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

Am J Clin Nutr. 2010 Dec;92(6):1359-68. doi: 10.3945/ajcn.2010.29771. Epub 2010 Oct 27.


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 ± SEM age: 66 ± 1 y; body mass index (in kg/m(2)): 34.4 ± 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 ± 0.3 units) or a high-GI diet (HiGIX; 80 ± 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)H(2)]-glucose), and oral glucose-induced insulin and incretin hormone secretion were examined.

Results: Both groups lost equal amounts of body weight (-8.8 ± 0.9%) and adiposity and showed similar improvements in peripheral tissue (+76.2 ± 14.9%) and hepatic insulin sensitivity (+27.1 ± 7.1%) (all P < 0.05). However, oral glucose-induced insulin secretion was reduced only in the LoGIX group (6.59 ± 0.86 nmol in the prestudy compared with 4.70 ± 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 β 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 β 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.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adiposity / physiology
  • Aged
  • Combined Modality Therapy
  • Exercise / physiology*
  • Female
  • Gastric Inhibitory Polypeptide / blood
  • Glucose Tolerance Test
  • Glycemic Index*
  • Humans
  • Hyperinsulinism / blood
  • Hyperinsulinism / therapy*
  • Insulin / blood*
  • Insulin / metabolism
  • Insulin Resistance / physiology*
  • Insulin Secretion
  • Liver / physiopathology
  • Male
  • Obesity / blood
  • Obesity / diet therapy
  • Obesity / therapy*
  • Postprandial Period
  • Weight Loss / physiology*


  • Insulin
  • Gastric Inhibitory Polypeptide