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/m2; age, 42 ± 14 years) and women (n = 28; body mass index, 21.4 ± 2.0 kg/m2; 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 ~8% lower, the insulin-mediated glucose uptake was ~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 ~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.Agency for Science, Technology and Research (A*STAR)The present study was supported by the Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research, Singapore (Award BMSI/16-07803C-R20H)