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Small Intestinal Glucose Delivery Affects the Lowering of Blood Glucose by Acute Vildagliptin in Type 2 Diabetes

Authors :
Tanya J. Little
Laurence G. Trahair
Carolyn F. Deacon
Karen L. Jones
Michelle J. Bound
Michael Horowitz
Xiang Zhang
Christopher K. Rayner
Tongzhi Wu
Wu, T
Zhang, X
Trahair, LG
Bound, MJ
Little, TJ
Deacon, CF
Horowitz, M
Jones, KL
Rayner, CK
Source :
The Journal of Clinical Endocrinology & Metabolism. 101:4769-4778
Publication Year :
2016
Publisher :
The Endocrine Society, 2016.

Abstract

Context: The rate of gastric emptying is an important determinant of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) secretion and may influence the magnitude of glucose lowering by dipeptidyl peptidase-4 (DPP-4) inhibitors. Objective: To evaluate the effects of the DPP-4 inhibitor, vildagliptin (VILD), during intraduodenal (ID) glucose infusion at 2 different rates within the physiological range of gastric emptying, in type 2 diabetes. Participants and Design: A total of 16 diet-controlled type 2 diabetic patients were studied on 4 separate days in double-blind, randomized, fashion. On each day, either 5-mg VILD or placebo (PLBO) was given 60 minutes before a 120-minute ID glucose infusion at 2 or 4 kcal/min (ID2 or ID4). Plasma glucose and hormones were measured frequently. Results: Plasma glucose, insulin, C-peptide, glucagon, total GIP, and total and intact GLP-1 concentrations were higher during ID4 than ID2 (P < .01 for each). Compared with PLBO, VILD was associated with higher intact GLP-1, insulin, and C-peptide and lower glucose and total GIP and GLP-1 (P < .01 for each), without affecting glucagon. There were significant interactions between the rate of ID glucose and VILD treatment on plasma glucose, intact and total GLP-1, and GIP (P < .05 for each) but not insulin, C-peptide, or glucagon. The reduction in glucose and the increment in intact GLP-1 after VILD vs PLBO were 3.3- and 3.8-fold greater, respectively, during ID4 compared with ID2. Conclusions/Interpretation: These observations warrant further study to clarify whether type 2 diabetic patients with relatively more rapid gastric emptying have greater glucose lowering during treatment with DPP-4 inhibitors.

Details

ISSN :
19457197 and 0021972X
Volume :
101
Database :
OpenAIRE
Journal :
The Journal of Clinical Endocrinology & Metabolism
Accession number :
edsair.doi.dedup.....66b3fc045df053925eb2369635fa07cd