Insulin resistance is associated with lipid and lipoprotein abnormalities in subjects with varying degrees of glucose tolerance.

We tested the hypothesis that insulin resistance, rather than high insulin level, is associated with lipid and lipoprotein changes favoring atherosclerosis independently of the glucose tolerance status. To this aim, 50 subjects with normal glucose tolerance, 28 subjects with impaired glucose tolerance, and 54 subjects with noninsulin-dependent diabetes (NIDDM) were studied. Subjects with low glucose disposal rate (GDR) or a high degree of insulin resistance as measured by the euglycemic hyperinsulinemic clamp technique had lower high density lipoprotein (HDL) cholesterol and higher total and very low density lipoprotein (VLDL) triglycerides than did subjects with high GDR (highest GDR tertile). These associations were independent of fasting insulin level and other confounding factors. In stepwise multiple linear regression analysis, GDR was the most important single variable associated with HDL cholesterol and VLDL triglyceride level independently of age, obesity, distribution of obesity (waist/hip ratio), 2-hour glucose level, and free fatty acid concentration. We conclude: 1) insulin resistance measured by the euglycemic clamp technique is associated with adverse lipid and lipoprotein changes favoring atherosclerosis not only in nondiabetic subjects (as shown in previous studies) but also in impaired glucose tolerance and NIDDM subjects; 2) the association of high insulin level with adverse lipid and lipoprotein changes indirectly reflects the association of insulin resistance with lipid and lipoprotein levels; and 3) HDL cholesterol and VLDL triglycerides are independently associated with insulin-mediated glucose uptake, which may indicate that these lipoproteins have separate sites of interaction with insulin action.