To test whether a sex difference in insulin-mediated suppression of nonesterified fatty acids (NEFAs) could account for sex differences in plasma triglyceride levels, we studied 632 normoglycemic men and women of European and South Asian descent aged 40 to 69 years. Mean fasting NEFA levels were 19% higher in women than in men. Between fasting and 2 hours after a 75-g oral glucose load, NEFA levels fell by 69% in women and 55% in men, so that mean NEFA levels at 2 hours after loading were 19% lower in women than in men. Plasma triglyceride and apolipoprotein B levels were correlated with 2-hour NEFA levels in each sex and ethnic group, and these associations were independent of glucose, insulin, and central obesity. These results are consistent with experimental studies of the effects of insulin and NEFAs on hepatic production of triglycerides and apolipoprotein B. Suppression of NEFA levels in response to insulin is greater in women than in men, and this may account for some of the sex differences in lipoprotein pattern and coronary heart disease risk. {Arteriosclerosis and Thrombosis 1993;13:1187-1192) KEY WORDS • triglyceride • apo B • insulin • fatty acids, nonesterified • obesity • sex factors • glucose T he higher coronary heart disease risk in men compared with women may be related to sex differences in lipoprotein pattern. 1 In comparison with women, men have higher levels of very-lowdensity lipoprotein (VLDL) triglyceride and apolipoprotein (apo) B, lower levels of high-density lipoprotein cholesterol (HDL-C), and a higher proportion of small, dense particles in the low-density lipoprotein (LDL) fraction. -4 The metabolic basis of these differences is poorly understood, although in both men and women HDL-C levels and LDL composition are closely dependent on plasma triglyceride levels. 56 Sex differences in the regulation of plasma triglyceride could thus account for some of the other sex differences in lipoprotein pattern.In a large population survey we demonstrated that elevated triglyceride levels and other metabolic disturbances associated with insulin resistance were more prevalent in people of South Asian (Indian, Pakistani, and Bangladeshi) descent than in Europeans, and that in both of these groups plasma triglyceride levels were higher in men than in women. 7 We also observed that the fall in plasma triglycerides in response to a glucose load was greater in women than in men: in Europeans the average change between fasting and 2 hours after loading was -6% in men and -16% in women, whereas in South Asians the average changes were -1% and -8%, respectively. 7Most triglycerides in plasma are carried in VLDL particles, which are produced in the liver and contain apoB. Elevation of VLDL triglyceride levels is closely related to an impairment in the ability of insulin to suppress nonesterified fatty acids (NEFAs), 89 which are the principal substrate for hepatic triglyceride synthesis. 10 We suggested that sex differences in the regulation of NEFA levels by insulin might thus account for the sex di...