title: Rapid effect of single-dose rosiglitazone treatment on endothelial function in healthy men with normal glucose tolerance: data from a randomised, placebo-controlled, double-blind study.
abstract: Antidiabetic thiazolidinediones (TZDs) improve endothelial function in patients with or without type 2 diabetes. The present randomised, placebo-controlled, double-blind study examined the time course of a single dose of rosiglitazone on flow-mediated endothelium-dependent vasodilation (FMD), metabolic parameters, and its effect on inflammatory markers in non-diabetic men. Forty non-obese, healthy men with normal glucose tolerance were randomised to a single dose of rosiglitazone (8 mg) or placebo, and FMD was assessed at baseline as well as after 6 h and 24 h. Rosiglitazone did not significantly affect blood glucose and insulin levels or lipid parameters after 6 and 24 h compared with placebo. Treatment with rosiglitazone significantly increased FMD after 6 h 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 24 h 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). 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.
authors.affiliation: Department of Internal Medicine II - Cardiology, University of Ulm, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Walcher
authors.forename: Daniel
authors.initials: D
authors.lastname: Walcher
authors.forename: Jürgen
authors.initials: J
authors.lastname: Hetzel
authors.forename: Catrin
authors.initials: C
authors.lastname: Mielke
authors.forename: Matthias
authors.initials: M
authors.lastname: Rau
authors.forename: Kilian
authors.initials: K
authors.lastname: Rittig
authors.forename: Bernd
authors.initials: B
authors.lastname: Balletshofer
authors.forename: Edzard
authors.initials: E
authors.lastname: Schwedhelm
authors.forename: Vinzenz
authors.initials: V
authors.lastname: Hombach
authors.forename: Rainer H
authors.initials: RH
authors.lastname: Böger
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Koenig
authors.forename: Nikolaus
authors.initials: N
authors.lastname: Marx
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000000981:diagnostic imaging / Q000187:drug effects*; D005858:Germany; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood; D008297:Male; D015990:Placebo Effect; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000008:administration & dosage*; D013997:Time Factors; D014463:Ultrasonography; D014664:Vasodilation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008055:Lipids; D045162:Thiazolidinediones; D000077154:Rosiglitazone