The Effect of DPP-4-protected GLP-1 (7-36) on Coronary Microvascular Function in Obese Adults

Overview

Journal Int J Cardiol Heart Vasc

Date 2019 Feb 12

PMID 30740510

Citations 4

Authors

Malin Nilsson

Kira Bang Bove

Elena Suhrs

Thomas Hermann

Sten Madsbad

Jens Juul Holst

Eva Prescott

Mette Zander

Affiliations

Soon will be listed here.

Abstract

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,  = 0.43) and no difference in peripheral endothelial function (ΔFMD 7.34 ± 11.5 % vs. ΔFMD -1.25 ± 9.23%,  = 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.

Citing Articles

Updates on Pharmacologic Management of Microvascular Angina.

Soleymani M, Masoudkabir F, Shabani M, Vasheghani-Farahani A, Behnoush A, Khalaji A Cardiovasc Ther. 2022; 2022:6080258.

PMID: 36382021 PMC: 9626221. DOI: 10.1155/2022/6080258.

Coronary Microvascular Dysfunction in Diabetes Mellitus: Pathogenetic Mechanisms and Potential Therapeutic Options.

Salvatore T, Galiero R, Caturano A, Vetrano E, Loffredo G, Rinaldi L Biomedicines. 2022; 10(9).

PMID: 36140374 PMC: 9496134. DOI: 10.3390/biomedicines10092274.

GLP-1 Receptor Agonists and Coronary Arteries: From Mechanisms to Events.

Pahud de Mortanges A, Sinaci E, Salvador Jr D, Bally L, Muka T, Wilhelm M Front Pharmacol. 2022; 13:856111.

PMID: 35370744 PMC: 8964343. DOI: 10.3389/fphar.2022.856111.

The additive effects of obesity on myocardial microcirculation in diabetic individuals: a cardiac magnetic resonance first-pass perfusion study.

Jiang L, Shi K, Guo Y, Ren Y, Li Z, Xia C Cardiovasc Diabetol. 2020; 19(1):52.

PMID: 32375795 PMC: 7201945. DOI: 10.1186/s12933-020-01028-1.

References

Saraste M, Koskenvuo J, Knuuti J, Toikka J, Laine H, Niemi P . Coronary flow reserve: measurement with transthoracic Doppler echocardiography is reproducible and comparable with positron emission tomography. Clin Physiol. 2001; 21(1):114-22. DOI: 10.1046/j.1365-2281.2001.00296.x. View

Zander M, Madsbad S, Madsen J, Holst J . Effect of 6-week course of glucagon-like peptide 1 on glycaemic control, insulin sensitivity, and beta-cell function in type 2 diabetes: a parallel-group study. Lancet. 2002; 359(9309):824-30. DOI: 10.1016/S0140-6736(02)07952-7. View

Vilsboll T, Krarup T, Sonne J, Madsbad S, Volund A, Juul A . Incretin secretion in relation to meal size and body weight in healthy subjects and people with type 1 and type 2 diabetes mellitus. J Clin Endocrinol Metab. 2003; 88(6):2706-13. DOI: 10.1210/jc.2002-021873. View

Nystrom T, Gutniak M, Zhang Q, Zhang F, Holst J, Ahren B . Effects of glucagon-like peptide-1 on endothelial function in type 2 diabetes patients with stable coronary artery disease. Am J Physiol Endocrinol Metab. 2004; 287(6):E1209-15. DOI: 10.1152/ajpendo.00237.2004. View

Deanfield J, Donald A, Ferri C, Giannattasio C, Halcox J, Halligan S . Endothelial function and dysfunction. Part I: Methodological issues for assessment in the different vascular beds: a statement by the Working Group on Endothelin and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005; 23(1):7-17. DOI: 10.1097/00004872-200501000-00004. View

Brunner H, Cockcroft J, Deanfield J, Donald A, Ferrannini E, Halcox J . Endothelial function and dysfunction. Part II: Association with cardiovascular risk factors and diseases. A statement by the Working Group on Endothelins and Endothelial Factors of the European Society of Hypertension. J Hypertens. 2005; 23(2):233-46. DOI: 10.1097/00004872-200502000-00001. View

Baggio L, Drucker D . Biology of incretins: GLP-1 and GIP. Gastroenterology. 2007; 132(6):2131-57. DOI: 10.1053/j.gastro.2007.03.054. View

Basu A, Charkoudian N, Schrage W, Rizza R, Basu R, Joyner M . Beneficial effects of GLP-1 on endothelial function in humans: dampening by glyburide but not by glimepiride. Am J Physiol Endocrinol Metab. 2007; 293(5):E1289-95. DOI: 10.1152/ajpendo.00373.2007. View

Holst J . The physiology of glucagon-like peptide 1. Physiol Rev. 2007; 87(4):1409-39. DOI: 10.1152/physrev.00034.2006. View

10.

Coppola A, Marfella R, Coppola L, Tagliamonte E, Fontana D, Liguori E . Effect of weight loss on coronary circulation and adiponectin levels in obese women. Int J Cardiol. 2008; 134(3):414-6. DOI: 10.1016/j.ijcard.2007.12.087. View

11.

Ban K, Noyan-Ashraf M, Hoefer J, Bolz S, Drucker D, Husain M . Cardioprotective and vasodilatory actions of glucagon-like peptide 1 receptor are mediated through both glucagon-like peptide 1 receptor-dependent and -independent pathways. Circulation. 2008; 117(18):2340-50. DOI: 10.1161/CIRCULATIONAHA.107.739938. View

12.

DeFronzo R, Okerson T, Viswanathan P, Guan X, Holcombe J, MacConell L . Effects of exenatide versus sitagliptin on postprandial glucose, insulin and glucagon secretion, gastric emptying, and caloric intake: a randomized, cross-over study. Curr Med Res Opin. 2008; 24(10):2943-52. DOI: 10.1185/03007990802418851. View

13.

Lanza G, Crea F . Primary coronary microvascular dysfunction: clinical presentation, pathophysiology, and management. Circulation. 2010; 121(21):2317-25. DOI: 10.1161/CIRCULATIONAHA.109.900191. View

14.

Thijssen D, Black M, Pyke K, Padilla J, Atkinson G, Harris R . Assessment of flow-mediated dilation in humans: a methodological and physiological guideline. Am J Physiol Heart Circ Physiol. 2010; 300(1):H2-12. PMC: 3023245. DOI: 10.1152/ajpheart.00471.2010. View

15.

Nerla R, Tarzia P, Sestito A, Di Monaco A, Infusino F, Matera D . Effect of bariatric surgery on peripheral flow-mediated dilation and coronary microvascular function. Nutr Metab Cardiovasc Dis. 2010; 22(8):626-34. DOI: 10.1016/j.numecd.2010.10.004. View

16.

Murthy V, Naya M, Foster C, Gaber M, Hainer J, Klein J . Association between coronary vascular dysfunction and cardiac mortality in patients with and without diabetes mellitus. Circulation. 2012; 126(15):1858-68. PMC: 3495105. DOI: 10.1161/CIRCULATIONAHA.112.120402. View

17.

Marzilli M, Merz C, Boden W, Bonow R, Capozza P, Chilian W . Obstructive coronary atherosclerosis and ischemic heart disease: an elusive link!. J Am Coll Cardiol. 2012; 60(11):951-6. DOI: 10.1016/j.jacc.2012.02.082. View

18.

Hajjar D, Gotto Jr A . Biological relevance of inflammation and oxidative stress in the pathogenesis of arterial diseases. Am J Pathol. 2013; 182(5):1474-81. PMC: 3644714. DOI: 10.1016/j.ajpath.2013.01.010. View

19.

Campbell J, Drucker D . Pharmacology, physiology, and mechanisms of incretin hormone action. Cell Metab. 2013; 17(6):819-837. DOI: 10.1016/j.cmet.2013.04.008. View

20.

Kawata T, Daimon M, Hasegawa R, Toyoda T, Sekine T, Himi T . Prognostic value of coronary flow reserve assessed by transthoracic Doppler echocardiography on long-term outcome in asymptomatic patients with type 2 diabetes without overt coronary artery disease. Cardiovasc Diabetol. 2013; 12:121. PMC: 3765788. DOI: 10.1186/1475-2840-12-121. View