title: Pioglitazone slows progression of atherosclerosis in prediabetes independent of changes in cardiovascular risk factors.
abstract: OBJECTIVE
  To determine whether changes in standard and novel risk factors during the Actos Now for Prevention of Diabetes trial explained the slower rate of carotid intima media thickness (CIMT) progression with pioglitazone treatment in persons with prediabetes.
  
  
  RESULTS
  CIMT was measured in 382 participants at the beginning and up to 3 additional times during follow-up of the Actos Now for Prevention of Diabetes trial. During an average follow-up of 2.3 years, the mean unadjusted annual rate of CIMT progression was significantly (P=0.01) lower with pioglitazone treatment (4.76×10(-3) mm/year; 95% CI: 2.39×10(-3)-7.14×10(-3) mm/year) compared with placebo (9.69×10(-3) mm/year; 95% CI: 7.24×10(-3)-12.15×10(-3) mm/year). High-density lipoprotein cholesterol, fasting and 2-hour glucose, HbA(1c), fasting insulin, Matsuda insulin sensitivity index, adiponectin, and plasminogen activator inhibitor-1 levels improved significantly with pioglitazone treatment compared with placebo (P<0.001). However, the effect of pioglitazone on CIMT progression was not attenuated by multiple methods of adjustment for traditional, metabolic, and inflammatory risk factors and concomitant medications, and was independent of changes in risk factors during pioglitazone treatment.
  
  
  CONCLUSIONS
  Pioglitazone slowed progression of CIMT, independent of improvement in hyperglycemia, insulin resistance, dyslipidemia, and systemic inflammation in prediabetes. These results suggest a possible direct vascular benefit of pioglitazone.
authors.affiliation: Phoenix Veterans Affair (VA) Health Care System, Phoenix, AZ, USA.
authors.forename: Aramesh
authors.initials: A
authors.lastname: Saremi
authors.forename: Dawn C
authors.initials: DC
authors.lastname: Schwenke
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Buchanan
authors.forename: Howard N
authors.initials: HN
authors.lastname: Hodis
authors.forename: Wendy J
authors.initials: WJ
authors.lastname: Mack
authors.forename: Maryann
authors.initials: M
authors.lastname: Banerji
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.forename: Stephen C
authors.initials: SC
authors.lastname: Clement
authors.forename: Robert R
authors.initials: RR
authors.lastname: Henry
authors.forename: Abbas E
authors.initials: AE
authors.lastname: Kitabchi
authors.forename: Sunder
authors.initials: S
authors.lastname: Mudaliar
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ratner
authors.forename: Frankie B
authors.initials: FB
authors.lastname: Stentz
authors.forename: Nicolas
authors.initials: N
authors.lastname: Musi
authors.forename: Devjit
authors.initials: D
authors.lastname: Tripathy
authors.forename: Ralph A
authors.initials: RA
authors.lastname: DeFronzo
authors.forename: Peter D
authors.initials: PD
authors.lastname: Reaven
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002340:Carotid Artery Diseases / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D059168:Carotid Intima-Media Thickness; D016009:Chi-Square Distribution; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis / Q000209:etiology / Q000517:prevention & control*; D018450:Disease Progression; D004311:Double-Blind Method; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000097:blood; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011236:Prediabetic State / Q000097:blood / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D045162:Thiazolidinediones / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D014481:United States
chemical_list: D052242:Adiponectin; D015415:Biomarkers; D001786:Blood Glucose; D008076:Cholesterol, HDL; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000077205:Pioglitazone; D017395:Plasminogen Activator Inhibitor 1; D045162:Thiazolidinediones; C499918:ADIPOQ protein, human; C051321:SERPINE1 protein, human; C517652:hemoglobin A1c protein, human