Small Intestinal Glucose Delivery Affects the Lowering of Blood Glucose by Acute Vildagliptin in Type 2 Diabetes
| Autor: | Tanya J. Little, Laurence G. Trahair, Carolyn F. Deacon, Karen L. Jones, Michelle J. Bound, Michael Horowitz, Xiang Zhang, Christopher K. Rayner, Tongzhi Wu |
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| Přispěvatelé: | Wu, T, Zhang, X, Trahair, LG, Bound, MJ, Little, TJ, Deacon, CF, Horowitz, M, Jones, KL, Rayner, CK |
| Rok vydání: | 2016 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine endocrine system medicine.medical_specialty Pyrrolidines Duodenum Endocrinology Diabetes and Metabolism medicine.medical_treatment Clinical Biochemistry Adamantane 030209 endocrinology & metabolism Type 2 diabetes Biochemistry Glucagon 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Endocrinology Double-Blind Method Diabetes mellitus Internal medicine Nitriles Outcome Assessment Health Care medicine Humans Infusions Parenteral Vildagliptin Aged Dipeptidyl-Peptidase IV Inhibitors Gastric emptying C-peptide business.industry Insulin digestive oral and skin physiology Biochemistry (medical) Middle Aged medicine.disease Glucagon-like peptide-1 030104 developmental biology Diabetes Mellitus Type 2 chemistry Female business hormones hormone substitutes and hormone antagonists medicine.drug |
| Zdroj: | The Journal of Clinical Endocrinology & Metabolism. 101:4769-4778 |
| ISSN: | 1945-7197 0021-972X |
| DOI: | 10.1210/jc.2016-2813 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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