title: Thiazolidinediones improve flow-mediated dilation: a meta-analysis of randomized clinical trials.
abstract: OBJECTIVE
  Thiazolidinediones administration is assumed to be related with an improvement of endothelial dysfunction (ED); nevertheless, previous studies have been inconsistent. For this reason, the present meta-analysis was directed to estimate if thiazolidinediones were related to endothelial dysfunction improvement by using flow-mediated dilation (FMD) measurement.
  
  
  METHODS
  Literature search of the PubMed, the Cochrane Library, the Web of Science, and the Scopus databases was performed covering the period until July 01, 2015, for randomized clinical trials that investigated an influence of thiazolidinediones on FMD. For the calculation of the pooled overall effect, a random effect model was used. Meta-regression and subgroup analyses were performed to evaluate the impact of study characteristics on the effect of thiazolidinediones administration on FMD.
  
  
  RESULTS
  This meta-analysis included 16 studies with 812 subjects. The obtained results demonstrated an improvement of endothelial dysfunction measured with FMD (16 studies, 812 subjects; WMD: 2.4 %, 95 % CI = 1.1 to 3.69 %; p = 0.0003). The significant heterogeneity was noted (I (2) = 95 %, p < 0.00001). Subgroup analysis demonstrated that pioglitazone and rosiglitazone were able to improve FMD. Also, thiazolidinediones improved FMD if treatment was longer than 12 weeks and if patients were younger than 65 years. Additionally, a lipid profile was found to influence thiazolidinediones effect on FMD.
  
  
  CONCLUSIONS
  The results of this meta-analysis demonstrated that thiazolidinediones were able to improve FMD, which in clinical terms can be further translated to the improvement of an impaired endothelial function. Nevertheless, the link between FMD and its predictive clinical relevance still requires further clarification.
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, PO Box 38, Belgrade, 11129, Serbia.
authors.forename: Marko
authors.initials: M
authors.lastname: Stojanović
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, PO Box 38, Belgrade, 11129, Serbia.
authors.forename: Milica
authors.initials: M
authors.lastname: Prostran
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology, Faculty of Medicine, University of Belgrade, PO Box 38, Belgrade, 11129, Serbia. mradenkovic@med.bg.ac.rs.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Radenković
mesh_terms: D000818:Animals; D004730:Endothelium, Vascular / Q000187:drug effects; D006801:Humans; D000077205:Pioglitazone; D016032:Randomized Controlled Trials as Topic; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000494:pharmacology* / Q000627:therapeutic use*; D014664:Vasodilation / Q000187:drug effects*
chemical_list: D045162:Thiazolidinediones; D000077154:Rosiglitazone; D000077205:Pioglitazone
keywords: Endothelial dysfunction; Flow-mediated dilation; Pioglitazone; Rosiglitazone; Thiazolidinediones