Objective: Glucagon-like-peptide-1 (GLP-1) receptor analogues have been shown to reduce cardiovascular events in patients with type 2 diabetes. However, the mechanism behind is still unknown. The aim of the study was to investigate the effect of intact GLP-1 (7-36) on coronary microcirculation in overweight adults.
Design and methods: A double-blinded randomized cross-over study was performed, with 12 overweight participants. Effects of intact GLP-1 (7-36) infusion were compared with a saline infusion on separate days. A DPP-4 inhibitor was administered to block degradation of intact GLP-1 (7-36) to the GLP-1 metabolite (9-36). Coronary microcirculation was assessed by Doppler coronary flow velocity reserve (CFVR) before and after 2 h of infusion. Peripheral endothelial function was assessed by flow mediated dilation (FMD) before and after one hour of infusion.
Results: CFVR was 3.77 ± 1.25 during GLP-1 infusion and 3.85 ± 1.32 during saline infusion, endothelial function was 16.3 ± 15.5 % during GLP-1 infusion and 7.85 ± 7.76 % during saline infusion. When adjusting for baseline values no significant differences in CFVR (ΔCFVR 0.38 ± 0.92 vs. ΔCFVR 0.71 ± 1.03, p = 0.43) and no difference in peripheral endothelial function (ΔFMD 7.34 ± 11.5 % vs. ΔFMD -1.25 ± 9.23%, p = 0.14) was found.
Conclusions: We found no effect of intact GLP-1 (7-36), protected from DPP4 mediated degradation on coronary microcirculation in overweight adults.
Keywords: CFVR, coronary flow velocity reserve; CMD, coronary microvascular dysfunction; Coronary flow velocity reserve; Coronary microcirculation; DPP-4, dipeptidyl peptidase-4; Endothelial function; FMD, flow mediated dilation; GLP-1, flow mediated dilation; GLP-1, glucagon-like peptide-1; Glucagon-like peptide-1 (7–36); LAD, left anterior descending artery; MACE, major adverse cardiac event; NMD, nitroglycerine-mediated dilation; QC, quality control; RPP, rate pressure product; TTDE, trans-thoracic Doppler echocardiography.