Differences in Insulin Suppression of Free Fatty Acid Levels by Gender and Glucose Tolerance Status

Most discussions of relations of insulin resistance to coronary heart disease risk factors have focused on insulin-stimulated glucose uptake, but insulin suppression of plasma free fatty acid (FFA) levels is also important in lipid and lipoprotein metabolism. To identify groups with impaired insulin suppression of FFAs, we studied a multiethnic cohort of 1521 women and men at four US centers that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with normal glucose tolerance, 352 with impaired glucose tolerance, and 487 with non-insulin-dependent diabetes. The FFA level 2 hours after a 75-gm oral glucose load adjusted for fasting FFAs was used as the measure of insulin suppression. After adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour insulin levels, 2-hour FFA levels were significantly higher in men than women and in persons with impaired glucose tolerance and non-insulin-dependent diabetes mellitus versus normal glucose tolerance. The gender difference was largely accounted for by differences in central obesity as measured by waist-hip ratio; the difference by glucose tolerance status was not affected by central obesity, suggesting a different mechanism. In multivariate regression analyses, 2-hour FFA levels were strongly related to fasting triglyceride and apoB levels, respectively, after adjustment for age, fasting and 2-hour insulin concentrations, and fasting FFA concentrations. In summary, elevated plasma apoB and triglyceride concentrations associated with male gender and with glucose intolerance are partly accounted for by differences in the ability of insulin to suppress FFA concentrations.