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Small Intestinal Glucose Delivery Affects the Lowering of Blood Glucose by Acute Vildagliptin in Type 2 Diabetes
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 19457197 and 0021972X
- Volume :
- 101
- Database :
- OpenAIRE
- Journal :
- The Journal of Clinical Endocrinology & Metabolism
- Accession number :
- edsair.doi.dedup.....66b3fc045df053925eb2369635fa07cd