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- Title
Effects of sitagliptin on blood pressure and heart rate in response to intraduodenal glucose infusion in patients with Type 2 diabetes: a potential role for glucose-dependent insulinotropic polypeptide?
- Authors
Wu, T.; Trahair, L. G.; Bound, M. J.; Deacon, C. F.; Horowitz, M.; Rayner, C. K.; Jones, K. L.
- Abstract
Aims To evaluate the effects of the dipeptidyl peptidase-4 inhibitor sitagliptin on blood pressure and heart rate, measured during a previously reported study, in which the effects of sitagliptin during intraduodenal glucose infusion at the rate of 2 kcal/min on glucose homeostasis were examined in patients with Type 2 diabetes. Methods A total of 10 people with Type 2 diabetes were studied on two different days, 30 min after oral ingestion of sitagliptin (100 mg) or placebo. Intraduodenal glucose was infused at 2 kcal/min (60 g over 120 min), and blood pressure, heart rate, plasma glucagon-like peptide-1 and glucose-dependent insulinotropic polypeptide (total and intact), glucose, insulin and glucagon responses were evaluated. Results In response to intraduodenal glucose infusion, heart rate (treatment effect: P = 0.001) and serum insulin concentration (treatment × time interaction: P = 0.041) were higher after sitagliptin treatment than placebo, without a significant difference in blood pressure, plasma glucagon or glucose. During intraduodenal glucose infusion, there was a substantial increase in plasma total glucose-dependent insulinotropic polypeptide on both days (time effect: P < 0.001), but not in total glucagon-like peptide-1. After sitagliptin, plasma intact glucagon-like peptide-1 concentration increased slightly (treatment × time interaction: P = 0.044) and glucose-dependent insulinotropic polypeptide concentration increased substantially (treatment × time interaction: P = 0.003).The heart rate response to intraduodenal glucose was related directly to plasma intact glucose-dependent insulinotropic polypeptide concentrations ( r = 0.75, P = 0.008). Conclusions Sitagliptin increased the heart rate response to intraduodenal glucose infusion at 2 kcal/min in people with Type 2 diabetes, which was associated with augmentation of plasma intact glucose-dependent insulinotropic polypeptide concentrations. These observations warrant further clarification of a potential role for glucose-dependent insulinotropic polypeptide in the control of the 'gut-heart' axis.
- Subjects
BLOOD sugar analysis; ENZYME inhibitors; MESENTERIC blood vessels; TYPE 2 diabetes treatment; HYPOGLYCEMIC agents; HYPOTENSION; DUODENUM; PEPTIDES; ANALYSIS of variance; BLOOD pressure measurement; BLOOD sugar; DRUG infusion pumps; CLINICAL drug trials; HEART rate monitoring; INGESTION; INSULIN; MEDICAL protocols; TYPE 2 diabetes; STATISTICS; GLUCAGON-like peptide 1; DATA analysis; RETROSPECTIVE studies; PATIENT selection; PHYSIOLOGY; SITAGLIPTIN; ANATOMY; THERAPEUTICS; DISEASE risk factors
- Publication
Diabetic Medicine, 2015, Vol 32, Issue 5, p595
- ISSN
0742-3071
- Publication type
Article
- DOI
10.1111/dme.12622