TY - JOUR

T1 - Small intestinal glucose delivery affects the glucose-lowering effect of acute vildagliptin in type 2 diabetes

AU - Wu, T

AU - Zhang, X

AU - Trahair, LG

AU - Bound, MJ

AU - Little, TL

AU - Deacon, Carolyn F.

AU - Horowitz, M

AU - Jones, KL

AU - Rayner, CK

PY - 2016

Y1 - 2016

N2 - 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 type2 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 concentrationswere higher during ID4 than ID2 (P .01 for each). Compared with PLBO, VILD wasassociated 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 intactGLP-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.

AB - 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 type2 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 concentrationswere higher during ID4 than ID2 (P .01 for each). Compared with PLBO, VILD wasassociated 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 intactGLP-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.

U2 - 10.1210/jc.2016-2813

DO - 10.1210/jc.2016-2813

M3 - Journal article

C2 - 27598511

VL - 101

SP - 4769

EP - 4778

JO - Journal of Clinical Endocrinology and Metabolism

JF - Journal of Clinical Endocrinology and Metabolism

SN - 0021-972X

IS - 12

ER -