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Syndrome X

A cluster of interrelated conditions that greatly increases the risk of developing Type 2 diabetes and heart disease.

Syndrome X is commonly characterized by insulin resistance, high blood pressure, obesity, abnormalities in blood levels of lipids (such as triglycerides and cholesterol), increased blood clotting, and a tendency toward inflammation. Other conditions that may be associated with the syndrome include acanthosis nigricans (brown or black velvety patches on the back of the neck or elsewhere), hyperuricemia (high blood levels of uric acid), and, in women, polycystic ovary syndrome. Syndrome X is also known under a variety of other names, sometimes reflecting slight differences in definition. Among these names are insulin resistance syndrome, metabolic syndrome, dysmetabolic syndrome X, cardiovascular metabolic syndrome, and Reaven syndrome (after Stanford University researcher Gerald Reavan, who provided a description of the syndrome in 1988).

Some authorities believe that insulin resistance is the primary problem that leads to the other conditions involved in the syndrome. Simply stated, insulin resistance is a condition in which insulin doesn’t work as well as it should. One of insulin’s jobs is to allow glucose in the blood to enter the cells of the body, where it can be used for energy. In people who are insulin resistant, more and more insulin is required to make this happen. Another of insulin’s jobs is to signal the liver to secrete less glucose into the bloodstream. In many insulin-resistant individuals, the liver may continue to secrete a lot of glucose into the bloodstream despite the presence of lots of insulin. Up to one-third of American adults are estimated to have some degree of insulin resistance.

Insulin resistance may lead to hyperinsulinemia, or too much insulin in the bloodstream. As the body becomes less and less efficient at using insulin, the pancreas must secrete more and more insulin to keep blood glucose levels in the normal range. Some scientists think that insulin resistance and hyperinsulinemia, independent of their effects on blood sugar levels, can promote heart disease through insulin’s effects on blood vessel walls and the blood’s tendency to clot.

Other components of syndrome X that increase the risk of heart disease are high blood pressure, obesity, and blood lipid abnormalities, such as increased triglyceride levels, decreased levels of “good” high-density lipoprotein (HDL) cholesterol, and increased levels of small low-density lipoprotein (LDL) cholesterol particles.

The syndrome is a major concern of treatment guidelines issued in 2005 by the National Cholesterol Education Program (NCEP), which refer to it as metabolic syndrome. The NCEP was established by the U.S. National Heart, Lung, and Blood Institute to help lower the toll in illness and death caused by heart disease. According to the NCEP, metabolic syndrome raises the risk of heart disease as much as cigarette smoking does. A person should be regarded as having metabolic syndrome, say the guidelines, if any three of the following risk factors are present:

  • Abdominal obesity (defined as a waist circumference of over 40 inches in men and over 35 inches in women)
  • High triglyceride level (150 mg/dl or above)
  • Low HDL-cholesterol level (less than 40 mg/dl in men and less than 50 mg/dl in women)
  • Elevated blood pressure (130/85 mm Hg or higher)
  • High fasting glucose level (100 mg/dl or above)

The NCEP guidelines give priority to treating the root causes of the metabolic syndrome that are susceptible to change — namely, excessive weight and physical inactivity. (Genetic factors that contribute to the syndrome cannot be reversed.) Lifestyle measures such as diet control and exercising can often reduce insulin resistance and other conditions associated with the syndrome. In some cases drug treatment of spe-cific conditions is recommended to reduce the risk of heart disease. The guidelines accordingly advise treating abnormal blood levels of lipids with lipid-altering drugs, high blood pressure with antihypertensive drugs, and blood clotting with aspirin. Although there exist blood-glucose-lowering drugs, including metformin, rosiglitazone, and pioglitazone, that are known to reduce insulin resistance, the NCEP guidelines note that it has not yet been definitely proved that they can reduce heart disease.

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