Sex Differences in Glucose and Fatty Acid Metabolism in Asians Who Are Nonobese

Context: The prevalence of diabetes is increasing throughout Asia, even in the absence of obesity, and is lower in women than in men. The underlying mechanisms are not well understood. Objective: To evaluate the sex differences in glucose and fatty acid metabolism in Asians who are nonobese. Design: Cross-sectional study. Setting: Clinical Nutrition Research Centre, Singapore. Participants: Healthy Asian men (n = 32; body mass index, 21.8 +/- 1.5 kg/m(2); age, 42 +/- 14 years) and women (n = 28; body mass index, 21.4 +/- 2.0 kg/m(2); age, 41 +/- 13 years). Main Outcome Measures: Insulin sensitivity (insulin-mediated glucose uptake normalized for steady-state insulin; hyperinsulinemic-euglycemic clamp), postprandial glucose, insulin and fatty acid concentrations, insulin secretion (mixed meal tolerance test with mathematical modeling), insulin clearance, body composition and fat distribution (dual-energy X-ray absorptiometry, MRI, and spectroscopy), cardiorespiratory fitness (maximal oxygen uptake; graded exercise test), and handgrip strength (dynamometry). Results: Women had more total body fat but less visceral fat than men; liver and muscle lipid contents were not different. Maximal oxygen uptake and handgrip strength were lower in women than men. The postprandial glucose concentrations were similar to 8% lower, the insulin-mediated glucose uptake was similar to 16% greater, and the meal-induced suppression of fatty acid concentrations was significantly greater in women than in men (P < 0.05 for all). However, muscle insulin sensitivity was not different between the sexes. No differences were found in postprandial insulin secretion and clearance rates; however, the steady-state insulin clearance was similar to 17% lower in women. Conclusions: Asian women who are nonobese are more insulin-sensitive than men at the level of adipose tissue but not skeletal muscle. Therefore, sex differences in glucose tolerance are likely the result of sexual dimorphism in hepatic insulin action.