Improvement of postprandial endothelial function after a single dose of exenatide in individuals with impaired glucose tolerance and recent-onset type 2 diabetes

Abstract

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.

Trial registration: ClinicalTrials.gov NCT00974272.

Figure 1

Data are means ± SE. The effects of exenatide and placebo on postprandial endothelial function (PAT index) in the entire cohort (A) and in subjects with IGT (B) or type 2 diabetes (C). Endothelial function was measured before and after a single high-fat breakfast meal. Participants received placebo and exenatide on separate visits in a crossover design. P values denote statistical significance of differences in postmeal values (adjusted for pre-meal and test sequence) between exenatide and placebo.