title: Increased high-density lipoprotein cholesterol predicts the pioglitazone-mediated reduction of carotid intima-media thickness progression in patients with type 2 diabetes mellitus.
abstract: BACKGROUND
  Measurement of carotid intima-media thickness (CIMT) has been validated as a measure of atherosclerosis and as a predictor of future cardiovascular events. Compared with glimepiride, pioglitazone has been shown to slow the progression of atherosclerosis measured by CIMT in patients with type 2 diabetes mellitus.
  
  
  RESULTS
  We evaluated individual cardiovascular risk factors as predictors of the change in CIMT produced by pioglitazone treatment by determining whether their addition to a baseline model resulted in loss of significance for the treatment effect on CIMT. Pioglitazone treatment led to improvement in levels of multiple cardiovascular risk markers, including high-sensitivity C-reactive protein, apolipoprotein B, apolipoprotein A1, high-density lipoprotein (HDL) cholesterol, triglyceride, insulin, and free fatty acid. At 24 weeks, there were significant differences in HDL cholesterol, triglyceride, total cholesterol, low-density lipoprotein cholesterol, insulin, body mass index, hip circumference, and high-sensitivity C-reactive protein between the pioglitazone and glimepiride treatment groups. After adjustment for 24-week on-treatment values of cardiovascular risk factors, only inclusion of the changes in HDL cholesterol and insulin significantly impacted the magnitude and significance of the treatment effect on CIMT. Furthermore, irrespective of treatment assignment, increased HDL cholesterol at 24 weeks was a significant predictor of reduced CIMT progression at 72 weeks.
  
  
  CONCLUSIONS
  The beneficial effect of pioglitazone on HDL cholesterol at 24 weeks predicted its beneficial effect for reducing CIMT progression at 72 weeks. Changes in HDL cholesterol at 24 weeks, irrespective of treatment, predicted less progression of CIMT at 72 weeks. These results suggest that suppression of atherosclerosis with pioglitazone therapy is linked to its ability to raise HDL cholesterol.
authors.affiliation: Pritzker School of Medicine, University of Illinois at Chicago, Chicago, IL 60612, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Davidson
authors.forename: Peter M
authors.initials: PM
authors.lastname: Meyer
authors.forename: Steven
authors.initials: S
authors.lastname: Haffner
authors.forename: Steven
authors.initials: S
authors.lastname: Feinstein
authors.forename: Ralph
authors.initials: R
authors.lastname: D'Agostino
authors.forename: George T
authors.initials: GT
authors.lastname: Kondos
authors.forename: Alfonso
authors.initials: A
authors.lastname: Perez
authors.forename: Zhen
authors.initials: Z
authors.lastname: Chen
authors.forename: Theodore
authors.initials: T
authors.lastname: Mazzone
mesh_terms: D000368:Aged; D002339:Carotid Arteries / Q000473:pathology; D002340:Carotid Artery Diseases / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D008076:Cholesterol, HDL / Q000097:blood*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications / Q000188:drug therapy* / Q000453:epidemiology; D018450:Disease Progression; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D000077205:Pioglitazone; D011237:Predictive Value of Tests; D012307:Risk Factors; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000627:therapeutic use*; D017539:Tunica Intima / Q000473:pathology; D017540:Tunica Media / Q000473:pathology
chemical_list: D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C057619:glimepiride; D000077205:Pioglitazone