TY - JOUR

T1 - Separate impact of obesity and glucose tolerance on the incretin effect in normal subjects and type 2 diabetic patients

AU - Muscelli, Elza

AU - Mari, Andrea

AU - Casolaro, Arturo

AU - Camastra, Stefania

AU - Seghieri, Giuseppe

AU - Gastaldelli, Amalia

AU - Holst, Jens Juul

AU - Ferrannini, Ele

PY - 2008/5

Y1 - 2008/5

N2 - 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.

AB - 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.

KW - Adult

KW - Blood Glucose

KW - Body Mass Index

KW - Diabetes Mellitus, Type 2

KW - Female

KW - Glucose Tolerance Test

KW - Humans

KW - Hypoglycemic Agents

KW - Insulin

KW - Insulin-Secreting Cells

KW - Male

KW - Middle Aged

KW - Obesity

KW - Reference Values

U2 - 10.2337/db07-1315

DO - 10.2337/db07-1315

M3 - Journal article

C2 - 18162504

VL - 57

SP - 1340

EP - 1348

JO - Diabetes

JF - Diabetes

SN - 0901-3652

IS - 5

ER -