Diabetes and Metabolic Syndrome

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Diabetes and Metabolic Syndrome
March 8, 2006
Johns Hopkins Medicine

For many years, physicians have recognized that elevated blood glucose levels, high blood pressure, obesity, and abnormal blood lipid levels tend to occur together in certain individuals. This cluster of symptoms—previously called “The Deadly Quartet,” syndrome X, or insulin resistance syndrome—is now commonly referred to as metabolic syndrome. Almost one in four American adults has metabolic syndrome, which increases the risk of diabetes, coronary heart disease, and stroke.

How Common Is Metabolic Syndrome?
In 2001, the National Cholesterol Education Program (sponsored by the National Heart, Lung, and Blood Institute) proposed the following criteria for the diagnosis of metabolic syndrome. A person needs to have at least three of the following five factors to be diagnosed with the condition:

1. abdominal obesity (a waist circumference greater than 40 inches in men or 35 inches in women)

2. triglyceride levels of 150 mg/dL or greater

3. high density lipoprotein (HDL) cholesterol levels of less than 40 mg/dL in men or 50 mg/dL in women

4. blood pressures of 130/85 mm Hg or higher, or taking antihypertensive medication

5. fasting blood glucose levels of 110 mg/dL or greater

While only 7% of men and women age 20 to 29 meet this definition of metabolic syndrome, the percentage rises to more than 40% of those age 60 and older. Metabolic syndrome is more common in Mexican Americans (32%) than in whites (24%) or blacks (22%).

What Causes Metabolic Syndrome?
Virtually all people with metabolic syndrome have insulin resistance, a decreased ability of the body’s tissues to respond to insulin. Insulin enables cells to take up glucose from the blood for use as a source of energy. In people with insulin resistance, the cells don’t respond adequately to the effects of insulin, and insufficient amounts of glucose enter the cells.

As a result, the pancreas produces more insulin to help move glucose into the cells, and blood insulin levels rise. Eventually, the pancreas can no longer produce enough insulin to compensate for the insulin resistance, blood glucose levels rise, and diabetes develops.

Even before the onset of diabetes, however, people may have elevated blood pressure. Increased production of triglycerides by the liver can lead to abnormalities in blood lipid levels, including high triglycerides, low levels of HDL cholesterol, and increased levels of small, dense low density lipoprotein (LDL), which is more likely to cause blood clots than less-dense LDL.

Exactly what causes insulin resistance is unclear. However, researchers do know that genetic factors, obesity, physical inactivity, diet, cigarette smoking, and older age each contribute to insulin resistance and therefore to metabolic syndrome.

Other factors that make a person more likely to develop insulin resistance include a family history of diabetes in a first-degree relative (a parent or sibling), a personal history of gestational diabetes (diabetes during pregnancy), or polycystic ovary syndrome (a condition characterized by infrequent or absent menstruation, infertility, and excessive body hair).

Complications of Metabolic Syndrome
Metabolic syndrome increases the risk of numerous complications. Because of its association with insulin resistance, people with metabolic syndrome are more likely to have type 2 diabetes. In turn, diabetes increases the risk of vision problems, kidney dysfunction, nerve problems, coronary heart disease, and stroke.

High blood pressure, high triglyceride levels, and low HDL cholesterol levels are all risk factors for atherosclerosis. Elevated insulin levels are also associated with an increased tendency for blood to clot. As a result, people with metabolic syndrome have a greater incidence of all types of cardiovascular disease (including nonfatal and fatal heart attacks and strokes) and are at increased risk for premature death from any cause.

Treating Metabolic Syndrome
Treatment of metabolic syndrome focuses on overcoming insulin resistance and correcting any associated abnormalities. The first step in treatment is lifestyle changes. The most important lifestyle change is weight loss through increased physical activity, decreased intake of calories (particularly simple carbohydrates), and increased fiber intake.

Physical activity aids in weight loss, improves responsiveness to insulin, increases HDL cholesterol levels, and decreases blood pressure. An increase in activity need not be dramatic to achieve significant health benefits—even a half hour of brisk walking most days of the week will help.

Weight loss improves insulin sensitivity, reduces elevated insulin levels, and lowers the risk of developing type 2 diabetes. While reduced insulin resistance can occur with as little as a 5-lb. weight loss, better results are achieved with a 7% to 15% decrease in body weight.

A diet rich in fiber-containing foods—such as fruits, vegetables, and whole grains—can help overcome insulin resistance. Smoking cessation can lessen insulin resistance and help to raise HDL cholesterol levels.

If lifestyle modifications do not correct the associated cardiovascular risk factors, medications can lower blood pressure and improve lipid levels.

Thiazide diuretics are considered first-choice therapy for high blood pressure because they also prevent heart attacks and strokes. In addition, ACE inhibitors are a good choice for those with metabolic syndrome because they may reduce the risk of type 2 diabetes in addition to lowering blood pressure.

Some people with metabolic syndrome may require statin drugs, which lower LDL cholesterol and raise HDL cholesterol levels. Niacin, gemfibrozil (Lopid), and fenofibrate (Lofibra, Tricor) can also raise HDL cholesterol and lower triglyceride levels.

Metformin (Glucophage) and the thiazolidinediones pioglitazone (Actos) and rosiglitazone (Avandia) are currently used to treat insulin resistance in people with type 2 diabetes. According to a study in The New England Journal of Medicine, people at high risk for diabetes (those who are overweight and have elevated blood glucose levels) can prevent or delay the development of diabetes with lifestyle changes and, less markedly, with metformin. However, it is not yet clear whether these medications should be used to treat the insulin resistance that leads to metabolic syndrome.