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https://hdl.handle.net/2440/104185
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Type: | Journal article |
Title: | Small intestinal glucose delivery affects the lowering of blood glucose by acute vildagliptin in type 2 diabetes |
Author: | Wu, T. Zhang, X. Trahair, L. Bound, M. Little, T. Deacon, C. Horowitz, M. Jones, K. Rayner, C. |
Citation: | Journal of Clinical Endocrinology and Metabolism, 2016; 101(12):4769-4778 |
Publisher: | Oxford University Press |
Issue Date: | 2016 |
ISSN: | 0021-972X 1945-7197 |
Statement of Responsibility: | Tongzhi Wu, Xiang Zhang, Laurence G. Trahair, Michelle J. Bound, Tanya J. Little, Carolyn F. Deacon, Michael Horowitz, Karen L. Jones, and Christopher K. Rayner |
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, during intraduodenal (ID) glucose infusion at two 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 four separate days in double-blind, randomized, fashion. On each day, either 50mg vildagliptin or placebo was given 60min prior to a 120min ID glucose infusion at 2 or 4kcal/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<0.01 for each). Compared with placebo, vildagliptin was associated with higher intact GLP-1, insulin and C-peptide, and lower glucose and total GIP and GLP-1 (P<0.01 for each), without affecting glucagon. There were significant interactions between the rate of ID glucose and vildagliptin treatment on plasma glucose, intact and total GLP-1, and GIP (P<0.05 for each), but not insulin, C-peptide or glucagon. The reduction in glucose and the increment in intact GLP-1 after vildagliptin vs. placebo were 3.3 and 3.8 fold greater respectively, during ID4 compared to 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. |
Keywords: | Duodenum Humans Diabetes Mellitus, Type 2 Adamantane Nitriles Pyrrolidines Blood Glucose Infusions, Parenteral Double-Blind Method Aged Middle Aged Female Male Dipeptidyl-Peptidase IV Inhibitors Vildagliptin Outcome Assessment, Health Care |
Rights: | Copyright © 2016 by the Endocrine Society |
DOI: | 10.1210/jc.2016-2813 |
Grant ID: | http://purl.org/au-research/grants/nhmrc/1066815 http://purl.org/au-research/grants/nhmrc/627011 |
Published version: | http://dx.doi.org/10.1210/jc.2016-2813 |
Appears in Collections: | Aurora harvest 7 Medicine publications |
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