and plants.

Lipoproteins are protein spheres that transport cholesterol, triglyceride, or other lipid molecules through the bloodstream. Most of the information about the effects of cholesterol and triglyceride actually concerns lipoproteins.

Lipoproteins are categorized into five types according to size and density. They can be further defined by whether they carry cholesterol or triglycerides.

Cholesterol-Carrying Lipoproteins. These are the lipoproteins commonly referred to as cholesterol.

Low density lipoproteins (LDL). (Often called the "bad" cholesterol.)
High-density lipoproteins (HDL), the smallest and most dense. (Referred to as the "good" cholesterol.)

Triglyceride-Carrying Lipoproteins.

Intermediate density lipoproteins (IDL). They tend to carry triglycerides.
Very low density lipoproteins (VLDL). These tend to carry triglycerides.
Chylomicrons (largest in size and lowest in density).

Lipoprotein(a). Lipoprotein(a), or lp(a) has a size and density somewhere between LDL and HDL. The molecules carry a protein that may interfere with the body's ability to dissolve blood clots. Lipoprotein(a) is being investigated as a possible marker or cause of heart disease.

Remnant Lipoproteins. Remnant lipoproteins are byproducts of chylomicrons, very low-density lipoproteins (VLDL), or both. Some research indicates that high levels may be an important risk factor for coronary artery disease, particularly in patients who have otherwise normal cholesterol levels.

Reducing LDL and total cholesterol levels, while at the same time boosting HDL levels, can prevent heart attacks and death in all people (with or without heart disease). Reducing LDL is the primary goal of most cholesterol therapy.

Blood tests can easily measure both HDL and overall cholesterol levels. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated by subtracting HDL and triglyceride levels from total cholesterol. The exact formula is:

LDL = TOTAL CHOLESTEROL - HDL - TRIGLYCERIDES/5.

In 2004, the National Cholesterol Education Program updated its clinical practice guidelines. The new recommendations set lower treatment goals for LDL levels based on a patient's risk factors for heart disease.

The risk factors include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides)

Two or more of these risk factors increases by 20% the chance of having a heart attack within 10 years.

The LDL cholesterol level is one of the most important factors in determining whether a patient needs cholesterol therapy and whether the treatment is working properly. In particular, the new guidelines emphasize lower LDL levels and earlier treatment for people with coronary artery disease, or other forms of atherosclerosis, and diabetes.


Risk Level	Goal (d/L)	OptimalGoal(d/L)
Very High Risk	70	70
High Risk	100	70
Moderate Risk	130	100
Low Risk	160	130

The following chart summarizes all goals.


Total Cholesterol Goals	LDL Goals	HDL Goals	Triglyceride Goals
Less than 200 mg/dL is desirable. Between 200 and 239 is borderline. Over 240 is high.	70 mg/dL is the new goal for very high-risk patients (recent heart attack; current active or unstable cardiovascular or cerebrovascular disease; or two multiple risk factors as defined above.) Below 100 mg/dL is optimal for everyone. It should be the goal for high-risk people including those with existing heart disease, diabetes, or two or more risk factors for heart disease; 70 mg/dL is an optimal goal for these individuals. 130 mg/dL or below for people with two or more risk factors; 100 mg/dL is an optimal goal. 160 mg/dL or below for people at less risk (one or zero risk factors); 130 mg/dL is an optimal goal. Anything above 160 is high, with levels above 190 being very high. LDL levels over 190 require medication even with no other cardiac risk factors present.	Levels above 40 mg/dL are desirable; levels above 60 mg/dL are optimal.	Below 150 mg/dL is normal. 150 - 199 is borderline high. 200 - 499 is high. Over 500 is very high.
*Risk factors for heart disease include a family history of early heart problems before age 55 for men (before age 65 for women), smoking, high blood pressure, diabetes, being older (over 45 for men and 55 for women), and having HDL levels below 35 mg/dL. People with two or more of these risk factors may have a 10-year risk of heart attack that exceeds 20%, and may therefore need to aim for LDL levels of 100 mg/dL or below.

Although current guidelines as described in the table are extremely useful, they do have pitfalls. For example, the following cholesterol levels pose some dilemmas:

Low LDL levels (protective) accompanied by low HDL, high triglycerides, or both (harmful)
High total cholesterol (harmful) accompanied by high HDL (protective)

Would individuals with these cholesterol balances be at high risk or low risk for developing heart disease? To resolve this dilemma, experts have devised a calculation for a risk ratio by dividing the total cholesterol by either total HDL or LDL. It is not clear at this point which ratio is a better predictor of heart disease, although the HDL ratio may be superior. Using this ratio, the following results indicate better to worse outlook:

The ideal ratio is 3.5 or below.
A ratio of 4.5 carries an average risk.
Ratios of 5 or higher are potentially dangerous.

For example, if a person has a high total cholesterol of 280 mg/dL but a high HDL level of 70 mg/dL, the risk ratio is 4, which actually carries a lower than average risk. The use of this ratio may predict coronary artery disease more accurately than using total cholesterol levels alone. Still, the primary goal of lipid-lowering therapy is reducing LDL levels. Evidence strongly suggests that the lower the LDL levels, the lower the risk for heart disease.

Cholesterol's Effect on the Heart

Coronary artery disease, commonly known as heart disease, is the leading cause of death in the U.S. and was responsible for nearly 500,000 deaths in 2003.

Atherosclerosis is a common disorder of the arteries. Fat, cholesterol, and other substances collect in the walls of arteries. Larger accumulations are called atheromas or plaque and can damage artery walls and block blood flow. Severely restricted blood flow in the heart muscle leads to symptoms such as chest pain.

As many as half of these deaths were probably due to unhealthy cholesterol and lipid levels. Strong evidence points to LDL as the villain and HDL as a hero in the process. The role of other lipids, notably triglycerides, is not entirely clear.

Unhealthy cholesterol, particularly low-density lipoprotein (LDL), forms a fatty substance called plaque, which builds up on the arterial walls. Smaller plaques remain soft, but older, larger plaques tend to develop fibrous caps with calcium deposits.

Click the icon to see an image of the developmental process of atherosclerosis.

The long-term result is atherosclerosis, commonly called hardening of the arteries. The heart is endangered in two ways by this process:

Eventually these calcified and inelastic arteries become narrower (a condition known as stenosis). As this process continues, blood flow slows and prevents sufficient oxygen-rich blood from reaching the heart. This condition leads to angina (chest pain) and, in severe cases, to heart attack.

Click the icon to see an image of a heart attack.

Smaller unstable plaques may rupture, triggering the formation blood clots on their surface. The blood clots block the arteries and are important causes of heart attack.

This process is accelerated and enhanced by other risk factors, including high blood pressure, smoking, obesity, diabetes, and a sedentary life style. When more than one of these risk factors is present, the risk is compounded.

The effects of cholesterol on the heart may involve more than just the arteries. There is some evidence that unhealthy levels may affect the heart muscles and increase the risk for heart failure. High cholesterol levels may even reduce the protection that aspirin provides for people with heart disease.

On an encouraging note, mortality rates associated with coronary artery disease have declined dramatically during the past 30 years. Some experts estimate that about 30% of the decline is due to better cholesterol management and statin drugs.

Studies consistently report a higher risk for death from heart disease with high total cholesterol levels (200 mg/dL and higher). The higher the cholesterol, the greater the risk. One study reported that men with total cholesterol levels higher than 240 mg/dL had a risk nearly two to four times that of men whose cholesterol was below 200 mg/dL. On average, every time a person's cholesterol level drops by a point, the risk of heart disease drops by 2%.

The primary villain in the cholesterol story is low-density lipoprotein (LDL). In a major study, the lowest incidence in heart disease was found among people with the lowest LDL levels. Lowering LDL is the primary goal of cholesterol drug and lifestyle therapy.

Low-density lipoprotein (LDL) transports about 75% of the blood's cholesterol to the body's cells. It is normally harmless. However, if it is exposed to a process called oxidation, LDL can penetrate and interact dangerously with the walls of the artery, producing a harmful inflammatory response. Oxidation is a natural process in the body that occurs from chemical combinations with unstable molecules. These molecules are known as oxygen-free radicals or oxidants.

When LDL collects on arterial walls these oxidants are released from the wall membranes.
Oxidants are missing an electron and tend to bind with other molecules in the body, a process called oxidation.
When the oxidation process modifies LDL, it signals the immune system that a harmful molecule has appeared.

Inflammation and Plaque. In response to oxidized LDL, the body releases various immune factors aimed at protecting the damaged walls. Unfortunately, in excessive quantities they cause inflammation and promote further injury to the areas they target:

White blood cells and other factors gather and form a fatty substance called plaque. (Of interest in this process is an enzyme called lipoprotein-associated phospholipase A2, which binds to oxidized LDL. Studies report that this enzyme may play a major role in the release of plaque-forming inflammatory factors.)
Other immune factors also cause inflammation and injure the endothelium, the layer of cells that line blood vessels.

Click the icon to see an image of the cut section of an artery.

Immune factors that increase the risk for blood clots are also mobilized.
Oxidized LDL plays another dangerous role by reducing levels of nitric oxide, a chemical that helps relax the blood vessels and allow blood to flow freely.

High density lipoprotein (HDL) appears to benefit the body in two ways:

It removes cholesterol from the walls of the arteries and returns it to the liver.

Click the icon to see an image of the liver.

It helps prevent oxidation of LDL. HDL actually appears to have its own antioxidant properties.

HDL helps keep arteries open and reduces the risk for heart attack. High levels of high HDL (above 60 mg/dL) may be nearly as important for the heart as low levels of LDL. HDL levels below 40 mg/dL are considered to be harmful. In one study, for each 4 mg/dL decline in HDL levels there was a 10% increase in coronary artery disease.

Triglycerides are major troublemakers for the heart. They appear to interact with HDL cholesterol in such a way that HDL levels fall as triglyceride levels rise. Low HDL is known to be harmful to the heart.

The harmful imbalance of high triglycerides with low HDL levels is also associated with obesity (particularly around the abdomen), insulin resistance, and diabetes. Insulin is a hormone essential for regulating the storage and use of glucose (sugar) and amino acids (proteins) in the body. Insulin resistance occurs when there are normal levels of insulin but the body cannot use it. Insulin resistance increases the risk for developing type 2 diabetes, and it is also associated with metabolic syndrome. Both of these conditions increase the risk for heart disease.

Some evidence also suggests that high triglycerides pose other dangers, regardless of cholesterol levels. Triglycerides, for example, may be responsible for blood clots that form and block the arteries. High triglyceride levels are also associated with the inflammatory response -- the harmful effect of an overactive immune system that can cause considerable damage to cells and tissues, including the arteries.

Studies are finding an elevated risk for angina and first heart attacks in people with elevated levels of lipoprotein(a), also known as or lp(a). This lipoprotein falls somewhere between HDL and LDL in density and may have some properties that increase the risk for blood clots. Some experts suggest, however, that high levels of lp(a) may merely be markers of late-stage atherosclerosis, not a cause. Because concentrations of lipoprotein(a) are usually inherited, they do not respond to dietary or lifestyle changes. At this time, few experts recommend drug treatments to reduce lp(a) levels. Older women, but not men, appear to be at greater risk for high lp(a) levels and their consequences.

Cholesterol's Effect on the Brain

Having adequate levels of HDL may be the most important lipid-related factor for preventing ischemic stroke, a type of stroke caused by blockage of the carotid arteries that carry blood to the brain. HDL may even reduce the risk for hemorrhagic stroke, a less common type of stroke caused by bleeding in the brain that is associated with low overall cholesterol levels.

The build-up of plaque in the internal carotid artery may lead to narrowing and irregularity of the artery's lumen, preventing proper blood flow to the brain. More commonly, as the narrowing worsens, pieces of plaque in the internal carotid artery can break free, travel to the brain, and block blood vessels that supply blood to the brain. This leads to stroke, with possible paralysis or other deficits.

The effects of high total cholesterol and LDL levels on ischemic stroke are less clear. One study suggested that the risk for ischemic stroke increases when total cholesterol is above 280 mg/dL. A 2002 study suggested that high cholesterol poses a risk for stroke only when specific proteins associated with inflammation are present.

Evidence points to high cholesterol levels, along with high blood pressure and a family history of the disease, as independent risk factors for AD. A major research target for common factors between cholesterol levels and AD has been apolipoprotein E (ApoE). ApoE plays a role in the movement and distribution of cholesterol for repairing nerve cells during development and after injury. People who carry a variant of this gene (ApoE4) are at significantly higher risk for AD.

High cholesterol may pose a risk for Alzheimer's regardless of this genetic factor, however. Some studies report that cholesterol is important within the brain for cell communication and memory.

Risk Factors

About half of all American adults have total cholesterol levels over 200 mg/dL. Over 25% have been told by doctors that they have unhealthy levels. Total cholesterol levels have been declining over the last several decades, at least among middle-aged and older adults. This decline may be partly due to the increased use of statins and other lipid-lowering medications. However, total cholesterol levels are getting higher among younger adults (ages 25 – 34 years). The major risk factor for these high rates may be the Western lifestyle. The typical high-fat/low-fiber American diet coupled with sedentary habits is largely responsible for this unfortunate trend.

Men. Heart disease is the major cause of death in men. On average, men develop coronary artery disease 10 - 15 years earlier than women do and have a greater risk for dying of heart disease at a younger age. A 2006 study suggested that high total cholesterol may also contribute to the development of high blood pressure in men.

Women. Coronary artery disease is also the number one killer of women. Women between the ages of 20 and 34, and after menopause (around age 55), have higher cholesterol levels than men. Some evidence suggests that HDL levels may be more significant in women than in men. In one study, at total cholesterol levels above 200, women with HDL levels below 50 had a higher death rate than those with levels above 50, regardless of their LDL cholesterol levels. Women also appear to be more susceptible to the high-triglyceride low-HDL syndrome, which may be a particular risk factor for heart disease.

Children and Adolescents. Children who have abnormal cholesterol levels are at increased risk of developing heart disease later in life. However, it is difficult to distinguish “normal” cholesterol levels in children. Changes in cholesterol levels occur between the ages of 8 - 18, and vary between genders and population groups. Cholesterol levels tend to naturally rise sharply until puberty, then decrease sharply, and then rise again.

In 2007, the American Heart Association established general LDL goals for children that take into account these fluctuations. The association’s LDL goals are 190 mg/dL or less for children with no additional heart disease risk factors and 160 mg/dL or less for children with additional risk factors (such as family history of high cholesterol, heart disease, and diabetes).

It is also clear that children who are overweight are at higher risk for high triglycerides and low HDL, which may be directly related to later unhealthy cholesterol levels. Studies have confirmed that childhood LDL levels and body-mass index (BMI) are strongly associated with cardiovascular risk during adulthood. The American Heart Association recommends that children who are overweight and obese, as well as those with a family history of high cholesterol, undergo cholesterol screening. Overweight and obese children who have high cholesterol should also get tested for high blood pressure, diabetes, and other conditions associated with metabolic syndrome.

As in adults, the primary source of unhealthy cholesterol levels in children comes from diets high in unhealthy fats: Saturated fats (found mainly in animal and dairy products) and trans fatty acids (found in commercial food products). Over-consumption of unhealthy fats increases the risk for both obesity and heart disease.

Less common causes of unhealthy cholesterol levels in children include:

Low-birth weight (associated with low HDL levels)
Low thyroid levels (hypothyroidism)
Kidney or liver diseases
Homozygous familial hypercholesterolemia. This is an uncommon inherited condition that causes severe cholesterol imbalances and can result in very early heart disease.
Certain medications such as specific antiseizure drugs, corticosteroids, and isotretinoin (Accutane)

Young and Middle-Aged Adults. The strongest evidence of unhealthy cholesterol levels and heart disease is in adults over age 45. However, a 2006 analysis found that while total cholesterol levels are decreasing among older adults, they are increasing in those age 25 - 34 years. Research strongly suggests that the younger a person is when unhealthy cholesterol levels develop, the greater the chance for serious heart and blood vessel problems in the future. A 2006 study in the New England Journal of Medicine indicated that keeping LDL levels low from an early age can help prevent heart disease later in life. In one important study, young men (ages 16 - 34) who had cholesterol levels at or above 240 mg/dL had two to four times the risk of dying from heart attack or other cardiac problems than did men whose cholesterol was lower than 200 mg/dL. Young men without cholesterol problems had a higher life expectancy, by up to 8 years. Other studies have suggested similar risks from unhealthy cholesterol in young women as well.

Elderly Adults. About 85% of people who die from coronary artery disease are over the age of 65. Because high cholesterol is an important risk factor for heart disease, experts strongly recommend statin or other lipid-lowering therapy for elderly people with high cholesterol levels. Surveys indicate that total cholesterol levels have been declining in older people over the last few decades. Many experts believe this is due in part to increased use of statin drugs.

In the U.S., obesity is at epidemic levels in all age groups. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, obese individuals tend to have high triglyceride levels and low HDL levels. This combination is a risk factor for heart disease. Obesity also causes other effects (high blood pressure, increase in inflammation) that pose major risks to the heart.

Obesity is a particularly hazard when it is one of the components of the metabolic syndrome, formerly known as syndrome X. This syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. Metabolic syndrome is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. A 2002 study estimated that 24% of the population now has this condition. Many experts recommend that patients with metabolic syndrome should be aggressively treated with high-dose statin therapy to lower LDL levels.

Obesity is also strongly associated with type 2 diabetes, which itself poses a significant risk for high cholesterol levels and heart disease.

Low thyroid levels (hypothyroidism) are associated with unhealthy lipid levels. (Lipids are fat molecules). Specifically, people with hypothyroidism are at higher risk for high total and LDL cholesterol, triglycerides, and other lipids associated with heart disease. Treating the thyroid condition can significantly reduce cholesterol levels. Some experts suggest that patients with high cholesterol should be evaluated for thyroid function before they are given cholesterol-lowering drugs. Research is mixed on whether mild hypothyroidism (subclinical hypothyroidism) is associated with unhealthy cholesterol levels. [See In-Depth Report #38: Hypothyroidism.]

Hypothyroidism is a decreased activity of the thyroid gland which may affect all body functions. In this condition, the rate of metabolism slows, causing mental and physical sluggishness. The most severe form of hypothyroidism is myxedema, which is a medical emergency.

Genetics play a major role in determining a person's blood cholesterol levels. Children from families with a history of premature heart disease should be tested for cholesterol levels after they are 2 years old. Genes may influence whether a person has low HDL levels, high LDL levels, high triglycerides, or high levels of other lipoproteins, such as lipoprotein(a).

Some inherited disorders and genetic abnormalities have been identified:

Familial hypercholesterolemia causes dangerous increases in cholesterol. It may be more common than previously thought. One European study reported familial hypercholesterolemia in 1 out of every 400 people.
Familial lipoprotein lipase deficiency is a very rare disorder that causes depletion of lipoprotein lipase. This is an enzyme that appears to be important in the removal of lipoproteins that are rich in triglycerides. People who are deficient in it have high levels of cholesterol and fat in their blood. A very low-fat diet is essential and is an effective treatment for these individuals.
Several studies have found a genetic mutation affecting neuropeptide Y in people with high total cholesterol and LDL levels. Neuropeptide Y is a compound in the brain that regulates appetite.
Researchers have identified a gene called APOAV, which may help detect patients at risk for elevated levels of triglycerides.

Other medical conditions strongly associated with unhealthy cholesterol levels include:

Polycystic ovarian syndrome. Women with this disorder, particularly those who are obese, appear to be at increased risk for high triglyceride and low HDL levels. This risk may be due to higher levels of the male hormone testosterone in these women.

Click the icon to see an image of a polycystic ovary.

Kidney disease

Symptoms

There are no warning signs for high LDL cholesterol levels. When symptoms finally occur, they usually take the form of angina or heart attack in response to the buildup of atherosclerotic plaque in the patient's arteries. This is definitely a condition where it pays to invest in preventive medicine before dangerous complications occur.

Atherosclerosis is a disease of the arteries in which fatty material is deposited in the vessel wall, resulting in narrowing and eventual impairment of blood flow. Severely restricted blood flow in the arteries to the heart muscle leads to symptoms such as chest pain. Atherosclerosis shows no symptoms until a complication occurs.

Diagnosis

A blood test for cholesterol should include the entire lipoprotein profile: LDL, total cholesterol, HDL, and triglycerides. It is very difficult to measure LDL levels by themselves, but LDL levels can be reliably calculated using total cholesterol and HDL levels.

To obtain a reliable cholesterol reading, experts advise:

Avoid strenuous exercise for 24 hours before the test.
Do not eat or drink anything but water for 12 hours beforehand.
If the test results are abnormal, a second test should be performed between 1 week and 2 months after the first test.

Home Tests. Tests are available for home use and in public locations, such as shopping malls and pharmacies. For example, the CholesTrak Test can be taken at home with results in 10 minutes, but it measures only total cholesterol. The BioSafe Cholesterol Panel Test is also a home test, but it needs to be sent to a laboratory. This test, however, is very accurate and provides a full lipid profile.

Certain blood tests for factors associated with inflammation in the arteries indicate a higher risk for heart disease, even in people without unhealthy lipids:

C-reactive protein (CRP). CRP is regulated by a very potent immune factor called interleukin-6. Elevated levels have been strongly associated with the inflammatory response and a higher risk for heart attack, even in people with normal cholesterol levels. CRP is also associated with high blood pressure, insulin resistance (the primary problem in type 2 diabetes), and obesity.
A high white blood cell count.
Elevated fibrinogen (a factor responsible for blood clotting).
Lipoprotein-associated phospholipase A2 may prove to be another marker for inflammation and heart disease. Studies suggest that it may play some causal role in coronary artery disease.

A new type of test measures cholesterol levels in the skin. High skin levels may indicate an increased risk for atherosclerosis and serious heart disease.

General Screening Recommendations. Experts groups differ slightly on when screening should start, but the following are generally accepted recommendations:

Periodic cholesterol testing in all adults starting at age 20. Adults with normal cholesterol levels do not need to have the test repeated for 5 years unless changes occur in lifestyle (including weight gain and diet). Adults with risk factors for heart disease or stroke should be rechecked every 2 years.
Selective screening of children who are at risk for high cholesterol and heart disease or familial hypercholesterolemia, which is genetically elevated cholesterol. Risk factors include having parents with total cholesterol levels greater than 240, or having a parent or grandparent who had symptomatic heart disease at age 55 or younger.
Patients already being treated for high cholesterol should be checked every 2 - 6 months.

Lifestyle Changes

Although most studies that prove that lowering cholesterol saves lives are done using drug therapy, the absolute mandate for improving cholesterol levels is to first make changes in lifestyle (both diet and exercise). Even when drugs are used, healthy diet and physical activity are critical companions.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:·

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. Walnuts in particular have cholesterol-lowering properties and are a good source of antioxidants and alpha-linolenic acid.
Avoid saturated fats (found mostly in animal products) and trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart healthy food choice.
Controlling weight, quitting smoking, and exercising are essential companions of any diet program.

After embarking on any heart healthy diet, it generally takes an average of 3 - 6 months before any noticeable reduction in cholesterol occurs. However, some people see improved levels in as few as 4 weeks. An intensive program may be necessary to achieve significant improvements in cholesterol levels and to reduce heart risk factors.

Therapeutic Lifestyle Changes (TLC) from the National Cholesterol Education Program. Guidelines from the National Cholesterol Education Program include these recommendations for preventing and managing high cholesterol levels in adults:

Choose five or more servings of fresh fruits and vegetables and six or more servings of whole grains, legumes. Soluble fiber is preferred (from cereal grains, beans, peas, legumes, and many fruits and vegetables).
Fats can be up to 35% of daily calories, but no more than 7% should be from saturated fat. (People with high triglycerides, low HDL, or both may need a higher fat intake.) Choose fats containing unsaturated fatty acids (from vegetables, fish, legumes, and nuts). Choose margarines containing sterols or stanols (Benecol, Take Control). Avoid trans fatty acids found in commercial baked products.
Protein choices should be fat-free and low-fat milk products, fish, legumes, skinless poultry, and lean meats.
Limit dietary cholesterol intake to less than 200 mg per day.
Maintain healthy body weight and a healthy level of physical fitness.

Mediterranean Diet. The Mediterranean diet is rich in heart-healthy fiber and nutrients, including omega-3 fatty acids and antioxidants. The diet consists of fruits, vegetables, and unsaturated “good” fats, particularly olive oil. Olive oil has been associated with lower blood pressure, a lower risk for heart disease, and possible benefits for people with type 2 diabetes. Olive oil also contains polyphenol, which are phytochemicals that may help boost HDL levels.

A 2006 study that compared several types of Mediterranean diets to a low-fat diet found that Mediterranean diets were better at lowering blood pressure, cholesterol levels, and blood sugar levels after only 3 months. And, in research presented at the 2007 American College of Cardiology annual conference, the Mediterranean diet proved just as good as the American Heart Association low-fat diet for preventing recurrence of heart attack, stroke, or other heart events.

There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Drink one or two glasses of wine each day if alcohol is enjoyable and there are no reasons to restrict its use.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Season with garlic, onions, and herbs. Unfortunately, garlic does not appear to help lower cholesterol, but it may have other heart benefits. [See Herbs and Supplements in this section.]

Low-Carbohydrate Diets. The Atkins, South Beach, The Zone, and other diet restrict carbohydrate intake include. A 2006 review of low-carbohydrate diets found that they did help weight loss in the short term. However, while these diets appeared to lower triglyceride and raise HDL (“good”) cholesterol levels, they also raised overall and LDL (“bad”) cholesterol levels.

In contrast, a 2007 Journal of the American Medical Association study that compared four different low-carbohydrate and low-fat diet plans (Atkins, Zone, Ornish, and LEARN) found that the Atkins diet was best at raising HDL levels and reducing triglyciderides. In terms of LDL reduction, the low-fat Ornish diet produced the best improvements while the Atkins diet had no effect on LDL. The Atkins diet did result in better moderate weight loss (an average of 10 pounds over the course of a year versus 4 - 6 pounds for the other diet plans), which in itself may have accounted for the improved heart risk factors.

Glycemic Index. Low-carb diets -- such as South Beach, The Zone, and Sugar Busters -- rely on a concept called the "glycemic index," or GI, which ranks foods by how fast and how high they cause blood sugar levels to rise. Foods on the lowest end of the index take longer to digest. Slow digestion wards off hunger pains. It also helps stabilize insulin levels. Foods high on the glycemic index include bread, white potatoes, and pasta while low-glycemic foods include whole grains, fruit, lentils, and soybeans. (These low-glycemic foods are also important components of low-fat diet plans.) A 2006 study indicated that a high-protein, low-glycemic index diet can help produce better reductions in total and LDL cholesterol than a high-protein, high-glycemic index diet. Reducing glycemic load may also help to promote weight loss, especially for women.

Low Fat Diets. Dietary guidelines recommend keeping total fat intake to 20 - 30% of total daily calories, with saturated fat less than 10% of calories. Low-fat diets generally restrict fat intake to 20% or less of total daily calories. The Ornish program, which is recommended for some heart disease patients, limits fats even more drastically. It aims at reducing saturated fats as much as possible, restricting total fat to 10%, and increasing carbohydrates to 75% of calories. In 2006, the largest study to date on low-fat diets found that they did not help prevent heart disease or cancer. Women in the study reduced their fat consumption to 24 - 29% of total daily calories. Some critics say that the study did not do enough to distinguish between good types of fats (monounsaturated omega-3 polyunsaturated) and bad fats (saturated and trans fats).

The DASH Diet. The DASH diet (Dietary Approaches to Stop Hypertension) is proven to help lower blood pressure. Results are sometimes seen within a few weeks. Restricting sodium improves results. The diet appears to have antioxidant effects and may help lower LDL cholesterol levels, although beneficial HDL levels also decline. This diet is not only rich in important nutrients and fiber but also includes foods that contain far more electrolytes, potassium (4,700 mg/day), calcium (1,250 mg/day), and magnesium (500 mg/day) than are found in the average American diet.

A diet that is effective in lowering blood pressure is called Dietary Approaches to Stop Hypertension (DASH).

The DASH diet recommends:

Limit salt intake to no more than 2,300 mg a day (a maximum intake of 1,500 mg a day is an even better goal).
Reduce saturated fat to no more than 6% of daily calories and total fat to 27% of daily calories. (But, include dairy products that are non- or low-fat. Low-fat dairy products appear to be especially beneficial for lowering systolic blood pressure).
When choosing fats, select monounsaturated oils, such as olive or canola oils.
Choose whole grains over white flour or pasta products.
Choose fresh fruits and vegetables every day. Many of these foods are rich in potassium, fiber, or both which may help lower blood pressure.
Include nuts, seeds, or legumes (dried beans or peas) daily.
Choose modest amounts of protein (no more than 18% of total daily calories). Fish, skinless poultry, and soy products are the best protein sources.
Other daily nutrient goals in the DASH diet include limiting carbohydrates to 55% of daily calories and dietary cholesterol to 150 mg. Patients should try to get at least 30 g of daily fiber.

Slight changes to the DASH diet might help lower blood pressure even more, as well as improve cholesterol and lipid levels. Researchers reporting in the Journal of the American Medical Association and at the 2005 American Heart Association meeting said that replacing some carbohydrates in the DASH diet with more protein (from mostly plant sources) or monounsaturated fats may help reduce heart disease risk factors.

Calorie Restriction. Calorie restriction has been the cornerstone of weight-loss programs. Restricting calories in such cases also appears to have beneficial effects on cholesterol levels, including reducing LDL and triglycerides and increasing HDL levels. At this point, reducing calories and increasing exercise is still the best method for maintaining weight loss and preventing serious conditions, notably diabetes. A 2006 study reported that a low-calorie, but nutritionally balanced diet can help prevent an aging-associated change in heart function. Patients in the small study took in 1,400 - 2,000 calories a day for an average of 6 years.

The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories, so one could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss.
To determine the daily calorie requirements for specific individuals, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year-old moderately active woman who wants to maintain a weight of 135 pounds might require only 12 calories per pound (1,620 calories a day). A 25-year-old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).

Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Inactivity is one of the four major risk factors for coronary artery disease, on par with smoking, unhealthy cholesterol, and high blood pressure. In fact, studies suggest that people who change their diet in order to control cholesterol only achieve a lower risk for heart disease when they also follow a regular aerobic exercise program.

People who maintain an active lifestyle have a 45% lower risk of developing heart disease than sedentary people. Even moderate exercise reduces the risk of heart attack. One study of women found that just 1 hour of walking a week was associated with a lower risk for heart disease. The effects were similar even in women at high risk for developing heart disease.
Some studies suggest that for the greatest heart protection, it is not the duration of a single exercise session that counts but the total daily amount of energy expended. Therefore, the best way to exercise may be in multiple short bouts of intense exercise.
Burning at least 250 calories a day (the equivalent of about 45 minutes of brisk walking or 25 minutes of jogging) seems to offer the greatest protection against coronary artery disease, most likely because it raises HDL ("good cholesterol") levels. Moderate exercise has little effect on HDL.
Aerobic exercise helps to open up blood vessels and, in combination with a healthy diet, may improve blood-clotting factors.
Resistance (weight) training offers a complementary benefit to aerobics by reducing LDL ("bad cholesterol") levels.
Exercises that train and strengthen the chest muscles may prove to be very important for patients with angina.

Cigarette smoking lowers HDL and is directly responsible for approximately 20% of all deaths from heart disease. The importance of breaking this habit cannot be emphasized enough. Once a person quits smoking, HDL cholesterol levels rise within weeks or months to levels that are equal to their nonsmoking peers. Passive smoking also reduces HDL levels in people exposed to cigarette smoke.

A number of studies have found heart protection from moderate intake of alcohol (one or two glasses a day). Moderate amounts of alcohol help raise HDL levels. Although red wine is most often cited for healthful properties, any type of alcoholic beverage appears to have similar benefit. Pregnant women, anyone who cannot drink moderately, and people with liver disease should not drink at all.

Manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following natural remedies are of interest for cholesterol control:

Garlic. Contrary to popular belief, garlic does not significantly reduce cholesterol, according to a 2007 Archives of Internal Medicine study. Researchers tested raw garlic and two types of garlic supplements in 192 patients with moderately high LDL levels. None of the forms of garlic had any effect on LDL levels. However, the researchers note that garlic may still help people with very high LDL levels and it may contain other heart-protective properties.

Policosonol. Policosanol is a nutritional supplement derived from sugar cane that has been promoted as having lipid-lowering benefits. In a randomized, placebo-controlled trial published in 2007 in the Archives of Internal Medicine, policosanol was no better than placebo in reducing LDL levels.

Treatment

In 2004, the National Cholesterol Education Program issued its latest recommendations for cholesterol control and management. These guidelines increase the number of Americans who should be taking LDL-lowering medication.

Starting Medications. Even modest lowering of high cholesterol levels, whether through drug therapy or lifestyle changes, reduces the risk of disability and death from heart disease. Most experts now focus on lowering LDL ("bad") cholesterol. Reducing LDL levels is particularly critical for patients with diabetes.

The doctor will start or consider medication when:

LDL cholesterol is 190 mg/dL or higher.
LDL cholesterol is 160 mg/dL or higher AND patient has one risk factor for heart disease.
LDL cholesterol is 130 mg/dL or higher AND patient has either diabetes or two other risk factors for heart disease.
LDL cholesterol is 100 mg/dL or higher AND patient has heart disease. (If patient has diabetes, even without heart disease, medication may be considered for an LDL cholesterol of 100 mg/dL.)
LDL cholesterol is greater than 70 mg/dL AND patient has had a recent heart attack or has known heart disease along with diabetes, current cigarette smoking, poorly controlled high blood pressure, or the metabolic syndrome (high triglycerides, low HDL, and obesity).

Risk factors for heart disease include:

Having a first-degree female relative diagnosed with heart disease before age 65 or a first-degree male relative diagnosed before age 55
Being male and over age 45 or female and over age 55
Cigarette smoking
Diabetes
High blood pressure
Metabolic syndrome (risk factors associated with obesity such as low HDL levels and high triglycerides)

Recent studies have found that aggressive lipid lowering with high-dose statin therapy is more beneficial than standard statin therapy in patients with existing heart disease. The Pravastatin or Atorvastatin Evaluation and Infection Trial (PROVE-IT) and the Reversal of Atherosclerosis with Aggressive Lipid-Lowering trial (REVERSAL) compared the benefits of standard statin therapy (pravastatin, 40 mg) with intensive statin therapy (atorvastatin, 80 mg) in treating patients with heart disease.

Results from PROVE-IT demonstrated that for high-risk patients, intensive statin therapy is more effective than standard therapy in lowering LDL cholesterol and C-reactive protein (CRP) levels, and that CRP levels predict risk even when LDL cholesterol has been lowered substantially. The REVERSAL data suggest that intensive statin therapy produces greater reductions in LDL and CRP levels, and that the more that statins can lower LDL, the more effective they are in reducing the progression of atherosclerosis.

An important 2006 study found that aggressive treatment with rosuvastatin (Crestor):

Helped lower LDL to below guideline levels
Moderately increased HDL levels
Reduced fatty plaque in the arteries

Experts hoped that these results suggested that statin therapy might have the potential to reverse coronary atherosclerosis. However, a follow-up 2007 study of rosuvastatin indicated that while the drug slowed the rate of atherosclerotic progression, it did not reverse heart disease. Future studies will continue to investigate this issue and to explore whether other statins have a similar positive effect on coronary artery disease. Rosuvastatin lowers LDL more than other statins, but it also carries greater risks for more serious side effects (see Adverse Effects section). Many experts believe that the more that LDL is reduced through statin therapy, the greater the reduction in risk for heart disease, heart attack, and stroke.

It is important to emphasize that cholesterol-lowering medications are used along with healthy lifestyle habits, not in place of them.

Choosing the Correct Lipid-Lowering Medication. Experts now recommend that drug treatments be tailored for raising or lowering specific lipids, depending on the patient's blood lipid picture:

Statins are now the standard drugs for most people who require LDL-lowering therapy. Bile-acid binding resins or niacin may be considered. If LDL goals are not achieved, combinations of a statin with a bile-acid resin or niacin should be considered.
Fibrates or niacin are beneficial for people who need to lower triglycerides and increase HDL.

Considerations for Children and Adolescents. In 2007, the American Heart Association (AHA) issued a scientific statement addressing the use of cholesterol drugs in children and adolescents. The AHA recommends that for children who are overweight or obese, lifestyle modifications (diet, exercise) are preferred over drug therapy and should be the first step in lowering cholesterol.

For children and adolescents who have high-risk cholesterol imbalances -- and have a family history of high cholesterol, heart attack, stroke, and diabetes -- the AHA now recommends statins as the first-line drug therapy.

Considerations for People with Diabetes. At this time, statins are recommended as the best drugs for improving cholesterol and lipid levels in people with diabetes. Studies suggest that they can reduce the risk for adverse heart events in people with diabetes, even if their cholesterol levels are normal or if their diabetes is mild. Furthermore, in one study, a statin was shown to reduce the risk of developing diabetes by 30% in people with high cholesterol. Fibrates may also be useful for people with type 2 diabetes. Niacin (nicotinic acid) has the best effect on the cholesterol profile of people with diabetes but it also increases blood sugar levels. One well-controlled study, however, found that people with diabetes who used niacin had little trouble with glucose control, and some experts believe it now may be used as an alternative to or in combination with statins.


	Effect on High LDL	Effect on Low HDL	Effect on High Triglycerides	Effect on Lp(a)
Statins	Decrease (18 - 55%)	Modest increase (5 - 15%)	Decrease (7 - 30%)	No change
Nicotinic acid (Niacin)	Modest decrease (5 - 25%) In combination with statins, may convert more dangerous LDL type to less dangerous.	Increase (15 - 35%) Drugs of choice for improving HDL levels	Decrease (20 - 50%) Drug of choice for lowering triglycerides	Decrease
Fibrates	Effect varies, but in general has little effect or modest decrease (5 - 20%)	Modest increase (6 - 20%)	Decrease (20 - 50%)	No change
Bile acid-binding resins	Decrease (15 - 30%)	Very modest increase (3 - 5%)	No change	No change

Statins are the most effective drugs for the treatment of high cholesterol, and may even prove important drugs for many people at risk for heart disease who have normal cholesterol levels. Statins inhibit the liver enzyme HMG-CoA reductase, which is used in the manufacturing of cholesterol. These drugs effectively reduce the risk of major coronary events, including first and second heart attacks, in both adult women and men of any age with unhealthy cholesterol levels. Experts estimate a 25 - 30% reduction in mortality rates when patients take statins after a heart attack. (Some believe the decrease may even be greater.) These drugs may also help improve the outcome in patients with heart disease who have had angioplasty.

Important studies have reported lower rates of heart attack, stroke, and mortality rates from all causes in statin users who were at high risk for heart disease, even if they had normal or low cholesterol levels. Benefits were similar in these people regardless of gender, age, or the presence of specific heart risk factors, such as diabetes or peripheral artery disease.

Brands. Statins are currently categorized into four groups:

So-called natural statins, including lovastatin (Mevacor, generics), pravastatin (Pravachol), and simvastatin (Zocor, generics). These are the most studied statins and have proven effectiveness and good safety record.
Synthetic statins include fluvastatin (Lescol) and atorvastatin (Lipitor). Studies using atorvastatin suggest they may reduce LDL more effectively than natural statins. In 2007, Lipitor was approved for additional indications to reduce the risk of heart attacks, strokes, certain types of heart surgery, hospitalization for heart failure, and chest pain in patients with heart disease. Lipitor is also approved for children.
The newer statins include rosuvastatin (Crestor), which was approved in 2003. Trial results have suggested that rosuvastatin is more effective in improving lipid profiles than atorvastatin, simvastatin, or pravastatin. However, like all statin drugs, rosuvastatin can cause serious side effects (see the Adverse Effects section in this report). The risks may be higher for Asian patients; this population should be started on the lowest rosuvastatin dose (5 mg).
Fixed-dose combination statins, which combine two drugs in one pill, first appeared on the market in 2004. Ezetimibe/simvastatin (Vytorin) combines two cholesterol medications that work in different ways. Simvastatin blocks cholesterol production in the liver, while ezetimibe (a non-statin cholesterol medication) blocks cholesterol absorption in the digestive tract. A 2005 study found that Vytorin was more effective than atorvastatin in lowering LDL and increasing HDL levels. Amlodipine/atorvastatin (Caduet) is a dual-therapy medication that combines the antihypertensive calcium channel blocker amlodipine with atorvastatin. It is used to treat simultaneously high blood pressure and high cholesterol.

Statins are generally administered once a day, typically in the evening because most cholesterol synthesis occurs between midnight and 3 a.m. (Atorvastatin and rosuvastatin, however, can be taken in the morning.) Statins are often prescribed along with other cholesterol-lowering drugs such as bile acid-binding resins, nicotinic acid (niacin), and fibrates.

Beneficial Effects on the Heart and Circulation.

Statins are particularly effective for lowering LDL levels. They also reduce triglycerides, apparently in direct proportion to their LDL-lowering effects. Statins also raise HDL levels, but to a lesser extent than other anti-cholesterol drugs. (The newer statins appear to produce more significant increases in HDL.) Evidence now strongly suggests that statins may offer other health benefits beyond lowering cholesterol:

Statins may improve the function of the endothelium (the lining of blood vessels), thereby improving blood flow. (This benefit apparently does not extend to people with diabetes.)
Statins appear to reduce inflammation in the arteries, which is now believed to be a major factor in blood vessel injury.
Some evidence suggests that statins may help prevent blood clotting, a major factor in heart attacks.

Beneficial Effects Outside the Heart. Studies also suggest that the benefits of statins go beyond the heart. At this time, nearly all studies on the following conditions have used natural statins:

Stroke. Statins may reduce the risk for ischemic stroke in high-risk patients with a wide range of cholesterol and lipid levels. (Ischemic strokes occur from blockage in the blood vessels that lead to the brain.) In 2003, statin therapy was shown to reduce both fatal and non-fatal stroke in patients with hypertension and at least three additional cardiovascular risk factors. A 2004 study of stroke patients found that those who were receiving statin therapy at the time of their stroke had more favorable long-term outcomes than patients who were not on statin therapy, suggesting that statin therapy may provide additional benefits to patients who develop stroke.
Diabetes. Statins may have a number of effects that are helpful for patients with diabetes, and may even prevent diabetes in some people with high cholesterol. Statins, however, do not appear to have any effect on blood vessel inflexibility in diabetes, which is an important risk factor for heart disease in these patients. A major 2003 study found that statin therapy helped prevent cardiovascular events including coronary death, heart attack, stroke, and the need for revascularization therapy in patients with diabetes, even in those who did not have high cholesterol levels or established coronary disease.
High Blood Pressure. In an important 2002 study, patients with high blood pressure but normal hMG-CoA reductase or slightly high cholesterol levels had fewer heart attacks and strokes when they took the statin atorvastatin. The study was stopped so all subjects could take statins. An earlier study showed similar benefits with the statin simvastatin.
Alzheimer's Disease. A number of studies have reported a significantly lower risk for Alzheimer's disease in people who take specific statins. Some evidence suggests they may even improve mental function in people without unhealthy cholesterol levels. Statins showing the greatest promise include lovastatin (Mevacor), pravastatin (Pravachol), and atorvastatin (Lipitor.) These statins appear to reduce levels of beta-amyloid. Other statins have not been associated with a lower risk for Alzheimer's. In fact, some researchers are concerned that certain statins that cross the blood-brain barrier may actually worsen Alzheimer's in people who already have it.
Kidney Disease. Statins may prove to protect against heart disease development in patients with mild kidney disorders. According to a 2004 study, statins may also help slow the progression of existing kidney disease.
Eye Disease. Studies are investigating whether statins can help prevent macular degeneration, an age-related eye disease that can lead to blindness. Research is still preliminary, and results have been mixed.

Macular degeneration is a disease of the retina that affects the macula in the back of the eye. The macula is important for clear central vision, allowing an individual to see fine details. There are two types of macular degeneration, dry and wet. Dry macular degeneration is more common and is characterized by the thinning of the retina and drusen, small white deposits that form within the retina. The dry form of macular degeneration is usually mild. Wet macular degeneration can happen more quickly and be more serious. It occurs when vessels under the retinal layer hemorrhage and cause the retinal cells to die, creating blind spots or distorted vision in the central vision. The disease becomes increasingly common among people in each succeeding decade over 50.

Adverse Effects. The statins tend to be better tolerated than other cholesterol-lowering drugs. In many studies the side effects reported were nearly the same as those taking placebo. Side effects may include gastrointestinal discomfort, headaches, skin rashes, muscle aches, sexual dysfunction, drowsiness, dizziness, nausea, constipation, and peripheral neuropathy (numbness or tingling in the hands and feet).

The primary safety concern with statins has involved an uncommon condition called myopathy, which can cause muscle damage and in some cases, muscle and joint pain. A specific myopathy, called rhabdomyolysis, can lead to kidney failure. Reports of rhabdomyolysis prompted the recall of cerivastatin (Baycol) in 2001. The risk for myopathy/rhabdomyolysis is highest at higher doses and in older people (over 65 years), those with hyperthyroidism, and those with renal insufficiency (kidney disease). Both statins and fibrates carry a risk for myopathy. The combination of the two drugs increases this side effect. Some people who use a statin-fibrate combination withdraw from the regimen because of muscle discomfort.

In 2005, the FDA issued a public health advisory for rosuvastatin (Crestor), noting that this drug, like other statins, increased the risk for myopathy and rhabdomyolysis. The risks were greatest at the highest dose level (40 mg). The FDA advises that patients should not start therapy at this dose. In addition, the FDA reported the results of a post-marketing study that found that people of Asian heritage had twice the blood levels of the drug as Caucasians who had taken the same dose. Because of this difference in drug metabolism, the FDA advises that Asian Americans should start treatment at the lowest rosuvastatin dose (5 mg). In general, all statin therapy should start at a lower dose and be raised incrementally until healthy cholesterol levels are maintained. Patients should immediately tell their doctor about any unusual muscle discomfort or weakness, fever, nausea or vomiting, or darkening of urine color.

Statins can also affect the liver, particularly at higher doses, so patients should have periodic liver function tests. Statins should not be taken by anyone with liver problems or by women during pregnancy or breast-feeding. Similarly, high statin doses increase the risk for kidney failure, particularly for patients with other existing risk factors (diabetes, hypertension, atherosclerosis, history of heart failure).

Interactions with Drugs and Food. Statins may have some adverse interactions with other drugs, including other cholesterol-lowering medications. Among the drugs that increase the risk for adverse effects are cyclosporine, macrolide antibiotics, and certain antifungals. Patients should tell their doctors about any other medications they are taking. Grapefruit juice and Seville oranges may increase statin potency.

Brands. Nicotinic acid is the active compound found in niacin, or vitamin B3. It is the first choice for patients with low HDL levels. Brands include Niacor, Nicolar, and Slo-Niacin. An extended-release form (Niaspan), administered at bedtime, may have fewer side effects, including headaches and flushing, than rapidly-acting niacin drugs. Although niacin is available over the counter, the active form used for cholesterol is given in much higher doses and is available only by prescription. It is important to take this medication under a doctor's direction in order to ensure its safety and effectiveness.

Benefits. When used in high doses, it has the following benefits:

Raises HDL levels higher than other anti-cholesterol drugs
Reducing triglyceride levels very effectively
Lowers LDL-cholesterol and lipoprotein(a)
Costs less than other anti-cholesterol drugs

Combinations with other drugs, particularly statins, may add significant benefits.

Side Effects. Many patients do not like the side effects of the rapidly-absorbed form of nicotinic acid. About a quarter of patients who use rapid-acting forms of nicotinic acid stop taking them. The most common side effects are flushing of the face and neck, itching, headache, blurred vision, and dizziness. They usually occur between 5 minutes to hours after taking the drug and can last for minutes to, uncommonly, hours. The body does eventually become tolerant to these effects, and they generally subside.

The following may reduce flushing and itching:

Starting with low doses taken at mealtime and gradually working up to the prescribed dose.
Taking low-dose aspirin about 30 minutes before taking nicotinic acid. This may help prevent flushing.
Avoiding hot drinks.
Choosing an extended release form. (Even with this form, it is wise to gradually increase the bedtime dose over time and take a low-dose aspirin a half-hour beforehand.)

Stomach problems are common. Other side effects include dry skin and mucous membranes and darkening of the skin.

About 30% of patients who take niacin experience elevated levels in blood glucose, which can be a problem for people with diabetes. Niacin's effects on HDL and triglycerides, however, are especially suited for the lipid imbalances that are common in diabetes. And, some studies report that people with diabetes who use niacin have little trouble with blood sugar control.

Potentially Serious Complications. About 3 - 5% of people taking nicotinic acid develop liver problems, which disappear after the medication is discontinued. The extended form (Niaspan) appears to be safe for the liver, but people with chronic liver disease should not use any form of nicotinic acid. People with gout should also avoid nicotinic acid because it elevates uric acid.

Bile-acid binding resins work, as their name suggests, by binding to bile in the digestive tract. This reduces cholesterol in the following way:

Bile is made in the liver and is used as one of the body's primary manufacturing components.

Click the icon to see an image of the gallbladder.

Once the resins bind to bile in the digestive tract, the bile is excreted in feces.
As the resins eliminate bile from the body, the liver takes more cholesterol from the bloodstream in order to produce more bile.
As cholesterol is taken out of the bloodstream, LDL levels drop.

When used in combination with dietary control, LDL levels are reduced by 15 - 20%. Combinations with nicotinic acid are even more effective, with reductions of 40 - 60% observed.

Brands. The bile-acid binding resins and similar drugs include cholestyramine (Questran, Questran Light). They are commonly used in a powder that is dissolved in liquid. Colesevelam (Welchol) is available in tablet form.

Side Effects. None of these drugs poses major risks. Most, however, cause constipation, heartburn, gas, and other gastrointestinal problems, side effects that many people cannot tolerate. One study found that only half the standard dose of colestipol was needed when psyllium, (a soluble fiber supplement found in Metamucil, Fiberall, and Perdiem), was added to the drink. In addition, bloating and constipation were reduced. Colesevelam, a newer resin, appears to have significantly fewer of these side effects.

Bile-acting drugs may contribute to calcium loss and therefore increase the risk for osteoporosis. Over time, deficiencies of vitamins A, D, E, and K may occur, and vitamin supplements may be necessary.

Rarely, toxic effects on the liver have been reported. Patients with liver disorders should be monitored.

Drug Interactions. Bile-acid binding resins may also interfere with other medications, including digoxin (Lanoxin), warfarin, beta-blocker drugs, and a number of medications used to treat low blood sugar. In order to prevent drug interactions, other drugs should be taken 1 hour before or 4 - 6 hours after taking the bile acid-binding resins.

Brands. Fibrates (sometimes called fibric acid derivatives) break down the particles that make triglycerides. Gemfibrozil is the standard fibrate. It is usually taken twice a day, 30 minutes before breakfast and before the evening meal. Newer fibrates, including fenofibrate (Lofibra, Tricor, Triglide), may be more effective in lowering cholesterol than gemfibrozil.

Benefits. Most fibrates have been shown to lower the risk of heart attack. In a 2001 study, men with both low HDL and LDL levels had a slightly lower risk of stroke after taking gemfibrozil. Fibric acid derivatives, or fibrates, have the following effects on cholesterol, lipids, and other factors:

They are good choices for many patients who need to lower triglyceride levels and increase HDL but who cannot take drugs ordinarily used for these purposes, such as nicotinic acid. In one study gemfibrozil, the standard fibrate, reduced the risk for adverse heart events by 22%.
Fibrates can produce modest reductions in LDL levels, although not as effectively as statins or other drugs. LDL may actually increase in patients with very high triglycerides who take these drugs. (The newer fibrates are much more effective in lowering LDL than gemfibrozil.)
A study on bezafibrate suggested it might have anti-inflammatory effects in patients with high triglyceride levels. Inflammation in the blood vessels is now recognized as a major contributor to the process leading to heart disease. However, according to a 2004 study, patients with diabetes or impaired fasting glucose levels were less likely to benefit from bezafibrate.
A study on fenofibrate further suggested that it reduced certain clotting factors (another risk factor for heart disease) and also uric acid (a risk factor for gout). Another study, published in 2004, demonstrated that like bezafibrate, fenofibrate has significant anti-inflammatory properties in patients with high triglyceride levels.

Concerns. Fibrates do not appear to reduce mortality rates. In one study, people who took gemfibrozil had higher rates of death from other causes, including cancer. Some evidence suggests that fibrates may affect receptors involved in cancer development. However, a number of studies have found no higher incidence of cancer.

Side Effects. Side effects may include gastrointestinal discomfort, aching muscles, sensitivity to sunlight, and skin rashes. Fibrates have been known to cause gallstones, so people with gallbladder problems should not use these drugs.

Click the icon to see an image of gallstones in the gallbladder.

The drugs may cause abnormal heart rhythms and can affect the liver and kidney.

Drug Interactions. Fibrates interact with a number of drugs and substances including warfarin, some oral drugs used for diabetes, certain antibiotics, and grapefruit juice.

Ezetimibe (Zetia) blocks absorption of cholesterol that comes from food. Ezetimibe is usually prescribed alone or in combination with a statin. In 2004, the FDA approved Vytorin, which combines ezetimbe and the statin simvastatin into a single pill.

In 2006, the FDA approved the use of ezetimbe in combination with fenofibrate (Tricor) for reduction of total cholesterol and LDL in patients with mixed hyperglycemia (high LDL levels, high triglycerides, low HDL levels) whose cholesterol has not been adequately controlled through diet alone. Fenofibrate is a cholesterol drug that is used along with diet to reduce LDL and triglycerides.

CETP Inhibitors. Cholesteryl ester transfer protein (CETP) inhibitors, such as the experimental drug torcetrapib, are a new drug class that is being investigated for its effect on raising HDL ("good" cholesterol) levels while lowering LDL ("bad") cholesterol levels. Torcetrapib was the most widely studied of these drugs. However, in December 2006, the drug’s manufacturer abruptly stopped late-stage clinical trials after discovering that torcetrapib significantly increased blood pressure and risk of death.

Several studies published in 2007 in the New England Journal of Medicine revealed that while torcetrapib does greatly boost HDL levels (by 61% in one study) and lower LDL, it has no effect on arterial plaque. Scientists are trying to understand why this drug did not work. One theory is that torcetrapib may have increased the quantity of HDL, but not the quality. It is still not clear whether the failure of trocetrapib is specific to this drug or the entire CETP drug class. Given the current findings, it is also unclear whether research will continue on other CETP drugs.

Selective Estrogen-Receptor Modulators(SERMs). Selective estrogen-receptor modulators (SERMs) have been designed to produce the benefits of estrogen without its risks. They are thought to act like estrogen in some tissues but behave like estrogen blockers (antiestrogens) in others. They include tamoxifen (Nolvadex), raloxifene (Evista), and droloxifene. Any beneficial effects of the SERMs on cholesterol and the heart are still unclear. SERMs pose a risk for deep vein blood clots, which may have implications for people with heart problems. Longer studies are needed on possible risks and benefits.

Recombinant ApoA-I Milano. ApoA-I Milano is a type of HDL protein that is found in people with very low levels of HDL. A 2003 study showed that treating patients with a synthetic form of HDL, derived from ApoA-I Milano, caused a significant regression of atherosclerosis. Ongoing trials will evaluate whether this drug can prevent cardiovascular events such as heart attack or death.

Plasmapheresis and Familial Hypercholesterolemia. Plasmapheresis is a blood-filtering procedure that is used to dramatically reduce triglycerides and may also be used to remove LDL. The procedure may be beneficial for patients with severe hereditary forms of high cholesterol who do not respond to other therapies. Studies suggest, for example, that plasmapheresis is particularly useful for patients with familial hypercholesterolemia. The process takes about 3 hours. If not performed regularly, its benefits last only about 2 weeks. People using this procedure are still advised to maintain a healthy diet and continue to take any prescribed medications to control cholesterol.

Resources

www.nhlbi.nih.gov/about/ncep -- National Cholesterol Education Program
www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.acc.org -- American College of Cardiology
www.americanheart.org -- American Heart Association
www.eatright.org -- American Dietetic Association

References

Berthold HK, Unverdorben S, Degenhardt R, Bulitta M, Gouni-Berthold I. Effect of policosanol on lipid levels among patients with hypercholesterolemiaor combined hyperlipidemia: a randomized controlled trial. JAMA. 2006 May 17;295(19):2262-9.

Crouse JR 3rd, Raichlen JS, Riley WA, Evans GW, Palmer MK, O'Leary DH, et al. Effect of rosuvastatin on progression of carotid intima-media thickness in low-risk individuals with subclinical atherosclerosis: The METEOR Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Deedwania P, Barter P, Carmena R, Fruchart JC, Grundy SM, Haffner S, et al. Reduction of low-density lipoprotein cholesterol in patients with coronary heart disease and metabolic syndrome: analysis of the Treating to New Targets study. Lancet. 2006 Sep 9;368(9539):919-28.

Jolliffe CJ, Janssen I. Distribution of lipoproteins by age and gender in adolescents. Circulation. 2006 Sep 5;114(10):1056-62. Epub 2006 Aug 28.

Kastelein JJ, van Leuven SI, Burgess L, Evans GW, Kuivenhoven JA, Barter PJ, et al. Effect of torcetrapib on carotid atherosclerosis in familial hypercholesterolemia. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

McCrindle BW, Urbina EM, Dennison BA, Jacobson MS, Steinberger J, Rocchini AP, et al. Drug therapy of high-risk lipid abnormalities in children and adolescents. A scientific statement from the American Heart Association Atherosclerosis, Hypertension, and Obesity in Youth Committee, Council of Cardiovascular Disease in the Young, With the Council on Cardiovascular Nursing. Circulation. 2007 Mar 21; [Epub ahead of print]

Nissen SE, Tardif JC, Nicholls SJ, Revkin JH, Shear CL, Duggan WT, et al. Effect of torcetrapib on the progression of coronary atherosclerosis. N Engl J Med. 2007 Mar 26; [Epub ahead of print]

Review Date:
7/23/2007
Reviewed By:
Alan Greene, MD, FAAP, Chief Medical Officer, A.D.A.M., Inc.; and Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Weight control and diet

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Biological and Medical Caus...
Cultural and Emotional Caus...
Risk Factors
Complications
Weight Loss and Maintenance...
Weight Management
Medications
Other Treatments
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Cancer and Weight Control:

Cancer prevention guidelines from the American Cancer Society stress the importance of maintaining a healthy weight throughout life. A healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Drug Warning:

The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

New Over-the-Counter Medication:

In February 2007, the FDA approved the first over-the-counter (OTC) weight-loss drug. Orlistat, previously available only by prescription as Xenical, will be available OTC at half its prescription strength. It will be sold under the name alli. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Research News:

A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets with varying amounts of fat and carbohydrates.
A study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9.

Effects of Obesity on the Body:

Obesity is associated with certain problems related to infertility, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.
People who are obese are at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands.
The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Introduction

A stable weight depends on a good balance between the energy you get from food and the energy you use. You use energy during the day in three ways:

As energy expended during rest (basal metabolism)
As energy used to break down food (thermogenesis)
As energy used during physical activity

Basal metabolism accounts for about two-thirds of spent energy. Your body generally uses this energy to keep your body temperature steady and keep the muscles of your heart and intestine working. Thermogenesis accounts for about 10% of spent energy.

When a person consumes more calories than the energy they use, the body stores the extra calories in fat cells. Fat cells function as energy reservoirs. They enlarge or shrink depending on how people use energy. If people do not balance energy input and output by eating right and exercising, fat can build up. This can lead to weight gain.

When energy input is equal to energy output, there is no expansion of fat cells (lipocytes) to accommodate excess. It is only when more calories are taken in than used that the extra fat is stored in the lipocytes and the person begins to accumulate fat.

Obesity is determined by measuring body fat, not just body weight. People might be over the weight limit for normal standards, but if they are very muscular with low body fat, they are not obese. Others might be normal or underweight, but still have excessive body fat. The following measurements and factors are used to determine whether or not a person is overweight to a degree that threatens their health:

Body mass index (BMI) (a measure of body fat)
Waist circumference (size around the waist)
Waist-hip ratio
Skin fold measurement (anthropometry)
The presence or absence of other disease risk factors (e.g., smoking, high blood pressure, unhealthy cholesterol levels, diabetes, relatives with heart disease)

A person's disease risk factors plus BMI may be the most important components in determining health risks with weight.

The Body Mass Index (BMI). The current standard measurement for obesity is the body mass index (BMI). In general, a BMI of 25 - 29.9 means you are overweight. Obesity is a BMI of 30 and above. Obesity is then classified into three categories:

Class 1: BMI of 30 - 34.9
Class II: BMI 35 - 39.9
Class III: BMI of 40 and greater

These guidelines are very important for people at risk for diabetes, heart disease, or certain cancers. It is also used to determine treatment approaches such as when surgery may be appropriate. The higher the BMI, the greater the risk for significant health problems.

Calculating Body Mass Index (BMI). One's body mass index (BMI) is calculated by multiplying a person's weight in pounds by 703, dividing by the height in inches, and then dividing that number by the height in inches. The steps are as follows:

Multiply one's weight in pounds by 703
Divide that answer by height in inches
Divide that answer again by height in inches

For example, a woman who weighs 150 pounds and is five feet eight inches (or 68 inches) tall has a BMI of 22.8.

Waist Circumference and Waist-Hip Ratio. The extent of abdominal fat can also be used in assessing risk of disease. Some studies suggest that:

Women whose waistlines are over 31.5 inches and men whose waists measure over 37 inches should watch their weight.
A waist size greater than 35 inches in women and 40 inches in men is associated with a higher risk for heart disease, diabetes, and impaired functioning.

Evidence strongly suggests that more body fat around the abdomen and hips (the apple-shape) is a more consistent predictor of heart problems and health risks than BMI.

The distribution of fat can be evaluated by dividing waist size by hip size. For example, a woman with a 30-inch waist and 40-inch hip circumference would have a ratio of 0.75; one with a 41-inch waist and 39-inch hips would have a ratio of 1.05. The lower the ratio the better. The risk of heart disease rises sharply for women with ratios above 0.8 and for men with ratios above 1.0.

Click the icon to see a depiction of the waist-to-hip ratio.

Anthropometry. Anthropometry is the measurement of skin fold thickness in different areas, particularly around the triceps, shoulder blades, and hips. This measurement is useful in determining how much weight is due to muscle or fat.

Biological and Medical Causes

Obesity results when a person consumes more calories than they need for the energy they use. Several different factors may influence weight gain.

About 90% of people who lose weight through dieting gain every pound back regardless of their weight-loss method.

Some evidence suggests that every person has an inherited weight. This range varies by only about 10% either up or down from some set point. For instance, a man whose "genetically-determined" weight is 200 pounds would tend to swing from 180 - 220 pounds. He would be unlikely to lose or gain more than this.

Genetic factors may play some part in 70 - 80% of obesity cases.

Appetite is determined by processes that occur both in the brain and gastrointestinal tract. Eating patterns are controlled by areas in the hypothalamus and pituitary glands (in the brain). The body produces a number of molecules that increases or decreases appetite. In some cases, the following factors may produce imbalances in this process:

Insulin. Insulin is a hormone that helps change blood sugar (glucose) into energy. During digestion, carbohydrates from our diet break down into different types of sugar molecules (including glucose). Proteins from our diet break down into smaller molecules called amino acids. Immediately after eating, blood glucose levels rise. This triggers the release of insulin, which pours into the bloodstream. Insulin pushes the glucose and amino acids into cells and muscles. Insulin and other hormones determine which nutrients will be burned for energy or stored for future use. The inability to use insulin efficiently (insulin resistance) has been associated with both obesity and diabetes.
Leptin. Leptin is a hormone that is released by fat cells. A number of scientists think this hormone may also be released by cells in the stomach. Leptin appears to play an important role in insulin resistance and fat storage in the body, but its role in obesity is unclear. The most likely scenario is that leptin levels rise as the cells store more fat. This increase in leptin levels decreases appetite. Falling levels of leptin make you feel hungry. In people who have genetically lower levels of leptin, however, the brain may be tricked into thinking that it is always starving because there is no leptin to decrease appetite. This can lead to weight gain.
Resistin. Resistin is a hormone produced by fat cells. It makes the body resistant to insulin activity. Some experts believe it may help explain the role of obesity in diabetes type 2.
Intestinal Chemicals. Ghrelin is a chemical produced in the stomach. It appears to be important in triggering the desire to eat. Peptide YY3–36 (PYY) is a substance secreted in the intestines after a meal. The level of PYY is proportionate to the number of calories a person eats. PYY tells the brain that you feel full. Deficiencies in ghrelin and PYY may contribute to some cases of obesity. Researchers are hoping that blocking ghrelin or infusing PYY may be possible treatments for obesity.
Other Chemicals. Many brain chemicals are being studied for their role in appetite stimulation and weight gain. Among them are neuropeptide Y, melanocortins, agouti-related protein, and melanocyte stimulating hormone. Pain-relieving chemicals called endorphins may be critical in reducing appetite and regulating energy use. Cholecystokinin, a hormone released in the upper intestine that stimulates digestive juices, may work to control meal size.

Insulin is a hormone produced by the pancreas that is necessary for cells to be able to use blood sugar.

Genetics may directly contribute to severe obesity in people with family histories of the problem. Genetic factors such as slow metabolisms may also make people more likely to be overweight. At least seven genetic mutations have been associated with specific and uncommon cases of severe obesity. Some are outlined below.

HOB1 (human obesity 1) is a gene that is linked to a high BMI in women.
Leptin gene variants have been linked to leptin deficiencies and obesity.
Melanocortin-4 receptor is a gene that helps turn off the urge to eat. It may not work properly in those with a family history of obesity.
Researchers have also identified a mutation in a gene for a protein called proopiomelanocortin, which results in a syndrome of obesity, red hair, and deficiencies in stress hormones.
A protein called agouti-related protein increases hunger. About 5% of severely obese people have mutations that over-respond to agouti-related protein.

Genetics also determine the number of fat cells a person has. Some people are simply born with more. It should be noted that even when genetic factors are present, a person can still control their diet.

The Thrifty Gene. Some experts think the existence of a so-called "thrifty" gene regulates changes in hormone levels, to accommodate seasonal changes. Theoretically, it works in the following manner:

In certain populations, hormones are released during seasons when food supplies have traditionally been low. This leads to insulin resistance and increased fat storage.
The process is reversed in seasons when food is readily available.
Because modern industrialization has made high carbohydrate and fatty foods available all year long, the gene no longer serves a useful function. Fat, originally stored for famine situations, is not used.

This theory could explain why the previously nomadic Native American tribes who now have Western dietary habits have such high rates of Type 2 diabetes and obesity. In the past, the traditional low-fat, high-fiber foods tribe members ate may have protected them from obesity and type 2 diabetes. Today, these tribes' diet consists of more Western foods, which are higher in fat. Furthermore, these foods are readily available year-round, and many members of the tribe are sedentary. The result is a very high incidence of Type 2 diabetes and obesity. Although genetic abnormalities may make it harder or easier to lose weight, the occurrence of obesity has dramatically increased over the past two decades, and genes cannot have changed within that short amount of time. Our ability to use the food that we eat evolved so that our body could conserve energy and store fat during times of famine. Most cases of obesity now occur in people with normal body function who live in industrialized nations, where there is more than enough food.

A number of medical conditions may contribute to being overweight, but rarely are they a primary cause of obesity.

Hypothyroidism is sometimes associated with weight gain. But, patients with an underactive thyroid generally show only a moderate weight increase of five to 10 pounds.
Very rare genetic disorders, including Froehlich's syndrome in boys, Laurence-Moon-Biedl, and the Prader-Willi syndromes, cause obesity.
Abnormalities or injury to the hypothalamus gland can cause hypothalamic obesity.
Cushing's disease is a rare condition caused by high levels of steroid hormones. It results in obesity, a moon-shaped face, and muscle wasting.
Obesity is also linked to polycystic ovarian syndrome, a hormonal disorder in women.

Click the icon to see an image of polycystic ovaries.

Some prescription medications contribute to weight gain, usually by increasing appetite. Such drugs include the following:

Corticosteroids
Female hormone treatments, including some oral birth control pills (effect is usually temporary), and certain progestins (such as Megestrol) used to treat cancer
Antidepressants and anti-psychotic drugs, including lithium and valproate
Insulin and insulin-stimulating drugs used to treat diabetes often lead to weight gain, a particularly unfortunate conflict of interest for obese individuals with type 2 diabetes

You should not stop taking any medications without your doctor's knowledge.

Cultural and Emotional Causes

Enough food is produced in the US to supply 3,800 calories every day to each man, woman, and child in the country, far more than the average person needs to sustain life. In a 2002 study, participants carefully recorded everything they ate and drank, and all activities and psychological factors surrounding the eating events. The people who gained weight ate more and their portions were larger than those who did not. This may be an obvious conclusion, but the public press often plays up biologic factors involved with obesity and overlooks the simple notion that Americans eat too much and exercise too little.

Obesity is dramatically increasing not only in American children and adults, but also in every country that has adopted similar cultural habits. The World Health Organization now considers obesity to be a global epidemic and a public health problem as more nations become "Westernized." In spite of the proven health risks of obesity, the government, insurance companies, and the medical profession do not spend nearly enough money to balance the commercial and cultural pressures that are producing millions of overweight people.

In 2007, the Robert Wood Johnson Foundation sounded a positive note with the announcement of a $500 million initiative, aimed at “reversing the childhood obesity epidemic by 2015.” The money will be used for research, education, and activities that promote healthy eating among America’s children.

Perhaps the primary reason for the dramatic rise in obesity is the sedentary (inactive) lives led by most Americans, including children and young people. In a 2003 study comparing modern life to the past, researchers found that labor saving devices had reduced a person's energy use by 111 calories a day -- adding up to an extra 11 pounds a year. Half the difference in energy use was due to less walking. At the same time, according to the U.S. Centers for Disease Control and Prevention, between 1970 and 2000 the typical American man increased his caloric intake by 168 calories a day (good for 17 pounds a year) while the average woman added 335 calories a day.

Regular television watching has been singled as the most hazardous pastime. According to a major 2003 study, for every 2 hours a person spends in front of the TV each day, the risk for obesity increases by 23% and for type 2 diabetes by 14%. In the study, TV watching produced the lowest metabolic rates compared to sewing, playing board games, reading, writing, and driving a car. Just the act of watching TV encourages unhealthy snacks and eating patterns. In addition, the advertising on the television complicates the problem by promoting fast foods, cereal, and snack products that are high in salt, fats, and carbohydrates. Even worse, much of these advertisements are directed at children -- the most vulnerable group.

People are not only eating more food than they did 20 years ago, they are also replacing home cooking with packaged foods, fast food, and dining out. This behavior, according to studies, places people at higher risk for obesity. Fast foods may be more harmful than restaurant cooking. These foods tend to be served in larger portions. They generally contain more calories and unhealthy fats, and less nutritious ingredients, than homemade or restaurant meals. Snack foods and sweet beverages, including juice and soft drinks, are specific problems that add to the increasing rates of obesity. Frequent small, healthy meals (instead of two or three large daily meals) have been associated with lower weights.

People react differently to stress. Some overeat and gain weight and others stop eating and lose weight. People who gain weight in response to stress often overeat foods high in sugar, fats, and salt. A 2003 study on rats suggested that stress hormones increase the pleasure of eating such so-called "comfort foods." Furthermore, the study supported previous research showing that stress-related eating was connected to the unhealthy accumulation of abdominal fat.

Risk Factors

Where you live plays a role in your risk for obesity. Simply living in the United States makes a person more susceptible to obesity. The prevalence of obesity in America has risen dramatically over the past few years and continues to increase.

According to the latest figures available, 32.2% of American adults (aged 20 and older) are obese (BMI over 30) -- up from about 23% in the early 1990s.
The number of Americans aged 20 - 74 who were overweight also increased -- from about 44.8% in 1960 to 65.2% in 2002.
The rate of extreme obesity (BMI > 40) increased from 0.8% in 1960 to 4.9% in 2002.
Obesity has increased in every state, in both men and women, across all age groups, and in every ethnic group, although some groups may face slightly higher risks than others.

Fat tends to settle in certain regions, depending on gender. Women gain fat predominantly in the stomach, hips and thighs, while men tend to gain fat in the belly and waist.

Risk by Age. People of any age are at risk for obesity. More children and adolescents are overweight in America than ever before. Gaining some weight is inevitable with age and adding about 10 pounds to a normal base weight over time is not harmful. The current weight gain in American adults over 50, however, is significant. By age 55, the average American has added nearly 40 pounds of fat during the course of adulthood. This condition is made worse by the fact that muscle and bone mass decrease with age.

Risk by Gender. In men, BMI tends to increase until age 50 and then it levels off. In women, weight tends to increase until age 70 before it plateaus. A 2000 study found that there are three high-risk periods for weight gain in women.

The first is at the onset of menstruation, particularly if it is early. In fact, a study released in March 2007 found that obesity in young girls results in early puberty -- as early as age 9. This, in turn, increases the risk for more weight gain as girls enter puberty.
The second is after pregnancy, with higher risk for women who are already overweight.
Finally, many women gain weight after menopause.

These findings are significant because they may allow women to target high-risk times, and consequently prevent unnecessary weight gain.

Risk by Economic Group. Obesity is more prevalent in lower economic groups. One 2002 study reported that women who reported that they did not have enough food were more likely to be overweight than those who said they had sufficient food. Researchers discovered that the low-income women tended to have fewer fruits and vegetables but were actually taking in more calories a day than higher-income women. However, obesity is increasing in young adults with college education as well as in other groups.

Ethnic Groups. Among ethnic groups in general, African-American women are more overweight than Caucasian women but African-American men are less obese than Caucasian men. (Currently, 80% of African-American women are overweight.) Hispanic men and women tend to weigh more than Caucasians.

US Regions. Regionally, the prevalence of obesity is lowest in the Western states and highest in the South.

A number of dietary habits put people at risk for becoming overweight:

Night-Eating Syndrome. Night-eating syndrome is defined as having no appetite in the morning, insomnia, and consuming more than half of daily food intake after 6:00 PM. It is associated with obesity and is difficult to treat. Stress reduction and relaxation techniques may be helpful.
Binge Eating and Eating Disorders. About 30% of people who are obese are binge eaters who typically consume 5,000 - 15,000 calories in one sitting. To be diagnosed as a binge eater, a person has to binge at least twice a week for 6 months. Many experts believe that binge-eating carbohydrates causes an increase in a natural opiate leading to dependence on carbohydrates. Therefore, this condition should be treated as an addiction. Other eating disorders are bulimia and anorexia. Bulimia is binge eating followed by purging in order to lose weight. Anorexia nervosa is a mental illness in which the person refuses to maintain weight at the normal level. The patient with anorexia has a terrible fear of getting fat, and an abnormal perception of what his or her body looks like. Both conditions pose risks for serious medical problems, and anorexia nervosa can be life-threatening. A combined approach using behavioral therapy and antidepressants may help these individuals. [See In-Depth Report #49: Eating disorders.]
Restrained Eating. Some people, mostly middle-aged women who have normal weight, have a pattern referred to as restrained eating. This pattern requires a high level of conscious control and usually maintains a lower weight. However, such restraint places these individuals at higher risk for loss of control and subsequent overeating.
Infrequent Eating. There is some evidence to suggest that eating small frequent meals uses more calories than infrequent large meals. It should be strongly noted, however, that packaged snack foods add calories and some do not produce a feeling of being full, so that people simply eat more than they should.

Anyone with Sedentary Lifestyles. Office workers, drivers, and anyone whose lifestyle involves sitting for long periods are at higher risk for obesity.

Ex-Smokers. The trend toward weight increase has followed the trend for quitting smoking. Nicotine increases the metabolic rate, and quitting, even without eating more, can cause weight gain, which may be considerable. It is important to note that weight control is not a valid reason to smoke. People in previous centuries did not smoke cigarettes, nor were they usually obese.

Shift-Workers. A recent study found that individuals who work late shifts (between 4 p.m. and 8 a.m.) tend to eat more and take longer naps than day workers and are more likely to gain excess weight.

People with Disabilities. Obesity rates are higher than average in people with physical or mental disabilities. Those with disabilities in the lower part of the body, such as the legs, are at highest risk.

Overweight in children and adolescents is rising at an alarming rate. In 2004, 19% of young children aged 6 - 11 were overweight, an increase of 8% from 1994. Among children aged 25, 13.9% were overweight in 2004, up from 7.2% 10 years earlier.

Definition of Overweight in Children

Children and adolescents are considered to be overweight if their BMI is above 95% of the children in their age and sex categories. Ethnic variations, timing of growth spurts, and higher normal fat levels around puberty can affect these measurements.

Causes and Risk Factors for Overweight in Children

Lifestyle Factors. Without educational or parental guidance, children are extremely vulnerable to the intense cultural pressures that are largely responsible for the obesity epidemic. The following are some specific problems created by the culture:

Excessive television watching plays a critical role in obesity in children. Not only is it a sedentary activity, but television also offers innumerable temptations with its advertisements for fast foods, sugar cereals, and unhealthy snacks. In one study obesity rates were lowest in children who watched television 1 hour or less a day and highest in those who watched 4 or more hours.
Sugar, particularly from soda, other sweetened beverages, and fruit juice, may be the major contributor to childhood obesity. One study reported that drinking soda regularly increases a child's risk for obesity by 60%. The average American adolescent consumes 15 - 20 extra teaspoons of sugar a day just from soda and sugary drinks. (Juice, while better than soda, is still filled with sugar.)
Less physical exercise and greater sedentary activities play another significant role in obesity in children. A high level of physical activity -- not just using up energy -- is important for weight control in young people. Unfortunately, according to one study, the annual distance walked by children has fallen by nearly 30% since 1972, partially because more parents are driving their children to school out of fear of abduction, molestation, and traffic accidents. Schools are also offering fewer opportunities for daily physical activities than in the past.

Neither the media nor the educational system has strong well-financed programs that encourage healthy alternatives, including exercise and healthy foods.

Family History. Parental obesity more than doubles the risk that a young child, whether thin or overweight, will become obese as an adult. In older children and teenagers, obesity in parents starts to count less as a predictor for body weight than their own weight. The risk for obesity may be due to environmental or genetic factors, or both.

Ethnic and Socioeconomic Factors. As in adult populations, children from lower socioeconomic groups and minority populations are at higher risk for obesity. For example, among young Mexican Americans and African-Americans, there has been an increase in overweight prevalence of about 13% to over 23%.

Factors Surrounding Birth. The following factors surrounding birth are associated with a child's weight:

Low birth weight is a risk factor for later obesity and diabetes. One theory is that humans have a "thrifty gene" that produces metabolic changes in infants with low birth weight. Such changes affect insulin and fat accumulation, in order to produce a "catch-up" weight in these young children as quickly as possible. This rapid weight gain in infancy increases the risk for obesity in children and young adults.
In a study of African-American children, having an overweight pregnant mother increased the risk for later weight gain, but low birth weight did not.

Although some small studies have reported protection against obesity from breastfeeding, evidence is weak. In a 2003 study, for example, children who were breast fed for 3 - 5 months had a lower risk for obesity, but prolonged breastfeeding had no effect. Nevertheless, given the healthful effects of breast feeding and the possibility that it may have even a slight impact on childhood obesity, it is highly recommended.

Biological Effect of Childhood Overweight on Adult Weight

Achieving a healthy weight becomes more difficult as children get older. The odds of obesity persisting into adulthood ranges from 20% in 4 year olds to 80% in teenagers. One reason for the persistence is biological. The fat cells change in number or mass depending on a person's age:

Fat cells themselves multiply during two growth periods: early childhood and adolescence. Overeating during those times increases the number of fat cells. Some people are also just born with more fat cells.
After adolescence, fat cells tend to increase in mass rather than quantity, so that adults who overeat and gain weight tend to have larger fat cells, not more of them. This growth in mass may be responsible for the greater risk of persistent obesity among teenagers compared to small children who are overweight. Losing weight after adolescence reduces the size of the fat cells but not their number, so weight loss becomes much more difficult.

Health Consequences of Childhood Overweight

Children and adolescents who are overweight have poorer health than other children. Studies are reporting unhealthy cholesterol levels and high blood pressure in overweight children and adolescents. Of great concern is the dramatic increase in type 2 diabetes in young people, which is largely due to the increase in overweight children. Overweight in children is also linked to asthma, gallbladder problems, sleep apnea, and liver abnormalities. Overweight girls are more likely to enter puberty early, according to a new study, and subsequently be at higher risk for breast cancer.

It is not clear yet how many of these childhood problems persist in people who achieve normal weight as adults. Staying overweight into adulthood certainly carries health risks.

Managing Overweight Children

Childhood obesity is best treated by a non-drug, multidisciplinary approach including diet, behavior modification, and exercise. Evidence suggests that reducing calories by only 200 - 260 per day would prevent weight gain in most overweight children. Here some tips for children who are overweight:

Limit (or avoid, if possible) take out, fast foods, high-sugar snacks, commercial packaged snacks, soda, and sugar-sweetened beverages (including too much juice).
Let children snack but make sure the snacks are healthy. Eating small frequent healthy meals (instead of two or three large ones) has been associated with being thinner and having a better cholesterol profile.
Let children choose their own food portions. One study indicated that children naturally ate 25% less when they chose their own portion size. When they were given larger portions their bite sizes were larger and they ate more.
Do not criticize a child for being overweight. It does not help and such attitudes could put children at risk for eating disorders, which are equal or even greater dangers to their health.
Limit television, video games, and computer use to a few hours a week. This can contribute significantly to weight control, regardless of diet and physical activity.
For young children, try the traffic-light diet. Food is designated with stoplight colors depending on their high caloric content: Green for go (low calories); yellow for "eat with caution" (medium calories); red for "stop" (high calories).
Try a low glycemic index diet. This may be as beneficial, and possibly more, than a standard reduced-fat diet in overweight children. Such a diet focuses on certain carbohydrates (for example, dried beans and soy), which raise blood sugar more slowly than other types of carbohydrates. This diet is sometimes used in diabetes, and as a dietary approach in overweight adults. [See In-Depth Report #42: Diabetes diet.]

Click the icon to see an image about TV watching.

Click the icon to see an image of childhood overweight.

Complications

General Adverse Effects of Obesity. Obesity, defined as a BMI of 30 or over, accounts for nearly 300,000 deaths in the U.S. each year. It is associated with more chronic health problems than smoking, heavy drinking, or poverty. Furthermore, given the current increase in obesity, it will surpass smoking as the most important preventable cause of death in America.

Some studies indicate the following health risks by body mass:

The lowest risks for heart disease, diabetes, and some cancers are in people with BMI values of 21 - 25.
The risks increase slightly when BMI values are between 25 - 27.
The risks are significant in BMIs between 27 - 30.
The same risks are dramatic at BMIs over 30.

Anyone with chronic health problems such as heart or lung disease, stroke, or arthritis, should be concerned about extra weight. This same concern also applies to people with known risk factors for such conditions.

Metabolic Changes. As fat stores increase, the fat cells themselves enlarge and produce chemicals that increase the risk for several diseases. Such diseases may include diabetes, high blood pressure, gallbladder disease, and some cancers.
Increased Mass. The increased body weight itself causes problems that result in injury and diseases, including osteoarthritis and sleep apnea.
Harmful Fat Cell Types. Weight concentrated around the abdomen and in the upper part of the body (the apple shape) poses a higher health risk than fat that settles around the hips and flank (the pear shape). Fat cells in the upper part of the body appear to have different qualities from those found in the lower parts. In fact, studies suggest a higher risk for diabetes in people with the "apple shape" and lower risk in those who are "pear shaped."

Weight gain in the area of and above the waist (apple type) is more dangerous than weight gained around the hips and flank area (pear type). Fat cells in the upper body have different qualities than those found in hips and thighs.

General Adverse Effects of Being Overweight (Not Obese). It is still not clear if being overweight (a BMI of 25 - 29.9) hurts healthy people with no risk factors for serious illnesses.

According to one 2001 study, just being overweight increased the risk for developing diabetes, gallstones, hypertension, heart disease, stroke, and colon cancer. The risk rose according to how much the individuals were overweight. In any case, adults who are overweight in middle age face a poor quality of life as they age, with the quality declining the greater the weight. One study suggested, however, that being over 65 and overweight (but not obese) is not associated with higher mortality rates.

Some experts argue, in fact, that in anyone who is not severely obese, it is the unhealthy diet and sedentary lifestyle that causes harm -- not weight per se. In support of this argument, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Being somewhat overweight may also have some benefits under specific circumstances:

In older women, some excess fat may produce extra estrogen that helps slow down bone loss, and insulates bones from fall-related injuries. It should be strongly noted, however, that when older overweight women lose weight they report less pain, improved vitality, and improved physical function. The same positive effect of overweight does not appear to hold in older men.
Conditioned athletes may have high BMIs because of very dense muscle tissue. Being fit in general may protect many overweight people.
Some evidence suggests that Caucasians have the lowest mortality with BMIs of 24.3 - 24.7 while African-Americans are better off in the range of 26.8 - 27.1.
Children may have higher normal fat levels during growth spurts and around puberty.

Individuals with a BMI of at least 30 have a 10 - 50% increased rate of death from all causes, compared with individuals with a BMI of 20 - 25. Mortality rates from many causes are higher in obese people, but heart disease is the primary cause of death. People who are obese have almost three times the risk for heart disease as people with normal weights. Being physically unfit adds to the risk.

Weight concentrated around the abdomen and in the upper part of the body (apple shape) is particularly associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Fat that settles in a pear shape around the hips and lower body appears to have a lower association with these conditions.

Obesity poses many dangers to the heart and circulatory system.

Damage in the Blood Vessels. As people age, changes in body fat (particularly increasing abdominal fat) seem to cause stiffness in the aorta, the major blood vessel leading from the heart. Studies are finding higher levels of a factor called C-reactive protein (CRP) in people with obesity and abdominal fat. CRP is now considered to be a marker for inflammation and damage in the arteries. (Losing weight reduces CRP levels.)

High Blood Pressure. High blood pressure is the health problem most commonly associated with obesity, and the greater the weight, the greater the risk. High blood pressure carries serious risks of stroke, heart attack, and heart failure. The link between obesity and high blood pressure is complex, and may be a combination of genetic, population, and biological factors. Many studies have reported that modest weight loss is beneficial for reducing existing high blood pressure. [See In-Depth Report #14: High blood pressure.]

Heart Failure. An important 2002 study reported that obesity might account for 11% of heart failure cases in men and 14% in women. This link existed independently of other risk factors, such as high blood pressure, sleep apnea, and diabetes, which are also associated with obesity. The biologic mechanisms involved in obesity that lead specifically to heart failure are not clear. [See In-Depth Report #13: Heart failure.]

Unhealthy Cholesterol Levels and Lipid Levels. The effect of obesity on cholesterol levels is complex. Although obesity does not appear to be strongly associated with overall cholesterol levels, among obese individuals triglyceride levels (the major form of fat storage in the body) are usually high, while HDL levels (the "good" cholesterol) tend to be low. Both conditions are risk factors for heart disease. [See In-Depth Report #23: Cholesterol.]

Click the icon to see an image of coronary artery disease.

Stroke. Obesity is also associated with a higher risk for stroke. [See In-Depth Report #45: Stroke.]

Type 2 Diabetes and Insulin Resistance. Most people with type 2 diabetes are obese and, in fact, studies strongly suggest that weight loss may be the key in controlling the current epidemic of type 2 diabetes. The common factor appears to be insulin resistance. Insulin is a critical hormone in the use of sugar. In type 2 diabetes, different factors cause the body to become insulin resistant -- that is, the body can no longer respond properly to insulin. This has the effect of increasing sugar levels in the blood, the hallmark of diabetes. Both obesity and insulin resistance, at different phases, are marked by high levels of certain chemicals. It is not known yet if the higher levels are simply a product of obesity, or play some role in causing diabetes.

Insulin resistance is also associated with high blood pressure and abnormalities in blood clotting. Some research indicates that obesity, in fact, is the one common element linking insulin resistance, diabetes type 2, and high blood pressure. [See In-Depth Report #60: Diabetes - type 2.]

Metabolic Syndrome. Metabolic syndrome (also called syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome. A combination of weight loss and exercise is an effective treatment for this syndrome.

The American Cancer Society released new cancer prevention guidelines in September 2006. The guidelines stress the importance of keeping a healthy weight throughout life. The Society indicates that healthy weight is even more important than eating specific healthy foods, when it comes to cancer prevention.

Obesity has been associated with a higher risk for cancer in general and specific cancers in particular. Studies have also suggested that restricting calories reduces the risk for cancer. Some experts believe that effective weight control for children and adults could reduce cancer rates by 30 - 40%. One way obesity may increase the risk for cancer is its association with high levels of hormones called growth factors, which can trigger rapid cell production leading to cancer.

Uterine Cancers. The risk of uterine cancer in obese women appears to be two or three times higher than in thinner women.

Prostate Cancer. New studies from 2005 and 2006 report that obesity is associated with an increase in prostate cancer mortality, although not with the risk for less aggressive forms of prostate cancer.

Click the icon to see an image of prostate cancer.

Breast Cancer. Studies are mixed on the association between obesity and breast cancer. A number of studies have linked obesity to breast cancer in postmenopausal women, particularly in women who begin to gain weight after age 18.

Click the icon to see an illustrated series detailing a breast cancer surgery (mastectomy).

Gallbladder Cancer. Obese women are at higher risk for gallbladder cancer.

Gastrointestinal Cancers. A number of cancers in the gastrointestinal tract have been associated with obesity:

Cancer of the esophagus may be due to a higher incidence of gastroesophageal reflux disorder (heartburn) in people who are overweight.
Colon cancer has been linked to increased body mass in both men and women.
Pancreatic cancer and obesity have been weakly linked, with one study reporting a lower risk in overweight people who are physically active.

Click the icon to see an illustrated series detailing a colon cancer surgery.

Muscles and Bones

Obesity places stress on bones and muscles. Studies report that the incidence of osteoarthritis is significantly increased in people who are overweight. People who are obese are also at higher risk for carpal tunnel syndrome and other problems involving nerves in their wrists and hands. It should be noted that some weight may be protective against osteoporosis (loss of bone thickness).

Obesity increases the risk for the following mouth and eye disorders:

Gum disease
Cataracts
Maculopathy, an eye disease related to aging

Infertility. Abnormal amounts of body fat, either 10 - 15% too high or too low, can contribute to infertility in women. Obesity is specially related to certain infertility problems, such as uterine fibroids or menstrual irregularities. In men, obesity can contribute to reduced testosterone levels.

Effect on Pregnancy. Obesity has many dangerous effects on pregnancy. These include high blood pressure, gestational diabetes (diabetes, usually temporary, that occurs during pregnancy), urinary tract infections, blood clots, prolonged labor, and higher fetal death rate in late stages of pregnancy. Obesity is also associated with increased rates of cesarean delivery. Infants of women who are obese are also at higher risk for neural tube birth defects, which affect the brain or spine. Folic acid supplements, ordinarily effective in preventing these conditions, may not be as protective in overweight women.

Obesity is thought to be a risk factor for symptoms of adult-onset asthma. Though there is evidence that obesity causes wheezing and shortness of breath, it does not appear to be strongly associated with the disease mechanisms in the lungs that cause true asthma.

Obesity also puts people at risk for hypoxia, a condition in which there is not enough oxygen to meet the body's needs. Obese people need to work harder to breathe. They tend to have breathing muscles and lungs that do not work as well as those in thinner people.

The Pickwickian syndrome, named for an overweight character in a Dickens novel, occurs in severe obesity when lack of oxygen produces intense and chronic sleepiness and, eventually, heart failure.

Nonalcoholic Fatty Liver Disease. People with obesity, particularly if they also have type 2 diabetes, are at higher risk for a condition called nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH). This condition causes liver damage that is similar to liver injury seen in alcoholism. In some cases, it can be very serious and require liver transplantation. It occurs in about half of people with diabetes, and 20 - 50% of obese people, depending on how severe their obesity is. NASH can also occur in overweight children.

Gallstones. The incidence of gallstones is significantly higher in obese women and men. The risk for stone formation is also high if a person loses weight too quickly. In people on ultra-low calorie diets, gallstones may be prevented by taking ursodeoxycholic acid (Actigall).

Click the icon to see an image of gallstones.

People who are obese and nap tend to fall asleep faster and sleep longer during the day. At night, however, it takes them longer to fall asleep, and they sleep less than people with normal weights. In an apparent vicious circle, studies have suggested that obesity not only interferes with sleep but that sleep problems may actually contribute to obesity.

Sleep Apnea. Obesity, particularly the apple shape, is strongly associated with sleep apnea, which occurs when the upper throat relaxes and collapses from time to time during sleep. This collapse temporarily blocks the passage of air. Sleep apnea is increasingly being viewed as a potentially serious health problem, which may lead to complications such as heart disease and stroke. Some studies suggest that among overweight people, those who have sleep apnea have a greater risk of heart disease than those without it. In one study, the more obese a person with sleep apnea was, the higher the pressure on the airway, and therefore the greater the obstruction of the airway. Obstructive sleep apnea may also add to obesity, however, as sleepy people tend to be sedentary. Some studies indicate that treating sleep apnea may help people lose abdominal fat.

Narcolepsy. A small European study found a link between narcolepsy (a sleep disorder characterized by excessive daytime sleepiness with frequent daily sleep attacks) and high BMI.

Depression. A number of studies have reported an association between depression and obesity, particularly in obese women. There may be a number of factors to explain the link. In some cases of atypical depression, people overeat and may gain weight. Overweight people may also become depressed because of social problems and a poor self-image. In these cases, depression usually disappears when people lose weight.

There is evidence, however, that obesity itself may impair levels of tryptophan -- a chemical needed to make serotonin, a brain chemical associated with mental well-being. In one study, even after people lost weight, tryptophan levels were lower than normal.

There does not appear to be any association between depression and obesity in men.

Social Problems. One long-term study reported that overweight young women completed fewer years of school, were 20% less likely to be married, and had 10% higher rates of household poverty than their thinner peer. Obese young men were also less likely to be married, and their incomes were lower than their thinner peers. Nevertheless, studies consistently show that overweight males (both boys and men) are not as severely emotionally affected as females of any age. Women and girls tend to blame themselves for being heavy, while males tend to blame being overweight on outside factors.

Weight Loss and Maintenance

Even modest weight loss can reduce the risk factors for heart disease and diabetes. The simplest (but still difficult) approach to weight loss is reducing calories and exercising at least 150 minutes a week. Behavioral and mental changes in eating habits, physical activity, and attitudes about food and weight are also essential to weight management. For people who are very overweight and cannot lose weight through lifestyle changes, a number of effective weight-loss medications are available. For those with severe obesity, surgical procedures are proving to be very beneficial.

Some Tips for Losing Weight. The following are some general suggestions for dieters:

Start with realistic goals. Diet failure is extremely common, and the odds of significant weight loss are low, particularly in people with the highest weights. People who are able to restrict calories, engage in an exercise program, and get help in making behavioral changes can expect to lose between 5 - 10% of their current body weight. That is generally all that is needed to achieve meaningful health changes. Certainly, the distorted image of a super-thin female shape should not be anyone's goal.
Maintain a regular exercise program, assuming you have no health problems that will stop you. Choose a program that you enjoy. Check with your doctor about any health considerations. [See In-Depth Report #29: Exercise.]
Do not use hunger pangs as cues to eat. A stomach that has been stretched by large meals will continue to signal hunger for large amounts of food until its size reduces over time with smaller meals.
Be honest about how much you eat and start by recording all calories in writing. Studies suggest that when many people report their own calories intake they significantly underestimate their consumption of high-calorie and over-estimate the low-calorie foods. People who do not carefully note everything they eat tend to take in too many calories when they believe they are dieting.
Observe weekend eating. People tend to eat more on the weekends. If it is difficult to monitor all meals during the week, it be may be useful to at least track eating habits during the weekends.
Once the pounds are lost, do your best to keep the healthier weight. Make daily, even hourly, conscious decisions about eating and exercising activities. Such thinking, in many cases, can become automatic and not painful.
Don't give up, even after repeated weight loss failures. Most studies indicate that yo-yo dieting or weight cycling have no bad psychological or physical effects. Repeated dieting also does not harm the body's ability to burn calories efficiently.
Weight loss, in any case, should not be the only or even the primary goal for people concerned about their health. The success of weight loss efforts should be evaluated according to improvements in disease risk factors or symptoms, and by the adoption of healthy lifestyle habits, not just by the number of pounds lost.


Lifestyle	Reduce rate of eating. Keep food records. Eliminate environmental triggers to eating. Identify high-risk situations for overeating. Separate eating from other activities.
Exercise	Face up to emotional barriers to exercise. Understand the link between exercise and weight control. Establish reasonable exercise goals. Develop a plan for regular activity. Add increased activity into daily lifestyle.
Attitudes	Develop reasonable weight-loss goals. Avoid "all or none" thinking. Focus attention away from the scale and toward behavior. Uncouple weight from self-esteem. If you "fall off the wagon," take steps to ensure the situation does not repeat (recover from lapses with constructive action).
Relationships	Understand the key role of social support to health. Identify supportive others. Match personal style to support-seeking activities. Be specific in making support requests. Be assertive but reinforcing in drawing help from others.
Nutrition	Resist the temptation of popular fad diets. Eat with your health in mind; do not concentrate on what should be "off-limits." Eat with moderation in mind. Maximize fiber. Develop a tailored plan.
From Brownell KD. The LEARN Program for Weight Control. 7th ed. Dallas, Tex: American Health Publishing Company; 1998.

Weight Management

There are many approaches to dieting and many claims for great success with various fad diets. To date, although many diets achieve effective immediate weight loss, none has emerged as an effective tool for maintaining healthy weight. The only definite recommendation that can be made about any diet plan is to be sure it includes an exercise program, assuming there are no health problems to forbid it.

The original food pyramid, with four food groups, has been replaced with an updated food guide called "My Pyramid." This illustrates the relative proportions of different foods that make up a nutritious, well-balanced diet and includes exercise.

Calorie restriction has been the cornerstone of obesity treatment. The standard dietary recommendations for losing weight are the following:

As a rough rule of thumb, one pound of fat equals about 3,500 calories. A person could lose a pound a week by reducing daily caloric intake by about 500 calories a day. Naturally, the more severe the daily calorie restriction, the faster the weight loss. Very-low calorie diets have also been associated with better success, but extreme diets can have some serious health consequences.
To determine your daily calories requirements, multiply the number of pounds of ideal weight by 12 - 15 calories. The number of calories per pound depends on gender, age, and activity levels. For instance, a 50-year old woman who wants to maintain a weight of 135 pounds and is mildly active might require only 12 calories per pound (1,620 calories a day). A 25-year old female athlete who wants to maintain the same weight might require 25 calories per pound 2,025 (calories a day).
Fat intake should be no more than 30% of total calories. Most fats should be in the form of monounsaturated fats (such as olive oil). Saturated fats (found in animal products) should be avoided.

Extreme diets of less than 1,100 calories carry health risks. They are also often followed by bingeing or overeating, and a return to the obese state. Such diets often do not have enough vitamins and minerals, which must then be taken as supplements. Most of the initial weight loss is in fluids. Later, fat is lost, but so is muscle, which can account for more than 30% of the weight loss. No one should be on severe diets for longer than 16 weeks, or fast for more than 2 or 3 days. Severe dieting has unpleasant side effects including fatigue, intolerance to cold, hair loss, gallstone formation, and menstrual irregularities. There have been rare reports of death from heart arrhythmias when liquid formulas did not have sufficient nutrients. Pregnant women who excessively diet during the first trimester put their unborn children at risk for birth defects. Of note, those whose diets include a high intake of fluids and much reduced protein and sodium are at risk for hyponatremia, which can cause fatigue, confusion, dizziness, and in extreme cases, coma and death.

This dietary approach requires counting only grams of fat with the goal of achieving 30% or fewer calories from fat. One gram of fat contains nine calories, while one gram of carbohydrates or protein has only four calories. Fat in your diet converts more readily to fat in the body, compared with carbohydrates or proteins. Simply switching to low-fat or skimmed dairy products may be enough for some people.

There are possible drawbacks to this approach:

Some people who reduce their fat intake may not get enough basic nutrients, including vitamins A and E, folic acid, calcium, iron, and zinc. People on low-fat diets should eat a wide variety of foods and take a multivitamin supplement, if appropriate. Calcium deficiencies may be particularly harmful in women at risk for osteoporosis.
Many people start eating foods with too many carbohydrates, believing that they are not adding calories. No one should use a low-fat diet as an excuse for eating too many carbohydrates, particularly starchy foods and sugar. A high-calorie diet from any source will add pounds.
A small study in Norway found that a diet low in fat and high in carbohydrates ("carbs") increases symptoms of psychological distress, such as depression and anger. The study compared three different diets that had varying amounts of fat and carbohydrates in each. The diets contained the same amount of calories, but differed in the percentage and type of fat. People on the low-fat, high-carbohydrate diet reported more anger and depression compared with the other two diets.
Replacing fatty foods, such as cakes, cookies, and chips, with their commercial "low-fat" counterparts does not constitute a low-fat diet. These foods generally contain more sugar and hence calories, not to mention other ingredients, which have virtually no nutritional value. In fact, a 2002 study suggested that increasing sugar may, over time, reduce levels of HDL ("good") cholesterol.
Very low-fat diets may increase the risk for stroke from hemorrhage in the brain.

Some fat in a diet is essential. It should come from plant oils and fish, however, and not from animal products or hardened oils, such as margarine. Trans-fatty acids, found in hardened oils, are actually more of a risk factor for obesity than saturated fats from animal products, although both should be avoided.

Fiber and Complex Carbohydrates. In all cases, complex carbohydrates found in whole grains and vegetables are preferred over those found in starch-heavy foods, such as pastas, white-flour products, and potatoes. Fiber is an important component of many complex carbohydrates. Fiber is almost always found only in plants, particularly vegetables, fruits, whole grains, nuts, and legumes (beans and peas). One exception is chitosan, a dietary fiber made from shellfish skeletons. Fiber cannot be digested but passes through the intestines, drawing water with it, and is eliminated as part of feces content. The following are specific advantages from high-fiber diets (up to 55 grams a day):

Insoluble fiber (found in wheat bran, whole grains, seeds, nuts, and fruit and vegetable peels) has been associated with weight loss. Studies also suggest that diets rich in fiber from whole grains reduce the risk for type 2 diabetes.
Soluble fiber (found in dried beans, oat bran, barley, apples, citrus fruits, and potatoes) has important benefits for the heart, particularly for achieving healthy cholesterol levels and possibly benefiting blood pressure as well. Simply adding breakfast cereal to a diet appears to reduce cholesterol levels. People who increase their levels of soluble fiber should also increase water and fluid intake.

High-protein, low carbohydrate diets, such as the Atkins and South Beach diets, have been touted as effective ways to produce short-term weight loss. Because of their emphasis on fats and proteins, many experts are concerned about long-term health problems. A report in the March 2006 Lancet linked the Atkins diet to life-threatening complications that caused the death of one woman. The 40-year-old woman had a deadly buildup of acids called ketones in her blood, a condition called ketoacidosis. Ketoacidosis can cause coma and death. Ketones are a known by-product of high protein, low carbohydrate diets. At low levels they can cause nausea, lightheadedness, and bad breath.

The long-term effects of these diets are still unknown. For example, the Atkins diet restricts some vegetables and most fruits, which are known to protect against serious diseases such as heart problems and cancer. The diet may also cause too much calcium to build up in the urine. This can increase the risk for kidney stones and osteoporosis. In addition, high-protein intake, particularly from meat, can be harmful in people with kidney problems. Individuals at risk for kidney stones, or those who have other kidney problems, should not go on high-protein diets without talking to their doctor first. Unfortunately, many people with diabetes are at risk of kidney problems, which could reverse any possible benefits a high-protein diet may bring them. Eating a lot of meat has also been associated with certain common cancers, notably prostate and colon cancers. A 2002 study suggested that such diets during pregnancy may increase the risk for high blood pressure in the child.

Still, significant studies say that such diets improve cholesterol and blood sugar levels. Studies in 2002 and 2003 have indicated that these diets lower blood glucose levels, which can be important in people who are diabetic. The diets also reduce triglyceride levels (unhealthy fat molecules) and increases HDL (" good") cholesterol levels. High triglyceride and low HDL levels are important risk factors for heart disease, and are common in people with type 2 diabetes. Studies are mixed on whether this type of diet reduces overall cholesterol or LDL ("bad") cholesterol levels.

Experts that promote the low carbohydrate approach argue that heart problems from obesity are due to insulin disturbances from sugar imbalances. Therefore, they believe that restricting carbohydrates is the best approach for obesity -- especially for overweight people with diabetes. More research is needed, however, to determine the long-term impact of such diets on health.

High-protein, low-carbohydrate diets include Atkins, Protein Power, Sugar Busters, and Dr. Stillman. The Atkins diet is one of the most popular and has a four-phase program:

Induction. For the first 2 weeks, individuals consume no more than 20 grams of carbohydrates a day. The diet consists of pure protein and fats. There is no fruit, bread, grains, starchy vegetables, or dairy products other than cheese, cream, or butter. This phase is not suitable for children, pregnant women, or anyone with kidney disease.
On-going Weight Loss. After the first phase, individuals continue to lose weight while they increase carbohydrate levels by five grams each day.
Premaintenance. When individuals get close to their weight goal, they add another 10 grams of carbohydrates per day as long as they do not begin to gain weight. Weight loss is very slow at this time, but the individual is now getting used to maintenance.
Maintenance. Lifetime maintenance is usually between 40 and 100 grams of carbohydrates a day, depending on steady weight level.

Anyone who chooses this diet should prefer fish or soy products to meat as protein sources. Fish may reduce leptin, a hormone associated with fat storage and heart diseases, and would be the best protein source. People on this diet should also choose monounsaturated fats (as in olive oil) over saturated fats or trans-fatty acids fat. Patients often need supplements, at least a multivitamin and possibly calcium, chromium, omega-3 fatty acids (found in fish oil), and other supplements.

The South Beach and Zone diets encourage healthy fats. They also allow certain carbohydrates. For example the Zone uses healthy carbohydrates (vegetables and dried beans) and unsaturated fats. The South Beach diet uses carbohydrates that have a lower impact on blood sugar levels. This is called a low-glycemic index. Low-glycemic foods include barley, dried bean and peas, milk, strawberries, and apples. High-glycemic foods include refined grains, white bread, white potatoes, and bananas and other tropical fruits. The glycemic index was developed for use in diabetes -- not for weight loss. Nevertheless, there is some evidence that foods with low glycemic indexes may produce a feeling of fullness and so discourage further eating. As with any high-protein diets, people at risk for kidney stones, or those who have other kidney problems, should avoid these plans.

Replacing fats and sugars with substitutes may help many people who have trouble maintaining weight. In fact, in one 2003 study, people with type 2 diabetes used the artificial sweetener sucralose and a beta-glucan fat substitute (derived from oats) as part of a low-calorie diet. At the end of the 4 weeks, they achieved better weight, glucose control, and HDL levels than those on a standard diabetic diet.

Fat Substitutes. Fat substitutes added to commercial foods or used in baking deliver some of the desirable qualities of fat, but do not add as many calories. It should be stressed that eliminating all fats from a diet can be harmful to general health.

Fat substitutes include the following:

Stanols. Stanols are plant compounds used in margarines (Benecol, Take Control). Benecol is derived from pine bark and Take Control from soybeans. Two servings a day of either brand, as part of a low-fat, diet can lower LDL and total cholesterol by impairing its absorption in the intestinal tract. Some studies have reported that the use of stanols can allow lower doses of statins (cholesterol lowering medications). Stanols do not appear to block absorption of fat-soluble nutrients or vitamins, as olestra does.
Olestra (Olean) passes through the body without leaving behind any calories from fat. Studies suggest that it improves cholesterol levels and helps people lose weight when it is used to replace a third of normal dietary fats. (Note that simply adding snacks containing olestra does not appear to have any effect on cholesterol or weight loss.) Early reports of cramps and diarrhea after eating food containing olestra have not proven to be significant. Of greater concern is the fact that even small amounts of olestra deplete the body of certain vitamins and nutrients that may help protect against serious diseases, including cancer. The FDA requires that the missing vitamins be added back to olestra products, but not other nutrients. The side health effects, if any, are unknown.
Beta-glucan is a soluble fiber found in oats and barley. Products using this substance (e.g., Nu-Trim) may reduce cholesterol and have additional health benefits.

A number of other fat-substitutes are also available. Although studies to date are not showing any significant side effects, these products' effect on weight control is uncertain, since many of the products containing them may be high in sugar.

Artificial Sweeteners. Many artificial or low-calories sweeteners are available. A 2002 study confirmed that people who consumed artificial sweeteners and reduced their sugar intake weighed less over time than those who took in similar types and amounts of drinks and food containing sugar. It should be noted that using these artificial sweeteners should not give dieters a license to increase their fat intake. Studies indicate that consuming some sugar is not a significant contributor to weight gain, as long as the total amount of calories in the diet is under control. There is some public concern about chemicals used to produce many of these sweeteners, and the side effects seen in studies using rats. Natural low-calories sweeteners are available that may be more acceptable to many people.

Saccharin (Sugar Twin, Sweet n' Low, Sucaryl, and Featherweight). Saccharin has been used for years. Some studies found that large amounts of saccharin cause bladder cancer in rats. However, the rats were fed huge amounts that do not apply to human diets. Currently there is no evidence that saccharin causes cancer in humans.
Aspartame (Nutra-Sweet, Equal, NutraTase). Aspartame has come under scrutiny because of rare reports of nervous system disorders, including headaches or dizziness, associated with its use. People with phenylketonuria (PKU), a genetic condition, should not use it. Studies have not reported any serious health dangers, but some people may be sensitive to it.
Sucralose (Splenda). Sucralose has no bitter aftertaste and works well in baking, unlike other artificial sweeteners. It is made from real sugar by replacing part of the sugar with chlorine. Some people are concerned because chlorinated molecules used in major industrial chemicals have been associated with cancer and birth defects. Over 100 studies have been conducted on sucralose over a 20-year period, with no reports of such risks.
Acesulfame-potassium (Sweet One, SwissSweet, Sunette). It has been used in the U.S. since 1988 with no reported side effects.
Neotame (Neotame). Neotame is a synthetic variation of aspartame, but was developed to avoid its side effects. The association with aspartame has raised some concerns. Studies to date have reported no effects that would cause alarm, and it appears to be safe for general consumption.
D-tagatose (Tagatose). This reduced-calorie sweetener is made from lactose, which is the sugar found in dairy products and other foods. It may be especially beneficial for people with type 2 diabetes. It may also have additional benefits that help the intestinal tract.
Alitame (Aclame) is formed from amino acids, the building blocks of proteins. It has the potential to be used in all products that contain sugar, including baked goods.
Stevioside (Stevia). This is a natural sweetener derived from a South American plant. It is available in health food stores. People with diabetes should avoid alcohol-based forms. It has not been carefully tested.

Other sugar substitutes being investigated include glycyrrhizin (derived from licorice) and dihycrochalcone (derived from citrus fruits).

Some studies have reported good success with meal replacement beverages (Slim-Fast, Sweet Success). They contain major nutrients needed for daily requirements. Each serving typically contains between 200 - 250 calories and replaces one meal. (Note: Using them for all meals reduces calories to a severe extent and can be harmful.)

One study reported that most subjects who had undergone a 12-week weight loss program and then used Ultra Slim Fast supplements as directed for maintenance kept off more than half their weight loss after more than 3 years. A quarter of the subjects were still losing weight.

Medical evidence suggests that a diet rich in magnesium could reduce a person's risk of metabolic syndrome, a cluster of problems including obesity, high blood pressure, and high cholesterol. Metabolic syndrome can lead to diabetes and heart disease. A long-term study of thousands of Americans found that the risk for metabolic syndrome decreased in those who consumed the most magnesium from meals. The findings were published in the journal Circulation.

Commercial and Non-Profit Support Programs for Weight Loss. There are many different types of weight-loss program. (This report cannot address all of the many commercial and nonprofit weight-loss programs currently available, nor can it assess their claims.)

Taking off Pounds Sensibly (TOPS), a nonprofit support organization with many local chapters, is one of the least expensive programs, costing $20 a year.

Most of the commercial programs such as Weight Watchers, Jenny Craig, and NutriSystem offer individual or group support, lifestyle changes and packaged meals. These programs tend to be expensive. There are few well-conducted studies on these programs. One 2003 study reported modest weight loss over 2 years with Weight Watchers compared to a self-help program. There were no differences in heart risk factors.

Cognitive Behavioral Approaches. Most support programs use some form of cognitive-behavioral methods to change the daily patterns associated with eating. They are very useful for preventing relapse after initial weight loss. The following is a typical approach:

The patient first records in a diary all activity related to eating patterns, including the times of day, length of meal, emotional states, companions, and, of course, the kind and amounts of food eaten. Most people -- even professional dieticians, according to one study -- tend to underreport their daily calorie intake. However, writing it down is still a good method for increasing a person's awareness of eating patterns. (One patient said that recording circumstances surrounding relapses was a particularly valuable guide for understanding the stresses leading to her own eating behaviors.)
The patient reviews the diary with a therapist or group to set realistic goals and identify patterns that the patient can change. For instance, if food is normally eaten while watching television, then the patient may be advised to eat in another room instead.
Good eating habits are reinforced by rewards. These rewards are other pleasures that substitute the high calorie consumption and sedentary activities.

Behavioral modification has been shown to be helpful particularly for people who have an overly strong response to the taste, smell, and appearance of food. It also may be useful for binge eaters.

Stress-Reduction Techniques. Stress reduction and relaxation techniques may be helpful for some people with obesity, such as those whose weight is related to night-eating syndrome. [See In-Depth Report #31: Stress.]

Changing Sedentary Habits. Making even small changes in physical activity can expend energy. For example, simply getting up to turn the TV on and off instead of using the remote, and standing (instead of sitting) while talking on the phone may help a person lose up to five pounds a year. Other suggestions include cooking one's own food (instead of eating take-out or fast food), walking to as many places as possible, using stairs instead of escalators or elevators, and gardening. Even fidgeting may be helpful in keeping pounds off, and, in one study, chewing gum increased energy expenditure.

No one should rely on such mild activities, however, for serious weight loss. Only high levels of physical activity -- not just using up energy -- help prevent obesity.

Approach to Exercise. Exercise, which replaces fat with muscle, is the critical companion for any weight control program. In a one-year study, women who regularly averaged 3.5 days (176 minutes) of exercise each week lost significantly more weight than women who did not exercise regularly. Women who exercised more than 195 minutes a week lost nearly 7% of their abdominal fat.

People who exercise are more apt to stay on a diet plan. Exercise improves psychological well-being and replaces sedentary habits that usually lead to snacking. Exercise may even act as a mild appetite suppressant. Moreover, exercise improves overall health even with modest weight loss. In support of this, a British study found that overweight fit individuals had half the death rate of unfit trim individuals.

Be aware, however, that the pounds won't melt off magically. Losing significant weight requires both intensive exercise and calorie restriction. In addition, if a person exercises but doesn't diet, any actual pounds lost may be minimal, because denser and heavier muscle mass replaces fat. Nonetheless, regardless of weight loss, a fit body will look more toned and be healthier. In addition, exercise benefits the heart even with modest weight loss.

The following are some suggestions and observations on exercise and weight loss:

The more strenuous the exercise, the better the chances for short-term and long-term success. With intense exercise, the metabolism continues to burn calories before returning to its resting level. This state of elevated metabolism can last for as little as a few minutes after light exercise to as long as several hours after prolonged or heavy exercise.
Of the standard aerobic machines, the treadmill burns the most calories. It may be particularly effective when used in short multiple bouts during the day. In fact, frequent exercise sessions as short as 10 minutes in duration (about four times a day) may be the most successful exercise program for obese people.
Resistance, or strength, training is excellent for replacing fat with muscles. It should be performed two or three times a week.
As people slim down, their initial level of physical activity becomes easier and they burn fewer calories per mile of walking or jogging. The rate of weight loss slows down, sometimes discouragingly so, after an initial dramatic head start using diet and exercise combinations. People should be aware of this phenomenon and keep adding to their daily exercise program.
As people age, they also need to exercise more to keep off the same amount of weight.
Changes in fat and muscle distribution may differ between men and women as they exercise. Men tend to lose abdominal fat (which lowers their risk for heart disease faster than reducing general body fat). Exercise, however, does not appear to have the same effect on weight distribution in women. In one interesting study, women in aerobic and strength training programs lost fat in their arms and trunk, but did not gain muscle tissue in these regions.

Warning Note. Because obesity is one of the risk factors for heart disease and diabetes, anyone who is overweight must discuss their exercise program with a doctor before starting. Sudden demanding exercise, in such cases, can be very dangerous. [See In-Depth Report #29: Exercise.]

Medications

There are several different drugs used for weight loss. Unless specifically instructed by a doctor, people should use non-drug methods for losing weight. Except under rare circumstances, pregnant or nursing women should never take diet medications of any sort, including herbal and over-the-counter remedies.

A 2001 study reported that 7% of American adults use nonprescription weight-loss products. People must be cautious when using any weight-loss medications, including over-the counter diet pills and herbal or so-called natural remedies. Buying unverified products over the Internet can be particularly dangerous.

Green tea. Perhaps the best alternative advice for people who are overweight is to drink tea. Studies have indicated that regular tea drinking is associated with lower weight, particularly in people who drink it for years. Green tea specifically has been associated with increased energy expenditure. One study reported that people who took a green tea extract (Exolise) lost weight and reduced their waist size. Better evidence is needed to confirm the results on this supplement.

Thermogenic Approach to Weight Loss. An approach to weight loss called thermogenic (also hepatothermic) therapy is based on the idea that certain natural compounds have properties that enable the liver to increase energy in the cells and stimulate the metabolism. Theoretically, the result would be fat loss. Among the natural substances used in such products are EPA-rich fish oil, sesamin, hydroxycitrate, pantethine, L-carnitine, pyruvate, aloe vera, aspartate, chromium, coenzyme Q10, green tea polyphenols, aloe vera, DHEA derivatives, cilostazol, diazoxide, and fibrate drugs.

Nearly all the current over-the-counter dietary aids contain some combination of these ingredients. There is no evidence that any of these ingredients can produce weight loss, and some may even have harmful effects.

Chromium is a common ingredient in many diet supplements (e.g., Xenadrine, Dexatrim, Acutrim Natural, Twinlab Diet Fuel). It is claimed to specifically promote fat loss, rather than lean muscle loss. Some evidence suggests that niacin-bound chromium may improve insulin sensitivity. On the negative side, animal studies have suggested that chromium may have damaging effects on genetic materials in cells. This could cause sterility.

Ephedra, Ephedrine, and Ma Huang. The FDA does not allow the sale of drugs that contain ephedrine. In May 2004, the FDA banned the sale of dietary supplements that contain ephedra (also called Ma Huang). Ephedra has been linked to serious side effects, including strokes and heart attacks.

Brazilian Diet Pill. The US Food and Drug Administration (FDA) is warning consumers not to buy a product known as the "Brazilian diet pill." This product is labeled as a dietary supplement, but contains several chemicals found in powerful prescription drugs. The products are also known as Emagrece Sim and Herbathin dietary supplements.

Conjugated Linoleic Acid (CLA). Conjugated linoleic acid is found in many dietary products (e.g., Biosculpt Liquid, Body Success, GNC Optibolic Body Answers Dietary Formula). There is no evidence that it produces weight loss. Furthermore, there is some concern that CLA might increase insulin resistance and a dangerous inflammatory response in people with obesity.

Tiratricol. Over-the-counter products containing tiratricol, a thyroid hormone, have been sold for weight loss. Such products may increase the risk for thyroid disorders, heart attack, and stroke.

Laxative Actions in Natural Substances. Many dietary herbal teas contain laxatives, which can cause gastrointestinal distress, and, if overused, may lead to chronic pain, constipation, and dependency. In rare cases, dehydration and death have occurred. Some laxative substances found in teas include senna, aloe, buckthorn, rhubarb root, cascara, and castor oil.

Guar Gum. Some fiber supplements containing guar gum have also caused obstruction of the gastrointestinal tract.

Chitosan. Chitosan, a dietary fiber from shellfish, prevents a small amount of fat from being absorbed in the intestine. Well-conducted studies, however, have not found it to be effective. Products containing it include Cheat & Lean Fat Blocker, Natrol, Chroma Slim, and Enforma. People who are allergic to shellfish should not take these supplements.

Plantain. Dietary remedies that list the ingredient plantain may contain digitalis, a powerful chemical that affects the heart. NOTE: This substance should not be confused with the harmless banana-like plant also called plantain.

Orlistat (Xenical) can help about one-third of obese patients with modest weight loss, and can assist in long-term maintenance of weight loss. It works by slowing the absorption of fat (by about 30%) in the intestine. Studies indicate that between 50 - 80% of patients can achieve weight loss of 5% or greater, depending on other lifestyle changes. However, many people regain a significant portion of this weight back within 2 years. It does not work for all patients, however. In one survey of patients who took it, 10% gained weight or did not lose any, and 43% lost less than 5%. Nevertheless, orlistat may delay or even prevent the onset or progression of diabetes and improve cholesterol levels, regardless of weight loss.

The drug can cause gastrointestinal problems and may interfere with absorption of the fat-soluble vitamins A, D, and E and other important nutrients. The most unpleasant side effect is oily leakage of feces from the anus. Restricting fats can reduce this effect. People with bowel disease should probably avoid it. In spite of these side effects, most patients are able to tolerate this agent.

In February 2007, the FDA approved an over-the-counter (OTC) version of orlistat. It will be sold under the name alli, and will be available at half the prescription strength of Xenical. Those eager to use the new pill should consider its cost and modest benefits compared with its side effects, most commonly oily diarrhea. This pill, which prevents fat absorption from food, also increases the risk of not absorbing important nutrients from food while using it. The FDA recommends taking a daily multivitamin supplement when using alli.

Sibutramine (Meridia) helps balance the brain chemicals serotonin and norepinephrine. This helps increase metabolism, causes a feeling of fullness, and increases energy levels. It may be particularly useful for binge-eaters. Studies indicate that sibutramine is effective in achieving weight loss, although the weight loss slows considerably after the first 3 months. The drug also appears to improve cholesterol and lipid (fat) levels, and may have other effects that benefit the heart.

Side effects of sibutramine are common. They include dry mouth, constipation, and insomnia. In one study, almost half the patients dropped out as a result of these side effects. There have been reports of increases in heart rate and blood pressure while taking this medication, although a 2001 study indicates that blood pressure stabilizes over time.

At this time, people who have a history of high blood pressure, stroke, heart disease, or arrhythmias should not take this drug. People taking decongestants, bronchodilators (such as for asthma), monoamine oxidase inhibitors, or serotonin reuptake inhibitors should also avoid sibutramine.

Phentermine and Other Sympathomimetics. Sympathomimetics are drugs that act like the stress hormone (and chemical messenger) norepinephrine. These medications act as stimulants in the brain. Some are approved for treating obesity, but only for short-term use. They include:

Phentermine (Ionamin, Adipex-P, Fastin)
Benzphetamine (Didrex)
Phendimetrazine (Adipost, Bontril, Melfiat, Plegine, Prelu-2, Statobex)

Phentermine is the most commonly prescribed appetite suppressant, and is less expensive than orlistat or sibutramine. Its effects are not long lasting, however. It can also raise blood pressure. In addition, phentermine is associated with depression, which is already a problem in many cases of obesity. A combination (Phen-Pro) containing phentermine and the antidepressant fluoxetine (Prozac) is being investigated to help reduce this problem. Note: Neither phentermine nor such combinations are associated with the heart problems linked to the previous phentermine combination known as Fen-Phen (phentermine and fenfluramine).

Amphetamines. The amphetamines dextroamphetamine (Dexedrine), methamphetamine (Desoxyn), and phenmetrazine (Pleudin) are powerful stimulants. They were used most often in the past but are no longer prescribed for weight loss. These drugs improve mood and produce some modest weight loss over the short term, but carry serious risks of addiction, agitation, and insomnia.

Rimonabant. Rimonabant (Accompli) belongs to a new class of drugs called selective CB1 blockers. The drug is designed to block receptors in the brain associated with the regulation of eating. Rimonabant also targets receptors in fat tissue. The Rimonabant in Obesity-Lipids (RIO-Lipids) study looked at how rimonabant affected metabolic risk factors in high-risk overweight or obese patients with blood fat disorders. The study involved more than 1,000 participants. The findings, published in the November 2005 New England Journal of Medicine, said that people who took the drug significantly reduced their body weight and size of their waist.

Earlier studies involving the drug reported that obese patients treated with 20 mg of rimonabant lost significantly more weight and inches from their waist than patients who received placebo. The drug also appeared to have beneficial effects on raising HDL ("good") cholesterol levels.

Note: Fake rimonabant has been found for sale on several web sites. Patients should be aware that this drug is still experimental, and rimonabant is not available for sale. Buying and taking counterfeit drugs can have serious health consequences. In addition, an FDA advisory panel in April 2007 rejected the drug, citing fears it may cause psychiatric problems and seizures in some patients.

Axokine. Axokine is a type of drug called a ciliary neurotrophic factor. It signals the brain to suppress one's appetite. It is proving to be effective in achieving weight loss, and also improves cholesterol, lipid, and glucose levels regardless of food intake. It could be particularly helpful for people with type 2 diabetes. Early study results found that severely obese patient who took the drug lost more weight than those who took a dummy pill (placebo). Nearly half (46%) of patients who took the drug lost at least 10 pounds, compared to 5% of those who received the placebo. Study participants tolerated the drug well. There were no reports of serious side effects.

Zonisamide. Zonisamide (Zonegran) is an anti-seizure medication that is also being investigated for weight loss. In one study, patients who took it lost more weight than those on placebo. Zonisamide increases the risk for kidney stones, which can be reduced with increased fluid intake and citrate. It has also been associated with reduced sweating and a sudden rise in body temperature, especially in hot weather. Other side effects include dizziness, forgetfulness, headache, and nausea.

Topiramate. Topiramate (Topamax) is another anti-seizure medication being investigated for weight reduction. Three clinical trials have reported that patients given topiramate lost more weight than those receiving placebo. Weight loss was sustained for up to 1 year. The drug is also being studied for binge-eating disorders associated with obesity.

Other Treatments

Surgical procedures for obesity may be appropriate for some dangerously obese people, and may reduce heart problems and many of the risks associated with obesity. These risks include high blood pressure, sleep apnea, and diabetes. In fact, some evidence suggests that surgery may provide much greater control of weight and diabetes than nonsurgical weight-loss methods. Studies are reporting significant reductions in diabetes, and the need for diabetic medications, after surgery. Other medical conditions that often improve after surgery include heartburn, arthritis, and other joint and circulation problems.

Bariatric surgeries produce weight loss through one of two approaches:

Restrictive Banding Procedures. These procedures restrict the amount of food by closing off parts of the stomach with bands.
Malabsorptive Bypass Procedures. This approach restricts the amount of food and also reduces absorption by using a bypass of parts of the intestine.

The malabsorptive procedures are more successful in achieving weight loss than the banding approach, but they carry a greater risk for nutritional deficiencies.

Most people who have bariatric surgery lose about two-thirds of excess weight within 2 years. In addition, diseases associated with obesity (such as diabetes, high blood pressure, sleep apnea, joint pain, and incontinence) often improve.

Researchers at the Mayo Clinic looked at records from patients who had the surgery between 1990 and 2003. They found that those who had bariatric surgery reduced their risk of cardiovascular events such as a heart attack much more than those who lost weight without surgery. The findings were published in the September 2005 Mayo Clinic Proceedings.

Other studies have shown that even though most patients maintain significant weight loss, the majority regain about to 10% of their weight. Patients must still develop a healthy life style and be calorie conscious after the operation. Follow-up must be life-long.

Any surgical candidate must have failed consistently in losing weight through less invasive methods. Experts recommend bariatric surgery only for the following:

Those whose BMI is above 40 (about 100 pounds overweight)
Those with BMIs of over 35 who have type 2 diabetes or serious obesity-related medical problems
Those with severe obesity that interfered with employment, normal physical activity (e.g., walking), and important relationship

About a third of people who undergo these procedures achieve normal weight, and 80% experience some weigh loss. They are less successful than the bypass procedures, but carry a lower risk of nutritional deficiencies.

Vertical Banded Gastroplasty. Vertical banded gastroplasty (VBG) was the most common restrictive procedure. It involves creating a hole through both stomach walls and sealing the edges with a staple. This narrows the stomach, similar to a funnel, and allows only small amounts of food to pass through.

Laparoscopic Gastric Banding. Laparoscopic gastric banding (the Lap-Band) usually does not require a major incision and avoids some of the major complications of gastric bypass:

It employs an adjustable silicone band that is placed around the upper part of the stomach.
A small balloon-like reservoir attached to the band under the abdominal skin contains saline, which can be added or removed to tighten or loosen the band.
The procedure restricts the amount of food a person can eat and gives the feeling of fullness.

The band is removable, if necessary. Studies to date indicate that the intestinal tract returns to normal afterward. Studies, including those done in the elderly, have reported significant weight loss and improved quality of life with the procedure.

Malabsorptive procedures produce greater weight loss than restrictive procedures. Patients generally achieve about two-thirds of their weight loss within 2 years. Furthermore, in a 2003 study, after standard bypass surgery, 83% of patients with type 2 diabetes experienced normal blood glucose levels and the rest had significant reductions.

Roux-en-Y Gastric Bypass Procedure. This is the most common and successful malabsorptive surgery in the United States. It involves creating a small stomach pouch that serves as a reservoir and restricts food intake. The pouch eventually holds up to 3 ounces of food and has a small outlet that delays emptying and causes a feeling of fullness. Then the surgeon creates a Y-shaped section in the small intestine that attaches to the pouch. This section allows food to bypass the lower stomach and upper part of the intestine. One 2003 study reported that this procedure was associated with significant weight loss, and 80% of patients with type 2 diabetes were able to reduce their medications. A more recent study, published in the March 14, 2006, issue of Archives of Surgery, found that gastric bypass surgery also helps lower the blood pressure of very obese patients.

The procedure produces greater and more sustained weight loss than banding procedures, but it is also more complicated, and carries a higher risk of nutritional deficiencies. Laparoscopy techniques, which are less invasive, are now preferred over open surgery. They achieve equally good results with fewer complications.

Biliopancreatic Diversion. This procedure is more complicated and removes portions of the stomach. The pouch that is created attaches directly to the lower part of the small intestine. It poses a higher risk for nutritional deficiencies than other procedures and is not used as often.

Click the icon to see an image of gastric bypass surgery.

General Side Effects and Complications. Side effects and complications of bariatric procedures are common, and up to 25% of patients require corrective or repeat procedures. After any of these procedures people must chew all their food carefully, and they cannot eat large amounts of food at one time. If patients do not follow these guidelines, they will experience nausea, abdominal distress, or both.

Complications from any bariatric procedure includes the following:

Vomiting: This is the most common complication, and it is most common with banding procedures.
Nutritional deficiencies: There is a strong risk of nutritional deficiencies, particularly with malabsorptive operations. This complication can lead to anemia and increase the risk of bone loss and osteoporosis. Taking enough mineral and vitamin supplements is important after bariatric surgery.
Deep-vein thrombosis: There is a significant risk for deep-vein thrombosis (blood clots in the veins).
Abdominal hernia: This is another common complication. Newer, laparoscopic techniques do not carry this risk, but not all individuals are candidates for this less-invasive approach.
Rapid weight loss after surgery: This complication puts people at high risk for gallstones.
Women who wish to be pregnant should wait until their weight has stabilized. Rapid weight loss and nutritional deficiencies can harm the fetus.

People at highest risk for complications are those with heart or lung problems, severe obesity, and a history of abdominal surgeries. The mortality rate from bariatric surgeries is 0.2%, which is lower than the morality rates from severe obesity itself. Other surgical variations and less invasive techniques using laparoscopy have been developed.

Specific Complications of Restrictive Banding Procedures. Nausea, vomiting, or both occurs in half the patients, and severe heartburn occurs in a third. Device-related complications include band slippage, pouch dilation (widening), or both in nearly a quarter of patients, and obstruction in 12% of patients. Very serious complications are rare, but include blood clots, bleeding, infection, pneumonia, and perforation (tearing) of the stomach.

Specific Complications of Malabsorptive Bypass Procedures. Vomiting often occurs. Nutritional deficiencies occur more often in these procedures. The so-called dumping syndrome is a common unpleasant side effect, which occurs when food waste moves too quickly through the intestine. Symptoms include nausea, weakness, sweating, and faintness (particularly after eating sweets).

Spot Exercising. Anyone seeking to lose weight must expect that the results may not be as cosmetically satisfying as one would wish. Spot exercising (training particular areas of the body) is ineffective in reducing fat in specific locations because exercise draws on fat stores throughout the body. Gimmicky devices such as bust developers, vacuum pants, and exercise belts do absolutely nothing to reduce fat or add bulk in specific locations. Electrical pads wrapped around the waist, arms, or thighs were reported to cause burns and fires.

Cellulite-Removal Creams. Many women try to reduce fat in their thighs (cellulite) with creams that contain aminophylline (Skinny Dip, Thermojetics Body Toning Cream, Smooth Contours). Studies provide no evidence that these creams are effective. Their apparent effect on fat may simply be from narrowing blood vessels and forcing water from the skin, which could be dangerous for people with blood flow problems.

Endermologie. Endermologie uses motorized rollers and regulated suction to smooth out cellulite. In one study, about 28.6% of patients reported improved appearance after using it.

Liposuction. Liposuction eliminates fat in specific areas, such as the abdomen, thighs, buttocks, or knees. Special instruments are inserted through the skin into the pockets and suction is used to move the fat, break it up, and remove it. Small tubes may be used to drain blood and fluid during the first few days. The pain after the operation can be severe and often the skin does not contract, resulting in a flabby look. Complications can include burns from the vibrators, bruising, blood clots, and bleeding. Weight gain generally tends to develop in other locations after the operation. Some doctors are using this procedure in overweight people with diabetes to remove abdominal fat. Although there is no proof that it has an effect on diabetes, some experts believe the procedure deserves attention.

Liposuction is not recommended for major weight loss.

Resources

www.healthierus.gov/dietaryguidelines -- Dietary Guidelines for Americans 2005
www.naaso.org -- North American Association for the Study of Obesity
www.eatright.org -- American Dietetic Association
www.nutrition.gov. -- Nutrition.gov
www.asbs.org -- American Society for Bariatric Surgery
www.cnpp.usda.gov -- Center for Nutrition Policy and Promotion
http://fnic.nal.usda.gov -- Food and Nutrition Information Center
www.americanheart.org -- American Heart Association
www.nationaleatingdisorders.org -- National Eating Disorders Organization
www.aabt.org -- Association for Advancement of Behavior Therapy
www.fda.gov -- Food and Drug Administration
http://win.niddk.nih.gov -- Weight-Control Information Network

References

US Food and Drug Administration FDA Approves Orlistat for Over-the-Counter Use. Rockville, MD: National Press Office; February 7, 2007.

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. Journal of the American Medical Association. 2006; 295:1549-1555.

National Center for Health Statistics. Chartbook on Trends in the Health of Americans. Health, United States, 2005. Hyattsville, MD: Public Health Service. 2005

National Institute of Diabetes and Digestive and Kidney Diseases - Weight-control Information Network. Statistics Related to Overweight and Obesity. Available online.

National Center for Health Statistics. Prevalence of Overweight Among Children and Adolescents: United States, 2003-2004.

Morino M, Toppino M, Bonnet G, Rosa R, et al. Laparoscopic vertical banded gastroplasty for morbid obesity. Assessment of efficacy. Surg Endosc. 2002 Nov;16(11):1566-72.

Brethauer SA, Schauer PR, Chand B. Risks and benefits of bariatric surgery: Current evidence. Cleveland Clinic Journal Of Medicine. 2006 Nov; 73(11): 993-1007.

Rosenthal RJ, Szomstein S, Kennedy CI, et al. Laparoscopic surgery for morbid obesity: 1,001 consecutive bariatric operations performed at The Bariatric Institute, Cleveland Clinic Florida. Obes Surg. 2006 Feb;16(2):119-24.

He K, Liu K, Daviglus ML, et al. Magnesium Intake and Incidence of Metabolic Syndrome Among Young Adults. Circulation. 2006: Published online before print. March 27, 2006.

Chen TY, Smith W, Rosenstock JL, Lessnau KD. A life-threatening complication of Atkins diet. Lancet. 2006 Mar 18;367(9514):958.

Lopez-Jimenez F, Bhatia S, Collazo-Clavell ML, Sarr MG, Somers VK. Safety and efficacy of bariatric surgery in patients with coronary artery disease. Mayo Clin Proc. 2005 Sep;80(9):1157-62.

Sidhaye A, Cheskin LJ. Pharmacologic treatment of obesity. Adv Psychosom Med. 2006;27:42-52.

Fernstrom JD, Courcoulas AP, Houck PR, Fernstrom MH. Long-term changes in blood pressure in extremely obese patients who have undergone bariatric surgery. Arch Surg. 2006 Mar;141(3):276-83.

Despres JP, Golay A, Sjostrom L; Rimonabant in Obesity-Lipids Study Group. Effects of rimonabant on metabolic risk factors in overweight patients with dyslipidemia. N Engl J Med. 2005 Nov 17;353(20):2121-34.

Lanningham-Foster L, Nysse LJ, Levine JA. Labor saved, calories lost: the energetic impact of domestic labor-saving devices. Obes Res. 2003 Oct;11(10):1178-81.

Review Date:
6/14/2007
Reviewed By:
A.D.A.M. Editorial Team: Greg Juhn, M.T.P.W., David R. Eltz, Kelli A. Stacy. Previously reviewed by Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital (4/30/2007).

A.D.A.M. Copyright

adam.com

Heart failure

FitSugar — Wed, 08 Oct 2008 17:35:10 -0700

In This Report

Highlights
Introduction
Causes
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Medications
Surgery and Devices
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Permanent Implantable Heart Approved

In 2006, the FDA approved the first permanent artificial heart. The AbiCor is intended for patients who are not eligible for heart transplants and who are only expected to survive about a month without medical treatment. Patients who received the AbiCor have survived, on average, about 5 months.

Statin Drug Approved for Heart Failure

In 2006, the FDA approved the cholesterol drug atorvastatin (Lipitor) to reduce the risks of hospitalization for heart failure in patients with heart disease.

Drug Research

The investigational drug tolvaptan improved symptoms in patients hospitalized with severe heart failure and fluid build-up in the lungs, according to several 2007 Journal of the American Medical Association (JAMA) studies. However, the drug did not reduce the risks of re-hospitalization and death.

Preserved Versus Reduced Ejection Fraction

Heart failure with preserved left-ventricular ejection fraction (LVEF) is becoming more common, suggests several 2006 studies published in JAMA and the New England Journal of Medicine. Unfortunately, this type of heart failure is less well studied than reduced LVEF. Experts are urging that more studies be conducted to determine better treatment options for preserved LVEF. Both types of heart failure have high mortality rates.

Systolic Blood Pressure Predictor of Mortality

Patients who are admitted to the hospital with heart failure and low systolic blood pressure have a poorer chance of survival than patients admitted with high blood pressure, indicates a 2006 JAMA study.

Diet and Lifestyle Factors

Daily consumption of whole-grain breakfast cereals may reduce the risk for heart failure, suggests research presented at a 2007 American Heart Association conference on heart disease prevention.
A drink or two a day is associated with lower risk of heart failure, indicates a 2006 Journal of the American College of Cardiology study. However, heavy alcohol consumption can increase the risk for heart failure.

Introduction

To understand what occurs in heart failure, it is useful to be familiar with the anatomy of the heart and how it works. The heart is composed of two independent pumping systems, one on the right side, and the other on the left. Each has two chambers, an atrium and a ventricle. The ventricles are the major pumps in the heart.

The external structures of the heart include the ventricles, atria, arteries, and veins. Arteries carry blood away from the heart while veins carry blood into the heart. The vessels colored blue indicate the transport of blood with relatively low content of oxygen and high content of carbon dioxide. The vessels colored red indicate the transport of blood with relatively high content of oxygen and low content of carbon dioxide.

The Right Side of the Heart. The right system receives blood from the veins of the whole body. This is "used" blood, which is poor in oxygen and rich in carbon dioxide.

The right atrium is the first chamber that receives blood.
The chamber expands as its muscles relax to fill with blood that has returned from the body.
The blood enters a second muscular chamber called the right ventricle.
The right ventricle is one of the heart's two major pumps. Its function is to pump the blood into the lungs.
The lungs restore oxygen to the blood and exchange it with carbon dioxide, which is exhaled.

The Left Side of the Heart. The left system receives blood from the lungs. This blood is now oxygen rich.

The oxygen-rich blood returns through veins coming from the lungs (pulmonary veins) to the heart.
It is received from the lungs in the left atrium, the first chamber on the left side.
Here, it moves to the left ventricle, a powerful muscular chamber that pumps the blood back out to the body.
The left ventricle is the strongest of the heart's pumps. Its thicker muscles need to perform contractions powerful enough to force the blood to all parts of the body.
This strong contraction produces systolic blood pressure (the first and higher number in blood pressure measurement). The lower number ( diastolic blood pressure) is measured when the left ventricle relaxes to refill with blood between beats.
Blood leaves the heart through the ascending aorta, the major artery that feeds blood to the entire body.

The Valves. Valves are muscular flaps that open and close so blood will flow in the right direction. There are four valves in the heart:

The tricuspid regulates blood flow between the right atrium and the right ventricle.
The pulmonary valve opens to allow blood to flow from the right ventricle to the lungs.
The mitral valve regulates blood flow between the left atrium and the left ventricle.
The aortic valve allows blood to flow from the left ventricle to the ascending aorta.

Click the icon to see an image of the internal structures of the heart.

The Heart's Electrical System. The heartbeats are triggered and regulated by the conducting system, a network of specialized muscle cells that form an independent electrical system in the heart muscles. These cells are connected by channels that pass chemically caused electrical impulses.

Click the icon to see an image of the conduction system of the heart.

Heart failure is not a disease. It is a condition or process in which the heart is unable to pump enough blood to meet the needs of the body's tissues. The heart doesn't "fail" in the sense of ceasing to beat (as occurs during a heart attack). Rather, it weakens, usually over the course of months or years, so that it is unable to pump out all the blood that enters its chambers. As a result, fluids tend to build up in the lungs and tissues, causing congestion. This condition used to be called "congestive heart failure," but the name was officially changed to heart failure in 2005.

Ways the Heart Can Fail. Heart failure can occur in several ways:

The muscles of the heart pumps (ventricles) become thin and weakened. They stretch (dilate) to the extent that they cannot pump the blood with enough force to reach all the body's tissues.
The heart muscles stiffen or thicken. Here, they lose elasticity and cannot relax. Insufficient blood enters the chamber, so not enough blood is pumped out into the body to serve its needs.
Sometimes the valves of the heart are abnormal. (Valves open or close to control the flow of blood entering or leaving the heart). They may narrow, such as in aortic stenosis, causing a back up of blood, or they may close improperly so that blood leaks back into the heart. The mitral valve (which regulates blood flow between the two chambers on the left side of the heart) often becomes leaky in severe heart failure -- a condition called mitral regurgitation.

Click the icon to see an image of the valves of the heart.

The very mechanisms that the body uses to compensate for inefficient heart pumping can, over time, change the architecture of the heart (called remodeling) and finally lead to irreversible problems.

The specific effects of heart failure on the body depend on whether it occurs on the left or right side. Over time, however, in either form of heart failure, the organs in the body do not receive enough oxygen and nutrients, and the body's wastes are removed slowly. Eventually, vital systems break down.

Failure on the Left Side (Left-Ventricular Heart Failure). Failure on the left side of the heart is more common than failure on the right side. The failure can be a result of abnormal systolic (contraction) or diastolic (relaxation) action:

Systolic. Systolic heart failure is a pumping problem. In systolic failure, the heart muscles weaken and cannot pump enough blood throughout the body. The left ventricle is usually stretched (dilated). Fluid backs up and accumulates in the lungs (pulmonary edema). Systolic heart failure typically occurs in men between the ages of 50 - 70 years who have had a heart attack.
Diastolic. Diastolic heart failure is a filling problem. When the left ventricle muscle becomes stiff and cannot relax properly between heartbeats, the heart cannot fill fully with blood. When this happens, fluid entering the heart backs up. This causes the veins in the body and tissues surrounding the heart to swell and become congested. Patients with diastolic failure are typically women, overweight, and elderly, and have high blood pressure and diabetes.

Failure on the Right Side (Right-Ventricular Heart Failure). Failure on the right side of the heart is most often a result of failure on the left. Because the right ventricle receives blood from the veins, failure here causes the blood to back up. As a result, the veins in the body and tissues surrounding the heart to swell. This causes swelling in the feet, ankles, legs, and abdomen.

Ejection Fraction. To help determine the severity of left-sided heart failure, doctors use an ejection fraction (EF) calculation, also called a left-ventricular ejection fraction (LVEF). This is the percentage of the blood pumped out from the left ventricle during each heartbeat. An ejection fraction of 50 - 75% is considered normal. Patients with left-ventricular heart failure are classified as either having a preserved ejection fraction (greater than 50%) or a reduced ejection fraction (less than 50%).

In general, systolic heart failure has been thought to be associated with a reduced ejection fraction, whereas diastolic heart failure was associated with a preserved (normal) ejection fraction. However, several 2006 studies indicated that diastolic heart failure can occur regardless of the ejection fraction, although it is more common in patients with a preserved ejection fraction. Mortality rates among patients with reduced LVEF and preserved LVEF are similar.

Although reduced LVEF heart failure is better studied, and its treatment goals more clearly defined, several important 2006 studies suggest that preserved LVEF heart failure is becoming increasingly common. The studies, published in the Journal of the American Medical Association and the New England Journal of Medicine, indicated that patients with preserved LVEF heart failure are more likely to be female and older, and have a history of high blood pressure and atrial fibrillation (a disturbance in heart rhythm). Experts are now urging that more studies focus on patients with preserved LVEF so that better treatment options can be established.

Causes

Heart failure has many causes and can evolve in different ways.

It can be a direct, last-stage result of heart damage from one or more of several heart or circulation diseases.
It can occur over time as the heart tries to compensate for abnormalities caused by these conditions, a condition called remodeling.

In all cases, the weaker pumping action of the heart means that less blood is sent to the kidneys. The kidneys respond by retaining water and salt. This in turn increases edema (fluid buildup) in the body, which causes widespread damage.

Uncontrolled high blood pressure (hypertension) is also a major cause of heart failure even in the absence of a heart attack. In fact, about 75% of cases of heart failure start with hypertension. It generally develops as follows:

The heart muscles thicken to make up for increased blood pressure.
The force of the heart muscle contractions weaken over time, and the muscles have difficulty relaxing. This prevents the normal filling of the heart with blood.

[See In-Depth Report #14:High blood pressure.]

Hypertension is a disorder characterized by consistently high blood pressure. Generally, high blood pressure consists of systolic blood pressure (the "top" number, which represents the pressure generated when the heart beats) higher than 140, or diastolic blood pressure (the "bottom" number, which represents the pressure in the vessels when the heart is at rest) over 90.

Coronary artery disease is the end result of a complex process called atherosclerosis (commonly called "hardening of the arteries"). It is the most common cause of heart attack and involves the build-up of unhealthy cholesterol in the arteries, with inflammation and injury in the cells of the blood vessels. The arteries narrow and become brittle. Heart failure in such cases most often results from a pumping defect in the left side of the heart. [See In-Depth Report #3: Coronary artery disease and angina ; and In-Depth Report #23: Cholesterol.]

Click the icon to see an image of atherosclerosis.

People now often survive heart attacks, but eventually many develop heart failure from the physical damage done to the heart muscles by the attack. Ironically, heart attack recovery is probably one of the major factors in the dramatic increase in heart failure cases over the past decade. On an encouraging note, however, new therapies that are reducing the severity of heart attacks may help stabilize heart failure rates. [See In-Depth Report #12: Heart attack.]

The valves of the heart control the flow of blood leaving and entering the heart. Abnormalities can cause blood to back up or leak back into the heart.

Click the icon to see an image of the heart valves.

In the past, rheumatic fever, which scars the heart valves and prevents them from closing, was a major cause of death from heart failure. Fortunately, antibiotics have relegated this disease to a minor cause of heart failure. Birth defects may also cause abnormal valvular development. Although more children born with heart defects are now living to adulthood, they still face a higher than average risk for heart failure as they age.

Cardiomyopathy is disease that damages the heart muscles and leads to heart failure. There are several different types. Injury to the heart muscles may cause the heart muscles to thin out (dilate) or become too thick (become hypertrophic). In either case, the heart doesn't pump correctly.

Dilated Cardiomyopathy. Dilated cardiomyopathy involves an enlarged heart ventricle. The muscles thin out, reducing the pumping action, usually on the left side. Although this condition is associated with genetic factors, the direct cause often is not known. (This is called idiopathic dilated cardiomyopathy.) Research strongly indicates that viruses, such as Coxsackie virus, or other infections may be at the base of this condition. Experts think that an autoimmune response occurs in which infection-fighting antibodies attack a person's own proteins in the heart, mistaking them for foreign substances.

Click the icon to see an image of dilated cardiomyopathy.

Hypertrophic Cardiomyopathy. In hypertrophic cardiomyopathy, the heart muscles become thick and contract with difficulty. Some research indicates that this occurs because of a genetic defect that causes a loss of power in heart muscle cells and, subsequently, lower pumping strength. To compensate for this power loss, the heart muscle cells grow. This condition, rare in the general population, is often the cause of sudden death in young athletes.

Click the icon to see an image of hypertrophic cardiomyopathy.

High blood pressure, heart attacks, or other initial processes that impair the pumping actions of the heart trigger a number of hormonal and neurochemical mechanisms to correct imbalances in pressure and blood flow. Unfortunately, while these corrective responses help in the short term, they increase the work of the heart. The mechanisms are now viewed as major contributors to the end stages of heart failure. Some are described briefly in the following sections.

Remodeling. The heart responds to high blood pressure and overload by enlarging in order to increase blood input. This leads to structural damage called remodeling:

In order to accommodate the increased blood input, the heart muscle cells elongate. The muscular walls of the heart that they form become thinner and inefficient.
The muscle cells undergo other changes that result in calcium loss. Calcium is a mineral that is crucial for healthy heart contractions.
The thinner heart muscles and the impaired heart contractions further weaken the heart's pump.
Mitral valve regurgitation is a possible outcome of remodeling. The mitral valve regulates blood flow between the two chambers on the left side of the heart. In response to remodeling, the structural changes in the heart may distort the mitral valve so that the blood leaks backward into the left atrium of the heart instead of flowing out into the body's circulation.
These changes are generally irreversible, although heart pacemakers and certain drugs, including beta-blockers and ACE inhibitors, may reverse some of the remodeling in some patients.

Activation of the Sympathetic Nervous System. The sympathetic nervous system consists of the nerve cells that automatically govern and regulate the beating heart.

This nervous system responds to the failing heart pump by signaling the release of stress hormones, in particular a powerful one called norepinephrine.
These hormones flood the heart, causing it to beat even faster.
These rapid heart beats, although intended to accommodate the weakened pumping actions, only accelerate the damage.

The Renin-Angiotensin-Aldosterone System (RAAS). The renin-angiotensin-aldosterone system (RAAS) is a group of hormones that are responsible for the opening and narrowing of blood vessels and retention of fluids. They also affect cell development in the heart.

The RAAS hormones are called into action by the failing heart.
They respond to the lower blood volume of the weakened heart by constricting the blood vessels and retaining fluids and sodium.
The heart then works harder to pump blood through these narrowed vessels. Blood pressure, then, is forced to increase, which creates a vicious cycle.

Immune System Response. The immune system may also compound the damage. In response to injury in the heart muscle cells or in other parts of the body that occurs as the heart fails, the immune system releases factors intended to protect these areas.

In excess, however, they can cause inflammation and damage.

The most important of these factors are called cytokines. Active cytokines include tumor necrosis factor (TNF) and possibly interleukins 1 and 6.
High levels of these cytokines have been observed in patients with the most severe classes of heart failure.
They may play an important role in the process leading to remodeling. High levels of these cytokines may actually trigger muscle cell growth and enlargement of the heart.

Other Players. Other molecules or compounds have been identified that might play a positive or negative role in the process of the failing heart.

Natriuretic peptides are a family of compounds released to counterbalance the effects of RAAS. Atrial natriuretic peptide (ANP) is a specific member of this family that opens blood vessels and counteracts the sodium-retaining properties of aldosterone (one of the RAAS hormones). It is of particular interest to researchers looking for new treatments.
Endothelin is a powerful protein involved in blood vessel constriction, cell proliferation and build-up, and other negative effects on the heart.
Nitric oxide is important for blood vessel dilation and elasticity.

Symptoms

Many symptoms of heart failure result from the congestion that develops as fluid backs up into the lungs and leaks into the tissues. Other symptoms result from inadequate delivery of oxygen-rich blood to the body's tissues. Since heart failure can progress rapidly, it is essential to consult a doctor immediately if any of the following symptoms are detected.

Fatigue and shortness of breath (dyspnea) are the first symptoms. They are caused by fluid in the lungs. Patients typically report that they feel out of breath after mild exertion. It is unlike the breathlessness of angina, which feels like a heavy weight pressing on the chest.

Fluid retention. Patients may complain of leg or abdominal swelling.
Wheezing or cough. Patients may have asthma-like wheezing or a dry hacking cough that occurs a few hours after lying down, but then stops after the patient sits up.
Central sleep apnea. This disorder results when the brain fails to signal the muscles to breathe during sleep. It occurs in up to half of people with heart failure. Sleep apnea causes disordered breathing at night. If heart failure progresses, the apnea may be so acute that a person, unable to breathe, may awaken from sleep in panic.
Loss of muscle mass. Over time, patients may lose muscle weight due to low cardiac output.

Ultimately, fluid in the lungs may build up. This is called pulmonary edema. When this happens, symptoms become more severe.

In addition to shortness of breath, patients sometimes have a cough that produces a pinkish froth.
Patients may experience a bubbling sensation in the lungs and feel as if they are drowning.
Typically, the skin is clammy and pale, sometimes nearly blue. This is a life-threatening situation, and the patient must go immediately to an emergency room.

Fatigue. As with left-side heart failure, an early symptom of right-side (right-ventricular) failure is extreme tiredness.
Fluid accumulation. This first occurs in the feet, then the ankles and legs, and finally in the abdomen. The liver may also be enlarged.
Weight gain. Although appetites are often depressed, patients with heart failure gain weight because they retain salt and water.
Loss of muscle mass.

Risk Factors

Nearly 5 million Americans currently suffer from heart failure. About 550,000 new cases of heart failure are now diagnosed each year. In 1970 there were only 250,000 new cases, so the annual numbers have risen dramatically. Such numbers represent an increasingly older population. Although there has been a dramatic increase over the last several decades in the number of people who suffer from heart failure, survival rates have been improving greatly.

Coronary artery disease and high blood pressure are the main causes of heart failure. Other diseases that damage or weaken the heart muscle or heart valves can also cause heart failure. Heart failure is most common in people over age 65, African-Americans, and women.

Heart failure is the most common reason for hospitalization in the elderly, and as the population ages, the incidence of heart failure is rising dramatically. According to one report, it occurs at a rate of about 10 in 1,000 people after age 65. The positive implication is, however, that people are living longer with heart failure.

Men are at higher risk for heart failure than women, although the difference narrows with age. Women also have a better survival rate than men do when heart failure is caused by valvular heart disease, high blood pressure, or alcohol abuse. (Some studies indicate that this is because men may be more susceptible to the process of heart muscle-cell remodeling, a damaging effect of hypertension.)

The survival rates of women and men are more similar, however, when heart failure evolves from coronary artery disease or heart attack. Women are much more likely to develop heart failure after a heart attack than men. In such cases, some evidence suggests that the reasons for this may include less aggressive approach to treatment for the initial heart conditions.

African-Americans are at higher risk for heart failure than Caucasians, and studies have reported that they tend to do much worse. In a 2003 study, however, in which Caucasians and African-Americans had comparable treatment, African-Americans actually had lower 1-year mortality rates (with slightly higher rates of rehospitalizations). Some evidence suggests that African-Americans are more often likely than Caucasians to develop diastolic heart failure (a failure of the heart muscle to relax normally), which is often a precursor to systolic heart failure (impaired ability to pump blood). Caucasians tend to develop systolic heart failure first.

According to a 2006 New England Journal of Medicine study, people whose parents had heart failure have a greatly increased risk of developing heart failure, particularly left-ventricular systolic heart failure. Earlier studies have suggested that a family history of early heart failure caused by cardiomyopathies (diseases that damage the heart muscle) may also predispose people to the disease. Researchers are looking for changes in specific genes that might regulate systems involved in heart failure and so increase susceptibility in certain populations.

Chronic alcohol abuse can damage the heart muscles, can cause hypertension, and may prove to be one cause of idiopathic dilated cardiomyopathy. Moderate alcohol consumption, on the other hand (generally defined as 2 drinks a day for men and 1 drink for women), may protect against heart failure. Non-drinkers, though, are not advised to begin drinking.

Coronary artery disease. More than 60% of heart failure cases may be due to coronary artery disease and its risk factors (smoking, sedentary living, obesity).
Heart attack. The injured heart after an attack is at high risk for failure. The improved survival rates from heart attack over the past decades have actually been responsible for the dramatic increase in heart failure rates.
High blood pressure. Hypertension is a significant risk factor and is present in 75% of patients with heart failure.
Diabetes. People with diabetes are at high risk for heart failure, particularly if they also have coronary artery disease. Even blood sugar abnormalities that precede diabetes increase the risk.
Obesity. Obesity is associated with both hypertension and type 2 diabetes, conditions that place people at risk for heart failure. Evidence strongly suggests that obesity itself is a major risk factor for heart failure, particularly in women. In a major 2002 study, about 14% of heart failure cases in women and 11% in men could be attributed to obesity. Both overweight and obese women had a significantly higher than normal risk for heart failure. Only obesity led to a significant risk in men.
Valvular heart disease. Specific valvular conditions that are common in patients with heart failure include aortic stenosis and mitral regurgitation.
Severe emphysema. Chronic obstructive pulmonary disease is a major risk factor for right-side heart failure.

Emphysema is a lung disease involving damage to the air sacs (alveoli).There is progressive destruction of alveoli and the surrounding tissue that supports them. As the disease gets worse, large air cysts take the place of normal lung tissue. Air is trapped in the lungs.

Cardiomyopathies due to various causes, including birth defects, HIV infection, and other infections.
In rare cases, heart failure can occur in women around the time of childbirth, a condition called peripartum cardiomyopathy.

Click the icon to see an image of peripartum cardiomyopathy.

An overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism) can have severe effects on the heart and increase the risk for heart failure.
Amyloidosis. A starchy protein (amyloid) that builds up in tissues and organs can lead to heart failure.
Surviving childhood cancers. Survivors face a risk for developing heart failure in later years, particularly those treated with chemotherapies such as doxorubicin. Newer cancer advances may reduce this risk.
Acute myocarditis. This rare viral infection involves the heart muscle and can produce temporary but potentially life-threatening heart failure.

Long-term use of anabolic steroids (male hormones used to build muscle mass) increases the risk for heart failure. The drug itraconazole (Sporanox), used to treat skin, nail, or other fungal infections, has been linked to heart failure. In 2006, the FDA warned that the cancer drug imatinib (Gleevec) has been associated with heart failure cases. Most patients who took imatinib and developed heart failure had a history of diabetes, high blood pressure, or heart disease.

Complications

At least 20% of hospitalizations in older adults are due to heart failure. For people over age 65, it is the number one cause of death, with nearly 290,000 people dying from this disease each year. Nevertheless, although heart failure produces very high mortality rates, treatment advances in hypertension, heart surgeries, and heart pacemakers are improving survival rates.

The most serious and life-threatening complications of heart failure are:

Arrhythmias (irregular beatings of the heart)
Acute pulmonary edema (fluid in the lungs)

Left-side heart failure tends to be more severe than right-side heart failure, particularly when it is associated with the following conditions:

Coronary artery disease
HIV infection
Amyloidosis (a metabolic disorder than can lead to organ failure)
Chemotherapy that uses the drug doxorubicin

The outlook is better in patients with left-side heart failure associated with:

Idiopathic cardiomyopathy (the cause is unknown)
Heart failure due to childbirth

Weight Issues. If patients with heart failure are overweight to begin with, their condition tends to be more severe. Once heart failure develops, however, an important indicator of a worsening condition is the occurrence of cardiac cachexia, which is unintentional rapid weight loss (a loss of at least 7.5% of normal weight within 6 months).

Impaired Kidney Function. Heart failure weakens the heart’s ability to pump blood. This can affect other parts of the body including the kidneys (which in turn can lead to fluid build-up). Decreased kidney function is common in patients with heart failure, both as a complication of heart failure and as a complication of other diseases associated with heart failure (such as diabetes). Studies suggest that in patients with heart failure, impaired kidney function increases the risks for heart complications including hospitalization and death.

Congestion (Fluid Buildup). In left-sided heart failure, fluid builds up first in the lungs. Later, as right-sided heart failure develops, fluid builds up in the legs, feet, and abdomen. According to one study, patients with severe symptoms who had congestion (fluid buildup) had poorer survival rates than those without fluid build up. Two-year survival rates were 87% in those who were congestion-free compared to 41 - 67% in patients with various signs of congestion (such as swelling, difficulty breathing when lying down, and weight gain from fluid buildup). Fluid buildup is treated with lifestyle measures, such as reducing salt in the diet, as well as drugs, such as diuretics. Sometimes, for hospitalized patients, an ultrafiltration device is used to remove excess water and salt from the body (see Surgery and Devices).

Atrial Fibrillation. This abnormal rhythm is a rapid quivering beat in the upper chambers of the heart. It is a major cause of stroke and very dangerous in people with heart failure.

Left Bundle Branch Block. Left bundle-branch block is an abnormality in electrical conduction in the heart. It develops in about 30% of patients with heart failure and is a major risk factor for serious adverse heart events.

Systolic Blood Pressure. An important 2006 study indicated that patients who arrive at the hospital with heart failure and low systolic blood pressure have a poorer prognosis than those who arrive with high systolic blood pressure. Researchers think that high systolic blood pressure may be a signal for unique clinical characteristics.

Sleep Apnea. With this disorder, a person stops breathing during the night, perhaps hundreds of times, usually for periods of 10 seconds or longer. It is a very strong risk factor for heart failure, and patients with apnea have a higher mortality rate than those who do not.

Depression. The presence of depression indicates a poorer outlook for the heart. Studies indicate that depression may have adverse biologic effects on the immune and nervous systems, blood clotting, blood pressure, blood vessels, and heart rhythms.

Seasonal and Daily Patterns. Studies have shown that more emergency room visits and higher mortality rates occur during winter months and on Mondays in patients with heart failure. One factor in this higher risk may be sudden and strenuous exertion, particularly snow-shoveling, which is associated with a risk for heart attack in people with heart problems.

Diagnosis

Doctors can often make a preliminary diagnosis of heart failure by medical history and careful physical examination.

The medical history risks for heart failure include:

High blood pressure
Diabetes
Poor cholesterol levels
Heart or peripheral vascular disease
Sleep apnea
Thyroid problems
Obesity
Lifestyle factors (smoking, alcohol use)

The following physical signs, along with medical history, strongly suggest heart failure:

Enlarged heart
Irregular heart sounds
Abnormal sounds in the lungs
Swelling or tenderness of the liver
Fluid retention in legs and abdomen
Elevation of pressure in the veins of the neck

Both blood and urine tests are used to check for problems with the liver and kidneys and to detect signs of diabetes. Lab tests can measure:

Cholesterol and lipid levels
Blood sugar (glucose)
Red blood cell count (to rule out anemia)
Blood sugar levels
Thyroid function

Urine tests can be used to assess the presence of a protein called albumin. Albumin in the urine is usually a sign of kidney disease, but even tiny amounts (microalbumin) signal an increased risk for heart failure in people with and without diabetes.

The exercise stress test measures heart rate, blood pressure, and oxygen consumption while a patient is performing physically, usually walking on a treadmill. It is an important diagnostic component in determining heart failure symptoms. Doctors also use exercise tests to gauge long-term outlook and the effects of particular treatments.

An electrocardiogram (ECG) cannot diagnose heart failure, but it can indicate underlying heart problems. It is sometimes called an EKG. The test is simple and painless to perform. It may be used to diagnose:

Enlargement of the heart muscle, which may help to determine long-term outlook
The presence of coronary artery disease
Abnormal cardiac rhythms. A rhythm pattern called a prolonged QT interval, for example, might predict people with heart failure who are at risk for severe complications and would need more aggressive therapies.

The major benefit of an ECG is that it can help determine which patients do not need an echocardiogram, a more accurate (but more expensive) diagnostic test.

The electrocardiogram (ECG, EKG) is used extensively to diagnose heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. There are several different types of electrocardiograms.

The best diagnostic test for heart failure is echocardiography. Echocardiography is a noninvasive, entirely safe test that uses ultrasound to image the heart as it is beating. Cardiac ultrasounds provide the following information:

Accurate indications of valve function
The amount of blood flow through the heart's chambers
The location of the failure and where it has occurred

Doctors use information from the echocardiogram for calculating the ejection fraction (how much blood is pumped out during each heartbeat), which is important for determining the severity of heart failure.

Radionuclide Ventriculography. Radionuclide ventriculography is an imaging technique that uses a tiny amount of radioactive material (called a trace element). The substance is injected into a patient. As it passes through the bloodstream it is picked up on x-rays. This is a very important imaging technique for patients with heart failure. It is very sensitive in revealing heart enlargement or evidence of fluid accumulation around the heart and lungs. It is typically used in concert with angiography.

Magnetic Resonance Imaging. Magnetic resonance imaging (MRI) scans that use contrast dyes to improve resolution are proving helpful for identifying patients with irreversible heart damage. Damage appears as very bright areas on the scan.

Doctors may recommend angiography if they suspect that blockage of the arteries is contributing to heart failure. This procedure is invasive.

A thin tube called a catheter is inserted into one of the large arteries in the arm or leg.
It is gently guided through the artery until it reaches the heart.
The catheter measures internal blood pressure at various locations, giving the doctor a comprehensive picture of the extent and nature of the heart failure.
Dye is then injected through the tube into the heart.
X-rays called angiograms are taken as the dye moves through the heart and arteries.
These images help locate problems in the heart's pumping action or blockage in the arteries.

Major complications of angiography are rare (about 0.1%) but can occur. They include stroke, heart attacks, and kidney damage. The more experienced the medical center in this procedure, the lower the risk.

Click the icon to see an image of cardiac catheterization.

Researchers are looking for biologic factors (called biomarkers) that will confirm a diagnosis or suggest a better or worse prognosis. Many are under investigation.

Tumor Necrosis Factor. Elevated levels of tumor necrosis factor (TNF) may be a very strong and accurate predictor of a poor outlook. This immune substance is known to be a potent substance in the inflammatory process.

Natriuretic Peptides. Natriuretic peptides are substances that help regulate salt and water balance in the body. Levels of these peptides increase as heart failure symptoms worsen. Blood tests for brain natriuretic peptide (BNP) are now used to help diagnose heart failure. There are two types of BNP tests: The enzyme-linked immunosorbent assay (ELISA) and the radioimmunosorbent assay (RIA). Research from 2006 suggested that the ELISA test may be more accurate, but it is also more expensive.

BNP testing can be very helpful in correctly diagnosing heart failure in patients who come to the emergency room complaining of shortness of breath (dyspnea). A 2006 study indicated that this test can also help predict which patients with dyspnea are at greatest risk of dying within a year from heart failure.

Brain Metabolites. High levels of a compound called N-acetylaspartate, generated as a byproduct of chemical processes in the brain, may indicate a poor outlook.

Treatment

Guidelines for evaluating the severity of heart failure and determining treatments use a staging system that is similar to the one used for major cancers:

Stage A: Patients are at high risk for heart failure, but there is no evidence of structural damage to the heart. Risk factors include high blood pressure, heart diseases, diabetes, obesity, metabolic syndrome, and previous use of medications that damage the heart (such as some chemotherapy).
Stage B: Patients have a structural heart abnormality but no symptoms of heart failure. Abnormalities include left ventricular hypertrophy and low ejection fraction, asymptomatic valvular heart disease, and a previous heart attack.
Stage C: Patients have a structural abnormality and current or previous symptoms of heart failure, including shortness of breath, fatigue, and difficulty exercising.
Stage D: Patients have end-stage symptoms that do not respond to standard treatments.

According to expert guidelines, the first step in managing heart failure is to treat the primary conditions causing or complicating heart failure. These include:

Coronary artery disease. Treatment includes a healthy diet, exercise, smoking cessation, medications, and, possibly, bypass or angioplasty. [See In-Depth Report #3: Coronary artery disease and angina.]
Cholesterol and lipid problems. Treatments include lifestyle management and medications, especially statins. [See In-Depth Report #23: Cholesterol.]
High blood pressure. A normal systolic blood pressure is considered below 120 mm Hg, and a normal diastolic blood pressure is below 80 mm Hg. Patients with diabetes or chronic kidney disease should maintain blood pressure readings of 130/80 or less, while other patients with high blood pressure should aim for readings no higher than 140/90. Effective reduction of blood pressure reduces the risk of heart failure by 30 - 50%. [See In-Depth Report #14: High blood pressure.]
Diabetes. Treating diabetes is extremely important for reducing the risk for heart disease. ACE inhibitors are especially beneficial, particularly for people with diabetes. Recent research suggests that metformin, a drug used to treat diabetes, may also help prevent heart failure. [See In-Depth Report #60: Diabetes - type 2; and In-Depth Report #9: Diabetes - type 1.]
Valvular abnormalities such as aortic stenosis and mitral regurgitation. Surgery may be required.
Abnormal health rhythms (arrhythmias). Ventricular assisted devices, notably biventricular pacers (BVPs), are proving to be important in preventing hospitalizations for patients with these conditions.
Anemia. Giving erythropoietin (EPO) and iron injections to patients with heart failure and underlying anemia not only reverses the anemia, but may markedly improve heart symptoms as well. [See In-Depth Report #57: Anemia.]
Thyroid function. Various medications are used to treat overactive thyroid (hyperthyroidism) or underactive thyroid (hypothyroidism). [See In-Depth Report #38: Hypothyroidism.]
Sleep apnea. Continuous positive airway pressure (CPAP) is an effective treatment for sleep apnea. CPAP may help reduce systolic blood pressure and improve left ventricular systolic function. [See In-Depth Report#65:Sleep apnea.]

Click the icon to see an image of CPAP treatment.

Treatments for patients with Stage B risk for heart failure include all of the treatments recommended in Stage A. In addition, the following types of drugs and devices may be recommended for some patients. These include:

Angiotensin-converting enzyme (ACE) inhibitors for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack if they have a low left ventricular ejection fraction (LVEF) and no heart failure symptoms. A reduced LVEF indicates that the heart’s left ventricle is not pumping blood efficiently.
Beta blockers for patients with a recent or past history of heart attack. Also for patients who have not had a heart attack but who do have reduced LVEF without heart failure symptoms.
Angiotensin-receptor blockers (ARBs) for patients who have had a heart attack or have low LVEF, but who cannot take ACE inhibitors.
Implantable defibrillators for patients who have weakened heart pumps (ischemic cardiomyopathy), who had a heart attack more than 40 days prior, and who have low LVEF.

Treat conditions as recommended in Stage A plus:

Restrict dietary salt. Lowering salt in the diet can help diuretics work better.
ACE inhibitors, beta blockers, and diuretics are recommended for most patients.
ARBs are recommended for patients who cannot tolerate ACE inhibitors.
Aldosterone inhibitors or digitalis may be used for some patients.
A hydralazine and nitrate combination (BiDil) may be used for African-American patients who are taking an ACE inhibitor and beta blocker and who still have heart failure symptoms.
Avoid drugs that can worsen heart failure symptoms. These include nonsteroidal anti-inflammatory drugs (NSAIDs), most calcium channel blockers, and most drugs used to treat irregular heart rhythms (arrhythmia).
Exercise training for appropriate patients.
Biventricular pacemakers and implantable defibrillators for some patients.

Treatment includes appropriate measures used for Stages A, B, and C plus:

Heart transplantation referral for appropriate patients.
Left-ventricular assist devices (LVADs) as permanent therapy for patients who are not candidates for heart transplants. LVADs are surgically implanted to help pump blood through the body.
Hospice and end-of-life care information for patients and families.

Medications

Many different medications are used in the treatment of heart failure. They include:

Angiotensin-converting enzyme (ACE) inhibitors
Angiotensin-receptor blockers (ARBs)
Beta blockers
Diuretics
Aldosterone blockers
Digitalis
Hydralazine and nitrates
Statins
Nesiritide (Natrecor)
Aspirin

Angiotensin-converting enzyme (ACE) inhibitors are among the most important drugs for treating patients with heart failure. ACE inhibitors open blood vessels and decrease the workload of the heart. They are used to treat high blood pressure but can also help improve heart and lung muscle function. Major studies suggest that ACE inhibitors may reduce the risk of death, heart attack, and hospital admissions by 28% in patients with existing heart failure.

ACE inhibitors are particularly important for patients with diabetes. A large study reported that patients with diabetes who took these drugs had fewer heart attacks and lower overall mortality rates than patients who took other types of high blood pressure medications. ACE inhibitors may also help slow progression of kidney disease, in addition to controlling blood pressure.

Doctors sometimes avoid giving aspirin to patients who are taking ACE inhibitors due to concerns that this drug combination can cause kidney problems. A 2005 study of patients with both coronary artery disease and heart failure indicated that an aspirin and ACE inhibitor combination is not harmful, and that aspirin can significantly reduce mortality risk for these patients.

Choosing an ACE inhibitor. ACE inhibitors treat Stage A high-risk conditions such as high blood pressure, heart disease, and diabetic nerve disorders (neuropathy). They also treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands and stages include:

Benazepril (Lotrel) -- (Stage A)
Captopril (Capoten) -- (Stages A, B, C)
Enalapril (Vasotec) -- (Stages A, B, C)
Fosinopril (Monopril) -- (Stages A, C)
Lisinopril (Prinivil, Zestril) -- (Stages A, B, C)
Moexipril (Univasc) -- (Stage A)
Perindopril (Aceon) -- (Stage A)
Quinapril (Accupril) -- (Stages A, C)
Ramipril (Altace) -- (Stages A, B, C)
Trandolapril (Mavik) -- (Stages A, B, C)

Side Effects of ACE Inhibitors:

Low blood pressure is the main side effect of ACE inhibitors. This can be severe in some patients, especially at the start of therapy.
Irritating cough is a common side effect, which some people find intolerable. Although all ACE inhibitors can have this side effect, sometimes switching to another brand will reduce this symptom.
Although ACE inhibitors can protect against kidney disease, they also increase potassium retention in the kidneys. This increases the risk for cardiac arrest if potassium levels become too high. Because of this action, they are not generally given with potassium-sparing diuretics or potassium supplements.
A rare but severe side effect is granulocytopenia, which is an extreme reduction in infection-fighting white blood cells.
In very rare cases, patients suffer a sudden and severe allergic reaction called angioedema that causes swelling in the eyes and mouth and may close off the throat.

Patients who have difficulty tolerating ACE inhibitor side effects are usually switched to an angiotensin-receptor blocker (ARB).

ARBs, also known as angiotensin II receptor antagonists, are similar to ACE inhibitors in their ability to open blood vessels and lower blood pressure. They may have fewer or less-severe side effects than ACE inhibitors, especially coughing, and are sometimes prescribed as an alternative to ACE inhibitors. Some patients with heart failure take an ACE inhibitor along with an ARB.

Brands and Indications. ARBs are used to treat Stage A high-risk conditions such as high blood pressure and diabetic nerve disorders (neuropathy). They are also used to treat Stage B patients who have had a heart attack or who have left ventricular systolic disorder, and Stage C patients with heart failure. Specific brands, and the stage of heart failure they are used for, are listed below.

Candesartan (Atacand) -- (Stages A, C)
Eprosartan (Teveten) -- (Stage A)
Irbesartan (Avapro) -- (Stage A)
Losartan (Cozaar) -- (Stages A, B)
Olmesartan (Benicar) -- (Stage A)
Telmisartan (Micardis) -- (Stage A)
Valsartan (Diovan) -- (Stages A, B, C)

Common Side Effects

Low blood pressure
Dizziness and lightheadedness
Raised potassium levels
Drowsiness

Beta blockers are almost always used in combination with other drugs, such as ACE inhibitors and diuretics. They help slow heart rate and lower blood pressure. Research presented at the 2006 American College of Cardiology meeting indicated that beta-blockers are an important treatment for most patients with left ventricular heart failure. Data from the study found that the beta blocker carvedilol (Coreg) significantly lowered the risk of death or rehospitalization within 3 - 6 months after hospital discharge.

Beta blockers can help patients with heart failure by:

Treating high blood pressure, angina, arrhythmias, and preventing heart attack in high-risk patients.
Preventing left ventricular remodeling in patients with enlarged heart chambers and weakened heart muscles (dilated cardiomyopathy), and in those who have suffered a first heart attack.
Blocking inflammatory immune factors called cytokines, including tumor necrosis factor (TNF). TNF may play a key role in the process leading to heart failure.
Preventing norepinephrine (adrenaline) from binding to heart cells. Elevated levels of norepinephrine, a stress hormone, can overstimulate the failing heart and are associated with severe heart failure.

Brands and Indications. Beta blockers treat Stage A high blood pressure. They are also treat Stage B patients (both those who have had a heart attack and those who have not had a heart attack but who have heart damage). Recent guidelines identify three drugs best for treating Stage C patients with heart failure. Specific brands and stages include:

Acebutolol (Sectral) -- (Stage A)
Atenolol (Tenormin) -- (Stages A, B)
Betaxolol (Kerlone) -- (Stage A)
Bisoprolol (Zebeta) -- (Stages A, C)
Cartelol (Cartrol) -- (Stage A)
Carvedilol (Coreg) -- (Stages A, B, C)
Labetalol (Trandate) -- (Stage A)
Metoprolol succinate (Toprol XL) -- (Stages A, C)
Metoprolol tartrate (Lopressor) -- (Stages A, B)
Nadolol (Corgard) -- (Stage A)
Penbutolol (Levatol) -- (Stage A)
Pindolol (Visken) -- (Stage A)
Propranolol (Inderal) -- (Stages A, B)
Timolol (Blocadren, Timolide) -- (Stages A, B)

Beta Blocker Concerns

Do not abruptly stop taking these drugs. The sudden withdrawal of beta blockers can rapidly increase heart rate and blood pressure. Your doctor may want you to slowly decrease the dose before stopping completely.
Beta blockers are categorized as non-selective or selective. Non-selective beta blockers such as carvedilol and propranolol can narrow bronchial airways. Patients with asthma, emphysema, or chronic bronchitis should not use these beta blockers.
Beta blockers can lower HDL (“good”) cholesterol.
These drugs can hide warning signs of low blood sugar (hypoglycemia) in patients with diabetes.
Beta blockers are usually used in combination with ACE inhibitors, but the two drugs are not started at the same time. Research presented at the 2005 European Society of Cardiology meeting indicates that either a beta blocker or an ACE inhibitor can be prescribed at first, and the other drug added on later.

Common Side Effects

Fatigue and lethargy
Vivid dreams and nightmares
Depression
Memory loss
Dizziness and lightheadedness
Reduced ability to exercise
Coldness in extremities (legs, toes, arms, hands)

Check with your doctor about any side effects. Do not stop taking these drugs on your own.

Diuretics cause the kidneys to rid the body of excess salt and water. Fluid retention is a major symptom of heart failure. Aggressive use of diuretics can help eliminate excess body fluids, while reducing hospitalizations and improving exercise capacity. These drugs are also important to help prevent heart failure in patients with high blood pressure. In addition, certain diuretics, notably spironolactone (Aldactone), block aldosterone, a hormone involved in heart failure. This drug class is beneficial for patients in late stages of heart failure (Stages C and D).

Diuretic Types and Brands. Diuretics come in many brands and are generally inexpensive. Some need to be taken once a day, some twice a day. Treatment is usually started at a low dose and gradually increased. Diuretics are virtually always used in combination with other drugs, especially ACE inhibitors and beta blockers. There are three main types of diuretics:

Potassium-sparing diuretics. These include amiloride (Midamor), spironolactone (Aldactone), and triamterene (Dyrenium).
Thiazide diuretics. These include chlorothiazide (Diuril), chlorthalidone (Hygroton), indapamide (Lozol), hydrochlorothiazide (Esidrix, HydroDiuril), and metolazone (Mykrox, Zaroxolyn).
Loop diuretics. Because loop diuretics act faster than other diuretics it is important to avoid dehydration and potassium loss. Loop diuretics include bumentanide (Bumex), furosemide (Lasix), and torsemide (Demadex).

Problems with Diuretics. Loop and thiazide diuretics deplete the body's supply of potassium, which, if left untreated, increases the risk for arrhythmias. Arrhythmias are heart rhythm disturbances that can, in rare instances, lead to cardiac arrest. In such cases, doctors will prescribe lower doses of the current diuretic, recommend potassium supplements, or use potassium-sparing diuretics either alone or in combination with a thiazide. Potassium-sparing drugs have their own risks, which include dangerously high levels of potassium in people with existing elevated levels of potassium or in those with damaged kidneys. However, all diuretics are generally more beneficial than harmful.

Common Side Effects

Fatigue
Depression and irritability
Urinary incontinence
Reduced sexual drive

Aldosterone is a hormone that is critical in controlling the body's balance of salt and water. Excessive levels may play important roles in hypertension and heart failure. Drugs that block aldosterone are prescribed for some patients with Stage C heart failure.

Spironolactone (Aldactone, Spirinol) is both a potassium-sparing diuretic and an aldosterone blocker. A major study of patients with heart failure found that spironolactone reduced death rate by 30%. Like all medications for heart failure, it must be used with care; elevated potassium levels are a potential risk of therapy.
Eplerenone (Inspra), a newer aldosterone blocker, has been specifically approved for treatment of heart failure. It is prescribed for patients who have heart failure following a heart attack. Its actions are similar to potassium-sparing diuretics and, like these drugs, it poses some risk for high potassium levels.

Digitalis is derived from the foxglove plant. It has been used to treat heart disease since the 1700s. Digoxin (Lanoxin) is the most commonly prescribed digitalis preparation. Digoxin decreases heart size and reduces certain heart rhythm disturbances (arrhythmias).

Unfortunately, digitalis does not reduce mortality rates, although it does reduce hospitalizations and worsening of heart failure. Controversy has been ongoing for more than 100 years over whether the benefits of digitalis outweigh its risks and adverse effects.

Digitalis may be useful for patients with left-ventricular systolic dysfunction who do not respond to other drugs (diuretics, ACE inhibitors). It is also used for patients who have atrial fibrillation.

Digitalis does not appear to help patients with left-ventricular diastolic heart failure. It may be harmful in patients with right-ventricular heart failure and those who stop taking digoxin after using it in combination with ACE inhibitors.

Side Effects and Problems. While digitalis is generally a safe drug, it can have toxic side effects due to overdose or other accompanying conditions. The most serious side effects are arrhythmias (abnormal heart rhythms that can be life-threatening). Early signs of toxicity may be irregular heartbeat, nausea and vomiting, stomach pain, fatigue, visual disturbances (such as yellow vision, seeing halos around lights, flickering or flashing of lights), and emotional and mental disturbances.

Many factors increase the chance for side effects.

Advanced age
Low blood potassium levels (which may be caused by diuretics)
Hypothyroidism
Anemia
Valvular heart disease
Impaired kidney function

Digitalis also interacts with many other drugs, including quinidine, amiodarone, verapamil, flecainide, amiloride, and propafenone.

A blood test that monitors drug levels in patients taking the drug can limit the rate of toxicity to about 2%. For most patients with mild-to-moderate heart failure, low-dose digoxin may be as effective as higher doses. If side effects are mild, patients should still consider continuing with digitalis if they experience other benefits.

Hydralazine and nitrates are two older drugs that help relax arteries and veins, thereby reducing the heart's workload and allowing more blood to reach the tissues. In 2005, the FDA approved BiDil, a drug that combines isosorbide dinitrate and hydralazine. BiDil is approved to specifically treat heart failure in African-Americans. African-Americans have a particularly high risk for heart failure. BiDil is the first drug approved for a specific racial group. The Food and Drug Administration (FDA) based its approval on a landmark 2004 study published in the New England Journal of Medicine, which showed that African-Americans who took the drug were 43% more likely to survive heart failure than patients who took placebo. Some experts suggest that BiDil could also benefit other racial groups.

Statins are important drugs used to lower cholesterol and to prevent heart disease leading to heart failure. These drugs include lovastatin (Mevacor), pravastatin (Pravachol), simvastatin (Zocor), fluvastatin (Lescol), atorvastatin (Lipitor), and rosuvastatin (Crestor). In 2007, the FDA approved atorvastatin to reduce the risks for hospitalization for heart failure in patients with heart disease.

In a 2006 Journal of the American Medical Association study, patients with heart failure who began taking a statin drug had a 24% lower relative risk of death and a 21% lower relative risk of hospitalization for heart failure than patient who did not take a statin. Statins appeared to help these patients regardless of whether or not they had co-existing coronary heart disease.

Aspirin is a type of non-steroid anti-inflammatory (NSAID). A 2005 study in the Journal of the American College of Cardiology indicated that aspirin is important for preventing heart failure death in patients with heart disease, and can safely be used with ACE inhibitors. However, some research has suggested that NSAIDs may increase the risk of heart failure for patients with a history of heart disease, especially when used in combination with ACE inhibitors or diuretics. Patients with heart disease should ask their doctor which NSAIDs are right for them.

Nesiritide treats patients who have arrived at a hospital with decompensated heart failure. Decompensated heart failure is a life-threatening condition in which the heart fails over the course of minutes or a few days, often as the result of a heart attack or sudden and severe heart valve problems. However, nesiritide may cause serious kidney damage.

In 2005, the FDA released recommendations from an expert panel concerning the appropriate and inappropriate use of nesiritide. The panel emphasized that nesiritide should be used to treat only patients with decompensated heart failure who have shortness of breath (dyspnea) and trouble breathing. The drug should not be a replacement for diuretics.

Despite these warnings, some doctors have prescribed nesiritide “off-label” to treat patients with severe heart failure outside of a hospital setting. Research presented at the 2007 American College of Cardiology annual conference criticized this practice by demonstrating that nesiritide plus standard treatment does not reduce the risk of heart- or kidney-related death or hospitalization. In addition, the research suggested some concerns about nesiritide’s overall safety.

Tolvaptan. Tolvaptan is an investigational drug that is being studied in combination with standard therapy for treatment of heart failure. It is especially being investigated for acute decompensated heart failure, a type of heart failure categorized by fluid build-up in the lungs (pulmonary edema) for which there are few available treatments. In patients hospitalized with heart failure, tolvaptan plus standard drugs improved breathing problems (dyspnea) and reduced fluid accumulation (edema) and body weight, according to two studies published in 2007 in the Journal of the American Medical Association. However, the drug did not appear to reduce the risk of re-hospitalization or death.

Levosimendan. Levosimendan is an experimental inotropic drug that is being investigated as a treatment for severely ill patients with heart failure. It belongs to a new class of drugs called calcium sensitizers that may help improve heart contractions and blood flow. Clinical trials suggest that levosimendan may improve survival in patients hospitalized for heart failure. The drug also appears to reduce levels of BNP (brain natriuretic peptide), a chemical marker for heart failure severity.

Prograf. Tacrolimus (Prograf) was approved in 2006 to help prevent organ rejection in patients who have received a heart transplant. The drug suppresses the immune system. Patients who receive this drug are at increased risk of developing lymphoma (a cancer of the immune system).

Surgery and Devices

Revascularization surgery helps to restore blood flow to the heart. It can treat blocked arteries in patients with coronary artery disease and may help selected patients with heart failure. Surgery types include coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI). CABG is a traditional type of open heart surgery. PCI, also called angioplasty, uses a catheter to inflate a balloon inside the artery. A metal stent may also be inserted during a PCI procedure. [See In-Depth Report#03:Coronary artery disease.]

A 2006 study suggested that early treatment with revascularization surgery may be particularly important for patients with systolic heart failure, a condition that occurs when the heart does not pump out enough blood. This condition has a very high death rate. Researchers found that CABG or PCI surgery halved the risk of dying compared to standard drug therapy. Patients in the study first underwent a positron emission tomography (PET) test to determine if they would be good candidates for surgery.

Click the icon to see an illustrated series detailing coronary artery balloon angioplasty.

Click the icon to see an illustrated series detailing heart bypass surgery.

In appropriate patients, mitral valve surgery may significantly reduce the severity of heart failure. In a study of 92 patients with late-stage heart failure and faulty valves, reconstruction of the heart's mitral valve drastically improved heart function.

An experimental mesh "heart sock" is being investigated as an adjunct to mitral valve repair surgery. Research presented at the 2004 American Heart Association Scientific Sessions suggested that the device reduced the progression of heart failure and halved the need for transplant surgery. The "sock" helps realign the shape of the heart and improve heart function. To date, it has been tested in patients with dilated cardiomyopathy.

Ventricular Remodeling. Ventricular remodeling (also called partial left ventriculectomy or the Batista procedure, after its inventor) may allow some patients with dilated cardiomyopathy to avoid a heart transplant.

The procedure involves the following:

The surgeon first performs ventriculectomy, which is the removal of a section of healthy heart muscle weighing about 3 ounces.
The surgeon then reshapes the heart to a more normal size and form.
Any faulty heart valves are repaired.

Ventricular remodeling is still relatively new, and mortality rates are very high. Studies on long-term improvement are mixed. More research is needed to target the patients who would most benefit.

Patients who suffer from severe heart failure and whose symptoms do not improve with drug therapy or mechanical assistance may be candidates for heart transplantation. Some 3,600 people are awaiting a transplant, although only about 2,000 operations are performed each year.

The most important factor for heart transplant eligibility is overall health. Chronological age is less important. Most heart transplant candidates are between the ages of 50 – 64 years. About 72% of transplant patients are male, and 70% are white.

While the risks of this procedure are high, the 1-year survival rate is about 86% for men and 84% for women. The 3-year survival rate is 78% for men and 75% for women. Five years after a heart transplant, about 71% of men and 67% of women remain alive. In general, the highest risk factors for death 3 or more years after a transplant operation are coronary artery disease and the adverse effects (infection and certain cancers) of immunosuppressive drugs used in the procedure. The rejection rates in older people appear to be similar to those of younger patients.

In 2004, the FDA approved a temporary artificial heart (Syncardia) intended to keep patients alive in the hospital while they waited for a heart transplant. In 2006, the FDA approved the first permanent implantable artificial heart (AbiCor). The AbiCor is available only for patients who are not eligible for a heart transplant and who are not expected to live more than a month without medical treatment. The device requires a large chest cavity, which means that most women will not be eligible for it. Of the 14 men who have received the AbiCor, the average survival was less than 5 months after surgery. Only one patient was discharged from the hospital. The device’s manufacturer is working on a new model that it hopes will extend survival by as long as 5 years.

A growing array of heart devices and machines are changing the face of heart failure treatment. They have gained widespread acceptance for use as a bridge to transplant in patients who are on medications but still have severe symptoms and are awaiting a donor heart. Increasingly, though, doctors are exploring the possibility that such devices may be satisfactory treatments themselves, forestalling the need for a transplant altogether in some patients.

Ventricular Assist Devices (VADs). Ventricular assist devices are machines that help improve pumping actions. Several models with slightly different features are in use or under investigation. Some include the following:

Left ventricular assist device (LVAD) are used for patients whose heartbeat has slowed dangerously (a condition called bradycardia) to help take over the pumping action of the failing heart. Studies suggest that in some people the use of an LVAD may allow some of the damaged heart muscle to heal, perhaps even helping some patients avoid heart transplants. These devices are also being studied in combination with drug therapy to help recover heart function and improve patients’ chances for survival. Until recently, these machines required remaining in the hospital. Smaller battery-powered LVAD units, however, are allowing many patients to leave the hospital and are proving to be effective bridges to heart transplants in adults. The HeartMate, for example, a portable LVAD about the size of a portable CD player (2 in. by 4 in.), is implanted in the upper abdomen. The implanted device plugs into an external power base, which is used when the patient is at rest to recharge the battery and provide continuous power.
Fully implanted miniature artificial pumps that assist the heart (not replace it) are also being tested. The DeBakey ventricular assist device (VAD) for example, is a tiny heart pump that weighs less than 4 ounces. It has been approved in Europe and is being tested in the United States. The Jarvik 2000 heart pump is also showing promise.
The intra-aortic balloon pump (IABP) is helpful for maintaining heart function in people with left-side failure waiting for transplants and in those who develop a sudden and severe deterioration of heart function. The IABP is an implanted thin balloon that is usually inserted into the artery in the leg and threaded up to the aorta leading from the heart. Its pumping action is generated by inflating and deflating the balloon at certain rates. Usually, it is used only for short periods, but some studies indicate that patients may be able to use it safely for somewhat longer periods (an average duration of 23 days in one study).

There are risks involved with many of these devices, including bleeding, blood clots, and right-side heart failure. Infections are a particular hazard.

Pacers (Pacemakers). Pacers, or pacemakers, help regulate the heart’s beating action, especially when the heart beats too slowly. Biventricular pacers (BVPs) are a special type of pacemaker used for patients with heart failure. Because BVPs help the heart’s left and right chambers beat together, this treatment is called cardiac resynchronization therapy (CST). BVPs may particularly help heart failure patients who have left bundle branch block, a condition in which the electrical impulses in the heart do not follow their normal pattern. In general, BVPs are recommended for patients with moderate-to-severe heart failure. A small 2006 study suggested that a defibrillator may be better suited for patients with moderate heart failure, while indicating a BVP might be best for patients with severe heart failure.

Implantable Cardioverter-Defibrillators. Devices called implantable cardioverter-defibrillators (ICDs), which are sometimes combined with pacemakers, work well for preventing arrhythmias (abnormal heart rhythms) in heart failure patients. Studies have also found them effective in preventing sudden death from severe rhythm disturbances in patients with weakened hearts from previous arrhythmias and in patients with genetic hypertrophic cardiomyopathy. Patients who have an ICD should avoid taking fish oil supplements. A 2005 Journal of the American Medical Association study found that omega-3 fatty acid supplements may increase the risk of rapid heart beat (ventricular tachycardia) or irregular heart rhythm (ventricular fibrillation) in some of these patients.

ICDs have many benefits, and recent expert guidelines recommend that they be used in more patients with heart failure. However, in June 2005, certain ICD models and biventricular pacemaker-defibrillators were recalled by the manufacturer because of a circuitry flaw that prevents the devices from delivering therapeutic electrical shocks when needed. The problem may result in patient death. Although the FDA did not make any specific recommendations, the agency encourages patients who may have such a device to ask their doctor if they should have it removed or replaced.

In April 2006, two studies published in the Journal of the American Medical Association evaluated data concerning the safety and reliability of implantable pacemakers and defibrillators. The studies found that from 1990 – 2002, pacemakers became increasingly reliable. From 1998 – 2002, ICDs had a significantly higher rate of malfunction than pacemakers, although the reliability of ICDs appeared to improve from 2003 – 2004.

In October 2006, the U.S. Heart Rhythm Society issued recommendations for doctors, manufacturers, and the FDA to help improve communication concerning performance and recalls of ICDs and pacemakers. Experts stress that the chance of an ICD or pacemaker saving a person’s life far outweigh the possible risks of these devices failing.

Ultrafiltration devices are used in hospitals to pump excess water and salt from the body. Catheters are inserted into several of the patient’s veins. The catheters are connected to a blood filter device. Blood is withdrawn through one of the catheters and filtered in the device to remove excess fluid. The filtered blood is then returned to the patient through another catheter. A 2006 study reported that ultrafiltration devices may work better than diuretic drugs for patients with acute decompensated heart failure (ADHF). ADHF is heart failure that has rapidly deteriorated so that patients require immediate hospitalization.

Lifestyle Changes

Between 30 - 47% of patients who require hospitalization for heart failure are back in the hospital within 6 months. Many people return because of lifestyle factors such as poor diet, failure to comply with medications, and social isolation.

In one study, elderly people who had no emotional support at home had triple the risk of a heart attack after hospitalization for heart failure than those who did have such support. (Women had eight times the risk.) In another study, the greatest risk factor for death and readmission to the hospital after a first hospitalization was being single, regardless of the health of the patient at discharge. A third study confirmed that a strong marriage predicted long-term survival. Evidence continues to mount that programs that offer intensive follow-up to ensure that the patient complies with lifestyle changes and medication regimens at home are reducing rehospitalization rates and improving survival. Patients without available rehabilitation programs should seek support from local and national heart associations and groups.

Patients should weigh themselves each morning and keep a record. Any changes are important:

A sudden increase in weight of more than 2 - 3 pounds may indicate fluid accumulation and should prompt an immediate call to the doctor.
Rapid wasting weight loss over a few months is a very serious sign and may indicate the need for surgical intervention.

Whole Grains. Evidence suggests that daily consumption of whole grain foods may help prevent heart failure. In research presented at a 2007 American Heart Association conference, people who ate whole-grain breakfast cereals seven or more times a week had a 28% lower risk of developing heart failure than those who never ate these cereals.

Mediterranean Diet. Evidence suggests that the Mediterranean diet helps protect the heart and may even reduce the risk for heart failure after a first heart attack. The diet emphasizes whole grains, fish, olive oil, garlic, and moderate daily intake of wine. There are several variations to the Mediterranean diet but general recommendations include:

Limit red meats.
Limit dairy products.
Eat moderate amounts of fish and poultry. Fish is the diet’s main protein source. Some studies suggest that fish is the primary heart-protective ingredient in this diet. However, patients who have an implantable defibrillator should not take fish oil supplements. A 2005 study suggested that these supplements may worsen heart rhythm problems in some patients.
Eat plenty of fresh fruits and vegetables, nuts, legumes, beans, and whole grains.
Daily glass or two of wine. Light-to-moderate alcohol use may reduce the risk for heart failure, (but heavy alcohol consumption is a risk factor).
Plenty of fresh fruits and vegetables, as well as nuts, legumes, beans, and whole grains.

DASH Diet. The Dietary Approaches to Stop Hypertension (DASH) diet is an important lifestyle step in managing blood pressure. It may also be useful for many patients with heart failure. This diet is not only rich in important nutrients and fiber but also includes foods that contain two and a half times the amounts of electrolytes, potassium, calcium, and magnesium found in the average American diet.

Potassium-rich foods, which are important for patients with heart failure, include bananas, oranges, prunes, cantaloupes, carrots, spinach, celery, alfalfa, mushrooms, lima beans, potatoes, avocados, and broccoli. However, patients who take potassium-sparing diuretics or ACE inhibitors, and those with kidney dysfunction, may have to restrict their potassium intake.

The DASH diet is rich in whole grains and fresh fruits and vegetables. It stresses avoiding saturated fats, as any healthy diet does, although it includes calcium-rich dairy products that are non- or low-fat. When choosing fats, the diet recommends monounsaturated oils such as olive or canola oil.

Salt Restriction. People with high blood pressure are generally urged to restrict salt, although certain people may be more susceptible to its effects. For example, a high intake of salt may be an independent risk factor for the development of heart failure in people who are overweight. All patients with heart failure should limit their salt intake, and in severe cases, very stringent salt restriction may be necessary. Patients should not add salt to their cooking and their meals. They should also avoid foods high in sodium. These salty foods include ham, bacon, hot dogs, lunch meats, prepared snack foods, dry cereal, cheese, canned soups, soy sauce, and condiments. Some patients may need to reduce their water intake as well. People with high cholesterol levels or diabetes require additional dietary precautions. [See In-Depth Report #43: Heart-healthy diet. ]

People with heart failure used to be discouraged from exercising. Now, experts think that exercise, when performed under medical supervision, is extremely important for many patients with stable conditions. Studies have reported that patients with stable conditions who engage in regular moderate exercise (three times a week) experience a better quality of life and lower mortality rates than those who do not exercise.

The following guidelines are critical:

Experts warn that exercise is not appropriate for all patients with heart failure. If you have heart failure, always consult your doctor before starting an exercise program.
People who are approved for, but not used to, exercise should start with 5 - 15 minutes of easy exercise with frequent breaks. Although the goal is to build up to 30 - 45 minutes of walking, swimming, or low-impact aerobic exercises three to five times every week, even shorter times spent exercising are useful.

Studies report benefits from specific exercises:

Progressive strength training may be particularly useful for patients with heart failure since it strengthens muscles, which commonly deteriorate in this disorder. Strength training typically uses light weights, weight machines, or even the body's weight (leg raises or sit-ups, for example). Even performing daily handgrip exercises can improve blood flow through the arteries.
Patients who exercise regularly using supervised treadmill and stationary-bicycle exercises can increase their exercise capacity by 14 - 36%. In one study, patients as old as 91 years increased their oxygen consumption significantly after 6 months of supervised treadmill and stationary bicycle exercises. Exercising the legs may help correct problems in heart muscles. In one study, patients who did leg extension exercises for 8 weeks had higher levels of an enzyme involved in forming new blood vessels. Exercise has also been associated with reduced inflammation in blood vessels.
Dancing may be a fun and beneficial alternative to standard aerobic exercise, according to research presented at the 2006 annual meeting of the American Heart Association. In a study of patients with stable chronic heart failure, dancing helped improve cardiopulmonary fitness, arterial elasticity, and quality of life. Patients in the study danced fast and slow waltzes for 21 minutes, three times a week.

Bed rest may be required in cases of severe heart failure. To reduce congestion in the lungs, the patient's upper body should be elevated. For most patients, resting in an armchair is better than lying in bed. Relaxing and contracting leg muscles is important to prevent clots. As the patient improves, a doctor will progressively recommend more activity.

Experts have traditionally recommended that people with heart failure avoid warm baths, which can increase the heart rate. Some studies now report that carefully controlled bathing for short periods may not be harmful and may actually be beneficial, reducing irregular heart beats and increasing cardiac output and ejection fraction. Warm water may behave like a vasodilating drug, opening up the vessels gently and improving circulation. In clinical trials, patients sat in warm water or a dry sauna for 10 minutes, with their bodies tilted at a 45 degree angle.

Warning Note: Prolonged periods in hot or even warm conditions can be dangerous. Any patient with heart failure should consult their doctor first, not bathe unaccompanied, and be sure that the temperature does not go above 106° Fahrenheit for water bathing or 140° Fahrenheit for dry saunas.

Stress reduction techniques, such as meditation and relaxation response methods, may have direct physical benefits for lowering stress hormones. These hormones include cortisol, which suppresses the immune system, and norepinephrine (also known as adrenaline), the chemical messenger associated with heart dysfunction.

Patients with heart failure may resort to alternative remedies. Such remedies are often ineffective and may have severe or toxic effects. Of particular note for patients with heart failure is an interaction between St. John's wort (an herbal medicine used for depression) and digoxin (a heart drug). St. John's wort can significantly interfere with this drug.

Arginine. Some evidence suggests that arginine (also called L-arginine) may have some benefit. This amino acid appears to reduce endothelin, a protein that causes blood vessel constriction and is found in high amounts in patients with heart failure. It can have adverse effects, however, including gastrointestinal problems. It can also lower blood pressure and change levels of certain chemicals and electrolytes in the body. It may increase the risk for bleeding. Some people have an allergic reaction to it, which in same cases may be severe. It may worsen asthma.

Coenzyme Q10 and Vitamin E. Small studies have suggested that coenzyme Q10 (CoQ10) may help patients with heart failure, particularly when combined with vitamin E. CoQ10 is a vitamin-like substance found in organ meats and soybean oil. More recent studies, however, have found that CoQ10 and vitamin E do not help the heart or prevent heart disease. According to a 2005 Journal of the American Medical Association study, vitamin E supplements can actually increase the risk of heart failure, especially for patients with diabetes or vascular diseases.

Crataegus Extract. An herbal remedy, Crataegus Extract WS1442, which is made from the leaves of the Crataegus tree, may have antioxidant properties that can help patients with heart failure. In a study presented at the 2007 American College of Cardiology annual meeting, over 2,000 patients with severe heart failure were randomized to receive either Crataegus Extract or placebo (plus standard drug treatment) for 2 years. The researchers noted a 20% reduction in heart-related deaths among patients who received the extract, and suggested that the herb extended patients’ lives by 4 months during the first 18 months of the study.

Other Vitamins and Supplements. A wide variety of other vitamins (thiamin, B6, and C), minerals (calcium, magnesium, zinc, manganese, copper, selenium), nutritional supplements (carnitine, creatine), and herbal remedies (hawthorn) have been proposed as treatments for heart failure. None have been adequately tested. There is no evidence that a particular vitamin or supplement can cure heart failure. In any case, vitamins are best consumed through the food sources contained in a healthy diet.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been several reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

Resources

www.nhlbi.nih.gov -- National Heart, Lung, and Blood Institute
www.americanheart.org -- American Heart Association
www.acc.org -- American College of Cardiology
www.hfsa.org -- Heart Failure Society of America
www.heartfailure.org -- Heart Failure Online
www.unos.org -- United Network for Organ Sharing
www.organdonor.org -- National Transplant Society
www.organdonor.gov -- US government organ donor site

References

Ahmed A, Rich MW, Fleg JL, Zile MR, Young JB, Kitzman DW, et al. Effects of digoxin on morbidity and mortality in diastolic heart failure: the ancillary digitalis investigation group trial. Circulation. 2006 Aug 1;114(5):397-403.

Battaglia M, Pewsner D, Juni P, Egger M, Bucher HC, Bachmann LM. Accuracy of B-type natriuretic peptide tests to exclude congestive heart failure: systematic review of test accuracy studies. Arch Intern Med. 2006 May 22;166(10):1073-80.

Bhatia RS, Tu JV, Lee DS, Austin PC, Fang J, Haouzi A, et al. Outcome of heart failure with preserved ejection fraction in a population-based study. N Engl J Med. 2006 Jul 20;355(3):260-9.

Birks EJ, Tansley PD, Hardy J, George RS, Bowles CT, Burke M, et al. Left ventricular assist device and drug therapy for the reversal of heart failure. N Engl J Med. 2006 Nov 2;355(18):1873-84.

Bursi F, Weston SA, Redfield MM, Jacobsen SJ, Pakhomov S, Nkomo VT, et al. Systolic and diastolic heart failure in the community. JAMA. 2006 Nov 8;296(18):2209-16.

Carlson MD, Wilkoff BL, Maisel WH, Carlson MD, Ellenbogen KA, Saxon LA, et al. Recommendations from the Heart Rhythm Society Task Force on Device Performance Policies and Guidelines Endorsed by the American College of Cardiology Foundation (ACCF) and the American Heart Association (AHA) and the International Coalition of Pacing and Electrophysiology Organizations (COPE). Heart Rhythm. 2006 Oct;3(10):1250-73.

Davis BR, Piller LB, Cutler JA, Furberg C, Dunn K, Franklin S, et al. Role of diuretics in the prevention of heart failure: the Antihypertensive andLipid-Lowering Treatment to Prevent Heart Attack Trial. Circulation. 2006 May 9;113(18):2201-10. Epub 2006 May 1.

Gheorghiade M, Abraham WT, Albert NM, Greenberg BH, O'Connor CM, She L, et al. Systolic blood pressure at admission, clinical characteristics, and outcomes inpatients hospitalized with acute heart failure. JAMA. 2006 Nov 8;296(18):2217-26.

Gheorghiade M, Konstam MA, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Short-term clinical effects of tolvaptan, an oral vasopressin antagonist, in patients hospitalized for heartfFailure: the EVEREST clinical status trials. JAMA. 2007 Mar 25; [Epub ahead of print]

Go AS, Lee WY, Yang J, Lo JC, Gurwitz JH. Statin therapy and risks for death and hospitalization in chronic heart failure. JAMA. 2006 Nov 1;296(17):2105-11.

Hildebrandt P. Systolic and nonsystolic heart failure: equally serious threats. JAMA. 2006 Nov 8;296(18):2259-60.

Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007 Mar 25; [Epub ahead of print]

Lee DS, Pencina MJ, Benjamin EJ, Wang TJ, Levy D, O'Donnell CJ, et al. Association of parental heart failure with risk of heart failure in offspring. N Engl J Med. 2006 Jul 13;355(2):138-47.Maisel WH. Pacemaker and ICD generator reliability: meta-analysis of device registries. JAMA. 2006 Apr 26;295(16):1929-34.

Maisel WH, Moynahan M, Zuckerman BD, Gross TP, Tovar OH, Tillman DB, et al. Pacemaker and ICD generator malfunctions: analysis of Food and Drug Administration annual reports. JAMA. 2006 Apr 26;295(16):1901-6.

Mueller C, Laule-Kilian K, Schindler C, Klima T, Frana B, Rodriguez D, et al. Cost-effectiveness of B-type natriuretic peptide testing in patients with acute dyspnea. Arch Intern Med. 2006 May 22;166(10):1081-7.

Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med. 2006 Jul 20;355(3):251-9.

Review Date:
4/11/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Diabetes - type 2

FitSugar — Wed, 08 Oct 2008 17:34:58 -0700

In This Report

Highlights
Introduction
Causes
Risk Factors
Symptoms
Screening Tests
Treatment
Lifestyle Changes
Medications
Long-Term Complications
Emergency Complications
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

Sitagliptin (Januvia), the first in a new class of diabetes drugs called DPP-4 inhibitors, was approved in 2006.
Janumet, a 2-in-1 pill that contains both sitagliptin and metformin, was approved in 2007.
These drugs are taken by mouth and may be more convenient for patients than exenatide (Byetta), a similar drug. DPP-4 inhibitors do not cause weight gain and may pose a lower risk for hypoglycemia than some other diabetes drugs.

Drug Safety Alert

Rosiglitazone (Avandia) may significantly increase the risk for heart attack, indicates a review published in the Journal of the American Medical Association. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Rosiglitazone and a similar drug, pioglitazone (Actos), are known to significantly increase the risks for heart failure. There is also evidence that these drugs increase the risk for bone fracture.

Anemia Drugs Warning

Patients with anemia associated with end-stage kidney disease, especially those on dialysis, should be aware of new warnings concerning dosing target levels of erythpoiesis-stimulating drugs. In 2007, the FDA warned that darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit) can increase the risk for blood clots, stroke, and heart attacks when excessive doses are given. The FDA has defined target hemoglobin levels and recommends that patients who receive these drugs have frequent blood tests. Patients should also report to their doctors any unusual symptoms.

Genetics Research Breakthroughs

Scientists have now identified 10 genes that are associated with increased risk for type 2 diabetes. Six of these genes were discovered in 2006 and 2007.

Diabetes and Pre-Diabetes

About 20 million Americans have type 2 diabetes, and an additional 54 million have pre-diabetes. According to a 2007 study by the U.S. Centers for Disease Control, the prevalence of type 2 diabetes has been increasing by 5% each year since 1990. Rising rates of obesity may be one factor.
For people with pre-diabetes, lifestyle changes, such as losing weight, appear to work as well as drug treatment in delaying the progression to diabetes, according to a 2007 British Medical Journal study.

Introduction

The two major forms of diabetes are type 1 (previously called insulin-dependent diabetes mellitus, IDDM, or juvenile-onset diabetes) and type 2 (previously called noninsulin-dependent diabetes mellitus, NIDDM, or maturity-onset diabetes).

Both type 1 and type 2 diabetes share one central feature: elevated blood sugar (glucose) levels due to insufficiencies of insulin, a hormone produced by the pancreas. Insulin is a key regulator of the body's metabolism. It works in the following way:

During and immediately after a meal the process of digestion breaks down carbohydrates into sugar molecules (including glucose) and proteins into amino acids.
Right after the meal, glucose and amino acids are absorbed directly into the bloodstream, and blood glucose levels rise sharply.
The rise in blood glucose levels signals important cells in the pancreas, called beta cells, to secrete insulin, which pours into the bloodstream. Within 10 minutes after a meal, insulin rises to its peak level.
Insulin enables glucose and amino acids to enter cells in the body, particularly muscle and liver cells. Here, insulin and other hormones direct whether these nutrients will be burned for energy or stored for future use. (The brain and nervous system are not dependent on insulin; they regulate their glucose needs through other mechanisms.)
When insulin levels are high, the liver stops producing glucose and stores it in other forms until the body needs it again.
As blood glucose levels reach their peak, the pancreas reduces the production of insulin.
About 2 - 4 hours after a meal, both blood glucose and insulin are at low levels, with insulin being slightly higher. The blood glucose levels are then referred to as fasting blood glucose concentrations.

The pancreas is located behind the liver and is where the hormone insulin is produced. Insulin is used by the body to store and utilize glucose.

Type 2 diabetes is the most common form of diabetes, accounting for 90 - 95% of cases. The disease mechanisms in type 2 diabetes are not wholly known, but some experts suggest that it may involve the following three stages in most patients:

The first stage in type 2 diabetes is the condition called insulin resistance. Although insulin can attach normally to receptors on liver and muscle cells, certain mechanisms prevent insulin from moving glucose (blood sugar) into these cells where it can be used. Most patients with type 2 diabetes produce variable, even normal or high, amounts of insulin. In the beginning, this amount is usually sufficient to overcome such resistance.
Over time, the pancreas becomes unable to produce enough insulin to overcome resistance. In type 2 diabetes, the initial effect of this stage is usually an abnormal rise in blood sugar right after a meal (called postprandial hyperglycemia). This effect is now believed to be particularly damaging to the body.
Eventually, the cycle of elevated glucose further impairs and possibly destroys beta cells, thereby stopping insulin production completely and causing full-blown diabetes. This is made evident by fasting hyperglycemia, in which elevated glucose levels are present most of the time.

In type 1 diabetes, the disease process is more severe and onset is usually in childhood:

Beta cells in the pancreas that produce insulin are gradually destroyed. Eventually insulin deficiency is absolute.
Without insulin to move glucose into cells, blood glucose levels become excessively high, a condition known as hyperglycemia.
Because the body cannot utilize the sugar, it spills over into the urine and is lost.
Weakness, weight loss, and excessive hunger and thirst are among the consequences of this "starvation in the midst of plenty."
Patients become dependent on administered insulin for survival. [See In-Depth Report #9: Diabetes - type 1.]

Click the icon to see an image of the pancreas.

Conditions that damage or destroy the pancreas, such as pancreatitis, pancreatic surgery, or certain industrial chemicals can cause diabetes. Polycystic ovaries are highly associated with diabetes. Certain drugs can also cause temporary diabetes, including corticosteroids, beta-blockers, and phenytoin. Rare genetic disorders (Klinefelter's syndrome, Huntington's chorea, Wolfram's syndrome, leprechaunism, Rabson-Mendenhall syndrome, lipoatrophic diabetes) and hormonal disorders (acromegaly, Cushing syndrome, pheochromocytoma, hyperthyroidism, somatostatinoma, aldosteronoma) are associated with or increase the risk for diabetes.

Causes

Type 2 diabetes is caused by a complicated interplay of genes, environment, insulin abnormalities, increased glucose production in the liver, increased fat breakdown, and possibly defective hormonal secretions in the intestine. The recent dramatic increase indicates that lifestyle factors (obesity and sedentary lifestyle) may be particularly important in triggering the genetic elements that cause this type of diabetes.

The characteristic features of most patients with type 2 diabetes are:

Insulin resistance in muscle cells
Normal or even excessive levels of insulin (to compensate for this resistance), eventually followed by a drop in insulin production

In addition, researchers are trying to determine the factors that might promote insulin resistance:

Both obesity and insulin resistance at different phases are marked by elevated levels of free fatty acids and the hormones resistin and leptin. It is not known yet if elevated levels are simply a product of obesity or play some causal role in diabetes.
Insulin resistance is associated with a chronic low inflammatory response, which involves a number of immune factors, such as TGH-beta 1 and C-reactive protein. Such factors can cause damage over time and may be responsible for the association between insulin resistance and heart disease.

Type 2 diabetes has a genetic component. In 2006 and 2007, major breakthroughs in genetic research identified six new genes associated with type 2 diabetes. Ten genes have now been positively confirmed as increasing the risk for type 2 diabetes: TCF7L2, SLC30A8, HHEX, PPARG, KCNJ11, IGF2B2, CDKAL1, CDKN2A, CDKN2B, and FTO.

Most of these genes play a role in regulating insulin action, including the processes that occur in the pancreas’ insulin-producing beta cells. The FTO gene increases the risk for obesity, which itself is a risk factor for type 2 diabetes. These genes appear to cluster around three genetic regions that include a number of chromosomes. Scientists hope that future research will help uncover how genes influence the progression from pre-diabetes to diabetes, and how lifestyle and medical intervention may help delay or prevent this process.

Risk Factors

Nearly 21 million Americans have diabetes; up to 95% of these cases are type 2. In addition, 26% of Americans age 20 and older (and 40% of Americans age 65 and older) have impaired fasting glucose, a pre-diabetes condition that increases the risk for diabetes. According to the American Diabetes Association, 54 million people have pre-diabetes, bringing a total of 75 million Americans who either have diabetes or are at risk of developing it.

Historically, type 2 diabetes usually developed after the age of 40, but it is now also increasing in children. The prevalence of diabetes in the U.S. has increased by 5% each year since 1990, and experts believe that obesity is the major factor behind this dramatic growth rate. Given the current epidemic of obesity, experts estimate that over a third of all people born in 2002 will eventually develop diabetes. Furthermore, the dramatic increase in diabetes is occurring worldwide as American lifestyles become global. Evidence strongly suggests that healthy lifestyles can prevent most cases of type 2 diabetes. People with pre-diabetes can substantially lower their risk by losing weight through diet and exercise.

Healthy adults age 45 and older should get tested for diabetes. Patients who are younger than age 45 and who are overweight or have other risk factors should also ask their doctors about testing. According to the National Institutes of Health, the following are major risk factors for diabetes and pre-diabetes:

Age 45 or older
Family history of diabetes
Overweight
Inactive lifestyle (exercise less than 3 times a week)
African-American, Hispanic/Latin American, American Indian and Alaska Native, Asian-American, or Pacific Islander ethnicity
High blood pressure (140/90 mm/Hg or higher)
HDL (“good”) cholesterol less than 35 mg/dL or triglyceride level 250 mg/dL or higher
Have had diabetes during pregnancy (gestational diabetes) or have given birth to a baby that weighed more than 9 pounds
Polycystic ovary syndrome (metabolic disorder that affects female reproductive system
Acanthosis nigricans (dark, thickened skin around neck or armpits)
History of disease of blood vessels to the heart, brain, or legs
Diabetes test history of impaired fasting glucose (IFG) or impaired glucose tolerance (IGT)

Obesity is the number one risk factor for type 2 diabetes. It is estimated that 80 - 95% of the current dramatic increases in type 2 diabetes are due to obesity. Excess body fat appears to play a strong role in insulin resistance, but the way the fat is distributed is also significant. Weight concentrated around the abdomen and in the upper part of the body (apple-shaped) is associated with insulin resistance and diabetes, heart disease, high blood pressure, stroke, and unhealthy cholesterol levels. Waist circumferences greater than 35 inches in women and 40 inches in men have been specifically associated with a greater risk for heart disease and diabetes. (People with a "pear-shape" -- fat that settles around the hips and flank -- appear to have a lower risk for with these conditions.) However, obesity does not explain all cases of type 2 diabetes. It is also common among people in countries where weights tend to be low, such as Asia or India.

Metabolic Syndrome. A set of conditions referred to as metabolic syndrome (also called Syndrome X) is a pre-diabetic condition that is significantly associated with heart disease and higher mortality rates from all causes. The syndrome consists of obesity marked by abdominal fat, unhealthy cholesterol levels, high blood pressure, and insulin resistance. A 2002 study estimated that nearly a quarter of the U.S. population now has this condition. Even worse, according to a 2003 study, nearly a million American teenagers have this syndrome.

Between 25 - 33% of patients with type 2 diabetes have family members with diabetes. Having a first-degree relative with the disease poses a 40% risk of developing diabetes. One study reported that people with diabetic family histories have a higher risk for developing the disease at an earlier stage and with more severe features. Because families share many lifestyle features (eating and exercise habits) it is difficult to determine when genetics or environment play the major role. When clusters of type 1 and type 2 diabetes appear within families, genetic factors should be strongly suspected.

The risk for type 2 diabetes varies among population groups. Diabetes also seems to pose higher or lower risks for specific complications among ethnic groups. Genetic and socioeconomic factors, or both, seem to be involved in some ethnic differences, but in most cases the observed increase in ethnic groups in Americans is due to changes in traditional lifestyles.

African-Americans. African-American men have twice the risk of developing type 2 diabetes as Caucasian men. African-Americans with diabetes are also at higher risk for amputations than Caucasians. This is most likely due to a higher incidence of high blood pressure and smoking as well as poorer health care in African-Americans. Genetic factors may also play a role. For example, there is some evidence that African-Americans process insulin in the liver differently from Caucasians, which may make them more susceptible to diabetes when other risk factors are present.
Native Americans. The Pima tribe in Arizona has an incidence of type 2 diabetes that is 19 times higher than that of the white population. The risk for diabetic complications among young Pima adults is also very high. Other Native American tribes in North America are also at high risk for type 2 diabetes. The association between diet and diabetes among this population remains critical, however, in assessing the reason for their higher risk. For example, Pimas who live in Mexico exercise more and eat less fat (but consume more calories) than Pima tribes in Arizona. Mexican Pimas have a prevalence of diabetes of only 6%, while half of their Arizona Pima neighbors have diabetes.
Hispanic Americans. The rate of type 2 diabetes is also very high among Mexican-Americans, approximately double that for Caucasians. This group may also be at higher risk for heart problems than other ethnic groups with diabetes.
Asian-Americans. Overweight Asian-Americans and Pacific Islanders are at increased risk for developing type 2 diabetes. The risk for some Asian ethnic groups (such as Native Hawaiians and Filipinos) is twice that of Caucasians.

Smoking increases the risk for diabetes. According to a 2006 study, smokers are more than twice as likely to develop diabetes as people who have never smoked. Another 2006 study found that exposure to second-hand cigarette smoke also increases the risk for diabetes in non-smokers.

Low birth weight is now a recognized risk factor for type 2 diabetes and heart disease in adulthood. The reasons are unclear, although studies suggest it may represent a genetic factor. Studies have observed that babies of fathers with type 2 diabetes and of women who later developed type 2 diabetes tend to weigh less than babies of parents without diabetes. Such studies suggest that some parents may have some specific gene that affects insulin factors, putting both themselves and their children at risk for future diabetes. Theoretically, such a gene might also affect insulin factors in the developing fetus, causing low birth weight. (Of note, mothers of very high-weight babies are also at risk for diabetes -- although in these cases it is most often associated with gestational diabetes.)

Obesity-Related Type 2 Diabetes in Children. Until recent years, diabetes in children was almost always type 1 (an autoimmune disease). Between 1982 - 1994, however, the incidence of type 2 diabetes in children increased 10-fold. By 1996, a study reported that a third of all new diabetes cases in children were type 2. This increase parallels the rising epidemic in childhood obesity that has occurred both in the U.S. and worldwide, notably Europe and Japan. In some areas of Japan, type 2 diabetes has now become the dominant form of diabetes in children and adolescents. Obesity in children is also related to abnormalities in cholesterol, blood pressure, and insulin levels in adults. Administering glucose tolerance tests in overweight children may be helpful in identifying those at high risk for diabetes.

Maturity-Onset Diabetes in Caucasian Youth. Maturity-onset diabetes in youth (MODY) is a rare genetic form of type 2 diabetes that develops only in Caucasian teenagers. It accounts for 2 - 5% of type 2 cases. (This form of type 2 diabetes is not associated with obesity.)

An estimated 5% of pregnant women develop a form of type 2 diabetes, usually temporary, in their third trimester called gestational diabetes.

Gestational diabetes is diabetes that first appears during pregnancy. It usually develops during the third trimester of pregnancy. After delivery, blood sugar (glucose) levels generally return to normal, although 25% of these women develop type 2 diabetes within 15 years.

Who Gets Gestational Diabetes? Estimates for the prevalence of gestational diabetes are generally about 4%. Some studies, however, have suggested significantly higher rates. In one German study, 13% of pregnant women were diagnosed with this form of diabetes, including many who did not have any risk factors.

A pregnant woman's risk factors include:

Family history of diabetes
African-American, Hispanic, Asian, or Pacific Islander ethnicity
Overweight
Older than 25 years
Gestational diabetes with past pregnancy
Having given birth to a child weighing over 9 pounds
Diagnosis of pre-diabetes

Who Should Be Tested for Gestational Diabetes? A number of expert groups recommend that all pregnant women be tested for gestational diabetes between their 24th - 28th week. Pregnant women at high risk for diabetes should be tested earlier. The only women who do not need to be tested are those at very low risk. Generally they have the following characteristics:

Under 25 years old
Normal weight
No first-degree relatives with diabetes
Not belonging to high-risk ethnic groups

Effect of Diabetes on the Fetus. Because glucose crosses the placenta, a woman with diabetes can pass high levels of blood glucose to the fetus. In response, the fetus secretes high level of insulin. Studies indicate that such conditions may affect the developing fetus as soon as it is conceived, placing the unborn child at risk for:

Excessive fetal weight gain, which can lead to complications during delivery
Birth defects
Breathing problems and delayed lung development
Low blood sugar
Higher future risk for obesity and diabetes

Effect of Diabetes on the Pregnant Woman. In addition to endangering the fetus, diabetes also presents risks to the pregnant woman.

The most serious potential complications from gestational diabetes are high blood pressure during pregnancy, a condition called preeclampsia that is potentially dangerous. Because gestational diabetes increases the size of the fetus, it is also increases the likelihood that a woman will require a Cesarean delivery. Gestational diabetes also increases the risk that a woman will later develop type 2 diabetes.

How Is Gestational Diabetes Managed? Some suggestions for preventing complications include:

In most cases, increases in glucose levels can be managed with diet and exercise. Aerobic exercise before and during pregnancy may lower glucose levels and help protect women at risk or those who have gestational diabetes. (Any pregnant woman should check with her doctor before embarking on a vigorous exercise regimen.)
If a woman with gestational diabetes cannot control her glucose with lifestyle measures, she is usually given insulin.

The placenta provides the fetus with oxygen and nutrients and takes away waste, such as carbon dioxide, via the umbilical cord.

Polycystic Ovary Syndrome. Polycystic ovary syndrome (PCOS) is a condition that affects about 6% of women and results in the ovarian production of high amounts of androgens (male hormones), particularly testosterone. It appears to be an important cause of many menstrual disorders. Women with PCOS are at higher risk for insulin resistance, and about half of PCOS patients also have diabetes.

Click the icon to see an image of polycystic ovary syndrome.

Schizophrenia. While no definitive association has been established, research has suggested an increased background risk of diabetes among people with schizophrenia. In addition, many of the new generation of antipsychotic medications may elevate blood glucose levels. Patients taking antipsychotic medications (such as clozapine, olanzapine, risperidone, aripiprazole, quetiapine fumarate, ziprasidone) should receive a baseline blood glucose level test and be monitored for any increases during therapy.

Depression. According to a 2007 study, adults who have severe clinical depression may have a greater risk of developing type 2 diabetes than those who have never experienced depressive symptoms.

Hepatitis C. Patients with hepatitis C have a higher incidence of type 2 diabetes. The reasons for this are unclear.

Symptoms

Type 2 diabetes usually begins gradually and progresses slowly. Symptoms in adults include:

Excessive thirst
Increased urination
Fatigue
Blurred vision
Weight loss
In women, vaginal yeast infections or fungal infections under the breasts or in the groin
Severe gum problems
Itching
Erectile dysfunction in men
Unusual sensations, such as tingling or burning, in the extremities

Symptoms in children are often different:

Most children are obese or overweight
Increased urination is mild or even absent
Many children develop a skin problem called acanthosis, which is characterized by velvety, dark colored patches of skin

Screening Tests

There are no clear-cut guidelines for when to screen for diabetes. Some experts recommend that everyone over age 45 be tested regularly for diabetes, although others do not feel this necessary in people without symptoms or risk factors. In fact, early screening may identify some people with impaired glucose levels that would eventually normalize. Such people might be treated unnecessarily with medications that pose a risk for high blood sugar (hypoglycemia).

Still, given the risk for serious complications with diabetes and the potential value of early treatments, most experts recommend that all adults over 45 be screened and that younger adults be screened if they have one or more of the following conditions:

A weight that is 20% more than ideal body weight
Risk factors for heart disease (high blood pressure, unhealthy cholesterol levels -- especially for patients with low HDL cholesterol and high triglyceride levels
A close relative with diabetes
A high-risk ethnic group background
In women, having delivered a baby weighing over 9 pounds or having a history of gestational diabetes

Some experts recommend that children over age 10 should be tested for type 2 diabetes (even if they have no symptoms), if they are overweight and have at least two of the above mentioned risk factors.

Fasting Plasma Glucose. The fasting plasma glucose (FPG) test is the standard test for diabetes. It is a simple blood test taken after 8 hours of fasting. Results indicate:

FPG levels are considered normal up to 100 mg/dL (or 5.5 mmol/L).
Levels between 100 - 125 mg/dL (5.5 - 7.0 mmol/L) are referred to as impaired fasting glucose or pre-diabetes. These levels are considered to be risk factors for type 2 diabetes and its complications.
Diabetes is diagnosed when FPG levels are 126 mg/dL (7.0 mmol/L) or higher.

The FPG test is not always reliable, so a repeat test is recommended if the initial test suggests the presence of diabetes, or if the test is normal in people who have symptoms or risk factors for diabetes. For example, people who take the test in the afternoon and show normal results may actually have abnormal levels that would be revealed if they were tested in the morning.

A 2005 study suggested that even people with FPG levels in the high end of the normal range (high 90s) may be at increased risk for developing type 2 diabetes. Obesity further increases this risk. Patients with FPG levels in the upper 90s should strive to exercise and lose weight to help lower their FPG levels.

Glucose Tolerance Test. The oral glucose tolerance test (OGTT) is more complex than the FPG and may overdiagnose diabetes in people who do not have it. Some experts recommend it as a follow-up after FPG, if the latter test results are normal but the patient has symptoms or risk factors of diabetes. The test uses the following procedures:

It first uses an FPG test.
A blood test is then taken 2 hours later after drinking a special glucose solution.

The following results suggest different conditions:

OGTT levels are considered normal up to 140 mg/dL.
Levels between 140 - 199 mg/dL are referred to as impaired glucose tolerance or pre-diabetes.
Diabetes is diagnosed when OGTT levels are 200 mg/dL or higher.

Both the FPG and OGTT require that the patient not eat for at least 8 hours prior to the test.

Test for Glycated Hemoglobin. Tests for blood levels of glycated hemoglobin, also known as hemoglobin A1c (HbA1c), are not currently used for an initial diagnosis, but they are useful for determining the severity of diabetes. Some experts think this test can help predict complications in people who have FPG levels between 110 - 139, which are above normal but do not indicate full-blown diabetes.

The basis for its use as a diagnostic measurement in diabetes is as follows:

Hemoglobin is a protein molecule found in red blood cells. When glucose binds to it, the hemoglobin becomes modified, a process called glycosylation.
Glycosylation affects a number of proteins, and elevated levels of glycolated hemoglobin are strongly associated with complications of diabetes.
A glycated hemoglobin level of 1% above normal range identifies diabetes in 98% of patients. Normal HbA1c levels do not necessarily rule out diabetes, but if diabetes is present and levels are normal, the risk for complications is low.

The test is not affected by food intake so it can be taken at any time. A home test has been developed that might make it easier to measure HbA1c. In general, measurements suggest the following:

Normal HbA1c levels should be below 7%.
Levels of 11 - 12% glycolated hemoglobin indicate poor control of carbohydrates. High levels are also markers for kidney trouble.

Screening for Heart Disease. All patients with diabetes should be tested for hypertension and unhealthy cholesterol and lipid levels and given an electrocardiogram. For cholesterol, people with diabetes should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL, and triglyceride levels below 150 mg/dL. Blood pressure goals should be 130/80 mmHg or lower. Other tests may be needed in patients with signs of heart disease.

The electrocardiogram (ECG, EKG) is used extensively in the diagnosis of heart disease, from congenital heart disease in infants to myocardial infarction and myocarditis in adults. Several different types of electrocardiogram exist.

Screening for Kidney Damage. The earliest manifestation of kidney damage is microalbuminuria, in which tiny amounts (30 - 300 mg per day) of protein called albumin are found in the urine. About 20% of type 2 patients show evidence of microalbuminuria upon diagnosis of diabetes. (However, not all people with type 2 diabetes eventually develop kidney disease.) Microalbuminuria typically shows up in patients with type 2 diabetes who have high blood pressure.

The American Diabetes Association recommends that people with diabetes receive an annual microalbuminuria urine test. Patients should also have their blood creatinine tested at least once a year. Creatinine is a waste product that is removed from the blood by the kidneys. High levels of creatinine may indicate kidney damage. A doctor uses the results from a creatinine blood test to calculate the glomerular filtration rate (GFR). The GFR is an indicator of kidney function; it estimates how well the kidneys are cleansing the blood.

Screening for Retinopathy. The American Diabetes Association recommends that patients with type 2 diabetes get an initial comprehensive eye exam by an ophthalmologist or optometrist shortly after they are diagnosed with diabetes, and once a year thereafter. (People at low risk may need follow-up exams only every 2 - 3 years.) The eye exam should include dilation to check for signs of retinal disease (retinopathy).

Screening for Neuropathy. All patients should be screened for nerve damage (neuropathy), including a comprehensive foot exam. Patients who have loss of sensation in their feet should be sure to have a foot exam every 3 - 6 months to check for ulcers or infections.

Screening for Thyroid Abnormalities. Thyroid function tests should be administered.

Treatment

Pre-diabetes precedes the onset of type 2 diabetes. People who have pre-diabetes have fasting blood glucose levels that are 100 - 125 mg/dL -- higher than normal, but not yet high enough to be classified as diabetes. (Pre-diabetes used to be referred to as “impaired glucose tolerance.”) Pre-diabetes greatly increases the risk for diabetes.

Treatment of pre-diabetes is very important. Research shows that lifestyle and medical interventions can help prevent, or at least delay, the progression to diabetes. While insulin-regulating drugs such as metformin (Glucophage) and acarbose (Precose) are sometimes prescribed, evidence indicates that lifestyle changes can be at least as effective as drug therapy. The most important lifestyle treatment for people with pre-diabetes is to lose weight through diet and regular exercise. Even a modest weight loss of 10 - 15 pounds can significantly reduce the risk of progressing to diabetes.

Because people with pre-diabetes have a higher risk for heart disease and stroke, diet and exercise are also very important for heart health, as is quitting smoking. It is also important to have your doctor check your cholesterol and blood pressure levels on a regular basis. Your doctor should also check your fasting blood glucose levels every 1 - 2 years.

The major treatment goals for people with type 2 diabetes are:

Treat all conditions that place the patients at risk for heart disease and stroke, which are the major killers of people with type 2 diabetes.
Control blood glucose levels. The goal is to achieve fasting blood glucose levels of less than 110 mg/dL and glycolated hemoglobin (HbA1c) levels of less than 7%. The objective is to reduce complications in small blood vessels and the nerve damage associated with diabetes.

An intensive multi-pronged approach is critical for reducing complications and improving survival rates in patients with diabetes. Intensive therapy includes:

Healthy lifestyle changes: Regular exercise; heart-healthy diet; quitting smoking.
Controlling blood sugar levels. Monitor blood sugar and hemoglobin HbA1C levels. Oral anti-hyperglycemic drugs such as metformin are first-line drug treatments. Insulin may eventually be needed.
Heart-protective drugs. These medications include various drugs to control high blood pressure (ACE inhibitors, diuretics, others) and cholesterol (statins, fibrates). Controlling high blood pressure is a proven factor in reducing mortality rates. Aspirin may help prevent blood clots and heart attack.

Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions. Treating children with type 2 diabetes depends on the severity of the condition at diagnosis. Metformin is approved for children. Formerly, only insulin was approved for treating children with diabetes.

Lifestyle Changes

A simple heart-healthy diet with weight control and exercise is important for people with pre-diabetes and may be sufficient for some people with type 2 diabetes. Some patients may be able to control their blood sugar with lifestyle measures and not need medication. Even for patients who do need to take drugs, lifestyle plays an essential role in controlling diabetes. Lifestyle changes can be difficult to initiate and sustain, however. Patients should surround themselves with a solid network of doctors, dietitians, family, and friends who understand both their condition and their needs.

Although there are many major dietary approaches for protecting health, experts generally agree on the following recommendations for heart protection:

Choose fiber-rich food (whole grains, legumes, nuts) as the main source of carbohydrates, along with a high intake of fresh fruits and vegetables. High fiber foods help improve blood glucose levels. Whole grain cereals, which are rich in both fiber and magnesium, may also help reduce the risk for diabetes.
Limit saturated fats (found mostly in animal products) to less than 7% of total daily calories and avoid trans fatty acids (found in hydrogenated fats and many commercial products and fast foods). Choose unsaturated fats (particularly omega-3 fatty acids found in vegetable and fish oils).
In selecting proteins, choose soy protein, poultry, and fish over meat. A 2006 study found that soy does not help improve cholesterol. However, experts still recommend it as a heart-healthy food choice.
Weight control, quitting smoking, and exercise are essential components of any diet program.

[See In-Depth Report #43: Heart-healthy diet.]

There is no such thing as a single diabetes diet. Patients should meet with a professional dietitian to plan an individualized diet within the general guidelines that takes into consideration their own health needs.

Healthy eating habits along with good control of blood glucose are the basic goals, and several good dietary methods are available to meet them. General dietary guidelines for diabetes recommend:

Carbohydrates should provide 45 - 65% of total daily calories. The type and amount of carbohydrate are both important. Best choices are vegetables, fruits, beans, and whole grains. These foods are also high in fiber. Patients with diabetes should monitor their carbohydrate intake either through carbohydrate counting or meal planning exchange lists.
Fats should provide 25 - 35% of daily calories. Monounsaturated (olive, peanut, canola oils; avocados; nuts) and omega-3 polyunsaturated (fish, flaxseed oil, walnuts) fats are the best types. Limit saturated fat (red meat, butter) to less than 7% of daily calories. Choose nonfat or low-fat dairy instead of whole milk products. Limit trans-fats (hydrogenated fat found in snack foods, fried foods, commercially baked goods) to less than 1% of total calories.
Protein should provide 12 - 20% of daily calories, although this may vary depending on a patient’s individual health requirements. Patients with kidney disease should limit protein intake to less than 10% of calories. Fish, soy, and poultry are better protein choices than red meat.

[For detailed information, including diabetic exchange lists and carbohydrate counting, see In-Depth Report #42: Diabetes diet.]

Being overweight is the number one risk factor for type 2 diabetes. Even modest weight loss can help prevent type 2 diabetes from developing. It can also help control or even stop progression of type 2 diabetes in people with the condition and reduce risk factors for heart disease. Patients should aim to lose weight if their body mass index (BMI) is 25 - 29 (overweight) or higher (obese).

Unfortunately, not only is weight loss difficult to sustain, but many of the oral medications used in type 2 diabetes cause weight gain as a side effect. For obese patients who cannot control weight using dietary measures alone, weight-loss drugs, such as orlistat (Xenical) or sibutramine (Meridia), may be helpful. Orlistat may have specific benefits for people with diabetes. It may not only help achieve weight but also improve glucose, cholesterol, and lipid levels. In 2007, the FDA approved a non-prescription form of orlistat (alli). [See In-Depth Report #53: Obesity.]

Sedentary habits, especially TV watching, are associated with significantly higher risks for obesity and type 2 diabetes. Regular exercise, even of moderate intensity (such as brisk walking), improves insulin sensitivity and may play a significant role in preventing type 2 diabetes -- regardless of weight loss. An important study reported a 58% lower risk for type 2 diabetes in adults who performed moderate exercise for as little as 2.5 hours a week.

Aerobic Exercise. Aerobic exercise has significant and particular benefits for people with diabetes. Regular aerobic exercise, even of moderate intensity, improves insulin sensitivity. People with diabetes are at particular risk for heart disease, so the heart-protective effects of aerobic exercise are especially important. Moderate exercise protects the heart in people with type 2 diabetes, even if they have no risk factors for heart disease other than diabetes itself.

For improving glycemic control, the American Diabetes Association recommends at least 150 minutes per week of moderate-intensity physical activity (50 - 70% of maximum heart rate) or at least 90 minutes per week of vigorous aerobic exercise (more than 70% of maximum heart rate). Exercise at least 3 days a week, and do not go more than 2 consecutive days without physical activity.

Strength Training. Strength training, which increases muscle and reduces fat, is also helpful for people with diabetes who are able to do this type of exercise. The American Diabetes Association recommends performing resistance exercise three times a week. Build up to three sets of 8 - 10 repetitions using weight that you cannot lift more than 8 - 10 times without developing fatigue. Be sure that your strength training targets all of the major muscle groups.

Exercise Precautions. The following are precautions for all people with diabetes, both type 1 and type 2:

Because people with diabetes are at higher than average risk for heart disease, they should always check with their doctors before undertaking vigorous exercise. For fastest results, frequent high-intensity (not high-impact) exercises are best for people who are cleared by their doctors. For people who have been sedentary or have other medical problems, lower-intensity exercises are recommended.
Strenuous strength training or high-impact exercise is not recommended for people with uncontrolled diabetes. Such exercises can strain weakened blood vessels in the eyes of patients with retinopathy. High-impact exercise may also injure blood vessels in the feet.

Patients who are taking medications that lower blood glucose, particularly insulin, should take special precautions before embarking on a workout program:

Monitor glucose levels before, during, and after workouts (glucose levels swing dramatically during exercise).
Avoid exercise if glucose levels are above 300 mg/dL or under 100 mg/dL.
Inject insulin in sites away from the muscles used during exercise; this can help avoid hypoglycemia.
Drink plenty of fluids before and during exercise; avoid alcohol, which increases the risk of hypoglycemia.
Insulin-dependent athletes may need to decrease insulin doses or take in more carbohydrates prior to exercise, but may need to take an extra dose of insulin after exercise (stress hormones released during exercise may increase blood glucose levels).
Wear good, protective footwear to help avoid injuries and wounds to the feet.
Some blood pressure drugs can interfere with exercise capacity. Patients who use blood pressure medication should consult their doctors on how to balance medications and exercise. Patients with high blood pressure should also aim to breathe as normally as possible during exercise. Holding the breath can increase blood pressure.

[See In-Depth Report #29: Exercise.]

According to the American Diabetes Association, people with diabetes should aim for preprandial (before eating) plasma glucose levels of 90 - 130 mg/dL and postprandial (after eating) plasma glucose levels less than 180 mg/dL. Hemoglobin A1C levels should be less than 7%.

Measuring Blood Glucose. In patients being treated with insulin or insulin-producing or sensitizing drugs, it is important to monitor blood glucose levels carefully to avoid hypoglycemia. Different goals may be required for specific individuals, including pregnant women, very old and very young people, and those with accompanying serious medical conditions.

Blood glucose levels are generally more stable in type 2 diabetes than in type 1, so experts usually recommend measuring blood levels only once or twice a day. For patients who have become insulin-dependent, more intensive monitoring is necessary. Usually, a drop of blood obtained by pricking the finger is applied to a chemically treated strip. The glucose level is read on a standard meter or a small, portable digital display device. For patients who have trouble controlling hypoglycemia (low blood sugar) or fluctuating blood sugar levels, continuous glucose sensor monitors are also available. In 2007, the FDA approved the STS-7 System, which continuously measures glucose levels for up to 7 days through a sensor inserted beneath the skin of the abdomen. Continuous glucose sensor monitors do not replace fingerstick glucose meters and test strips, but are used in combination with them. [See In-Depth Report #9: Diabetes - type 1.]

Measuring Hemoglobin A1C. Hemoglobin A1c (also called HbA1c , HA1c, or A1C) is measured periodically every 2 - 3 months to determine the average blood-sugar level over the lifespan of the red blood cell. Normal A1C levels should be below 7%. Home tests are also available for measuring A1C.

To monitor the amount of glucose within the blood a person with diabetes should test their blood regularly. The procedure is quite simple and can often be done at home.

Some research suggests that not getting enough sleep may impair insulin use and increase the risk for obesity. More research is needed, but it is always wise to improve sleep habits.

Medications

The American Heart Association now recommends that patients should aim for the following test results for intensive control of glucose levels:

Fasting plasma glucose concentrations below 110 mg/dL.
Glycolated hemoglobin (HbA1c) levels of less than 7%. Controlling HbA1c is the most important factor for reducing the risk of complications in patients with diabetes. According to one 2000 study, a 1% reduction in people with elevated glycolated hemoglobin levels lowers the risk for complications by 21%.

Evidence clearly supports strict glycemic control for reducing complications in the nervous system and blood vessels that occur in both type 1 and type 2 diabetes. Research shows that tight glucose control can help prevent heart disease and complications.

Managing risk factors for heart disease and stroke, particularly strict control of blood pressure, may be more important for improving survival than strict control of blood glucose levels for some patients. Such goals also seem to be more attainable for many patients with type 2 diabetes.

Oral Anti-Hyperglycemic Drugs. Many oral anti-hyperglycemic drugs are available to help patients with type 2 diabetes control their blood sugar levels. Most of these drugs are aimed at using or increasing sensitivity to the patient's own natural stores of insulin. Metformin is the only drug to date that achieves lower mortality rates. Oral type 2 diabetes drugs include:

Biguanides (metformin). Metformin increases tissue sensitivity to available insulin. Metformin also has beneficial effects on cholesterol, blood pressure, and clotting factors. It does not cause weight gain or hypoglycemia. Diarrhea and digestive problems are the most common side effects. Metformin produces lower mortality rates than other drugs, including insulin, and should be considered as first-line therapy for most patients with type 2 diabetes.
Sulfonylureas (glyburide, glipizide, glimepiride, repaglinide). Stimulate insulin secretion but can cause hypoglycemia more than other drugs.
DPP-4 inhibitors (sitagliptin). Also called gliptins, DPP-4 inhibitors were first approved in 2006 and are the newest class of oral diabetes drugs. Like metformin, they do not cause weight gain and have low risks for hypoglycemia.
Meglitinides (repaglinide, nateglinide). Stimulate insulin secretion. These newer drugs are better than sulfonylureas in controlling glucose spikes after meals.
Thiazolidinediones (pioglitazone and rosiglitazone). Reduce insulin resistance. These drugs improve cholesterol levels and may reduce the risk for blood clots. However, they can cause swelling from fluid build-up, which can worsen heart failure or even precipitate it. They may also injure the liver.
Alpha-glucosidase inhibitors (acarbose and miglitol). Slow intestinal absorption of carbohydrates. Have only modest effects on diabetes and have gastrointestinal side effects. Can slightly raise HDL (“good”) cholesterol levels.
Combinations of these drugs, particularly with metformin, are often used to increase effectiveness.

A 2007 review in the Annals of Internal Medicine compared these various classes of medications. The review found that older drugs -- such as metformin and sulfonylureas -- are less expensive than and work as well as newer diabetes drugs. In particular, the review cited metformin as a safe and effective drug because it does not cause weight gain or too-low blood sugar. Metformin can also help lower LDL (“bad”) cholesterol.

Injectable Anti-Hyperglycemic Drugs. In 2005, the FDA approved two new injectable drugs to help patients improve blood sugar control:

Exenatide (Byetta). Exenatide is the first drug in a new class of drugs called incretin mimetics. It lowers blood glucose levels by increasing insulin secretion. Exenatide is used in combination with oral antihyperglycemics, such as metformin or a sulfonylurea drug.
Pramlintide (Symlin). Pramlintide is a first-in-class drug that is a synthetic form of the hormone amylin. The drug is meant for patients who take insulin but still have difficulty controlling their glucose levels.

Insulin Replacement. Insulin replacement may be required when natural insulin reserves are depleted. It is typically started in combination with an oral drug. Eventually, some patients may need to go on full insulin replacement. In addition to injectable forms of insulin, an inhaled insulin product (Exubera) is now available.

Metformin (Glucophage) is a biguanide, which works by reducing glucose production in the liver and by making tissues more sensitive to insulin. Many experts recommend it as a first choice for most patients with type 2 diabetes who are insulin resistant, particularly if they are overweight. Metformin achieves lower mortality rates from diabetes and all causes than other drugs. In one comparison study, it achieved the lowest mortality rates (8%) compared to insulin (28%), a sulfonylurea (16%), and a thiazolidinedione (14%). Combinations with insulin-secreting drugs, other insulin-sensitizing drugs, or insulin itself are particularly effective.

Metformin does not cause hypoglycemia or add weight, so it is particularly well-suited for obese patients with type 2 diabetes. (In some studies, in fact, patients lost weight.) Metformin also appears to have beneficial effects on cholesterol and lipid levels and may help protect the heart. Some research has suggested that it significantly reduces the risk for heart attack. It is also the first choice for children who need oral drugs and is proving to be very effective for women with polycystic ovary syndrome and insulin resistance.

Side Effects. Side effects include:

A metallic taste
Gastrointestinal problems, including nausea, and diarrhea
Interference with absorption of vitamin B12 and folic acid, (which are important for protection against heart disease)
Rare reports of lactic acidosis, a potentially life-threatening condition, particularly in people with risk factors for it. Major studies, however, found no greater risk with metformin than with any of the other drugs used for type 2 diabetes.

Certain people should not use this drug, including anyone with heart failure or kidney or liver disease. It is rarely suitable for adults over age 80.

Sulfonylureas are oral drugs that stimulate the pancreas to release insulin. They are also first-line oral drugs. For adequate control of blood glucose levels, the drugs should be taken only 20 - 30 minutes before a meal. A number of brands are available, including chlorpropamide (Diabinese), tolazamide (Tolinase), acetohexamide (Dymelor), glipizide (Glucotrol), tolbutamide (Orinase), glyburide (Micronase), glimepiride (Amaryl), and repaglinide (Prandin).

Most patients can take sulfonylureas for 7 - 10 years before they lose effectiveness. Combinations with small amounts of insulin or with other oral anti-hyperglycemic drugs (such as metformin or a thiazolidinedione) may extend their benefits. A combination of glyburide and metformin in one pill (Glucovance) is available. Glucovance may be particularly beneficial for patients with unhealthy cholesterol levels and poor control of their blood sugar levels. Some doctors recommend the combination as first-line treatment.

An encouraging 2000 study of patients with severe type 2 diabetes reporting that combinations of insulin with either chlorpropamide or glipizide achieved better glucose control over the long term than insulin alone.

Side Effects and Complications. In general, sulfonylureas should not be used by women who are pregnant or nursing or by individuals who are allergic to sulfa drugs. Side effects may include:

Weight gain (some sulfonylureas, such as glimepiride, may produce less weight gain than others)
Water retention
Although sulfonylureas pose a lower risk for hypoglycemia than insulin does, the hypoglycemia produced by sulfonylureas may be especially prolonged and dangerous. The newer sulfonylureas, such as glimipiride, have much less risk of hypoglycemia than older sulfonylureas.
Some sulfonylureas may pose a slight risk for cardiac events.

Sulfonylureas interact with many other drugs, and patients should be sure to inform their doctor of any medications they are taking, including alternative or over-the-counter drugs.

Meglitinides stimulate beta cells to produce insulin. They include repaglinide (Prandin), nateglinide (Starlix), and mitiglinide. These drugs are rapidly metabolized and short-acting. If taken before every meal, they actually mimic the normal effects of insulin after eating. Patients, then, can vary their meal times with this drug. (Nateglinide appears to work more quickly and is shorter-acting than repaglinide). These drugs may be particularly helpful in combination with metformin or other drugs. They may also be a good choice for people with potential kidney problems.

Side Effects. Side effects include diarrhea and headache. As with the sulfonylureas, repaglinide poses a slightly increased risk for cardiac events. (Newer drugs, such as nateglinide, may pose less of a risk.) People with heart failure or liver disease should use them with caution and be monitored.

Thiazolidinediones, also known as peroxisome proliferator-activated receptor (PPAR) agonists, include rosiglitazone (Avandia) and pioglitazone (Actos). They improve insulin sensitivity by activating certain genes involved in fat synthesis and carbohydrate metabolism. These drugs are usually taken once or twice per day; however, it may take several days before the patient notices any results from them and several weeks before they take full effect. Thiazolidinediones are usually taken in combination with other oral drugs or insulin.

Side Effects. Thiazolidinediones can have serious side effects. They tend to increase fluid-build up, which can cause or worsen heart failure in some patients. Combinations with insulin increase the risk. They should not be used by patients with existing heart failure and should be used cautiously in those with risk factors for heart failure.

In 2007, a study published in the New England Journal of Medicine (NEJM) raised serious concerns that rosiglitazone may increase the risk of heart attack. The study reviewed 42 clinical trials of rosiglitazone. Results suggested that patients who took rosiglitazone were 43% more likely to have a heart attack, and 64% more likely to die from overall heart causes, than patients with diabetes who did not take the drug. A subsequent interim analysis in the NEJM found that while rosiglitazone was definitely associated with increased risk of heart failure, the data were insufficient to determine if the drug increases heart attack risk. The FDA has concluded that rosiglitazone may increase the risk of heart attack and will likely restrict its use. In 2007, a panel of experts from the Food and Drug Administration (FDA) agreed the drug increases the risk of heart attacks -- but concluded it should remain on the market. The panel did, however, recommend the FDA require rosiglitazone's maker to add warnings to the drug's label. Patients who take rosiglitazone, especially those who have heart disease or who are at high risk for heart attack, should discuss their treatment options with their doctors.

Thiazolidinediones may cause more weight gain than other diabetes medications or insulin. Any patient who experiences sudden weight gain, water retention, or shortness of breath should immediately call their doctor. These drugs have also been linked to increased risks for bone fracture.

There have been rare reports of rosiglitazone causing or worsening diabetic macular edema. This is an eye condition associated with diabetic retinopathy that causes swelling in the macular area of the retina. Symptoms include blurred vision and decreased color sensitivity. Most patients who had this side effect also had swelling in the feet and legs (peripheral edema). The condition resolved or improved when patients stopped taking the drug.

Thiazolidinediones can also cause liver damage. Patients who take these drugs should have their liver enzymes checked regularly.

Alpha-glucosidase inhibitors, including acarbose (Precose, Glucobay) and miglitol (Glyset), reduce glucose levels by interfering with the absorption of starch in the small intestine. Acarbose tends to lower insulin levels after meals, a particular advantage, since higher levels of insulin after meals are associated with an increased risk for heart disease. Some evidence suggests that early use of these drugs may reduce heart risk factors, including high blood pressure. A 2002 study of acarbose suggested that these drugs may possibly delay the development of type 2 diabetes in high-risk individuals. Alpha-glucosidase inhibitors are not as effective alone as other single oral drugs, but combinations, such as with metformin, insulin, or a sulfonylurea, increase their effectiveness.

Side Effects. These medications need to be taken with meals. Unfortunately, about a third of patients stop taking the drug because of flatulence and diarrhea, particularly after high-carbohydrate meals. The drug may also interfere with iron absorption.

Alpha-glucosidase inhibitors do not cause hypoglycemia when used alone, but combinations with other drugs do. In such cases, it is important that the patient receive a solution that contains glucose or lactose, not table sugar. This is because acarbose inhibits the breakdown of complex sugar and starches, which includes table sugar.

Incretin mimetics belong to a new class of drugs that help improve blood sugar control. Incretins include glucagon-like peptide-1 (GLP-1) inhibitors and DDP-4 inhibitors.

In 2005, the FDA approved exenatide (Byetta), the first GLP-1 inhibitor drug. Exenatide is an injectable drug that is a synthetic version of the hormone found in the saliva of the Gila monster, a venomous desert lizard. Exenatide is injected twice a day, 1 hour before morning and evening meals. It is prescribed for patients with type 2 diabetes who have not been able to control their glucose with metformin or a sulfonylurea drug. It can be taken in combination with these drugs or alone.

Side Effects. Exenatide stimulates insulin secretion only when blood sugar levels are high and so has less risk for causing low blood sugar (hypoglycemia) when it is taken alone. However, the risk for hypoglycemia increases when exenatide is taken along with a sulfonylurea drug. There does not appear to be a risk for hypoglycemia when exenatide is used along with metformin. Other side effects may include nausea, vomiting, and diarrhea.

A 2005 study compared exenatide to insulin for improving glucose control in patients taking metformin and a sulfonylurea. Both insulin and exenatide worked well for glucose control. Patients lost weight with exenatide and gained weight with insulin. However, patients who received exenatide had significantly more problems with nausea, vomiting, and diarrhea than those who received insulin.

Dipeptidyl peptidase-4 (DPP-4) inhibitors, also called gliptins, are the second class of incretin drugs. In October 2006, the FDA approved the first DPP-4 inhibitor -- sitagliptin (Januvia). It can be used alone or in combination with metformin or a thiazolidinedione drug. In April 2007, the FDA approved Janumet, which combines sitagliptin with metformin in one pill. Other DPP-4 drugs being studied include vildagliptin (Galvus) and saxagliptin.

DPP-4 inhibitors work in a similar way to GLP-1 inhibitors. However, unlike exenatide, which is given by injection, DPP-4 inhibitor drugs are taken as pills by mouth.

Like exenatide, DPP-4 inhibitors do not cause weight gain, have low risks for hypoglycemia, and have few severe side effects. The most common side effects include upper respiratory tract infection, sore throat, and diarrhea.

Insulin replacement is the best treatment for strict control of blood glucose and is required once natural insulin reserves are depleted. Because type 2 diabetes is progressive, most patients eventually require insulin, typically starting it in combination with an oral anti-hyperglycemic drug. However, when a single oral drug fails to control blood sugar it is not clear whether it is better to add insulin replacement or to add a second or third oral drug.

Some experts advocate using insulin as early as possible for optimal control. However, in patients who still have insulin reserves, there is concern that extra natural insulin will have adverse effects. Low blood sugar (hypoglycemia) and weight gain are the main side effects of insulin therapy. Some research suggests that insulin may also cause heart complications. A 2006 study reported that insulin therapy increases the risk of developing high blood pressure (hypertension). It is still not clear if insulin replacement improves survival rates compared to oral drugs, notably metformin.

One approach is to combine insulin with metformin, which achieves blood glucose control without added weight gain. Newer forms of insulin analogues, such as glargine, may be especially helpful for people with type 2 diabetes and reduce the risk for hypoglycemia.

Fortunately, studies to date have not reported any adverse cardiac effects in patients with type 2 diabetes who take insulin. In fact, insulin has been associated, in some cases, with improvement in heart risk factors. More research is needed to clarify these important issues.

Forms of Insulin. Experts are working toward administering insulin so that it closely mimics the daily pattern of insulin, which responds to blood sugar levels by surging after meals and then falling to a steady base level afterward. To achieve this, doctors may use two insulin types:

Fast-Acting Insulins for Surges. Insulin lispro and aspart are fast-acting insulins. They mimic insulin's response to food intake. They are taken before meals, and their short action reduces the risk for hypoglycemia afterward.
Slower Insulins for Base Levels. Intermediate forms (including NPH and lente) and long-acting forms (glargine, ultralente) were developed to provide a steady level of insulin throughout the day. To date, glargine (Lantus) seems to be the most successful in achieving this goal in type 2 diabetes.

In 2006, the FDA approved the first non-injected form of insulin. Exubera is an inhaled form of insulin. It is approved for adults but should not be used by patients who smoke or have quit smoking within the past 6 months. Patients with asthma, bronchitis, or emphysema should also not use inhaled insulin. Clinical trials indicate that Exubera can provide sustained blood sugar control over a 2-year period. Patients in the trials who took Exubera experienced half as much weight gain as those who took injected insulin. Scientists are also developing other types of non-injected insulin, including spray formulas.

In a 2005 trial, Exubera improved blood sugar control when it was added to or substituted for combination oral drug therapy (sulphonylurea and thiazolidenedione). However, as with other forms of insulin, Exubera caused more hypoglycemia and weight gain than the oral anti-hyperglycemic drugs.

Pramlintide (Symlin) is a new type of injectable drug that may help patients who take insulin but still need better blood sugar control. The FDA approved this drug in 2005. Pramlintide is a synthetic form of amylin, a hormone that is related to insulin. Pramlintide is used in combination with insulin to lower blood sugar levels in the 3 hours after meals.

[See In-Depth Report #9: Diabetes - type 1.]

Sodium Glucose Uptake Transporter 2 (SGLT-2) Inhibitors. SGLT-2 inhibitors are a new class of drug being investigated for treatment of type 2 diabetes. Preliminary trials for two of these drugs, dapagliflozin and serglifozin, have shown promising results in helping improve blood glucose control. The drugs are being tested in combination with metformin.

Long-Term Complications

Patients with diabetes have higher mortality rates than people who do not have diabetes regardless of sex, age, or other factors. Heart disease and stroke are the leading causes of death in these patients. All lifestyle and medical efforts should be made to reduce the risk for these conditions.

People with type 2 diabetes are also at risk for nerve damage (neuropathy) and abnormalities in both small and large blood vessels (vascular injuries) that occur as part of the diabetic disease process. Such abnormalities produce complications over time in many organs and structures in the body. Although these complications tend to be more serious in type 1 diabetes, they still are of concern in type 2 diabetes. All people with diabetes should aim for fasting blood glucose levels of less than 110 mg/dL and hemoglobin HbA1C of less than 7%.

There are two important approaches to preventing complications from diabetes:

Intensive control of blood glucose and keeping glycosylated hemoglobin (HbA1c) levels below 7%. Tight blood glucose and HbA1c control can prevent complications due to vascular (blood vessel) abnormalities and nerve damage (neuropathy) that can cause major damage to organs, including the eyes, kidneys, and heart.
Managing risk factors for heart disease. Control of blood glucose also helps the heart, but its benefits occur over time. It is very important that people with diabetes control blood pressure, cholesterol levels, and other factors associated with heart disease.

Heart attacks account for 60% and strokes for 25% of deaths in patients with diabetes. Diabetes affects the heart in many ways:

Both type 1 and 2 diabetes speed the progression of atherosclerosis (hardening of the arteries). Diabetes can adversely affect blood lipid levels by lowering HDL ("good cholesterol") and increasing triglycerides. This can lead to coronary artery disease, heart attack, or stroke. According to a 2007 study, the risk of stroke doubles within 5 years of type 2 diabetes diagnosis.
Impaired nerve function (neuropathy) associated with diabetes also causes heart abnormalities. Some experts estimate that the mortality rates from neuropathy-related heart conditions range between 15 - 53%.
Women with diabetes are at particularly high risk for heart problems. A 2007 study indicated that while progress has been made in reducing mortality rates among men with diabetes, women with diabetes continue to face a high risk of death from heart disease and overall causes.

Tight blood sugar control may help protect blood vessels and reduce the risk for blood clotting. It is still not known whether intensive control will have a major protective effect on the heart, however. People with diabetes must be sure to use other measures as well to protect the heart.

Aspirin for Reducing the Risk for Blood Clots. Taking a daily aspirin (75 - 162 mg/day) reduces the risk for blood clotting and may help protect against heart attacks and heart disease. In a 2000 study, low-dose aspirin was associated with a 30% lower risk for death from heart disease in adults with type 2 diabetes.

Controlling Blood Pressure. Strict control of blood pressure is critical for preventing complications of diabetes and has proven to improve survival rates. Patients should strive for blood pressure levels of less than 130/80 mm Hg (systolic/diastolic). (Controlling systolic pressure may be especially important for reducing the risk for kidney complications.)

Dozens of anti-hypertensive drugs are available. Most fall into the following categories:

Diuretics rid the body of extra sodium (salt) and water. There are three main types of diuretics: Potassium-sparing, thiazide, and loop.
Angiotensin-converting enzyme (ACE) inhibitors reduce the production of angiotensin, a chemical that causes arteries to narrow.
Angiotensin-receptor blockers (ARBs) block angiotensin.
Beta-blockers block the effects of adrenaline and ease the heart’s pumping action.
Calcium-channel blockers (CCBs) decrease the contractions of the heart and widen blood vessels.

The American Diabetes Association (ADA) recommends any of these classes of drugs as first-line treatment for hypertension. New research suggests, however, that beta-blockers are less effective at preventing strokes and heart attacks than other types of blood pressure medications. Many patients require more than one type of drug to control blood pressure. For patients with diabetes who have microalbuminuria, the ADA strongly recommends ACE inhibitors or ARBs. Microalbuminuria is an accumulation of protein in the blood, which can signal the onset of kidney disease (nephropathy).

Anti-hypertensive drugs that block or reduce angiotensin are the first option for many people with diabetes. Angiotensin is a natural chemical that influences all aspects of blood pressure control and also interferes with insulin's normal metabolic signaling. In fact, angiotensin may be the common factor linking diabetes and high blood pressure.

The 2005 landmark Antihypertensive and Lipid Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) indicated that a thiazide-type diuretic works as well as an ACE inhibitor or CCB for patients with diabetes and high blood pressure. Compared with ACE inhibitors or CCBs, diuretics appeared to be better at lowering systolic blood pressure and preventing heart failure. In addition, the trial suggested that diuretics are especially helpful for African-Americans, by offering greater protection than ACE inhibitors or CCBS in preventing strokes.

Several 2006 studies suggested that anti-hypertensive drugs may increase the risk of developing diabetes. One study found more risk for thiazide diuretics and beta-blockers than ACE inhibitors and CCBs. Another study indicated that the ACE inhibitor ramipril had a lower risk of causing diabetes in African-Americans than a CCB or beta-blocker. A 2007 review in the Lancet also found a higher risk for new-onset diabetes with beta-blockers and diuretics, a medium risk with CCBs, and the lowest risk with ARBs and ACE inhibitors.

Research in this subject is important for patients with pre-diabetes who have high blood pressure. Results of future research may help doctors decide which treatment is most appropriate for patients with high blood pressure who are at high risk for diabetes. [See In-Depth Report #14: High blood pressure.]

Improving Cholesterol and Lipid Levels. Abnormal cholesterol and lipid levels are common in diabetes. High LDL (“bad”) cholesterol should always be lowered, but people with diabetes also often have additional harmful imbalances including low HDL (“good”) cholesterol and high triglycerides. Patients should aim for LDL levels below 100 mg/dL, HDL levels over 50 mg/dL and triglyceride levels below 150 mg/dL. Patients with diabetes and existing heart disease should strive for even lower LDL levels; the American Diabetes Association recommends LDL levels below 70 mg/dL for these patients.

Statins are the best cholesterol-lowering drugs. They include atorvastatin (Lipitor), lovastatin (Mevacor, generics), pravastatin (Pravachol), simvastatin (Zocor, generics), fluvastatin (Lescol), and rosuvastatin (Crestor). These drugs are very effective for lowering LDL cholesterol levels. Recent studies indicate that aggressive high-dose statin therapy may be an important treatment approach for high-risk patients who need to substantially lower their LDL levels. A 2006 study found that patients with diabetes and heart disease who were treated with 80 mg daily of atorvastatin had a 25% lower risk of heart attack and stroke than patients who received the standard 10 mg daily dose.

The primary safety concern with statins has involved myopathy, an uncommon condition that can cause muscle damage and, in some cases, muscle and joint pain. A specific myopathy called rhabdomyolysis can lead to kidney failure. People with diabetes and risk factors for myopathy should be monitored for muscle symptoms

Although lowering LDL is beneficial, statins are not as effective as other medications -- such as fibrates, niacin, ezetimbe, or bile acid sequesters -- in addressing HDL and triglyceride imbalances. This is a common problem in type 2 diabetes. Combinations of statins with one of these drugs may be helpful for people with diabetes who have heart disease, low HDL, and near-normal LDL levels. Although combinations of statins and fibrates or niacin increase the risk of myopathy, both combinations are considered safe if used with extra care. Research presented at the 2007 annual meeting of the American Diabetes Association suggested that statins and fibrates may also help reduce the risk of developing peripheral neuropathy, the diabetes-associated nerve damage that can lead to loss of sensation in the feet.

Gemfibrozil (Lopid) and fenofibrate (Tricor) are usually the first choice for fibrate drugs. Niacin has the most favorable effect on raising HDL and lowering triglycerides of all the cholesterol drugs. However, about 30% of patients who take high-dose niacin experience increased blood glucose levels. Moderate doses of niacin can achieve lipid control without causing serious blood glucose problems. [See In-Depth Report #23: Cholesterol.]

Kidney disease (nephropathy) is a very serious complication of diabetes. With this condition, the tiny filters in the kidney (called glomeruli) become damaged and leak protein into the urine. Over time this can lead to kidney failure. Urine tests showing microalbuminuria (small amounts of protein in the urine) are important markers for kidney damage.

Prevention and Treatment of Nephropathy. Tight control of blood sugar and blood pressure is essential for preventing the onset of kidney disease. Long-term studies report that strict control of these two conditions produces a 60% reduction in new cases of nephropathy and a delay in progression of the disease. ACE inhibitors and ARBs, two classes of blood pressure medications, are very helpful for preventing or slowing the progression of diabetic kidney disease.

A doctor may recommend a low-protein diet for patients whose kidney disease is progressing despite tight blood sugar and blood pressure control. Protein-restricted diets can help slow disease progression and delay the onset of end-stage renal disease (kidney failure). However, patients with end-stage renal disease who are on dialysis generally require higher amounts of protein. [See In-Depth Report #42: Diabetes diet.]

Diabetic nephropathy occurs in about 20 - 40% of patients with diabetes and is the leading cause of end-stage renal disease. If the kidneys fail, dialysis is required. Symptoms of kidney failure may include swelling in the feet and ankles, itching, fatigue, and pale skin color.

Anemia is a common complication of end-stage kidney disease. Patients on dialysis usually require injections of erythropoiesis-stimulating drugs to increase red blood cell counts and control anemia. Dosing target levels of erythropoiesis-stimulating drugs are controversial, especially for patients with chronic kidney disease. In 2006, two important New England Journal of Medicine studies indicated that aggressive dosing to completely normalize hemoglobin levels does not work better than standard dosing that only partially corrects anemia.

In 2007, the FDA issued new warnings on darbepoetin alfa (Aranesp) and epoetin alfa (Epogen and Procrit). The warnings describe an increased risk with blood clots, strokes, and heart attacks in patients with end-stage kidney disease when these drugs were given at higher than recommended doses. The FDA has set new dosing and hemoglobin target levels for these drugs.

Another controversy surrounding erythropoiesis-stimulating drugs concerns their overuse at dialysis centers. A 2007 study in the Journal of the American Medical Association suggested that large, for-profit dialysis centers tend to administer higher-than-appropriate doses of these drugs compared to nonprofit facilities. The study suggested that for-profit centers are giving higher doses for financial, not medical, reasons.

The FDA recommends that patients with end-stage kidney disease who receive erythropoiesis-stimulating drugs should:

Maintain hemoglobin levels that do not exceed 12 g/dL
Receive frequent blood tests to monitor hemoglobin levels
Contact their doctors if they experience such symptoms as shortness of breath, pain, swelling in the legs, or increases in blood pressure

[See In-Depth Report #57: Anemia.]

Click the icon to see an image of the pancreas and kidneys.

Diabetes reduces or distorts nerve function, causing a condition called neuropathy. Neuropathy refers to a group of disorders that affect nerves. The two main types of neuropathy are:

Peripheral (affects nerves in the toes, feet, legs, hand, and arms)
Autonomic (affects nerves that help regulate digestive, bowel, bladder, heart, and sexual function)

Peripheral neuropathy particularly affects sensation. It is a common complication that affects nearly half of people with type 1 or type 2 diabetes after 25 years. The most serious consequences of neuropathy occur in the legs and feet and pose a risk for ulcers and, in very severe cases, amputation. Peripheral neuropathy usually starts in the fingers and toes and moves up to the arms and legs (called a stocking-glove distribution). Symptoms include:

Tingling
Weakness
Burning sensations
Loss of the sense of warm or cold
Numbness (if the nerves are severely damaged, the patient may be unaware that a blister or minor wound has become infected)
Deep pain

Autonomic neuropathy can cause digestive problems (constipation, diarrhea, nausea, vomiting), bladder infections, and erectile dysfunction. In some cases, neuropathy may mask angina, the chest pain warning for heart disease and heart attack. Patients with diabetes should be aware of other warning signs of a heart attack, including sudden fatigue, sweating, shortness of breath, nausea, and vomiting.

Blood sugar control is the only treatment for neuropathy. Studies show that tight control of blood glucose levels delays the onset and slows progression of neuropathy. A 2005 study also suggested that heart disease risk factors can increase the likelihood of developing neuropathy. Lowering triglycerides, losing weight, reducing blood pressure, and quitting smoking may help prevent the onset of neuropathy.

Prevention of Neuropathy. Patients with type 2 diabetes should receive regular screenings for loss of sensation in feet and other signs of neuropathy. A 2007 study suggested that statin and fibrate drugs, which are used to control cholesterol, may help protect against diabetic peripheral neuropathy.

Pain Relief for Peripheral Neuropathy. A number of different drugs are used for peripheral neuropathy pain relief. They include:

Nonprescription analgesics such as aspirin, acetaminophen, and non-steroidal anti-inflammatory drugs (NSAIDs). (Patients with stomach or kidney problems should check with their doctors before using these drugs.)
Prescription painkillers, such as tramadol (Ultram). Tramadol is a drug that is similar to opioids. It can help relieve pain but has significant side effects, including nausea, constipation, and headache.
Topical medications, particularly capsaicin (the active ingredient in hot peppers), are applied to the skin to relieve minor local pain. A 5% lidocaine patch has also shown good results in clinical trials.
Tricyclic antidepressants, such as amitriptyline (Elavil) or doxepin (Sinequan), are effective in reducing pain from neuropathy in up to 75% of patients. A combination of doxepin and capsaicin (applied to the skin) may be particularly beneficial. Unfortunately, tricyclics may cause heart rhythm problems.
Duloxetine (Cymbalta) is a serotonin and norepinephrine reuptake inhibitor, a newer type of antidepressant, which was approved in 2004 for treatment of pain associated with diabetic peripheral neuropathy.
The anti-convulsant drug pregabalin (Lyrica) was approved in 2004 for neuropathic pain management. It is classified as a controlled substance (like narcotics), which indicates a potential risk for abuse. Other anti-seizure drugs used for peripheral neuropathy pain relief include gabapentin (Neurontin) and valproate (Depakote).

Treatments under investigation include acetyl-l-carnitine and intravenous alpha-lipoic acid. Patients may also benefit from transcutaneous electrostimulation (TENS), a treatment that involves administering mild electrical pulses to painful areas. Alternative treatments such as hypnosis, biofeedback, relaxation techniques, and acupuncture have helped some patients manage pain. Doctors also recommend lifestyle measures such as walking and wearing elastic stockings.

Treatments for Other Complications of Neuropathy. Neuropathy also impacts other functions, and treatments are needed to reduce their effects. If diabetes affects the nerves in the autonomic nervous system, then abnormalities of blood pressure control and bowel and bladder function may occur. Erythromycin, domperidone (Motilium), or metoclopramide (Reglan) may be used to relieve delayed stomach emptying caused by neuropathy.

Erectile dysfunction is also associated with neuropathy. Evidence shows that phosphodiesterase type 5 (PDE-5) drugs, such as sildenafil (Viagra), vardenafil (Levitra), and tadalafil (Cialis), are safe and effective, at least in the short term, for patients with diabetes. Typical side effects are minimal but may include headache, flushing, and upper respiratory tract and flu-like symptoms.

Perhaps the most serious consequences of diabetic neuropathy occur in the lower limbs. An estimated 15% of patients with diabetes experience serious foot problems. They are the leading cause of hospitalizations for these patients.

Diabetes is responsible for more than half of all lower limb amputations performed in the U.S. Each year there are about 88,000 non-injury amputations, 50 - 75% of them due to diabetes. The number is increasing as the prevalence in diabetes type 2 rises. According to a 2005 study in the Lancet, every 30 seconds someone in the world receives a lower limb amputation due to diabetes. About 85% of amputations start with foot ulcers, which develop in about 12% of people with diabetes.

In general, foot ulcers develop from infections, such as those resulting from blood vessel injury. A 2006 study reported that people with diabetes who develop foot infections are 155 times more likely to have an amputation than people who did not develop infections. Foot infections often develop from injuries. Even minor infections can develop into severe complications. Numbness from nerve damage, which is common in diabetes, compounds the danger since the patient may not be aware of injuries. About one-third of foot ulcers occur on the big toe.

A 2003 government survey found that those at higher risk for foot ulcers tend to be people with diabetes who are overweight, smokers, and those with a long history of diabetes. People who have the disease for more than 20 years and are insulin-dependent are at the highest risk. Related conditions that put people at risk include peripheral neuropathy, peripheral artery disease, foot deformities, and a history of ulcers. [See In-Depth Report #102: Peripheral artery disease and intermittent claudication.]

Charcot Foot. Charcot foot or Charcot joint (medically referred to as neuropathic arthropathy) occurs in about 2.5% of people with diabetes. Early changes appear like an infection, with the foot becoming swollen, red, and warm. A seriously affected foot can become deformed. The bones may crack, splinter, and erode, and the joints may shift, change shape, and become unstable. It typically develops in people who have neuropathy to the extent that they cannot feel sensation in the foot and are not aware of an existing injury. Instead of resting an injured foot or seeking medical help, the patient often continues normal activity, causing further damage.

Charcot foot is initially treated with strict immobilization of the foot and ankle; some centers use a cast that allows the patient to move and still protects the foot. A 2001 study in the U.K. concluded that a single dose of pamidronate, a bisphosphonate, reduces bone turnover, symptoms, and disease activity. When the acute phase has passed, patients usually need lifelong protection of the foot using a brace initially and custom footwear.

Measures to Prevent Foot Ulcers. Preventive foot care can significantly reduce the risk of ulcers and amputation. Some tips for preventing problems include:

Patients should inspect their feet daily and watch for changes in color or texture, odor, and firm or hardened areas, which may indicate infection and potential ulcers.
When washing the feet, the water should be warm (not hot), and the feet and areas between the toes should be thoroughly dried afterward. Check water temperature with the hand or a thermometer before stepping in.
Moisturizers should be applied, but not between the toes.
Corns and calluses should be gently pumiced and toenails trimmed short and the edges filed to avoid cutting adjacent toes.
Patients should not use medicated pads or try to shave the corns or calluses themselves.
Well-fitting footwear is very important. People should be sure the shoe is wide enough; according to a 2001 study, 30% of patients with diabetes wear shoes that are too narrow. Patients should also avoid high heels, sandals, thongs, and going barefoot. Shoes with a rocker sole reduce pressure under the heel and front of the foot by 35 - 65% and may be particularly helpful. Custom-molded boots increase the surface area over which foot pressure is distributed. This reduces stress on the ulcers and allows them to heal.
Shoes should be changed often during the day.
Wear socks, particularly with extra padding (which can be specially purchased).
Patients should avoid tight stockings or any clothing that constricts the legs and feet.
Foot pain, numbness, or tingling is worse at night; diphenhydramine (Benadryl) may help.
A specialist in foot care should be consulted for any problems.

People with diabetes are prone to foot problems because the disease can cause damage to the blood vessels and nerves, which may result in decreased ability to sense trauma to the foot. The immune system is also altered, so that the patient cannot efficiently fight infection.

Treating Foot Ulcers in Diabetes. About one-third of foot ulcers will heal within 20 weeks with good wound care treatments. Treatments include:

Antibiotics are generally given. In some cases, hospitalization and intravenous antibiotics for up to 28 days may be needed for severe foot ulcers.
In virtually all cases, wound care requires debridement, which is the removal of injured tissue until only healthy tissue remains. Debridement may be accomplished using chemical (enzymes), surgical, or mechanical (irrigation) means.
Hydrogels (Nu-Gel, Intrasite Gel, Scherisorb, Clearsite, Duoderm, Geliperm) are helpful in healing ulcers and are noninvasive and soothing.
Felted foam may be helpful in healing ulcers on the sole of the foot. Felted foam uses a multi-layered foam pad over the bottom of the foot with an opening over the ulcer.

Other Treatments for Foot Ulcers. Doctors are also using or investigating other treatments to heal ulcers. These include:

Administering hyperbaric oxygen (oxygen given at high pressure) is showing promise in promoting healing. In one study, patients who had had ulcers that had not responded to treatment for over 3 months received daily treatments that lasted 90 minutes for 2 weeks. About 15 days after completion, patients who received oxygen had significant reduction in ulcers, sometimes with complete healing. Other studies are also demonstrating good results.
Monochromatic near-infrared photo energy (MIRE) uses light therapy to improve sensation in the feet of patients with peripheral neuropathy.
Total-contact casting (TCC) uses a cast that is designed to match the exact contour of the foot and to distribute weight along the entire length of the foot. It is usually changed weekly. It may be helpful for ulcer healing and for Charcot foot. Although it is very effective in healing ulcers, recurrence is common.

Diabetes accounts for 12,000 - 24,000 of new cases of blindness annually and is the leading cause of new cases of blindness in adults age 20 - 74. The most common eye disorder in diabetes is retinopathy. People with diabetes are also at higher risk for developing cataracts and certain types of glaucoma, such as primary-open angle glaucoma (POAG). The risk for POAG is especially high for women with type 2 diabetes. [See In-Depth Report #26: Cataracts and In-Depth Report #25: Glaucoma.]

Description of Retinopathy. Retinopathy is a condition in which the retina in the eye becomes damaged. The two primary abnormalities that occur are a weakening of the blood vessels in the retina and the obstruction in the capillaries -- probably from very tiny blood clots. Retinopathy generally occurs in one or two phases:

Click the icon to see an image of diabetic retinopathy.

The early and more common type of this disorder is called nonproliferative or background retinopathy. The blood vessels in the retina are abnormally weakened. They rupture and leak, and waxy areas may form. If these processes affect the central portion of the retina, swelling may occur, causing reduced or blurred vision.
If the capillaries become blocked and blood flow is cut off, soft, "woolly" areas may develop in the retina's nerve layer. These woolly areas may signal the development of proliferative retinopathy. Often there are no symptoms of progressing retinopathy. In this more severe condition, new abnormal blood vessels form and grow on the surface of the retina. They may spread into the cavity of the eye or bleed into the back of the eye. Major hemorrhage or retinal detachment can result, causing severe visual loss or blindness. The sensation of seeing flashing lights may indicate retinal detachment.

Click the icon to see an animation on diabetic retinopathy.

According to a 2003 study, about 40% of young adults with type 1 diabetes had developed retinopathy within 10 years of diagnosis. (Although this rate is high, it is significantly lower than in previous years when blood glucose control was not as strict.) The risk is lower in patients with type 2 diabetes, although in one study over 20% had signs of retinopathy 6 years after diagnosis. Patients who are newly diagnosed with type 2 diabetes should get a comprehensive eye examination, including dilation. In general, all patients with diabetes should have a yearly eye examination. Patients with no signs of retinal damage or low risk factors for retinopathy may only require screening every 2 - 3 years.

Prevention of Retinopathy. Fortunately, severe and even moderate vision loss is largely preventable with tight control of blood glucose levels. (Intense glucose control can cause early worsening of retinopathy, although this is nearly always counterbalanced by long-term benefits.) Tight control of blood pressure can also help protect against retinopathy. Aspirin therapy does not help prevent retinopathy.

Treatment of Retinopathy. Patients with severe diabetic retinopathy or macular edema (swelling of the retina) should be sure to see an eye specialist who is experienced in the management and treatment of diabetic retinopathy. Once damage to the eye develops, laser eye surgery may be needed. Laser surgery can help reduce vision loss in high-risk patients.

Studies indicate that patients with type 2 diabetes face a higher than average risk of developing dementia caused either by Alzheimer's disease or problems in blood vessels in the brain. Problems in attention and memory can occur even in people under age 55 who have had diabetes for a number of years. In one study of people with type 1 diabetes, high glucose levels (hyperglycemia) were associated with slower brain function, including less verbal fluency and slower ability to do mental arithmetic.

Respiratory Infections. People with diabetes face a higher risk for influenza and its complications, including pneumonia, possibly because the disorder neutralizes the effects of protective proteins on the surface of the lungs. In fact, deaths among people with diabetes increase by 5 - 15% during flu epidemics, and they are six times more likely to be hospitalized with complications from flu than nondiabetic patients who have flu. Everyone with diabetes should have annual influenza vaccinations and a vaccination against pneumococcal pneumonia.

Urinary Tract Infections. Women with diabetes face a significantly higher risk for urinary tract infections, which are likely to be more complicated and difficult to treat than in the general population.

Diabetes doubles the risk for depression. Furthermore, according to one study, depression, in turn, increases the risk for hyperglycemia and complications of diabetes. Restoring mental health, both through medication and psychotherapy, not only improves quality of life but may help patients control their blood sugar levels.

Diabetes changes bone quality and density, but the effects differ, depending on type:

Type 1 diabetes is associated with a slightly reduced bone density, putting patients at risk for osteoporosis and possibly fractures. The best medications for bone loss in patients with diabetes are bisphosphonates, such as alendronate (Fosamax) and risedronate (Actonel). They not only help prevent bone loss but may even reduce daily insulin requirements in patients taking insulin. [See In-Depth Report #18: Osteoporosis.]
Type 2 diabetes, on the other hand, is associated with an increased bone density but is also associated with fractures. In such cases, the bone quality itself may be impaired.

Older patients with either type of diabetes are at risk for falling, which compounds the risk for fracture.

Diabetes increases the risk for other conditions, including:

Hearing loss
Periodontal disease
Carpal tunnel syndrome
Nonalcoholic fatty liver disease, also called nonalcoholic steatohepatitis (NASH), a particular danger for people who are obese
Colorectal cancer
Uterine cancer

Emergency Complications

People with diabetes who need to intensively control glucose levels are at risk for low blood sugar (hypoglycemia). Hypoglycemia, also called insulin shock, develops if blood sugar levels fall below normal. It may also be caused by insufficient intake of food, excess exercise, or alcohol intake. The condition is usually manageable, but occasionally it can be severe or even life threatening, particularly if the patient fails to recognize the symptoms. Mild hypoglycemia is common among people with type 2 diabetes, but severe episodes are rare, even among those who are taking insulin. Still, all patients who intensively control blood sugar (glucose) levels should be aware of warning symptoms.

Risk Factors for Severe Hypoglycemia. People at highest risk for severe hypoglycemia are those who intensively control blood glucose and also have one or more of the following conditions:

Long-term diabetes
Less education on their condition
A previous history of severe hypoglycemia
Hypoglycemia unawareness

Hypoglycemia unawareness is a condition in which people become insensitive to hypoglycemic symptoms. It affects about 25% of patients who use insulin, nearly always people with type 1 diabetes. In such cases, hypoglycemia appears suddenly, without warning, and can escalate to a severe level. Even a single recent episode of hypoglycemia may make it more difficult to detect the next episode. With vigilant monitoring and by rigorously avoiding low blood glucose levels, patients can often regain the ability to sense the symptoms. However, even very careful testing may fail to detect a problem, particularly one that occurs during sleep.

Symptoms. Mild hypoglycemia symptoms usually occur at moderately low and easily correctable levels of blood glucose. They include:

Sweating
Trembling
Hunger
Rapid heartbeat

Severely low blood glucose levels can cause neurologic symptoms, such as:

Confusion
Weakness
Disorientation
Combativeness
In rare and worst cases, coma, seizure, and death

Preventive Measures. The following tips may help avoid hypoglycemia or prepare for attacks:

Patients are at highest risk for hypoglycemia at night. Bedtime snacks may be helpful.
Patients who intensively control their blood sugar should monitor blood levels as often as possible, four times or more per day. This is particularly important for patients with hypoglycemia unawareness.
In adults, it is also particularly critical to monitor blood glucose levels before driving, when hypoglycemia can be very hazardous.
Patients who use medications that put them at risk for hypoglycemia should always carry hard candy, juice, sugar packets, or commercially available glucose substitutes designed for individuals with diabetes.

Family and friends should be aware of the symptoms and be prepared:

If the patient is helpless (but not unconscious), family or friends should administer three to five pieces of hard candy, two to three packets of sugar, half a cup (four ounces) of fruit juice, or a commercially available glucose solution.
If there is inadequate response within 15 minutes, additional oral sugar should be provided or the patient should receive emergency medical treatment, including intravenous administration of glucose.
Family members and friends can learn to inject glucagon, a hormone, which, in contrast to insulin, raises blood glucose.

Click the icon to see a glucagon kit.

Diabetic ketoacidosis (DKA) is a life-threatening complication caused by insulin depletion. Until recently, it was a complication almost exclusively of type 1 diabetes. In such cases, it is nearly always due to noncompliance with insulin treatments. However, DKA is being reported increasingly in type 2 diabetes, especially among Hispanic- and African-Americans. It is not clear what causes total insulin depletion in these patients. Researchers are trying to learn which individuals are at particular risk.

Diabetic ketoacidosis often develop as follows:

The process is usually triggered in insulin-deficient patients by a stressful event, most often pneumonia or urinary tract infections. Other triggers include alcohol abuse, physical injury, pulmonary embolism, heart attacks, or other illnesses.
Severely low insulin levels cause excessive amounts of glucose in the bloodstream (hyperglycemia).
Fat breakdown then accelerates and increases the production of fatty acids.
These fatty acids are converted into chemicals called ketone bodies, which are toxic at high levels.

Symptoms and complications may include:

Nausea and vomiting
Abnormally deep and rapid breathing with frequent sighing
Rapid heartbeat
If the condition persists, coma and, eventually, death, may occur; however, over the past 20 years, death from DKA has decreased to about 2% of all cases.
Other serious complications from DKA include aspiration pneumonia and adult respiratory distress syndrome.

Life-saving treatment uses rapid rehydration with a saline solution followed by low-dose insulin and potassium replacement.

Resources

www.diabetes.org -- American Diabetes Association
www.niddk.nih.gov -- National Institute of Diabetes and Digestive and Kidney Diseases
www.americanheart.org -- American Heart Association
www.kidney.org -- National Kidney Foundation
www.nei.nih.gov -- National Eye Institute
www.medicalert.org -- Medic Alert
www.eatright.org -- American Dietetic Association
http://limaye.ecri.org -- Limaye Center

References

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Zeggini E, Weedon MN, Lindgren CM, Frayling TM, Elliott KS, Lango H, et al. Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. 2007 Jun 1;316(5829):1336-41. Epub 2007 Apr 26.

Review Date:
7/31/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

adam.com

Parkinson's disease

FitSugar — Wed, 08 Oct 2008 17:35:13 -0700

In This Report

Highlights
Introduction
Symptoms
Risk Factors
Complications
Diagnosis
Treatment
Levadopa (L-dopa)
Other Medications
Surgery
Lifestyle Changes
Resources
References

HEALTH GUIDE REFERENCE FROM A.D.A.M

Highlights

Drug Approvals

In 2007, the FDA approved the first skin patch drug for treatment of Parkinson’s disease. Transdermal rotigotine (Neupro) is a dopamine agonist drug that may help improve symptoms of early-stage Parkinson’s disease. The patch is applied daily.
Rivastigimine (Exelon), an Alzheimer’s disease drug, was approved in 2006 for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Drug Withdrawal

In 2007, the FDA withdrew the dopamine agonist pergolide (Permax) from the market due to safety concerns. Several articles published in 2007 in the New England Journal of Medicine indicated that pergolide and a similar drug, cabergoline (Dostinex), are associated with heart valve problems. Cabergoline is not approved in the U.S. for treatment of Parkinson’s disease.

Dietary Supplements

In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine may help slow the progression of Parkinson’s disease. Creatine is a nutritional supplement that is sometimes used to enhance exercise performance.
Coenzyme Q10, an antioxidant dietary supplement, does not help improve Parkinson’s disease symptoms, according to a study published in 2007 in the Archives of Neurology.

Deep-Brain Stimulation

Deep-brain stimulation outperformed drug therapy in a randomized trial comparing these two treatment approaches. In a study published in 2006 in the New England Journal of Medicine, patients who received deep-brain stimulation had better symptom and quality of life improvement than those who were treated with only medications. However, more serious side effects were reported in the deep-brain stimulation group. Deep-brain stimulation is a surgical technique that involves implanting electrodes in a target area of the brain.

Introduction

Parkinson's disease (PD) is a slowly progressive disorder that affects movement, muscle control, and balance. Parkinson's disease is referred to as idiopathic, which means that the cause is unknown. This term distinguishes the primary disease from parkinsonism, which are the symptoms occurring from a known cause. In addition to its effects on motor control, Parkinson's disease is now recognized as a broader condition that can include cognitive and behavioral disturbances, sleep disorders, speech difficulties, and other problems.

Parkinson's disease occurs from the following process in the brain:

PD develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra.

Parkinson's disease is a slowly progressive disorder that affects movement, muscle control, and balance. Part of the disease process develops as cells are destroyed in certain parts of the brain stem, particularly the crescent-shaped cell mass known as the substantia nigra. Nerve cells in the substantia nigra send out fibers to tissue located in both sides of the brain. There the cells release essential neurotransmitters that help control movement and coordination.

Nerve cells in the substantia nigra send out fibers to the corpus stratia, gray and white bands of tissue located in both sides of the brain.
There the cells release dopamine, an essential neurotransmitter (a chemical messenger in the brain). Loss of dopamine in the corpus stratia is the primary defect in Parkinson's disease.

Dopamine. Dopamine deficiency is the hallmark feature in PD. It is one of three major neurotransmitters known as catecholamines, which help the body respond to stress and prepare it for the fight-or-flight response. Loss of dopamine negatively affects the nerves and muscles controlling movement and coordination, resulting in the major symptoms characteristic of Parkinson's disease. Dopamine also appears to be important for efficient information processing, and deficiencies may also be responsible for problems in memory and concentration that occur in many patients.

Although it is clear that dopamine deficiency is the primary defect in Parkinson's disease, it is not clear what causes dopamine loss. The culprit is less likely to be a single cause than a combination of genetic and biologic factors, which are triggered by some environmental assault.

Other Changes. The PD disease process also appears to impair nerve endings in the heart to cause dysautonomia-- changes in the autonomic (also called sympathetic) nervous system. Such changes may impair the release of norepinephrine, a hormone that regulates blood pressure, pulse rate, perspiration, and other automatic responses to stress. Evidence suggests this may be responsible for the abrupt drops in blood pressure when standing that occur in PD. Further research is underway to determine if the loss of nerve terminals is confined to the heart or if it affects other organs as well.

Click the icon to see an animation about Parkinson's disease.

Apoptosis and Alpha Synuclein. Important research now suggests that three molecules are critical in the development of inherited PD: alpha synuclein, parkin, and ubiquitin, which all interact in the normal brain. Abnormally high levels of alpha synuclein, which is produced in dopamine-rich nerve cells, may play a central role. Normally, two other molecules, parkin and ubiquitin, are involved in the natural self-destruction of synuclein -- a natural process of programmed cell death called apoptosis. If this process goes awry, for instance, with a defective parkin gene, cell death fails to occur. If synuclein is not eliminated in these cells, it builds up and becomes toxic to dopamine. In such cases, synuclein accumulates in Lewy bodies, the deposits of fibrous tissue found in all patients with PD.

Another protein, beta amyloid, also increases the build-up of synuclein. Beta amyloid is a known factor in Alzheimer's disease, and may help explain the co-existence between Alzheimer's and Parkinson's disease in many patients.

Lewy Bodies. The fibrous deposits known as Lewy bodies are the hallmark signs of Parkinson's disease. They are found in the substantia nigra, the place in the brain where dopamine is first released. It is not clear whether Lewy bodies are the major killers of the nerve cells or whether they are simply a byproduct of the degenerative process. They are found not only in the brains of patients with Parkinson's disease but, in rare cases, may show up in cells in other parts of the body (the heart, intestine), causing severe disabling symptoms. These substances are also present in other diseases that cause dementia, such as Alzheimer's, and can occur in people without neurologic symptoms.

The Mitochondria and Oxygen-Free Radicals. Some research has observed that certain patients with PD have significantly low levels of complex I, an enzyme found in the mitochondria, sausage-like structures that are the primary source of energy within cells. Some theories suggest that low amounts of complex I may make nerve cells vulnerable to the assault of oxygen free radicals (also called oxidants). Oxidants are unstable molecules that bind to other molecules in the body. They are normally produced by the natural chemical processes in the body. If the body is subjected to environmental stresses, however, they can be over-produced. In excess, they can damage any cell, including nerve cells in the brain, and even interfere with their DNA.

NMDA Receptors. Also of interest in PD are processes that occur in an area of the brain called the subthalamic nucleus. Here, receptors known as glutamatergic N-methyl-D-aspartate (NMDA) become persistently overexcited and produce high levels of calcium ions within brain cells. This in turn leads to a cascade of events that trigger oxygen-free radicals and cell damage.

Immune Factors and the Inflammatory Response. An over-responsive immune system triggered by initial damage may also play a role in perpetuating Parkinson's disease. When the immune system becomes overactive, it produces excessive numbers of potent factors called cytokines, which cause inflammation and further injury in brain cells. Important cytokines under investigation are interleukin-1 and tumor necrosis factor.

Specific genetic factors appear to play a strong role in early-onset Parkinson's disease, an uncommon form of the disease. Research from the last several years suggests that multiple genetic factors may also be involved in late-onset Parkinson’s disease. Several important studies, published in 2005, lay the groundwork for potential genetic screening for this disease. Researchers identified the leukine-rich repeat kinase 2 (LRRK2) gene, located on a region of chromosome 12 known as PARK8, as a key gene involved in inherited forms of Parkinson’s. The researchers estimate that a single gene mutation in LRRK2 may be responsible for 5% of inherited Parkinson’s cases and about 2% of isolated cases.

Early Onset PD. The cases of genetic early-onset Parkinson's disease have most often been detected in specific family groups.

Defective genes that regulate the molecules alpha synuclein and parkin, which are important in the PD disease process, may be responsible for a number of early-onset cases. For example, genetic abnormalities the alpha synuclein protein have been detected in some early-onset Parkinson's patients of European descent.
The parkin gene may be the cause of many cases of early-onset Parkinson's in young adults. (Parkinson's cases associated with this mutation tend to progress slowly and respond well to treatment, even after years of symptoms. Dementia is also rare with this form.)

Late Onset PD. Two landmark studies published in the Journal of the American Medical Association provided the first evidence of a genetic link to late-onset Parkinson’s disease. In these 2001 studies, researchers found that regions on chromosomes 5, 6, 8, 9, and 17 were implicated with Parkinson’s. The parkin gene (located on chromosome 6) and the tau gene (located on chromosome 17) were both found in families that had late onset Parkinson’s. Parkin was previously thought to be responsible only for early-onset Parkinson’s, but this research identified it in families that had both early- and late-onset disease forms. These studies also bolstered the theory that Parkinson’s does have a genetic component and is not caused solely by environmental factors. A 2005 study found that a G2019S mutation in the LRRK gene, located on the PARK8 region of chromosome 12, was definitively associated with late-onset Parkinson’s disease in North American and European families.

Environmental toxins, infections, and other triggers can provoke excessive production in the body of oxygen free-radicals, damaging particles that may play a major role in the deterioration of nerve cells that lead to Parkinson's.

Infectious Organisms. Some research has identified immune factors that suggest a viral presence in the Lewy bodies and swollen nerve pathways of Parkinson's brains. Influenza and other potent viruses have long been known to be a cause of parkinsonism. In one well-known example, a major flu epidemic causing encephalitis in the early twentieth century left many of its victims with parkinsonism.

Environmental and Industrial Chemicals. Intense exposure to certain environmental and industrial chemicals is also being studied.

Pesticides and Herbicides. Some evidence implicates pesticides and herbicides as important factors in many cases of Parkinson's disease. A higher incidence of parkinsonism has long been noted in people who live in rural areas, particularly those who drink private well water or are agricultural workers. A large 2000 study found a strong link between high exposure to insecticides and herbicides at home and a 50 - 70% increase in risk of Parkinson's.
Other Chemicals. Intense exposure to other industrial chemicals and metals (manganese, copper, lead, iron, mercury, zinc, aluminum, and others) has also been linked with parkinsonism, a cause that is often reversible. The role of long-term exposure in the development of Parkinson's disease is unclear. High levels of iron content observed in critical parts of the brain in PD are under particular scrutiny.

Most, but not all, Parkinson's victims are elderly. Some studies indicate that the very elderly are not susceptible to the disease, indicating that the aging process itself is not the major player in the disease. Aging does appear to reduce the concentration of dopamine in structures called dopamine transporters, which carry the neurotransmitter back and forth between nerve cells. Some researchers posit that any excessive stress on these transporters might trigger Parkinson's disease in the aging, and more vulnerable, brain.

Symptoms

Parkinson's disease (PD) symptoms often start with tremor, which may occur in the following ways:

Tremors may first be only occasional, starting in one finger and spreading over time to involve the whole arm. The tremor is often rhythmic, 4 - 5 cycles per second, and frequently causes an action of the thumb and fingers known as pill rolling.
Tremors can occur when the limb is at rest or when it is held up in a stiff unsupported position. They usually disappear briefly during movement and do not occur during sleep.
Tremors can also eventually occur in the head, lips, tongue, and feet. Symptoms can occur on one or both sides of the body. In one study, 44% of patients reported experiencing internal tremors lasting less than half an hour, but occurring several times a week.

In younger patients tremor is usually predominant and often suggests a less aggressive form of the disease. Some evidence suggests that tremor in PD may occur from mechanisms in the brain that are different from those that cause other PD symptoms.

A number of PD symptoms involve motor impairment caused by the abnormalities in the brain that regulate movement:

Slowness of motion (bradykinesia) is one of the classic symptoms of Parkinson's disease. Patients may eventually develop a stooped posture and a slow, shuffling walk. The gait can be erratic and unsteady. After a number of years, muscles may freeze up or stall, usually when a patient is making a turn or passing through narrow spaces, such as a doorway.
Intestinal motility (the ability to swallow, digest, and eliminate) may slow down, causing eating problems and constipation.
Muscles may become rigid (akinesia). This symptom often begins in the legs and neck. Muscle rigidity in the face can produce a mask-like, staring appearance.
Motor abnormalities that limit action in the hand may develop in late stages. Handwriting, for instance, often becomes diminutive.
Normally spontaneous muscle movements, such as blinking, may need to be done consciously.

The traditional view of Parkinson's disease is shifting to reflect growing awareness that it is much more than a motor disease. Many non-motor components and their treatments are now under study. The following symptoms should be carefully monitored by doctors and caregivers:

Depression is the most common psychiatric problem associated with PD, affecting about 40% of patients. Because depression is a common problem in older people, it is likely not to be recognized as a symptom.
Anxiety affects about 30% of patients.
Dementia and paranoia are more common than previously understood.
Orthostatic hypotension -- some patients experience a sudden drop in blood pressure when they stand. This can cause dizziness and fainting.
Changes in sensations of temperature, hot flashes, and excessive sweating.
Daytime sleepiness and other sleep disorders are common.

Risk Factors

Parkinson's disease affects about 3% of Americans over 65 years old. Experts estimate that this percentage could double in the next 30 - 40 years. The symptoms of parkinsonism (tremor, gait disturbance, bradykinesia, and rigidity) occur in even more people, estimated to be 8 million over age 65. In a study that included very mild symptoms, parkinsonism occurred in about 15% of people 65 - 74 years of age, about 30% in those 75 - 84, and over half of people older than age 85.

The average age of onset of Parkinson's disease is 55. About 10% of Parkinson's cases are in people younger than 40 years old. Older adults are at higher risk for both parkinsonism and Parkinson's disease. There is some evidence, however, that the risk declines significantly after age 75 and that the very elderly are at low risk.

Some research indicates that men may face up to twice the risk as women. Estrogen may offer some protection for women up until menopause. A 2001 study, for example, reported a higher rate of Parkinson's disease in women who had undergone hysterectomy. Other studies suggest that the disease also progresses more rapidly in men than women. Older women seem to be more at risk for gait disturbance and men for rigidity and tremor.

People with siblings or parents who developed Parkinson's at a younger age are at higher risk for Parkinson's disease, but relatives of those who were elderly when they had the disease appear to have an average risk.

African- and Asian-Americans have a lower risk than Caucasians. Some evidence suggests that non-Caucasians may be more vulnerable to an atypical form of PD, which causes early impairment in thinking and has a poor response to levodopa, the primary PD treatment.

Increasing weight gain in middle age was associated with a higher risk of PD in a 2002 study.

Complications

Parkinson's disease (PD) is not fatal, but it can reduce longevity. The disease progresses more quickly in older than younger patients, and may lead to severe incapacity within 10 - 20 years. Older patients also tend to experience freezing and greater declines in mental function and daily functioning than younger people. If PD starts without signs of tremor, it is likely to be more severe than if tremor had been present. Having other family members with PD does not appear to have any effect on the severity of the disease.

Parkinson's disease can seriously impair the quality of life in any age group. The physical and emotional impact on the family should not be underestimated as the patient becomes increasingly dependent on their support.

Treatment advances are increasingly effective in alleviating symptoms and even slowing progression of the disease. Taking many of the medications over time, however, can produce significant side effects. Newer drugs may help reduce these occurrences.

The negative effect of overall motor and muscle impairment on daily life can be considerable. Some motor complications can be life-threatening.

Disturbed gait and unstable posture are common and serious problems in elderly patients, since they increase the risk for falling and injury. Some studies have suggested that the appearance of these symptoms early in the course of the disease predict a faster decline than having tremor as the predominant symptom.
Swallowing problems (dysphagia). The presence of dysphagia is associated with shorter survival time. Motor impairment of the muscles in the throat not only impairs swallowing but it also poses a risk for aspiration pneumonia.
Constipation is a major problem and occurs both as a result of the disease and a side effect of its treatment. Laxatives, stool softeners, and other medications may be prescribed.
Bladder control and urinary incontinence are also important complications of PD.
Speech problems occur in more than 70% of patients, by some estimates. Speech difficulty can be caused by rigidity of the facial muscles, loss of motor control, and impaired breath control. Tone can become monotonous, words may be repeated over and over, or the rate of speech may even be very fast.

Depression is extremely common, affecting up to 40% of patients with Parkinson's. PD poses multiple threats on the emotional health:

The disease process itself causes changes in chemicals in the brain that affect mood and well-being.
The complications of its symptoms have a profound impact on daily life that can be emotionally devastating without help and support.
Some drug treatments (levodopa combined with a dopamine agonist) can cause compulsive behavior, such as gambling, shopping, and increased sexuality. Patients who have pre-existing tendencies to novelty-seeking behavior, or a family or personal history of alcohol abuse, may be more likely to develop compulsive gambling. Deep brain stimulus (DBS) surgery may also increase the risk for compulsive gambling in patients who have a history of gambling.

Impaired Thinking (Cognitive Impairment). Defects in thinking, memory, language, and problem solving skills may occur early on in untreated patients or late in the course of the disease. Medications may play a role in thinking problems. In one study, for example, patients with PD were slower in detecting associations, although (unlike in Alzheimer's disease) once they discovered them they were able to apply this knowledge to other concepts. After they were taken off medication, however, they had no problems with the tasks.

Dementia. Dementia is three to six times more common in the elderly Parkinson patient than in the average older adult. It is most likely to occur in older patients who have had major depression. PD marked by muscle rigidity (akinesia), rather than tremor, and early hallucinations also increase the risk for dementia. (Visual hallucinations can also occur in about a third of patients from PD medication.) Unlike in Alzheimer's, language is not usually affected in Parkinson's related dementia.

A number of other problems associated with Parkinson's disease affect daily life:

Vision Problems. Vision is also affected, including impaired color perception and contrast sensitivity. These problems progress and can impair motor functioning.

Sleep Disorders. Excessive daytime sleepiness and other sleep disorders are common in PD, both from the disease itself and from the drugs that treat it. In general, patients have a 25% higher risk for daytime sleepiness, including suddenly falling asleep, than patients with other neurologic diseases.

Restless legs syndrome, an irresistible urge to move the calves, which often occurs at night, affects many patients. However, Parkinson's disease itself does not seem to increase the risk for RLS. Nor does RLS early in life predispose to Parkinson's later on. The common connection between RLS and Parkinson's disease may derive from iron deficiencies that can play a role in both conditions.

Many patients also suffer from nighttime leg cramps. And, some of the medications cause vivid dreams as well as waking hallucinations.

Impaired Sexuality. Although Parkinson's disease and its treatments can cause compulsive sexual behavior, the disease can also affect patients' self-esteem and inhibit sexuality. This is an area not often studied but which is important for many patients' well-being. A 2000 study reported that not only did sexual dysfunction occur, but also affectionate touching and expression of feelings were reduced, even though both partners maintained a desire for intimacy.

Worsened Sense of Smell. The sense of smell is impaired in about 70% of patients.

Osteoporosis. Parkinson’s disease may increase the risk for low bone density and osteoporosis. Both men and women are at risk. Experts recommend that patients with Parkinson’s disease get tested for osteoporosis, especially if they have problems with walking.

Diagnosis

It is difficult to diagnose Parkinson's in early stages. The disease is primarily diagnosed by its symptoms, and studies indicate that doctors make an incorrect initial diagnosis of Parkinson's disease in 8 - 35% of cases. Even neurologists have difficulties in correctly identifying the disease.

A medical and personal history should include any relevant symptoms as well as any medications taken, and information on exposure to environmental toxins.

Early Symptoms. Early treatment may help slow progression, so an early diagnosis of Parkinson's is highly desirable. Early symptoms are often mild, however, so Parkinson's disease can be missed, particularly in young adults. Repeated assessment of symptoms over time is important for improving the accuracy of diagnosis. Too often a younger person with Parkinson's may be diagnosed with mental illness, because the doctor associates the disease only with older people.

Parkinson's may be suspected in patients with the following symptoms:

Slowness and difficulty of movement. These are usually the first symptoms. The patient will be asked to walk and to get out of a chair, preferably a deep one. Early gait disturbance, however, often indicates a disease other than Parkinson's disease.
A tremor when their limb is relaxed. (As many as 25% of patients, however, will not have a tremor.)
Symptoms on one side of the body.

Later Symptoms. In later stages of Parkinson's disease, the symptoms are usually unmistakable, and the problem can often be diagnosed using simple physical tests and a medical and personal history.

The loss of smell is associated with loss of dopamine receptors in the brain. “Scratch and sniff” smell tests can help a doctor diagnose Parkinson’s disease. Smell tests can help differentiate Parkinson’s disease from other conditions with similar symptoms. Some patients with a very similar condition called multiple system atrophy will have a good initial response to levodopa, but it is not usually sustained.

Levodopa and apomorphine can confirm a diagnosis of Parkinson’s disease. If patients’ symptoms improve when they take these drugs, they likely have Parkinson’s, ruling out other neurological diseases.

According to 2006 guidelines from the American Academy of Neurology, there is not enough evidence to recommend for or against the use of imaging techniques such as computerized tomography (CT), magnetic resonance imaging (MRI), or positron-emission tomographic (PET) to diagnose PD.

When symptoms resemble Parkinson's disease but have an identifiable cause, the syndrome is known as parkinsonism. People who have parkinsonism, but not Parkinson's disease, often have additional neurologic symptoms. A number of conditions can also have similar or some of these symptoms.

Other Neurologic Conditions. Many medical conditions may cause symptoms of Parkinson's disease:

Hardening of the arteries (arteriosclerosis) in the brain can cause multiple small strokes, which can produce loss of motor control.

Click the icon to see an image of plaque in an artery.

Alzheimer's disease can be very similar. In one study 23% of people with Alzheimer's also met the criteria for Parkinson's disease. The two diseases often coexist, and research suggests that Alzheimer's and Parkinson's disease may sometimes share a common biologic origin, the accumulation of the protein alpha synuclein and Lewy bodies in the brain.
Lewy bodies variant (LBV), also called dementia with Lewy bodies, is a separate disease from both Alzheimer's and Parkinson's disease. It has similar symptoms to both but is marked by early dementia.
Encephalitis caused by influenza has been known to cause parkinsonism.
Primary progressive freezing gait is a progression condition, in which freezing gait occurs at the onset. Other Parkinson-like features, such as slow movement, often develop. Although very similar to PD, this condition does not respond to L-dopa or other PD medications.
Essential tremor, unlike the tremor of Parkinson's disease, often occurs in the head and voice and is usually worse during motion, as opposed to rest.
Progressive supranuclear palsy has similar symptoms, but involves less tremor and earlier rigidity, and it tends to affect both sides of the body symmetrically. Magnetic resonance imaging scans that measure parts of the midbrain may be a reliable method for distinguishing between PD and progressive supranuclear palsy.
Multiple system atrophy (previously called Shy-Drager syndrome) is a degenerative nerve disease that also affects movement and blood pressure and has many of the symptoms of Parkinson's disease. Some research suggests that a trial using the drug apomorphine may help differentiate between the two.
Other problems that may mimic Parkinson's disease include Wilson's disease, thyroid abnormalities, hydrocephalus, tumors, having the fragile X trait (but not the full disorder), and a number of degenerative neurologic diseases.

Drugs. Certain drugs or medications account for about 4% of all cases of parkinsonism. According to some studies, patients who experience drug-induced parkinsonism may actually be at an increased risk of developing Parkinson's disease later in life. A number of drugs can cause these symptoms, including antipsychotic and antiseizure drugs. Anyone with parkinsonism should discuss their medications with their doctor.

The American Academy of Neurology (AAN) recommends the Beck Depression Inventory or the Hamilton Depression Rating Scale to screen for depression in patients with Parkinson’s disease. The AAN recommends the MMSE and CAMCOG tests to screen for dementia. During these tests, the patient answers a series of questions.

Treatment

Drugs, physical therapy, and surgical interventions can manage Parkinson's disease. The goals of treatment for Parkinson's disease are to:

Relieve disabilities
Balance the problems of the disease with the side effects of the medications

Treatment is very individualized for this complicated disease. Patients must work closely with doctors and therapists throughout the course of the disease to customize a program suitable for their particular and changing needs. Patients should never change their medications without consulting their doctor, and they should never stop taking their medications abruptly.

The American Academy of Neurology recommends the following therapies for the initial treatment of Parkinson’s disease:

Levodopa (L-dopa). Levodopa, or L-dopa, has been used for years and is the gold standard for treating Parkinson's disease. The drug increases brain levels of dopamine. It is used in nearly all phases of the disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, a drug that slows the breakdown of levodopa. Levodopa is better at improving motor problems than dopamine agonists but increases the risk of involuntary movements (dyskinesia).

Dopamine Agonists. Dopamine agonist drugs mimic dopamine to stimulate the dopamine system in the brain. These drugs include pramipexole (Mirapex), ropinirole (Requip), bromocriptine (Parlodel), and rotigotine (Neupro). The Food and Drug Administration (FDA) pulled the dopamine agonist pergolide (Permax) from the market in March 2007 over safety concerns that included potentially fatal heart valve damage.

Selegiline (Eldepryl) and rasagiline (Azilect). Selegiline is a monoamine oxidase B (MAO-B) inhibitor that may have some mild benefit as an initial therapy. However, unlike levodopa, it does not slow the progression of Parkinson’s disease. Another MAO-B inhibitor, rasagiline (Azilect), was approved in May 2006. Unlike selegiline, which needs to be taken by mouth twice a day, rasagiline needs to be taken only once a day.

Drug treatments for Parkinson disease do not consistently control symptoms. At certain points during the day, the beneficial effects of drugs wear off, and patients can experience a return of symptoms, such as uncontrolled muscular motor function, difficulty walking, and loss of energy. In 2006, the American Academy of Neurology (AAN) reviewed evidence for the various drugs used to treat “off time.” The AAN found that the following drugs had the strongest evidence for controlling off time symptoms:

Entacapone (Comtan) belongs to a class of drugs called catechol-o-methyl transferase (COMT) inhibitors. COMT inhibitors help prolong the effects of levodopa by blocking an enzyme that breaks down dopamine.
Rasagiline (Azilect) belongs to a class of drugs called monoamine oxidase (MAO) inhibitors. These drugs slow the breakdown of dopamine that occurs naturally in the brain and dopamine produced from levodopa.

The AAN also found good evidence for the dopamine agonists ropinirole (Requip) and pramipexole (Mirapex), and the COMT inhibitor tolcapone (Tasmar). Deep brain stimulation is a surgical treatment that may help improve motor fluctuations in some patients.

Both Levodopa and dopamine agonists can cause involuntary movements (dyskinesia). The AAN has not found any strong evidence to recommend any drug for treating dyskinesia. However, weak evidence suggests that the antiviral drug amantadine (Symmetrel) may help reduce stiffness and improve dyskinesia. There is also weak evidence that deep brain stimulation of the subthalamus area may be helpful.

Conditions associated with motor impairment and other symptoms of Parkinson's disease may require a variety of treatments.

Depression. Although depression is very common in PD, there have been surprisingly few controlled studies. Antidepressants used for PD include tricyclics, particularly amitriptyline (Elavil). Some studies have found that selective serotonin-reuptake inhibitors (SSRIs) -- which include fluoxetine (Prozac), sertraline (Zoloft), and paroxetine (Paxil) -- may worsen symptoms of Parkinson's. Doctors should monitor patients taking SSRIs.

Psychotic Side Effects. Studies indicate that clozapine (Clozaril) and quetiapine (Seroquel), antipsychotic drugs used to treat schizophrenia, may be the best drugs for treating psychosis in patients with Parkinson's disease. A similar drug, olanzapine (Zyprexa), should not be used for patients with PD because it can worsen their psychotic symptoms.

Dementia. The cholinesterase inhibitor drugs donepezil (Aricept) and rivastigmine (Exelon) are used to treat Alzheimer’s disease. Studies suggest that these drugs may also help treat dementia associated with Parkinson’s disease. In 2006, rivastigimine was approved for treatment of mild-to-moderate dementia associated with Parkinson’s disease.

Daytime Sleepiness. Modafinil (Provigil), a drug used to treat narcolepsy, is proving to be very helpful for patients with sleepiness related to their disease.

Drooling. In search of a simple solution for the problem of drooling, scientists have reported that injections of very small amounts of botulinum toxin effectively reduce saliva production and drooling. In such small amounts the toxin is safe.

Voice Loss. A relatively simple procedure using collagen injections in the neck appears to be a safe and effective method of improving the voice and speech disorders caused by PD. The procedure augments the collagen in the vocal fold and works best in patients who can still initiate speech. A 2001 study reported improvements that lasted from 2 - 7 months in 61% of patients.

Erectile Dysfunction. Sildenafil (Viagra) is proving to be very helpful for men who suffer from impotence from Parkinson's disease. However, the drug may worsen orthostatic hypotension, a side effect of some PD medications.

Eventually, symptoms such as stooped posture, freezing, and speech difficulties may not respond to drug treatment. (Total unresponsiveness is unlikely, however, even after 20 years of treatment.) The following approaches may be tried:

Simply increasing the dose of levodopa or its frequency raises an unacceptable risk of the distressing side effects. Some doctors have tried hospitalizing patients, totally withdrawing the levodopa, and then re-administering it. Benefits were seen for only a few months, however, and there were some dangerous risks to the process of withdrawal, including pneumonia and blood clots in the lungs.

An embolus is a blockage of an artery in the lungs by fat, air, tumor tissue, or blood clot.

Surgical treatments, including deep brain stimulation and pallidotomy, may help some patients.
Research is ongoing to develop drugs and procedures that will manage advanced disease and possibly even reverse the process.

Levadopa (L-dopa)

Levodopa, also called L-dopa, which is converted to dopamine in the brain, remains the gold standard for treating Parkinson's disease. The standard preparations (Sinemet, Atamet) combine levodopa with carbidopa, which improves the action of levodopa and reduces some of its side effects, particularly nausea. Levodopa can also be combined with benserazide (Madopar) with similar results, but Sinemet is almost always used in America. Dosages vary, although the preparation is usually taken in three or four divided doses per day. In 2004, the FDA approved a new oral form of carbidopa-levodopa (Parcopa) that dissolves on the tongue.

In general L-dopa has the following effects on Parkinson's disease:

It is most effective against rigidity and slowness.
It produces less benefit for tremor, balance, and gait.

In many patients, levodopa significantly improves the quality of life for many years. If symptoms do not improve after 2 - 3 months, one of the following reasons may account for the failure:

Other neurologic problems may be causing the symptoms.
Some patients have abnormalities in other brain sites that do not respond to L-dopa.
Sometimes patients are so depressed they cannot tell if the drug is beneficial or not. Only a series of physical examinations by the doctor will indicate that the drug is actually helping.

Studies suggest that levodopa may help slow disease progression and protect against brain cell degeneration.

The toxic effects of levodopa with or without carbidopa are considerable.

Physical Side Effects. The physical side effects are as follows:

Low blood pressure. Low blood pressure is a common problem during the first few weeks, particularly if the initial dose is too high. The addition of extra supplements of carbidopa reduces this effect to some degree. The patient should drink lots of fluids and possibly increase salt intake to maintain normal blood pressure.
Arrhythmia. In some cases the drug may cause abnormal heart rhythms.
Gastrointestinal effects. Stomach and intestinal side effects are common even with carbidopa. Taking the drug with food can alleviate the nausea. However, proteins interfere with intestinal absorption of levodopa, and some doctors recommend not eating any protein until nighttime in order to avoid this interference. The drug can also cause gastrointestinal bleeding.
Effects in the lung. Levodopa can cause disturbances in breathing function, although it may benefit patients who have upper airway obstruction.
Hair loss.

Psychiatric and Mental Side Effects. The major adverse effects of the drug are psychiatric. Patients taking levodopa, especially in combination with other drugs, can experience:

Confusion.
Extreme emotional states, particularly anxiety.
Vivid dreams.
Visual and possibly auditory hallucinations. The drug may even unmask dementia that had not been previously noticed.
Effects on learning. L-dopa appears to have mixed effects on learning. It may improve working memory. However, some evidence suggests that it impairs areas of the brain related to other learning functions and social behavior.
Sleepiness and sleep attacks.

Levodopa causes fewer psychiatric side effects than other drugs used for Parkinson's disease, including anticholinergics, selegiline, amantadine, and dopamine agonists. Because psychiatric side effects often occur at night, if they are severe some doctors recommend reducing or stopping the evening dose.

Within 4 - 6 years of treatment with levodopa, the effects of the drug in many patients begin to last for shorter periods of time (called the wearing-off effect) and the following pattern may occur:

Patients may first notice slowness (bradykinesia) or tremor in the morning before the next dose is due.
Less commonly, some experience painful dystonia, muscle spasms that can cause sustained contortions of various parts of the body, particularly the neck, jaw, trunk, and eyes and possibly the feet.
Patients must increase the frequency of levodopa doses. This puts them at risk for dyskinesia (the inability to control muscles), which usually occurs when the drug level peaks. Dyskinesia can take many forms, most often uncontrolled flailing of the arms and legs or chorea, rapid and repetitive motions that can affect the limbs, face, tongue, mouth, and neck. Dyskinesia is not painful, but it is very distressing.
In some people, eventually L-dopa is effective only for 1 - 2 hours and most patients start to experience motor fluctuations. In about 15 - 20% of patients such fluctuations become extreme, a phenomenon known as the on-off effect, which consists of unpredictable, alternating periods of dyskinesia and immobility. Sometimes the symptoms switch back in forth within minutes or even seconds. (The transition may follow such symptoms as intense anxiety, sweating, and rapid heartbeats.)

Reasons for the Wearing-Off Effect. Debate is ongoing about the cause of the wearing-off effect and dyskinesia. Some theories suggested for these effects are:

The disease progresses beyond the ability of levodopa to control it.
Some patients become tolerant to prolonged exposure to dopamine and, at the same time, the disease is progressing.
The brain's own dopamine neurons become incapable of storing dopamine. When the levodopa wears off, little or no natural dopamine remains.
Levodopa itself accelerates the disease by producing oxygen free radicals, unstable particles that increase injuries to the brain and dopamine degradation.

Preventing the Wearing-Off Effect. To reduce the effects of fluctuation and the wearing-off effect, it is important to maintain as consistent a level of dopamine as possible. Unfortunately, levodopa is poorly absorbed and may remain in the stomach a long time. A number of strategies are being developed to take care of these problems:

Some patients take multiple small doses on an empty stomach, crushing the pills and mixing them with a lot of liquid.
A liquid form of Sinemet may produce fewer fluctuations and a prolonged "on" time compared with the tablet.
A prolonged release version of levodopa and carbidopa (Sinemet CR) is also available to control fluctuations for some people. (Some evidence suggests that there is no actual difference in symptom control between the sustained and immediate release forms, but patients on Sinemet CR tend to experience a better quality of life.)

Other Medications

Selegiline (Eldepryl, Movergan, Zelepar), also known as deprenyl, is an antioxidant drug that blocks monoamine oxidase B (MAO-B), an enzyme that degrades dopamine. Until recently, selegiline was the drug most commonly used in early-onset disease and in combination with levodopa for maintenance. A major 2002 study reported, however, that although selegiline delays the need for L-dopa by a few months, it has no effect on long-term progression.

Rasagiline (Azilect), another MAO-B inhibitor, was approved in May 2006 for the initial treatment of Parkinson’s disease. It is used alone during early-stage PD and in combination with L-dopa for moderate-to-advanced PD. Unlike selegiline, which is taken twice a day, rasagiline is taken once a day.

Other Adverse Effects. MAO-B inhibitors may have severe side effects:

One of the most important side effects is orthostatic hypotension, particularly in people taking Sinemet plus selegiline. This condition is a sudden drop in blood pressure that causes dizziness and lightheadedness when a patient stands up. Orthostatic hypotension can also occur with other Parkinson's drugs.
Can cause high blood pressure (hypertension) if combined with drugs that increase serotonin levels -- such drugs include nearly every major antidepressant. Patients suffering from depression and taking selegiline should discuss all treatment options with their doctor.
Can also cause a dangerous increase in blood pressure if patients eat foods rich in the amino acid tyramine. Patients should avoid the following foods while taking selegiline or rasagiline and for 2 weeks after stopping medication: aged cheeses, air-dried meats, pickled herring, yeast extract, aged red wines, draft beers, sauerkraut, and soy sauce

Debate over Mortality Rates. Some major studies have reported higher mortality rates in patients with advanced PD. Such findings may be due to adverse effects on the heart and blood vessels. Although other studies have not reported lower survival rates, some experts believe that, given its modest effects, selegiline may be a poorer drug choice than others, particularly in patients with risk factors for heart disease.

Dopamine agonists stimulate dopamine receptors in the substantia nigra, the part of the brain in which Parkinson's is thought to originate. Dopamine agonists are effective in delaying motor complications during the first 1 or 2 years of treatment.

Newer Dopamine Agonists. The most commonly prescribed dopamine agonists are pramipexole (Mirapex) and ropinirole (Requip). They are used either alone or in combination with L-dopa. Pramipexole appears to work better and have fewer side effects than ropinirole.

Studies still report, however, that L-dopa is superior for improving motor function. In one study, motor function was no different in disease progression among all of the drugs by the third year of treatment. Recent research suggests that L-dopa is better at improving motor disability and dopamine agonists are better at reducing motor complications. L-dopa has a higher risk for dyskinesia side effects than dopamine agonists, but dyskinesia can also occur with dopamine agonists.

Side Effects. Side effects of pramipexole and ropinirole vary but can be severe and include:

Gastrointestinal side effects (nausea and constipation). Nausea can be controlled by drugs, such as domperidone.
Headache
Orthostatic hypotension (sudden drop in blood pressure upon standing up)
Nasal congestion
Nightmares, hallucinations, and psychosis (more severe than with L-dopa for both drugs)
Sudden sleep attacks. These can be very serious, particularly if patients are driving. (Sleep attacks may occur -- although less commonly -- with other PD drugs.)

Other Dopamine Agonists.

Specific dopamine agonists that contain ergot alkaloids include bromocriptine (Parodel), pergolide (Permax), cabergoline (Dostinex), and lisuride (Dopergin). As of 2007, bromocriptine is the only ergot dopamine agonist approved for Parkinson’s treatment in the United States. In January 2007, the New England Journal of Medicine (NEJM) published two studies indicating that pergolide and cabergoline are associated with heart valve damage. In March 2007, due to these safety concerns, the FDA withdrew pergolide from the U.S. market. Cabergoline and lisuride are not approved in the U.S. for Parkinson’s disease treatment but are used for this purpose in other countries. The NEJM studies did not find any heart valve problems associated with bromocriptine or lisuride.
Rotigotine transdermal (Neupro) is a dopamine agonist that is delivered through a skin patch that is changed daily. In 2007, the FDA approved rotigotine transdermal for treatment of symptoms of early Parkinson’s disease. It is the first skin patch approved for Parkinson’s disease. Side effects are similar to those of other dopamine agonists.
Apomorphine is a dopamine agonist used as a "rescue" drug in people experiencing on-off effects severe enough to require going off L-dopa for a few days. In 2004, the FDA approved apomorphine for treating off-time episodes of Parkinson’s disease. Apomorphine is given by injection. Because it causes severe nausea and vomiting, it must be taken with an anti-nausea drug.

Catechol-O-methyl transferase (COMT) inhibitors increase concentrations of existing dopamine in the brain. Entacapone (Comtan, Stalevo) is the current standard COMT inhibitor. (Stalevo combines entacapone and levodopa into a single pill.) It improves motor fluctuations related to the wearing-off effect and has shown good results in improving on time and reducing the requirements for L-dopa. If the patient does not respond to the drug within 3 weeks, it should be withdrawn. No one should withdraw abruptly from these drugs.

Side Effects. Side effects include:

Involuntary muscle movements
Mental confusion and hallucinations
Cramps, nausea, and vomiting
Insomnia
Headache
Urine discoloration (a harmless side effect but should be reported to the doctor)
Diarrhea
Less commonly, constipation, susceptibility to respiratory infection, sweating, dry mouth

Of major concern are reports of a few deaths from liver damage in patients taking the COMT inhibitor tolcapone (Tasmar). The drug has been taken off the market in many countries and is recommended in the U.S. only for patients who cannot tolerate another other drugs. Entacapone does not appear to have the same effects on the liver and does not require monitoring. A 2003 3-year study suggested that the drug is safe and effective over the long term. Still, patients should watch out for symptoms of liver damage, including jaundice (yellowish skin), fatigue, and loss of appetite.

Jaundice is a condition produced when excess amounts of bilirubin circulating in the bloodstream dissolve in the subcutaneous fat (the layer of fat just beneath the skin), causing a yellowish appearance of the skin and the whites of the eyes. With the exception of normal newborn jaundice in the first week of life, all other jaundice indicates overload or damage to the liver, or inability to move bilirubin from the liver through the biliary tract to the gut.

Anticholinergics were the first drugs used for PD, but have largely been replaced by dopamine drugs. They are generally used only against tremor in the early stages. They are not as effective against bradykinesia and posture problems and may increase the risk for dementia in late stages. Among the many anticholinergics are trihexyphenidyl (Artane, Trihexy), benztropine (Cogentin), biperiden (Akineton), procyclidine (Kemadrin), and ethopropazine (Parisdol). Orphenadrine (Norflex) is a drug with anticholinergic properties, but is also a muscle relaxant and does not cause urinary retention.

Side effects of Anticholinergics. Anticholinergics commonly cause dryness of the mouth (which can actually be an advantage in some people who experience drooling). Other side effects are nausea, urinary retention, blurred vision, and constipation. These drugs can also increase heart rate and worsen constipation. Anticholinergics can sometimes cause significant mental problems, including memory loss, confusion, and even hallucinations. People with glaucoma should use these drugs cautiously.

Amantadine (Symadine, Symmetrel) stimulates the release of dopamine and may be used for patients with early mild symptoms. It has some benefit against muscle rigidity and slowness and may help some patients in advanced stages who are unresponsive to other drugs. It is less powerful than levodopa and may lose its effectiveness after 6 months. It may also reduce motor fluctuations brought on by levodopa, however, and these benefits appear to persist for at least a year. Large, well-conducted studies are still needed to determine its true benefits and safety.

Side Effects. Side effects are similar to those of anticholinergic drugs and also may include swollen ankles and mottled skin. It can also cause visual hallucinations. Overdose can cause serious and even life-threatening toxicity. Patients with Parkinson's should not withdraw from this drug abruptly. In rare instances, it can cause acute delirium or a life-threatening condition called neuroleptic malignant syndrome. Pregnant or nursing women should not use this drug.

Anticonvulsants. Zonisamide (Zonegran), a drug used to treat epilepsy, is showing promise in treating tremors, motor problems, and involuntary movements in patients with Parkinson’s disease.

Budipine and Other Glutamate Blockers. A number of experimental drugs are being investigated for Parkinson's disease because they block the actions of glutamate, an amino acid that is a particularly potent nerve cell killer. Some of these drugs block a receptor group to glutamate called N-methyl-D-aspartate (NMDA). Investigational NMDA antagonists include remacemide, memantine, riluzole, and budipine.

Stem Cell Transplantation. Scientists are investigating whether transplanting embryonic stem cells into the brain may help treat Parkinson’s disease. Researchers hope that the transplanted stem cells may be able to stimulate dopamine production. However, stem cell transplantation research is still in its very early stage. It will be many years before clinical trials will be conducted in humans.

Surgery

Surgical procedures are recommended for specific patients with advanced Parkinson’s disease who no longer respond to drug treatments. Surgical treatment cannot cure Parkinson's disease, but it may help control symptoms such as motor fluctuations and dyskinesia. Pallidotomy and thalamotomy are older procedures that destroy tissue in certain parts of the brain. Deep brain stimulation, the current standard surgical practice for Parkinson’s disease, has largely replaced the older operations.

In deep brain stimulation (DBS), also called neurostimulation, an electric pulse generator controls symptoms. The generator is similar to a heart pacemaker. It sends electrical pulses to specific regions of the brain. Candidates for surgery are generally patients who have responded well to levodopa drug treatment. Patients who have had PD for fewer than 16 years may experience greater benefit from DBS than patients who have had the disease longer.

Evidence indicates that DBS improves motor function and reduces dyskinesia best when the procedure targets the subthalamic nucleus (STN) of the brain. Many studies demonstrate the effectiveness of STN stimulation. Procedures that target the globus pallidus interna or ventral intermediate nucleus of the thalamus can also sometimes treat rigidity and tremors. However, there is not yet enough evidence to support stimulation of these parts of the brain.

The procedure is performed as follows:

The surgeon implants a tiny pulse generator near the collarbone, which is connected to four electrodes that have been implanted in the target area in the brain.
The generator delivers programmed pulses to this area, which the patient can turn on and off using a magnet held over the skin.
When on, the pulses suppress symptoms. Complications occur in 2 - 4% of operations. The most serious ones are bleeding in the brain and infection. Depression is common.

In a 2006 study of patients with advanced Parkinson’s disease and severe motor symptoms, patients who received DBS had better improvement in symptoms and quality of life than those who received only drug therapy. However, patients in the neurostimulation group had more serious side effects than those who were treated only with medications. Researchers are also studying whether DBS can benefit patients with earlier-stage Parkinson’s disease.

Pallidotomy and thalamotomy are surgical procedures that destroy brain tissue in regions of the brain associated with Parkinson’s symptoms such as dyskinesia, rigidity, and tremor. In these procedures, a surgeon drills a small hole in the patient’s skull and inserts an electrode to destroy brain tissue. Pallidotomy targets the global pallidus area. Thalamotomy targets the thalamus. Because these procedures permanently eliminate brain tissue, most experts now recommend deep brain stimulation instead of pallidotomy or thalamotomy.

Surgical complications may include behavioral or personality changes, trouble speaking and swallowing, facial paralysis, and vision problems. Weight gain after surgery is also common.

Scientists are investigating whether stem cells may eventually help treat Parkinson disease. Experimental surgery has shown promise using fetal brain cells rich in dopamine implanted in the substantia nigra area of the brain. Because the use of embryonic stem cells is controversial, researchers are studying alternative types of cells, including stem cells from adult brains and cells from human placentas or umbilical cords. Studies are also using gene therapies and other advanced treatments for transplanting dopamine-producing cells or nerve-protecting cells into the brain. All of this research is still in preliminary stages.

Lifestyle Changes

No special diets or natural foods have been shown to slow down the progression of Parkinson's disease, but there are some dietary recommendations.

Protein. High levels of proteins compete with levodopa for transport to the brain and reduce its effectiveness. Avoiding protein altogether is not the solution, since malnutrition can result. Most experts now recommend trying to maintain a carbohydrate-to-protein ratio of 7:1 throughout the day. This may be difficult to calculate and some doctors recommend simply keeping proteins to 12% of total daily calories.

As an aid in calculation, food labels indicate proteins in grams. One gram of protein equals four calories. Good control of protein intake may help minimize fluctuations and wearing-off and may allow some patients to reduce their daily levodopa dosage.

Fruits and Vegetables and Increasing Fiber. Eating whole grains, fresh fruits, and vegetables is the best approach for any healthy life. A diet rich in fruits and vegetables may help protect nerve cell function. Many of these foods are also often rich in fiber, which is particularly important for helping to prevent constipation.

Dietary fiber is the part of food that is not affected by the digestive process in the body. Only a small amount of fiber is metabolized in the stomach and intestine, the rest is passed through the gastrointestinal tract and makes up a part of the stool. There are two types of dietary fiber, soluble and insoluble. Soluble fiber retains water and turns to gel during digestion. It also slows digestion and nutrient absorption from the stomach and intestine. Soluble fiber is found in foods such as oat bran, barley, nuts, seeds, beans, lentils, peas, and some fruits and vegetables. Insoluble fiber appears to speed the passage of foods through the stomach and intestines and adds bulk to the stool. It is found in foods such as wheat bran, vegetables, and whole grains. Fiber is very important to a healthy diet and can be a helpful aid in weight management. One of the best sources of fiber comes from legumes, the group of food containing dried peas and beans.

People whose diets have been low in fiber should increase it gradually. It is best to obtain dietary fiber, soluble or insoluble, in the natural form of whole grains, nuts, legumes, fruits, and vegetables. If it proves difficult to do so, psyllium, a grain naturally found in India, is an excellent soluble fiber supplement (Metamucil, Fiberall, Perdiem Fiber). Fluids are particularly important in preventing constipation.

Fish Oil. Omega-3 fatty acids, which are found in oily fish, are proving to have powerful anti-inflammatory effects and may also be nerve protective.

Click the icon to see an image of foods that contain omega-3 fatty acids.

Dairy Products. A 2002 study reported a higher risk for Parkinson's disease in men (but not in women) who consumed high amounts of dairy products. This association was not linked to fats in dairy foods and high intake of calcium or protein from other sources did not increase the risk. A 2005 prospective study of men found that milk consumption in midlife was associated with increased risk of Parkinson’s disease. As with prior research, the researchers did not find that calcium itself carried a risk. They suggested that some unidentified neurotoxic contaminant in milk may be responsible.

Vitamins.

B Vitamins. Most B vitamins play important roles in the brain and central nervous system. Vitamin B6 (pyridoxine) theoretically has benefits for PD because it is necessary in the production and metabolism of dopamine. Folate deficiency may increase toxic effects against dopamine neural pathways, perhaps by increasing levels of homocysteine, an amino acid that may play a destructive role in many diseases, including heart and neurologic disorders. Some evidence suggests that L-dopa elevates homocysteine levels, so folate supplements may be particularly important for patients. Although the major food sources of B vitamins are meats and dairy products, which are high in protein, these vitamins are also found in whole grains and are added as supplements to commercial cereals.

Click the icon to see an image of the benefits of vitamin B6.

Click the icon to see an image of foods that contain vitamin B6.

Click the icon to see an image of foods that contain folate.

Vitamin E. Researchers have investigated antioxidant vitamins, especially vitamin E, for their effect on the brain. Some, but not all, studies have reported slower mental decline and lower risk for Parkinson's and Alzheimer's disease in people who ate large amounts of foods rich in vitamin E. Such foods include vegetable oils (particularly wheat germ oil), sweet potatoes, turnip greens, mangos, avocados, nuts, sunflower seeds, and soybeans. Vitamin E supplements, however, do not appear to be helpful for slowing disease progression or improving symptoms.

Both smoking and coffee drinking have been associated with lower risk for PD. Researchers are attempting to discover if these substances protect nerve cells. One interesting study suggested that the early disease process in PD produces changes in the dopamine pathway that actually protects an individual from caffeine and nicotine addiction, so that fewer patients have a history of smoking and caffeine. Research is needed to determine why these toxic substances protect against PD.

Smoking and Nicotine Replacement. Cigarette smokers appear to have a 40% lower risk for Parkinson's disease, indicating some protection by nicotine. This finding, of course, is no excuse to smoke, but such protection may help researchers develop new therapies. Studies on nicotine replacement, such as gum or patches, have been conflicting, however, with some short-term studies reporting no benefits. A 2002 study suggested that nicotine replacement may help smokers with early PD, but not nonsmokers.

Coffee Consumption. Studies have indicated that the risk for PD in coffee drinkers is about 30% lower than for non-coffee drinkers. In a 30-year study of Japanese-American men, coffee consumption was associated with a lower risk for Parkinson's disease, and the more coffee they drank, the lower their risk became. Coffee and tea can reduce fluids by increasing urination, however, and so may increase constipation in PD.

Regular use of ibuprofen may reduce the risk of Parkinson’s disease according to research presented at the 2005 annual meeting of the American Academy of Neurology. In this prospective study, people who took at least two ibuprofen tablets per week for at least 1 year lowered their risk of developing Parkinson’s by 35% compared to nonusers or irregular users. For those who took ibuprofen daily, the comparative risk was 38% lower. Other non-steroidal anti-inflammatory drugs (NSAIDS) did not appear to affect disease risk.

Generally, manufacturers of herbal remedies and dietary supplements do not need FDA approval to sell their products. Just like a drug, herbs and supplements can affect the body's chemistry, and therefore have the potential to produce side effects that may be harmful. There have been a number of reported cases of serious and even lethal side effects from herbal products. Always check with your doctor before using any herbal remedies or dietary supplements.

The following dietary supplements are being studied for treatment of Parkinson's disease:

Creatine. Creatine is a nutritional supplement that is sometimes used to improve exercise performance. In 2007, the U.S. National Institutes of Health launched a large-scale clinical trial to study whether creatine can slow the progression of Parkinson’s disease. The trial will enroll patients who have been diagnosed with PD within the last 5 years and who have received levodopa therapy for no more than 2 years.

Coenzyme Q10 (Ubiquinone). Coenzyme Q10 (also called ubiquinone) is an antioxidant being studied for the treatment of Parkinson's disease. This enzyme is important for cellular energy, which may be impaired in PD. In one study, patients who took coenzyme Q10 had slower decline in daily activities and mental and motor skills compared to patients on placebo. However, a 2007 study found that small doses of coenzyme Q10 had no effect on improving Parkinson’s symptoms. Researchers are still investigating whether larger doses given over a long period of time may benefit patients.

Exercise early in adult life may help protect against later development of Parkinson’s disease. Exercise is also an important component of rehabilitation. Physical therapy is extremely important and usually includes active and passive exercise, gait training, practice in normal activities, and if needed, hot or cold treatments, water therapy, and electrical stimulation. Exercise is also essential for well-being and helps patients maintain productive years. To date, no specific approach has been proven to be better than others.

Exercise Programs. Exercise programs are defined as passive or active.

Passive exercise, mostly stretching and manipulation of muscles by a physical therapist, is aimed at preventing muscles from shortening. A passive exercise program that begins with slow and gentle exercises and becomes progressively more intense may improve mobility in patients with early and mid-stage Parkinson's disease.
Active exercises are used to help range-of-motion, coordination, and speed. Patients should continually make efforts to practice movement, even simple ones, such as marching in place, making circular arm movements, and raising the legs up and down while sitting. Patients who enjoy sports or the use of exercise equipment should continue with these activities even if their skills diminish, assuming there are no other medical conditions that would prevent participation.

Gait Training. Practicing new methods for standing, walking, and turning may help retain balance. The following tips may be helpful:

Take large steps when walking forward, raising the toes at the forward step, and hitting the ground with the heel.
Take small steps while turning.
When walking or turning, have the legs 12 - 15 inches apart to provide a wide base.
Do not wear rubber or crepe-soled shoes because they grip the floor and may cause the patient to fall forward.
Using devices that keep a rhythmic beat, such a metronome (a simple device used by musicians to keep time), may be very effective, possibly more than music itself, in helping patients to walk faster and take longer steps. One study found that setting a metronome rhythm to about 10% faster than the patient's fastest gait offers significant improvement over walking to no rhythm at all or to a rhythm that matches the gait.

Reducing Muscle Freezing. The patient should practice regular daily activities that simplify actions and reduce the incidence of muscle freezing. Most often, freezing occurs when a patient begins to move or is presented with an obstacle. The following tips may be helpful:

Rock from side to side.
If the legs feel frozen, lift the toes. This simple action may free spasm in some cases.
Hum marching tunes. In fact, music has been shown to help people move and to get out of bed in the morning. Some studies report that wearing a Walkman and turning music on in situations associated with freezing, such as crossing a street, is helpful.
Divide actions into separate events, which may prevent freezing that occurs from trying to coordinate too many physical operations at one time. For instance, when going through a doorway, approach the door, stop at the door, open it, stop, and then walk through the doorway.
A cane equipped with a laser pointer may be helpful, at least temporarily.
Simply being touched by another person can sometimes release the patient (although a patient with PD should never be pulled or pushed).

Sleep Deprivation Therapy. Sleep deprivation therapy may have a role in treating some cases of depression and some studies are finding some benefits on the depression, tremor, and rigidity experienced by patients. Scientists believe that sleep deprivation produces certain anticholinergic effects, which may improve both depression and Parkinson's symptoms.

Mental Tasks. Mental training may increase dopamine in the brain. Some studies indicate that being mentally fit may be as important for patients as being physically fit. Helpful approaches include:

Select and learn new hobbies that require finger and hand mobility, such as sewing, carpentry, fishing, or playing cards.
Practice deep breathing and relaxation exercises. These may help maintain proper speech control, control tremor, and reduce anxiety.
Both the patient and any caregivers should consider psychological therapy and support for depression and loss of motivation. If psychological therapy is too costly, inexpensive support programs and groups are widely available and can be invaluable for the patient and the family.

Speech Therapy. Speech therapy may help those who develop a monotone voice and lose volume, particularly in combination with medications. There are no well-conducted studies comparing specific speech therapies, but the Lee Silverman Voice Treatment (LSVT) appears to be an example of an effective technique. It has five major components:

Focus on the voice ("think loud/think shout")
High effort (pushes patients to overcome limitations)
Intensive treatment (16 sessions in 1 month)
Calibration (learning to know and accept the amount of effort needed to produce normal sound so it becomes automatic)
Quantification (continuous feedback to objectively document success)

LSVT may help swallowing as well as speech.

Equipment and Devices. A number of devices can be helpful for maintaining stability and preventing falls. The following are some examples:

Rails installed where the patient needs support in getting up or down, such as along the bed and in the bathroom.
Walkers with locking wheels. (Walkers do not appear to be helpful for freezing.)
Chairs with straight backs, firm seats, and arm rests.
Firm mattresses and satin sheets or less expensive sheets with high thread counts. (These are useful for helping patients slide out of bed.)

Resources

www.ninds.nih.gov -- National Institute of Neurological Disorders and Stroke
www.aan.com -- American Academy of Neurology
www.apdaparkinson.org -- American Parkinson's Disease Association
www.pdf.org -- Parkinson's Disease Foundation
www.parkinson.org -- National Parkinson Foundation
www.michaeljfox.org -- Michael J. Fox Foundation for Parkinson's Research
www.wemove.org -- Worldwide Education and Awareness for Movement Disorders
www.parkinsonsaction.org -- Parkinson's Action Network

References

Deuschl G, Schade-Brittinger C, Krack P, Volkmann J, Schafer H, Botzel K, et al. A randomized trial of deep-brain stimulation for Parkinson's disease. N Engl J Med. 2006 Aug 31;355(9):896-908.

Murata M, Hasegawa K, Kanazawa I. Zonisamide improves motor function in Parkinson disease: a randomized, double-blind study. Neurology. 2007 Jan 2;68(1):45-50.

Schade R, Andersohn F, Suissa S, Haverkamp W, Garbe E. Dopamine agonists and the risk of cardiac-valve regurgitation. N Engl J Med. 2007 Jan 4;356(1):29-38.

Schupbach WM, Maltete D, Houeto JL, du Montcel ST, Mallet L, Welter ML, et al. Neurosurgery at an earlier stage of Parkinson disease: a randomized, controlled trial. Neurology. 2007 Jan 23;68(4):267-71. Epub 2006 Dec 6.

Storch A, Jost WH, Vieregge P, Spiegel J, Grelich W, Durner J, et al. Randomized, double-blind, placebo-controlled trial on symptomatic effects of coenzyme Q10 in Parkinson disease. Arch Neurol. 2007 July;64.

Voon V, Thomsen T, Miyasaki JM, de Souza M, Shafro A, Fox SH, et al. Factors associated with dopaminergic drug-related pathological gambling in Parkinson disease. Arch Neurol. 2007 Feb;64(2):212-6.

Watts RL, Jankovic J, Waters C, Rajput A, Boroojerdi B, Rao J. Randomized, blind, controlled trial of transdermal rotigotine in early Parkinson disease. Neurology. 2007 Jan 23;68(4):272-6. Epub 2007 Jan 3.

Zanettini R, Antonini A, Gatto G, Gentile R, Tesei S, Pezzoli G. Valvular heart disease and the use of dopamine agonists for Parkinson's disease. N Engl J Med. 2007 Jan 4;356(1):39-46.

Review Date:
6/4/2007
Reviewed By:
Harvey Simon, MD, Associate Professor of Medicine, Harvard Medical School; Physician, Massachusetts General Hospital.

A.D.A.M. Copyright

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