Abstract 407: Rapid Effect of Single Dose Rosiglitazone Treatment on Endothelial Function in Healthy Men with Normal Glucose Tolerance: Data from a Randomized, Placebo-Controlled, Double-Blind Study
Antidiabetic thiazolidinediones(TZDs) improve endothelial function in patients with or without type 2 diabetes. Recent data from our group suggest an early effect of rosiglitazone on flow-mediated endothelium-dependent vasodilation (FMD) in healthy men after one day of treatment. This randomized, placebo-controlled, double-blind study examined the time course of a single dose of rosiglitazone on endothelial function, metabolic parameters, as well as its effect on inflammatory markers in non-diabetic men. Forty non-obese, healthy men with normal glucose tolerance were randomized to a single dose of rosiglitazone (8mg) or placebo, and FMD was assessed at baseline as well as after 6 and 24h. Rosiglitazone did not significantly affect blood glucose and insulin levels or lipid parameters after 6 and 24h compared with placebo. Treatment with rosiglitazone significantly increased flow-mediated, endothelium-dependent vasodilation after 6h from 4.3 % (3.3;4.9) to 7.6 % (5.6;9.2) (p<0.0001 vs. baseline) resulting in a highly significant effect compared with placebo (p=0.0001 for difference between groups). After 24h FMD was still significantly higher in the rosiglitazone group compared with baseline (p<0.001), but the effect was no longer statistically significant versus placebo (p<0.171). There was no significant effect of rosiglita-zone on markers of vascular function (ADMA, L-arginine) or inflammatory biomarkers (TNF-alpha, adiponectin, hsCRP) at any time point during the 24 h study period. Our study shows a very rapid effect of single dose rosiglitazone treatment on endothelial function in non-diabetic healthy men, underscoring the hypothesis that TZDs may exhibit direct effect in the vasculature independent of their metabolic action.