A number of
coronary heart disease risk factors have been identified that often cluster together to increase the risk of macrovascular disease. This cluster is referred to as the
insulin resistance syndrome, and the risk factors commonly include
dyslipidemia, elevated blood pressure, an android pattern of body fat distribution, and
glucose intolerance. Whether
hyperinsulinemia or
insulin resistance per se provides a common pathway for these metabolic abnormalities is unclear. The authors studied 50 nondiabetic persons who had completed a euglycemic hyperinsulinemic clamp protocol in addition to a 75-g oral
glucose tolerance test and other measures of the coronary risk profile. Using principal-component analysis, we reduced nine coronary risk factors to two uncorrelated factors that explained 54.5% of the variance. Factor 1 consisted of positive loadings for
uric acid, systolic and diastolic blood pressure,
triglyceride concentration, and waist girth and negative loadings for
HDL cholesterol and the rate of
insulin-mediated
glucose disposal (M, in milligrams per kilogram of
body weight per minute). M also loaded on factor 2, along with fasting
insulin and
glucose concentrations, diastolic blood pressure, and waist girth. The observation that M loaded on both factors suggests that a resistance to
insulin action may provide the mechanism uniting the features of the
insulin resistance syndrome.
Hyperinsulinemia with concomitant
insulin resistance may be necessary to produce this metabolic derangement, as well as the increased risk of macrovascular complications.