DIFFERENCES IN INSULIN SUPPRESSION OF FREE FATTY-ACID LEVELS BY GENDER AND GLUCOSE-TOLERANCE STATUS - RELATION TO PLASMA TRIGLYCERIDE AND APOLIPOPROTEIN-B CONCENTRATIONS

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 al so important in lipid and lipoprotein metabolism. To identify groups w ith impaired insulin suppression of FFAs, we studied a multiethnic coh ort of 1521 women and men at four US centers that comprise the Insulin Resistance Atherosclerosis Study (IRAS): 682 with normal glucose tole rance, 352 with impaired glucose tolerance, and 487 with non-insulin-d ependent diabetes. The FFA level 2, hours after a 75-gm oral glucose l oad adjusted for fasting FFAs was used as the measure of insulin suppr ession. After adjustment for age, center, ethnicity, body mass index, and fasting and 2-hour insulin levels, 2-hour FFA levels were signific antly higher in men than women and in persons with impaired glucose to lerance and non-insulin-dependent diabetes mellitus versus normal gluc ose tolerance. The gender difference was largely accounted for by diff erences in central obesity as measured by waist-hip ratio; the differe nce by glucose tolerance status was not affected by central obesity, s uggesting a different mechanism. In multivariate regression analyses, 2-hour FFA levels were strongly related to fasting triglyceride and ap oB levels, respectively, after adjustment for age, fasting and 2-hour insulin concentrations, and fasting FFA concentrations. In summary, el evated plasma apoB and triglyceride concentrations associated with mal e gender and with glucose intolerance are partly accounted for by diff erences in the ability of insulin to suppress FFA concentrations.