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 sex differences in glucose and fatty acid metabolism in non-obese Asians.

Design: Cross-sectional study.

Setting: Clinical Nutrition Research Centre, Singapore.

Participants: Healthy Asian men (n=32, BMI=21.8±1.5 kg/m2, age=42±14 years) and women (n=28, BMI=21.4±2.0 kg/m2, age=41±13 years).

Main Outcome Measures: Insulin sensitivity (M-value 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, magnetic resonance imaging and spectroscopy), cardiorespiratory fitness (VO₂max; 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. VO₂max and handgrip strength were lower in women than men. Postprandial glucose concentrations were ∼8% lower, M-value was ∼16% greater and the meal-induced suppression of fatty acid concentrations was significantly greater in women than in men (all P<0.05). However, muscle insulin sensitivity (M/I ratio) was not different between the sexes. There were no differences in postprandial insulin secretion and clearance rates, but steady-state insulin clearance was ∼17% lower in women.

Conclusions: Non-obese Asian women 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.