• Nisa M Maruthur, Yong Ma, Linda M Delahanty, Julie A Nelson, Vanita Aroda, Neil H White, David Marrero, Frederick L Brancati, Jeanne M Clark, and Diabetes Prevention Program Research Group.
• The Johns Hopkins University School of Medicine, Baltimore, MD, USA, dppmail@biostat.bsc.gwu.edu.
• J Gen Intern Med. 2013 Dec 1; 28 (12): 1629-36.

BackgroundRecommendations for diabetes prevention in patients with prediabetes include lifestyle modification and metformin. However, the significance of early weight loss and glucose measurements when monitoring response to these proven interventions is unknown.ObjectiveTo quantify the relationship between early measures of weight and glucose and subsequent diabetes in patients undergoing diabetes prevention interventions.DesignAnalysis of results from a randomized controlled trial in 27 academic medical centers in the United States.Participants/Interventions3,041 adults with hyperglycemia randomized to lifestyle (n = 1,018), metformin (n = 1,036), or placebo (n = 987) with complete follow-up in The Diabetes Prevention Program.Main MeasuresIndependent variables were weight loss at 6 and 12 months; fasting glucose (FG) at 6 months; hemoglobin A1c (HbA1c) at 6 months; and post-load glucose at 12 months. The main outcome was time to diabetes diagnosis.Key ResultsAfter 6 months, 604 participants developed diabetes in the lifestyle (n = 140), metformin (n = 206), and placebo (n = 258) arms over 2.7 years. In the lifestyle arm, 6-month weight loss predicted decreased diabetes risk in a graded fashion: adjusted HR (95 % CI) 0.65 (0.35-1.22), 0.62 (0.33-1.18), 0.46 (0.24-0.87), 0.34 (0.18-0.64), and 0.15 (0.07-0.30) for 0-<3 %, 3-<5 %, 5-<7 %, 7-<10 %, and ≥10 % weight loss, respectively (reference: weight gain). Attainment of optimal 6-month FG and HbA1c and 12-month post-load glucose predicted >60 % lower diabetes risk across arms. We found a significant interaction between 6-month weight loss and FG in the lifestyle arm (P = 0.038).ConclusionWeight and glucose at 6 and 12 months strongly predict lower subsequent diabetes risk with a lifestyle intervention; lower FG predicts lower risk even with substantial weight loss. Early reduction in glycemia is a stronger predictor of future diabetes risk than weight loss for metformin. We offer the first evidence to guide clinicians in making interval management decisions for high-risk patients undertaking measures to prevent diabetes.

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