Tongzhi Wu1, Xiang Zhang1, Laurence G Trahair1, Michelle J Bound1, Tanya J Little1, Carolyn F Deacon1, Michael Horowitz1, Karen L Jones1, Christopher K Rayner1. 1. Discipline of Medicine (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; Centre of Research Excellence in Translating Nutritional Science to Good Health (T.W., X.Z., L.G.T., M.J.B., T.J.L., M.H., K.L.J., C.K.R.), The University of Adelaide, Adelaide, Australia; and Department of Biomedical Science (C.F.D.), University of Copenhagen, Copenhagen, Denmark.
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.
RCT Entities:
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 diabeticpatients 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 diabeticpatients with relatively more rapid gastric emptying have greater glucose lowering during treatment with DPP-4 inhibitors.
Authors: Hung Pham; Iselin S Holen; Liza K Phillips; Seva Hatzinikolas; Lian Q Huynh; Tongzhi Wu; Trygve Hausken; Christopher K Rayner; Michael Horowitz; Karen L Jones Journal: Nutrients Date: 2019-11-05 Impact factor: 5.717
Authors: Ryan J Jalleh; Tongzhi Wu; Karen L Jones; Christopher K Rayner; Michael Horowitz; Chinmay S Marathe Journal: J Clin Endocrinol Metab Date: 2022-08-18 Impact factor: 6.134