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1 Department of Internal Medicine, Karolinska Institutet, Stockholm, Sweden
2 Department of Medical Phyisiology, Panum Institute, University of Copenhagen, Copenhagen, Denmark
3 Department of Medicine, Lund University, Lund, Sweden
* To whom correspondence should be addressed. E-mail: thomas.nystrom{at}sos.sll.se.
Glucagon-like peptide-1 (GLP-1) stimulates insulin secretion, suppresses glucagon secretion, delays gastric emptying and inhibits small bowel motility, all actions that contribute to the anti-diabetogenic effect of the peptide. Endothelial dysfunction is strongly associated with insulin resistance and type 2 diabetes mellitus, and may be causing the angiopathy typifying this debilitating disease. Therefore, any intervention affecting both endothelial dysfunction and insulin resistance may prove useful in improving survival in patients with type 2 diabetes. We have in this study investigated GLP-1's effect on endothelial function and insulin sensitivity in two separate groups 1) Twelve type 2 diabetes patients with stable coronary artery disease and 2) Ten healthy subjects with normal endothelial function and insulin sensitivity. Subjects underwent infusion of recombinant GLP-1 or saline in a random cross-over study. Endothelial function was measured by post-ischemic flow-mediated vasodilation (FMD) of the brachial artery using ultrasonography. Insulin sensitivity index (SI) was measured by hyperinsulinemic isoglycemic clamp technique. In type 2 diabetes subjects, GLP-1 infusion significantly increased the relative changes in brachial artery diameter from baseline FMD(%) (3.1±1.4 vs. 6.6±1.5 %, P<0.05), with no significant effects on SI (4.5±0.8 vs 5.2±0.9 [10-4dl.kg-1.min-1/(µU/mL)], P=NS). In contrast, in healthy subjects GLP-1 infusion affected neither FMD(%) (11.9[±0.9 vs. 10.3±1.0 %, P=NS) nor SI (14.8±1.8 vs 11.6±2.0 [10-4dl.kg-1.min-1/(µU/mL)], P=NS). We conclude that GLP-1 improves endothelial dysfunction, but not insulin resistance, in type 2 diabetic patients with coronary heart disease. This beneficial vascular effect of GLP-1 adds yet another salutary property of the peptide useful in diabetes treatment.
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