title: Impact of rosiglitazone on body composition, hepatic fat, fatty acids, adipokines and glucose in persons with impaired fasting glucose or impaired glucose tolerance: a sub-study of the DREAM trial.
abstract: OBJECTIVE
  Thiazolidinediones reduce ectopic fat, increase adiponectin and reduce inflammatory adipokines, fatty acids and glucose in people with Type 2 diabetes. We aimed to measure these effects in people with impaired fasting glucose and/or impaired glucose tolerance.
  
  
  METHODS
  After approximately 3.5 years of exposure to rosiglitazone 8 mg (n = 88) or placebo (n = 102), 190 DREAM trial participants underwent abdominal computed tomography and dual-energy X-ray absorptiometry scans. Visceral and subcutaneous adipose tissue areas, estimated hepatic fat content, total fat and lean mass were calculated and changes in levels of fasting adipokines, free fatty acids, glucose and post-load glucose were assessed.
  
  
  RESULTS
  Compared with the placebo, participants on rosiglitazone had no difference in lean mass, had 4.1 kg more body fat (P < 0.0001) and 31 cm(2) more subcutaneous abdominal adipose tissue area (P = 0.007). Only after adjusting for total fat, participants on rosiglitazone had 23 cm² less visceral adipose tissue area (P = 0.01) and an 0.08-unit higher liver:spleen attenuation ratio (i.e. less hepatic fat; P = 0.02) than those on the placebo. Adiponectin increased by 15.0 μg/ml with rosiglitazone and by 0.4 μg/ml with placebo (P < 0.0001). Rosiglitazone's effect on fat distribution was not independent of changes in adiponectin. Rosiglitazone's effects on fasting (-0.36 mmol/l; P = 0.0004) and 2-h post-load glucose (-1.21 mmol/l; P = 0.0008) were not affected by adjustment for fat distribution or changes in adiponectin or free fatty acids.
  
  
  CONCLUSIONS
  In people with impaired fasting glucose/impaired glucose tolerance, rosiglitazone is associated with relatively less hepatic and visceral fat, increased subcutaneous fat and increased adiponectin levels. These effects do not appear to explain the glucose-lowering effect of rosiglitazone.
authors.affiliation: Population Health Research Institute, Hamilton Health Sciences, McMaster University, Hamilton, ON, Canada; Department of Medicine, McMaster University, Hamilton, ON, Canada.
authors.forename: Z
authors.initials: Z
authors.lastname: Punthakee
authors.forename: N
authors.initials: N
authors.lastname: Alméras
authors.forename: J-P
authors.initials: JP
authors.lastname: Després
authors.forename: G R
authors.initials: GR
authors.lastname: Dagenais
authors.forename: S S
authors.initials: SS
authors.lastname: Anand
authors.forename: D L
authors.initials: DL
authors.lastname: Hunt
authors.forename: A M
authors.initials: AM
authors.lastname: Sharma
authors.forename: H
authors.initials: H
authors.lastname: Jung
authors.forename: S
authors.initials: S
authors.lastname: Yusuf
authors.forename: H C
authors.initials: HC
authors.lastname: Gerstein
mesh_terms: D015502:Absorptiometry, Photon; D054392:Adipokines / Q000378:metabolism; D000328:Adult; D001786:Blood Glucose / Q000187:drug effects; D001823:Body Composition / Q000187:drug effects*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D005227:Fatty Acids / Q000378:metabolism; D005230:Fatty Acids, Nonesterified / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050152:Intra-Abdominal Fat / Q000187:drug effects / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009765:Obesity / Q000188:drug therapy* / Q000503:physiopathology / Q000517:prevention & control; D000077154:Rosiglitazone; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D016896:Treatment Outcome
chemical_list: D054392:Adipokines; D001786:Blood Glucose; D005227:Fatty Acids; D005230:Fatty Acids, Nonesterified; D045162:Thiazolidinediones; D000077154:Rosiglitazone; D005947:Glucose