Adiponectin, Change in Adiponectin, and Progression to Diabetes in the Diabetes Prevention Program

Adiponectin, Change in Adiponectin, and Progression to Diabetes in the Diabetes Prevention Program Kieren J. Mather 1 , Tohru Funahashi 2 , Yuji Matsuzawa 2 , Sharon Edelstein 3 , George A. Bray 4 , Steven E. Kahn 5 , Jill Crandall 6 , Santica Marcovina 7 , Barry Goldstein 8 , Ronald Goldberg 9 and for the Diabetes Prevention Program * 1 Division of Endocrinology and Metabolism, Indiana University School of Medicine, Indianapolis, Indiana 2 Department of Internal Medicine and Molecular Science, Osaka University, Osaka, Japan 3 The Biostatistics Center, George Washington University, Rockville, Maryland 4 Pennington Biomedical Research Center/LSU System, Baton Rouge, Louisiana 5 Division of Metabolism, Endocrinology and Nutrition, Department of Medicine, VA Puget Sound Health Care System and University of Washington, Seattle, Washington 6 Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 7 Northwest Lipid Metabolism and Diabetes Research Laboratories, University of Washington, Seattle, Washington 8 Division of Endocrinology, Diabetes and Metabolic Diseases, Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania 9 Diabetes Research Institute, University of Miami School of Medicine, Miami, Florida Address correspondence and reprint requests to Diabetes Prevention Program Coordinating Center, The Biostatistics Center, George Washington University, 6110 Executive Blvd., Suite 750, Rockville, MD 20852. E-mail: dppmail{at}biostat.bsc.gwu.edu 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). RESEARCH DESIGN AND 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 ∼3 μg/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 μg/ml in the lifestyle group, 0.23 ± 0.05 μg/ml in the metformin group, and 0.10 ± 0.05 μg/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 ∼1 μg/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. DPP, Diabetes Prevention Program Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 11 January 2008. DOI: 10.2337/db07-1419. Clinical trial reg. no. NCT00004992, clinicaltrials.gov. * * Members of the Diabetes Prevention Program Research Group are listed in online appendix I at http://dx.doi.org/10.2337/db07-1419 . The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted January 7, 2008. Received October 4, 2007. DIABETES