title: Change in adiponectin explains most of the change in HDL particles induced by lifestyle intervention but not metformin treatment in the Diabetes Prevention Program.
abstract: OBJECTIVE
  In addition to slowing diabetes development among participants in the Diabetes Prevention Program (DPP), intensive lifestyle change and metformin raised HDL-cholesterol (HDL-C) compared to placebo treatment. We investigated the lifestyle and metabolic determinants as well as effects of biomarkers of inflammation, endothelial dysfunction and coagulation and their changes resulting from lifestyle and metformin interventions on the increase in HDL-C in the DPP.
  
  
  METHODS
  The effects of a 1year period of intensive lifestyle change aimed at achieving 7% weight loss or metformin 850mg twice daily versus placebo on HDL-C were assessed in 3070 participants with impaired glucose tolerance, and on HDL particle concentration (HDL-P) and size in a subgroup of 1645 individuals. Treatment-associated changes in lifestyle and metabolic factors as well as in novel biomarkers were investigated for their associations with change in HDL-C using multiple regression analysis.
  
  
  RESULTS
  After adjusting for BMI, insulin resistance, glycemia, dietary saturated fat, alcohol intake, physical activity and nine different biomarkers, only adiponectin accounted for the effect of intensive lifestyle change on HDL-C via an increase in large HDL-P. By contrast baseline and change in BMI and tissue plasminogen activator levels attenuated the effect of metformin on HDL-C, with adiponectin having no specific effect.
  
  
  CONCLUSIONS
  While both lifestyle and metformin interventions used to prevent diabetes increase HDL-C, the mechanisms involved differ between the two treatments and may have consequences for future risk of cardiovascular disease.
authors.affiliation: Diabetes Research Institute, University of Miami, 1450 NW 10th Avenue, Suite 2054, Miami, FL, 33136. Electronic address: dppmail@bsc.gwu.edu.
authors.forename: Ronald B
authors.initials: RB
authors.lastname: Goldberg
authors.affiliation: The George Washington University, Biostatistics Center, 6110 Executive Blvd, Suite 750, Rockville, MD, 20852.
authors.forename: Marinella
authors.initials: M
authors.lastname: Temprosa
authors.affiliation: The George Washington University, Biostatistics Center, 6110 Executive Blvd, Suite 750, Rockville, MD, 20852.
authors.forename: Lisa
authors.initials: L
authors.lastname: Mele
authors.affiliation: University of Pittsburgh, 3512 Fifth Avenue, Pittsburgh, PA, 15213.
authors.forename: Trevor
authors.initials: T
authors.lastname: Orchard
authors.affiliation: Department of Medicine, Indiana University, 541 Clinical Drive CL 365, Indianapolis, IN, 46202.
authors.forename: Kieren
authors.initials: K
authors.lastname: Mather
authors.affiliation: Pennington Biomedical Research Center, Louisiana State University, 6400 Perkins Rd, Baton Rouge, LA, 70808.
authors.forename: George
authors.initials: G
authors.lastname: Bray
authors.affiliation: Section on Clinical, Behavioral & Outcomes Research, Joslin Diabetes Center, One Joslin Place, Boston, MA, 02215; Department of Medicine, Harvard Medical School, 25 Shattuck St, Boston, MA, 02115.
authors.forename: Edward
authors.initials: E
authors.lastname: Horton
authors.affiliation: Division of Endocrinology, University of Tennessee Health Science Center, 920 Madison Ave Suite 300A, Memphis, TN, 38163.
authors.forename: Abbas
authors.initials: A
authors.lastname: Kitabchi
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, 1550 E. Indian School Road, Phoenix, AZ, 85014.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Krakoff
authors.affiliation: University of Washington, Northwest Lipid Research Labs, 401 Queen Anne Avenue, North Seattle, WA, 98109.
authors.forename: Santica
authors.initials: S
authors.lastname: Marcovina
authors.affiliation: Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado Anschutz Medical Campus, 12801 E. 17th Ave., Aurora, CO, 80045.
authors.forename: Leigh
authors.initials: L
authors.lastname: Perreault
authors.affiliation: Washington University School of Medicine, 660 South Euclid Ave, St. Louis, MO, 63110.
authors.forename: Neil
authors.initials: N
authors.lastname: White
mesh_terms: D052242:Adiponectin / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002318:Cardiovascular Diseases / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D008076:Cholesterol, HDL / Q000097:blood*; D015331:Cohort Studies; D003131:Combined Modality Therapy; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology / Q000209:etiology / Q000517:prevention & control*; D018752:Diet, Fat-Restricted; D004038:Diet, Reducing; D004311:Double-Blind Method; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008019:Life Style; D008297:Male; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D009043:Motor Activity; D050177:Overweight / Q000097:blood / Q000178:diet therapy / Q000503:physiopathology / Q000628:therapy*; D011236:Prediabetic State / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D015431:Weight Loss
chemical_list: C499918:ADIPOQ protein, human; D052242:Adiponectin; D015415:Biomarkers; D008076:Cholesterol, HDL; D007004:Hypoglycemic Agents; D008687:Metformin
keywords: Adiponectin; HDL; Lifestyle change; Metformin