Improvement of Postprandial Endothelial Function After a Single Dose of Exenatide in Individuals With Impaired Glucose Tolerance and Recent-Onset Type 2 Diabetes

OBJECTIVE: Endothelial dysfunction is frequently present in individuals with insulin resistance or type 2 diabetes and can be induced by high-fat or high-carbohydrate meals. Because exenatide reduces postprandial glucose and lipid excursions, we hypothesized that it may also improve postprandial endothelial function. RESEARCH DESIGN AND METHODS: In a double-blinded randomized crossover design, postprandial endothelial function was examined in 28 individuals with impaired glucose tolerance or recent-onset type 2 diabetes after a single injection of exenatide or placebo given just before a high-fat meal. Endothelial function was determined with peripheral arterial tonometry pre- and postprandially. RESULTS: Postprandial endothelial function was higher after exenatide compared with placebo (P = 0.0002). In the placebo phase, postprandial change in endothelial function was inversely associated with mean postprandial concentrations of triglycerides (r = -0.62, P = 0.0004). Changes in postprandial triglyceride concentrations explained 64% of exenatide's effect on postprandial endothelial function. CONCLUSIONS: Exenatide ameliorates postprandial endothelial dysfunction after a high-fat meal.