The effect of DPP-4-protected GLP-1 (7-36) on coronary microvascular function in obese adults.
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.
['Nilsson|Malin|M|', 'Bové|Kira Bang|KB|', 'Suhrs|Elena|E|', 'Hermann|Thomas|T|', 'Madsbad|Sten|S|', 'Holst|Jens Juul|JJ|', 'Prescott|Eva|E|', 'Zander|Mette|M|']
Coronary microcirculation Coronary flow velocity reserve Endothelial function CFVR, coronary flow velocity reserve CMD, coronary microvascular dysfunction DPP-4, dipeptidyl peptidase-4 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