title: The impact of pioglitazone on ADMA and oxidative stress markers in patients with type 2 diabetes.
abstract: OBJECTIVE
  To determine whether pioglitazone 30 mg daily reduces levels of ADMA in adult patients with diabetes, and whether there is improvement in markers of oxidative stress.
  
  
  METHODS
  Prospective randomized cross-over placebo-controlled study of 36 adults age 40-75 years with type 2 diabetes recruited from a single academic health center. Intervention was for 12 weeks, followed by a 4-week wash-out period, followed by a second 12-week cross-over treatment period. The main outcome was comparison of the change in ADMA levels in the two treatment periods. Secondary outcomes included change in NOx and F2-isoprostanes.
  
  
  RESULTS
  Thirty-six patients were enrolled in the study, 31 completed the protocol; the study enrollment met the sample size required to detect a change of 18% in levels. There were no differences in ADMA, NOx and F2-isoprostanes levels in the two treatment periods. Non-study medication changes or changes in dose were infrequent, and a statin was added during the study period in only one patient.
  
  
  CONCLUSIONS
  Despite previous animal data that showed an effect of pioglitazone on ADMA, the current study in human patients did not demonstrate any differences in ADMA, NOx, or F2-isoprostane levels. The results do not favor that pioglitazone has a significant impact on ADMA levels in human patients with diabetes.
authors.affiliation: Department of Family Medicine, The Medical University of South Carolina, 295 Calhoun Street, Charleston, SC 26425, United States. kingde@musc.edu
authors.forename: Dana E
authors.initials: DE
authors.lastname: King
authors.forename: Marty
authors.initials: M
authors.lastname: Player
authors.forename: Charles J
authors.initials: CJ
authors.lastname: Everett
mesh_terms: D000046:Academic Medical Centers; D001120:Arginine / Q000031:analogs & derivatives* / Q000097:blood; D015415:Biomarkers / Q000097:blood; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000188:drug therapy*; D015237:Dinoprost / Q000031:analogs & derivatives / Q000097:blood; D028441:F2-Isoprostanes / Q000097:blood; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D000077205:Pioglitazone; D011446:Prospective Studies; D013022:South Carolina; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D028441:F2-Isoprostanes; D007004:Hypoglycemic Agents; D009566:Nitrates; D009573:Nitrites; D045162:Thiazolidinediones; C075750:8-epi-prostaglandin F2alpha; C018524:N,N-dimethylarginine; D001120:Arginine; D015237:Dinoprost; D000077205:Pioglitazone