Low insulin sensitivity is associated with clustering of cardiovascular disease risk factors

Hyperinsulinemia is associated with multiple metabolic disorders including high triglyceride level, low high density lipoprotein (HDL) cholesterol level, hypertension, and impaired glucose tolerance (IGT). This metabolic constellation is also called the insulin resistance syndrome. All previous data on clustering of these risk factors are, however, based on insulin levels. Therefore, the authors examined the association of insulin sensitivity estimated by means of a frequently sampled intravenous glucose tolerance test and the minimal model with the number of metabolic disorders (dyslipidemia [high triglyceride level or low HDL cholesterol level or both], hypertension, and IGT according to the World Health Organization criteria). Of 153 nondiabetic subjects aged 53-61 years who had participated in a previous population-based study, 79 had no disorders, 55 had one disorder, 16 had two disorders, and 3 had three disorders. Insulin sensitivity index (S1) decreased with the increasing number of disorders (4.1, 3.5, 1.8, and 1.4 x 10(-4) min-1 microU-1 mL-1, in subjects with 0, 1, 2, and 3 disorders, respectively; p < 0.001 for trend). Similarly, fasting (7.5, 7.8, 15.3, and 22.0 microU/mL; p < 0.001) and 2-hour insulin levels (39.9, 49.0, 98.7, and 149.6 microU/mL; p < 0.001) increased by the increasing number of disorders. The relations of S1 and fasting and 2-hour insulin levels with multiple metabolic disorders were independent of sex, obesity, and body fat distribution. Furthermore, these associations were similar in men and women and in lean and obese subjects. The authors conclude that a clustering of cardiovascular disease risk factors in nondiabetic subjects is not only associated with hyperinsulinemia but also with insulin resistance.