Overcoming the Manifestations of Syndrome X

Although therapeutic efforts aimed at enhancing insulin sensitivity may be limited, there is no reason to adopt a nihilistic approach to attenuating the CHD risk <j factors in patients with syndrome X. Indeed, there are both dietary and pharmacological interventions that can substantially reduce the manifestations of syndrome X.

1. Macronutrient Composition

As indicated earlier, weight loss will significantly improve insulin sensitivity in overweight, insulin-resistant individuals. However, not all overweight patients are able to lose weight, nor are all patients with syndrome X obese. In both of these situations, changes in macronutrient composition can be of substantial benefit.

Dietary recommendations to reduce CHD have until quite recently been based upon the principle that hypercholesterolemia (more specifically, an elevated LDL cholesterol level) is the only CHD risk factor that needs to be addressed. The result has been almost total emphasis on the use of low-fat-high-carbohydrate (CHO) diets. More to the point, advice to replace saturated fat (SF) with CHO in order to lower LDL cholesterol concentrations continues to be given, regardless of how insulin resistant the individual. Unfortunately, this dietary approach will make all of the manifestations of syndrome X worse. The greater the CHO content in an isocaloric diet, the more insulin must be secreted in order to maintain glucose homeostasis. This poses no danger to insulin-sensitive individuals, but low-SF/high-CHO diets will significantly increase the already high day-long plasma insulin concentrations in patients with syndrome X. As a consequence, fasting plasma TG concentrations will increase, as will the day-long postprandial accumulations of remnant lipoproteins. In addition, HDL cholesterol concentrations will further decrease, as will LDL particle diameter. In order to avoid this problem, SF should be replaced with monounsaturated (MUF) and polyunsaturated fat (PUF). This maneuver results in a fall in LDL cholesterol concentration as great as is seen with low-SF/high-CHO diets, without any untoward effects on the manifestations of syndrome X. Given this information, weight maintenance diets containing (as percent of total calories) approximately 15% protein, 40% fat (<10% SF, ~20% MUF, and the rest as PUF), and 45% CHO will decrease LDL cholesterol concentrations without accentuating the manifestations of syndrome X.

2. Pharmacological Agents

There are effective drugs to address the abnormalities of lipoprotein metabolism present in patients with syndrome X, as well as to lower blood pressure when hypertension is one of the manifestations of syndrome X. 1

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