Coronary Microvascular Dysfunction Clinical Trial
Official title:
Effect of Intact GLP-1 (7-36) and GLP-1 Metabolite (9-36) on Coronary and Peripheral Vascular Function in Adults
GLP-1 is an agent for treatment of type 2 diabetes and may have protective effects on the
cardiovascular system. The mechanism is complex and there seems to be a dual function with
intact GLP-1 (7-36), acting through the GLP-1 receptor, and the GLP-1 (9-36) metabolite
acting independently of the GLP-1 receptor.
Coronary flow reserve (CFR) is the ratio of flow through the coronary arteries during stress
to during rest and it reflects coronary microcirculation. Impaired CFR is a strong predictor
of poor prognosis of cardiovascular disease.
The aim of the study is to investigate the acute effects of GLP-1 on coronary
microcirculation and endothelial function in adults with obesity.
Several studies have shown beneficial effects of glucagon-like-peptide-1 (GLP-1) on the
cardiovascular system. Native GLP-1 is secreted from L-cells in the intestine as GLP-1(7-36)
1 but is rapidly metabolised by the ubiquitous enzyme dipeptidyl-peptidase-4 (DPP4) to the
metabolite GLP-1(9-36). However, the physiological effect of GLP-1 on the cardiovascular
system is complex and there seems to be a dual function with intact GLP-1 (7-36), acting
through the GLP-1 receptor, and the GLP-1 (9-36) metabolite acting independently of the GLP-1
receptor.
The aim of the study is to investigate the acute effects of intact GLP-1 and GLP-1 metabolite
on coronary microcirculation and endothelial function in adults.
Method 20 adults with obesity are recruited to a double-blind randomized cross-over study.
The first 10 included adults will receive 2½ hours infusion of intact GLP-1 (7-36) together
with a DPP-IV inhibitor and 2½ hours infusion of saline, on two separate occasions. The
infusions will be given in randomized order with a minimum of 24 hours washout period.
The next 10 included adults will receive 2½ hours infusion of GLP-1 (9-36) metabolite and 2½
hours infusion of saline. These will also be given in randomized order with a minimum of 24
hours washout period. Endothelial function and CFR will be measured before and after one,
respectively two, hours of infusion.
The effect of GLP-1 infusions on microvascular function is evaluated by coronary flow reserve
(CFR), the ratio between echocardiographic measured coronary flow velocity in LAD during
adenosine induced myocardial hyperaemia and rest. The effect on endothelial function is
assessed by flow mediated dilation (FMD).
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