Relationship between lipoprotein levels and in vivo insulin action in normal young white men

In epidemiologic studies, hyperinsulinemia has been found to be an independent risk factor for coronary heart disease (CHD). However, the mechanisms responsible for its role in atherogenesis remain unclear. We studied the relationship of in vivo insulin action and plasma lipids and lipoproteins in 44 normotriglyceridemic white men (aged 18 to 34 years). The euglycemic, hyperinsulinemic glucose clamp technique was used to quantitate insulin-mediated glucose disposal ( M I value) at a plasma insulin concentration of approximately 100 μU/mL. The M I value correlated negatively with plasma triglycerides (r = -0.553, P < .0001), as well as with fasting plasma insulin levels (r = -0.483, P < .001), independent of age, body mass index, and fasting plasma glucose levels. A negative correlation of the M I value was also observed with very low density lipoprotein (VLDL)-cholesterol (r = -0.347, P < .05), VLDL-triglycerides (r = -0.474, P < 0.005), and total cholesterol/high density lipoprotein (HDL)-cholesterol ratio (r = -0.431, P < .01). The relationship between the M I value and the total cholesterol/HDL-cholesterol ratio was independent of VLDL-cholesterol and VLDL-triglycerides, however, not independent of plasma triglycerides. No relationship was observed between insulin-mediated glucose uptake and total cholesterol, low density lipoprotein (LDL)-cholesterol, and HDL-cholesterol values. Individual differences in plasma triglycerides, fasting insulin concentration, and the total cholesterol/HDL-cholesterol ratio accounted for about half the variance observed in the M I value. In conclusion, our findings in normal healthy men support the contention that hyperinsulinemia or insulin resistance may enhance the risk of CHD by adversely affecting lipoprotein levels such as VLDL-cholesterol, VLDL-triglyceride, and the ratio of total cholesterol/HDL-cholesterol.