We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Separate Impact of Obesity and Glucose Tolerance on the Incretin Effect in Normal Subjects and Type 2 Diabetic Patients.
- Authors
Muscelli, Elza; Mari, Andrea; Casolaro, Arturo; Camastra, Stefania; Seghieri, Giuseppe; Gastaldelli, Amalia; Holst, Jens J.; Ferrannini, Ele
- Abstract
OBJECTIVE--To quantitate the separate impact of obesity and hyperlycemia on the incretin effect (i.e., the gain in β-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[sup 2]). C-peptide deconvolution was used to reconstruct insulin secretion rates, and β-cell glucose sensitivity (slope of the insulin secretion/glucose concentration doseresponse 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 β-cell glucose sensitivity and the GLP-1 response to oral glucose were significantly reduced in diabetes compared with NGT or IGT (P ≤ 0.05). The results were similar when subjects were stratified by BMI tertile (P ≤ 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 ≤ 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. Diabetes 57:1340-1348, 2008
- Subjects
OBESITY; HYPERGLYCEMIA; PANCREATIC secretions; INSULIN; BLOOD sugar; GLUCAGON-like peptide 1; TYPE 2 diabetes
- Publication
Diabetes, 2008, Vol 57, Issue 5, p1340
- ISSN
0012-1797
- Publication type
Academic Journal
- DOI
10.2337/db07-1315