METABOLIC RESPONSES TO VARIATION IN DIETARY COMPOSITION

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Atherosclerotic coronary artery disease (CAD) is positively asociated with levels of low density lipoprotein cholesterol (LDL-C), imtermediate density lipoprotein cholesterol (IDL-C), very low density lipoprotein cholesterol (VLDL-C), and lipoprotein (a), or Lp(a), and is negatively associated with levels of high density lipoprotein cholesterol (HDL-C). Recently research has focused on the role that insulin resistance plays in the establishment of coronary heart disease. It has been shown that the ability of dietary cholesterol to raise plasma cholesterol concentration in individuals with combined hyperlipidemia (increased cholesterol and triglycerides) is greater than those who have other lipid phenotypes. Individuals with combined hyperlipidemia often present with a cluster of abnormalities which increase the risk of coronary heart disease. These abnormalities consist of higher fasting triglyceride and lower high density (HDL) lipoprotein concentrations, an enhanced degree of postprandial lipemia, smaller and denser low density lipoprotein (LDL)- particles, hyperuricemia, hypertension and hyperinsulinemia. Based upon our laboratory observations that subjects with combined hyperlipidemia show a greater response to dietary cholesterol, there is an excellent chance that subjects with insulin resistance (or a subset thereof) represent a significant fraction of the population that have an exaggerated response to dietary cholesterol. In an effort to test this hypothesis that differences in insulin metabolism account for the variability in the ability of dietary cholesterol to raise plasma cholesterol, it is necessary to select a population in which these studies should be performed. In this context, postmenopausal women were selected as our representative subset. They comprise a large and rapidly growing segment of our population of generally healthy non-obese, non-diabetic individuals over a wide range of in vivo insulin action. The goal of our study will be to prove that the untoward effects on glucose, insulin, and lipoprotein metabolism of variations in dietary cholesterol intake are significantly acentuated in postmenopausal women defined as being insulin resistant as compared to insulin sensitive.