Determinants of insulin sensitivity and consequences for lipoproteins and blood pressure in subjects with non-insulin-dependent diabetes mellitus.

The aim of the present study was to investigate the possible determinants of insulin sensitivity and the relationships of these determinants and insulin sensitivity to lipoprotein levels and blood pressure in patients with non-insulin-dependent diabetes mellitus (NIDDM). We studied 46 patients with NIDDM (26 women, 20 men) treated either with diet alone or in combination with sulfonylureas. Insulin sensitivity was assessed as the insulin-mediated glucose uptake rate (M value) with the hyperinsulinemic euglycemic clamp technique. In a multiple regression model, only percent body fat, waist to hip ratio (WHR), and resting energy expenditure (REE) emerged as significant independent determinants of the M value, with a multiple R2 for the model of 44%, whereas age, hemoglobin A1c (HbA1c) level, thyroid function, fitness level, smoking status, alcohol consumption, and dietary habits did not contribute significantly. The M value was independently and negatively associated with the concentrations of triglyceride (TG) and very-low-density lipoprotein (VLDL) cholesterol and positively associated with high-density lipoprotein (HDL) cholesterol subfractions and apolipoprotein A1. In our predominantly normotensive subjects, we found no association between the M value and blood pressure. Moreover, fasting insulin contributed directly, ie, independent of the M value, to the variation of TG, but not to the other lipoproteins and not to blood pressure. The results suggest that in NIDDM (1) insulin sensitivity is determined mainly by percentage body fat and REE, (2) the insulin level determines the TG level directly, whereas the lipoproteins are influenced indirectly as a reflection of the degree of insulin resistance, and (3) insulin sensitivity is not related to blood pressure in a normotensive population.