Sex differences in insulin action and body fat distribution in overweight and obese middle-aged and older men and women

Controversy exists as to whether there are differences in insulin action between older men and women, and what factors contribute to these differences. This study tests the hypothesis that sex differences in regional fat distribution contribute to a disparity in insulin sensitivity in older men vs. older women. Healthy, older (50–71 years), sedentary men (n = 28) and women (n = 29) were recruited to participate in the study. Body fat, fat-free mass (FFM), and visceral (VAT) and subcutaneous abdominal (SAT) adipose tissue areas were measured by DXA and computed tomography (CT). For measurements of insulin-stimulated glucose disposal (M), insulin was infused at a constant rate of 240 pmol·m–2·min–1, and M was calculated between the 90th and 120th min of the hyperinsulinemic–euglycemic clamp. The men weighed 16% more and had 16% higher waist and 4% lower hip circumferences than women (p < 0.05 for all). Total fat mass and SAT were 21% and 33% lower and FFM was 49% higher in men than in women, whereas waist-to-hip ratio (WHR) and VAT:SAT ratio were 21% and 56% higher in men than in women (p < 0.05 for all). Although insulin concentrations during the glucose clamp were higher in men, M was 47% lower in men vs. women (21.7 ± 1.1 vs. 46.7 ± 3.1 µmol·L–1·kgFFM–1·min–1, p < 0.05). The sex-related differences in M persisted after controlling for insulin concentrations during the glucose clamp, for waist, WHR, and VAT:SAT. Older men are more insulin resistant than women, despite lower body fat and subcutaneous abdominal fat. This difference in insulin sensitivity is not explained by abdominal fat distribution, therefore other metabolic factors contribute to the sex differences in insulin sensitivity.