Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients

Diabetes. 2008 May;57(5):1340-8. doi: 10.2337/db07-1315. Epub 2007 Dec 27.


Objective: To quantitate the separate impact of obesity and hyperglycemia on the incretin effect (i.e., the gain in beta-cell function after oral glucose versus intravenous glucose).

Research design and methods: Isoglycemic oral (75 g) and intravenous glucose administration was performed in 51 subjects (24 with normal glucose tolerance [NGT], 17 with impaired glucose tolerance [IGT], and 10 with type 2 diabetes) with a wide range of BMI (20-61 kg/m(2)). C-peptide deconvolution was used to reconstruct insulin secretion rates, and beta-cell glucose sensitivity (slope of the insulin secretion/glucose concentration dose-response curve) was determined by mathematical modeling. The incretin effect was defined as the oral-to-intravenous ratio of responses. In 8 subjects with NGT and 10 with diabetes, oral glucose appearance was measured by the double-tracer technique.

Results: The incretin effect on total insulin secretion and beta-cell glucose sensitivity and the GLP-1 response to oral glucose were significantly reduced in diabetes compared with NGT or IGT (P <or= 0.05). The results were similar when subjects were stratified by BMI tertile (P <or= 0.05). In the whole dataset, each manifestation of the incretin effect was inversely related to both glucose tolerance (2-h plasma glucose levels) and BMI (partial r = 0.27-0.59, P <or= 0.05) in an independent, additive manner. Oral glucose appearance did not differ between diabetes and NGT and was positively related to the GLP-1 response (r = 0.53, P < 0.01). Glucagon suppression during the oral glucose tolerance test was blunted in diabetic patients.

Conclusions: Potentiation of insulin secretion, glucose sensing, glucagon-like peptide-1 release, and glucagon suppression are physiological manifestations of the incretin effect. Glucose tolerance and obesity impair the incretin effect independently of one another.

MeSH terms

  • Adult
  • Blood Glucose / metabolism*
  • Body Mass Index
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / drug therapy
  • Female
  • Glucose Tolerance Test*
  • Humans
  • Hypoglycemic Agents / therapeutic use
  • Insulin / blood
  • Insulin / metabolism
  • Insulin Secretion
  • Insulin-Secreting Cells / physiology
  • Male
  • Middle Aged
  • Obesity / complications
  • Obesity / physiopathology*
  • Reference Values


  • Blood Glucose
  • Hypoglycemic Agents
  • Insulin