Inflammatory processes are increasingly being recognized as a critical step in the pathogenesis of both diabetes and heart disease and may constitute a biological link between the two diseases. Inflammatory cytokines increase vascular permeability, change vasoregulatory responses, increase leukocyte adhesion to endothelium, and facilitate thrombus formation by inducing procoagulant activity, inhibiting anticoagulant pathways, and impairing fibrinolysis. Leukocyte adhesion to arterial endothelial cells is thought to be an important step in the development of atherosclerosis, and adhesion molecules, such as intercellular adhesion molecule-1 (ICAM-1) and L-selectin, play key roles in this process. Therefore, identifying novel therapeutic approaches that would favorably affect inflammation, endothelial function, and glucose is of significant interest. Investigators have recently demonstrated that, relative to placebo, sitagliptin treatment resulted in a significant reduction in plasma levels of various inflammatory markers and cell adhesion molecules. The results also suggest that the beneficial effects of sitagliptin on both inflammation and endothelial function are most likely mediated by an elevation in plasma GLP-1 levels and global improvement of the glucose-insulin homeostasis. However, the mechanisms underlying the beneficial effects of sitagliptin on these markers remain to be fully elucidated. The proposed study will address this key issue.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
20
Sitagliptin 100 mg/d for 6 weeks
Placebo for 6 weeks
Laval University
Québec, Quebec, Canada
Measurement of C-reactive Protein Production Rate With Stable Isotope During Postprandial Period
Time frame: 6 weeks
Measurement of Serum Amyloid A Production Rate With Stable Isotope During Postprandial Period
Time frame: 6 weeks
Measurement of L-selectin Production Rate With Stable Isotope During Postprandial Period
Time frame: 6 weeks
Measurement of ICAM-1 Production Rate With Stable Isotope During Postprandial Period
Time frame: 6 weeks
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