Leiden University Scholarly Publications

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Eyk, H.J. van (2023)

GLP-1 receptor agonism to improve cardiometabolic health

Doctoral Thesis
Glucagon-like peptide-1 (GLP-1) receptor agonists are a relatively new treatment option for obesity and type 2 diabetes. Treatment has been shown to result in in weight loss and improved glycemic control. In this thesis, the effects of treatment on the different adipose tissue depots and on cardiac function are described. In a randomised controlled trial, we treated patients with type 2 diabetes from South Asian descent, a population with increased risk to develop type 2 diabetes and cardiovascular disease compared to Western Europeans, with liraglutide, a GLP-1 receptor agonist, or placebo, and studied these subjects with MRI. We concluded that liraglutide and possibly other GLP-1 receptor agonists can be a good strategy to reduce the volume of visceral adipose tissue. This reduction was accompanied by a significant improvement of glycemic control. Lastly, we provided evidence that liraglutide does not improve cardiac function and myocardial tissue characteristics and thus does...Show moreGlucagon-like peptide-1 (GLP-1) receptor agonists are a relatively new treatment option for obesity and type 2 diabetes. Treatment has been shown to result in in weight loss and improved glycemic control. In this thesis, the effects of treatment on the different adipose tissue depots and on cardiac function are described. In a randomised controlled trial, we treated patients with type 2 diabetes from South Asian descent, a population with increased risk to develop type 2 diabetes and cardiovascular disease compared to Western Europeans, with liraglutide, a GLP-1 receptor agonist, or placebo, and studied these subjects with MRI. We concluded that liraglutide and possibly other GLP-1 receptor agonists can be a good strategy to reduce the volume of visceral adipose tissue. This reduction was accompanied by a significant improvement of glycemic control. Lastly, we provided evidence that liraglutide does not improve cardiac function and myocardial tissue characteristics and thus does not improve diabetic cardiomyopathy. In addition, in another study, we studied the mechanism behind GLP-1 receptor agonism induced weight loss and concluded that liraglutide induces weight loss in humans by decreasing energy intake rather than by activating brown adipose tissue or increasing energy expenditure.
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Type 2 diabetes
Obesity
Ectopic fat
Cardiovascular function
South Asian
Glucagon-like peptide-1 (GLP-1)
Energy expenditure
Brown adipose tissue
All authors
Eyk, H.J. van
Supervisor
Rensen, P.C.N.; Lamb, H.J.
Co-supervisor
Jazet, I.M.
Committee
Pijl, H.; Rossem, E.F.C. van; Raalte, D.H. van; Geehoed-Duijvesteijn, P.H.
Qualification
Doctor (dr.)
Awarding Institution
Faculty of Medicine, Leiden University Medical Center (LUMC), Leiden University
Date
2023-06-28
ISBN (print)
9789463618595

Funding

Sponsorship
This thesis was partly financially supported by Roba Metals B.V., IJsselstein, the Netherlands. The investigator-initiated MAGNA VICTORIA study was funded by a grant of Novo Nordisk B.V., Denmark. The printing of this thesis was kindly supported by Chipsoft B.V., Amsterdam, the Netherlands.