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Diabetes. 2008 May;57(5):1340-8. Epub 2007 Dec 27.

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

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  • 1Department of Internal Medicine, Consiglio Nazionale delle Ricerche (CNR), Institute of Clinical Physiology, University of Pisa, Italy.

Abstract

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.

PMID:
18162504
DOI:
10.2337/db07-1315
[PubMed - indexed for MEDLINE]
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