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

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Elza Muscelli, Andrea Mari, Arturo Casolaro, Stefania Camastra, Giuseppe Seghieri, Amalia Gastaldelli, Jens Juul Holst, Ele Ferrannini

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

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.

Original languageEnglish
JournalDiabetes
Volume57
Issue number5
Pages (from-to)1340-8
Number of pages9
ISSN0901-3652
DOIs
Publication statusPublished - May 2008

    Research areas

  • Adult, Blood Glucose, Body Mass Index, Diabetes Mellitus, Type 2, Female, Glucose Tolerance Test, Humans, Hypoglycemic Agents, Insulin, Insulin-Secreting Cells, Male, Middle Aged, Obesity, Reference Values

ID: 132049607