Publication Description
Regression From Pre-Diabetes to Normal Glucose Regulation in the Diabetes Prevention Program Leigh Perreault , MD 1 , Steven E. Kahn , MBCHB 2 , Costas A. Christophi , PHD 3 , William C. Knowler , MD, DRPH 4 , Richard F. Hamman , MD, DRPH 5 and the Diabetes Prevention Program Research Group * 1 Department of Medicine, Division of Endocrinology, Metabolism and Diabetes, University of Colorado at Denver School of Medicine, Aurora, Colorado; 2 Department of Medicine, Division of Metabolism, Endocrinology and Nutrition, VA Puget Sound Health Care System and University of Washington, Seattle, Washington; 3 The Biostatistics Center, George Washington University, Diabetes Prevention Program Coordinating Center, Rockville, Maryland; 4 Diabetes Epidemiology and Clinical Research Section, Division of Intramural Research, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, Arizona; 5 Department of Epidemiology, Colorado School of Public Health, University of Colorado at Denver, Aurora, Colorado. Corresponding author: Diabetes Prevention Program Coordinating Center, dppmail{at}biostat.bsc.gwu.edu . Abstract OBJECTIVE Participants in the Diabetes Prevention Program (DPP) randomized to intensive lifestyle modification (ILS) or metformin had a significantly reduced incidence of diabetes compared with those randomized to placebo, yet most were still at risk because they had pre-diabetes. We explored the effect of baseline characteristics, weight change, ILS, and metformin on regression from pre-diabetes to the lowest-risk state of normal glucose regulation (NGR) defined by American Diabetes Association criteria. RESEARCH DESIGN AND METHODS The DPP was a prospective randomized trial. Cox proportional hazards modeling was used to identify predictors of regression from pre-diabetes to NGR over 3 years of follow-up. RESULTS Lower baseline fasting (hazard ratio 1.52, P < 0.01) and 2-h (1.24, P < 0.01) glucose predicted regression to NGR, as did younger age (1.07, P < 0.01) and greater insulin secretion (1.09, P = 0.04). ILS (2.05, P < 0.01) and weight loss (1.34, P < 0.01) had significant and independent effects on regression. A nonsignificant trend for regression was also observed for metformin (1.25, P = 0.06), male sex (1.17, P = 0.08), and insulin sensitivity (1.07, P = 0.09). In those entering the study with both impaired fasting glucose (IFG) and impaired glucose tolerance (IGT), male sex and insulin sensitivity predicted regression to isolated IFG, whereas ILS, metformin, female sex, and greater insulin secretion predicted regression to isolated IGT. CONCLUSIONS Insulin secretion, and other biologic processes retained with younger age, are key in restoring NGR in people with pre-diabetes. However, NGR may also be attained through weight loss and additional aspects of ILS. Footnotes ↵ *A list of the Diabetes Prevention Program Research Group is available in an online appendix at http://care.diabetesjournals.org/cgi/content/full/dc09-0523/DC1 . Clinical trial reg. no. NCT00004992, clinicaltrials.gov . The opinions expressed are those of the investigators and do not necessarily reflect the views of the Indian Health Service or other funding agencies. 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. Received March 17, 2009. Accepted June 13, 2009. © 2009 by the American Diabetes Association.