Syndrome X

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Abstract
The manifestations of syndrome X increase the risk of coronary heart disease (CHD) as much, if not more so, than elevated low-density lipoprotein (LDL) cholesterol concentrations. The fundamental abnormality leading to the manifestations that comprise syndrome X is resistance to insulin regulation of muscle glucose uptake and adipose tissue lipolysis. To prevent decompensation of glucose tolerance, patients with syndrome X secrete large amounts of insulin. Treatment should be aimed at 1) increasing insulin sensitivity, 2) attenuating day-long hyperinsulinemia, and 3) pharmacologic treatment of the specific manifestations of syndrome X if lifestyle interventions are not entirely successful. The two major lifestyle modulators of insulin action are body weight and physical fitness--the heavier and the more sedentary a patient is, the greater the degree of insulin resistance and compensatory hyperinsulinemia. In overweight, insulin-resistant patients, the magnitude of insulin resistance is attenuated with weight loss (10 to 15 pounds). Aerobic exercise (30 minutes a session, three to four times a week) is equally effective, irrespective of the presence of obesity. In the absence of associated weight loss, the usually recommended low-fat, high-carbohydrate diet makes the manifestations of syndrome X worse. This is because the more carbohydrates present in the insulin-resistant patient's diet, the greater the insulinogenic stimulus to the pancreas, and hence day-long plasma insulin levels are higher. Replacing saturated fat with monounsaturated and polyunsaturated fat instead of carbohydrates provides the same favorable effect on LDL cholesterol concentrations without the insulin-stimulating effect of low-fat, high-carbohydrate diets. This intervention does not affect insulin resistance, but maintains day-long insulin levels as low as possible. Although lifestyle changes can be very effective in attenuating the manifestations of syndrome X, it may be necessary to initiate pharmacologic treatment aimed at controlling dyslipidemia and hypertension. The major obstacle to reducing the risk of CHD in patients with syndrome X is becoming aware of its manifestations. After this is accomplished, the relatively simple approaches outlined herein are an effective treatment strategy.