title: Adiponectin, change in adiponectin, and progression to diabetes in the Diabetes Prevention Program.
abstract: OBJECTIVE
  To determine whether baseline adiponectin levels or intervention-associated change in adiponectin levels were independently associated with progression to diabetes in the Diabetes Prevention Program (DPP).
  
  
  METHODS
  Cox proportional hazards analysis was used to evaluate the contribution of adiponectin and treatment-related change in adiponectin to risk of progression to diabetes.
  
  
  RESULTS
  Baseline adiponectin was a strong independent predictor of incident diabetes in all treatment groups (hazard ratio per approximately 3 microg/ml higher level; 0.61 in the lifestyle, 0.76 in the metformin, and the 0.79 in placebo groups; all P < 0.001, P = 0.13 comparing groups). Baseline differences in adiponectin between sexes and race/ethnicity groups were not reflected in differences in diabetes risk. DPP interventions increased adiponectin levels ([means +/- SE] 0.83 +/- 0.05 microg/ml in the lifestyle group, 0.23 +/- 0.05 microg/ml in the metformin group, and 0.10 +/- 0.05 microg/ml in the placebo group; P < 0.001 for increases versus baseline, P < 0.01 comparing groups). These increases were associated with reductions in diabetes incidence independent of baseline adiponectin levels in the lifestyle and placebo groups but not in the metformin subjects (hazard ratio 0.72 in the lifestyle group (P < 0.001), 0.92 in the metformin group (P = 0.18), and 0.89 in the placebo group; P = 0.02 per approximately 1 microg/ml increase, P = 0.02 comparing groups). In the lifestyle group, adjusting for change in weight reduced, but did not remove, the effect of increased adiponectin.
  
  
  CONCLUSIONS
  Adiponectin is a powerful marker of diabetes risk in subjects at high risk for diabetes, even after adjustment for weight. An increase in adiponectin in the lifestyle and placebo groups was associated with a reduction in diabetes risk. However, these changes in adiponectin were comparatively small and less strongly related to diabetes outcome than baseline adiponectin levels.
authors.affiliation: Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, Indiana, USA.
authors.forename: Kieren J
authors.initials: KJ
authors.lastname: Mather
authors.forename: Tohru
authors.initials: T
authors.lastname: Funahashi
authors.forename: Yuji
authors.initials: Y
authors.lastname: Matsuzawa
authors.forename: Sharon
authors.initials: S
authors.lastname: Edelstein
authors.forename: George A
authors.initials: GA
authors.lastname: Bray
authors.forename: Steven E
authors.initials: SE
authors.lastname: Kahn
authors.forename: Jill
authors.initials: J
authors.lastname: Crandall
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.forename: Barry
authors.initials: B
authors.lastname: Goldstein
authors.forename: Ronald
authors.initials: R
authors.lastname: Goldberg
mesh_terms: D052242:Adiponectin / Q000097:blood; D000328:Adult; D015415:Biomarkers / Q000097:blood*; D003920:Diabetes Mellitus / Q000097:blood* / Q000188:drug therapy / Q000517:prevention & control*; D018450:Disease Progression; D005006:Ethnicity; D005260:Female; D018149:Glucose Intolerance / Q000097:blood; D005951:Glucose Tolerance Test; D006801:Humans; D006943:Hyperglycemia / Q000097:blood; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008019:Life Style; D008297:Male; D008687:Metformin / Q000627:therapeutic use*; D008875:Middle Aged; D044469:Racial Groups; D012016:Reference Values; D012307:Risk Factors
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D007004:Hypoglycemic Agents; D008687:Metformin