Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women

Controversy exists regarding the relative importance of adiposity, physical fitness, and physical activity in the regulation of insulin-stimulated glucose disposal. To address this issue, we measured insulin-stimulated glucose disposal [mg.kg fat-free mass (FFM)(-1).min(-1); oxidative and nonoxidative components] in 45 nondiabetic, nonobese, premenopausal women (mean +/- SD; 47 +/- 3 yr) by use of hyperinsulinemic euglycemic clamp (40 mU.m(-2).min(-1)) and [6,6-H-2(2)]glucose dilution techniques. We also measured body composition, abdominal fat distribution, thigh muscle fat content, maximal oxygen consumption ((V) over dot O-2max), and physical activity energy expenditure ((H2O)-H-2-O-18 kinetics) as possible correlates of glucose disposal. (V) over dot O-2max was the strongest correlate of glucose disposal (r = 0.63, P< 0.01), whereas whole body and abdominal adiposity showed modest associations (range of r values from -0.32 to -0.46, P< 0.05 to P< 0.01). A similar pattern of correlations was observed for nonoxidative glucose disposal. None of the variables measured correlated with oxidative glucose disposal. The relationship of (V) over dot O-2max to glucose disposal persisted after statistical control for FFM, percent body fat, and intra-abdominal fat (r = 0.40, P< 0.01). In contrast, correlations of total and regional adiposity measures to insulin sensitivity were no longer significant after statistical adjustment for (V) over dot O-2max. (V) over dot O-2max was the only variable to enter stepwise regression models as a significant predictor of total and nonoxidative glucose disposal. Our results highlight the importance of (V) over dot O-2max as a determinant of glucose disposal and suggest that it may be a stronger determinant of variation in glucose disposal than total and regional adiposity in nonobese, nondiabetic, premenopausal women.