A low–glycemic index diet combined with exercise reduces insulin resistance, postprandial hyperinsulinemia, and glucose-dependent insulinotropic polypeptide responses in obese prediabetic humans

Background: The optimal lifestyle intervention that reverses diabetes risk factors is not known. Objective: We examined the effect of a low–glycemic index (GI) diet and exercise intervention on glucose metabolism and insulin secretion in obese, prediabetic individuals. Design: Twenty-two participants [mean 6 SEM age: 66 6 1 y; body mass index (in kg/m 2 ): 34.4 6 0.8] underwent a 12-wk exercise-training intervention (1 h/d for 5 d/wk at ’85% of maximum heart rate) while randomly assigned to receive either a low-GI diet (LoGIX; 40 6 0.3 units) or a high-GI diet (HiGIX; 80 6 0.6 units). Body composition (measured by using dual-energy X-ray absorptiometry and computed tomography), insulin sensitivity (measured with a hyperinsulinemic euglycemic clamp with [6,6- 2 H2]-glucose), and oral glucose–induced insulin and incretin hormone secretion were examined. Results : Both groups lost equal amounts of body weight ( 28.8 6 0.9%) and adiposity and showed similar improvements in peripheral tissue (+76.2 6 14.9%) and hepatic insulin sensitivity (+27.1 6 7.1%) (all P , 0.05). However, oral glucose–induced insulin secretion was reduced only in the LoGIX group (6.59 6 0.86 nmol in the prestudy compared with 4.70 6 0.67 nmol in the poststudy, P , 0.05), which was a change related to the suppressed postprandial response of glucose-dependent insulinotropic polypeptide. When corrected for changes in b cell glucose exposure, changes in insulin secretion were attenuated in the LoGIX group but became significantly elevated in the HiGIX group. Conclusions: Although lifestyle-induced weight loss improves insulin resistance in prediabetic individuals, postprandial hyperinsulinemia is reduced only when a low-GI diet is consumed. In contrast, a high-GI diet impairs pancreatic b cell and intestinal K cell function despite significant weight loss. These findings highlight the important role of the gut in mediating the effects of a low-GI diet on type 2 diabetes risk reduction. Am J Clin Nutr doi: 10.3945/ajcn. 2010.29771.