Body Size and Shape Changes and the Risk of Diabetes in the Diabetes Prevention Program (DPP) Received for publication 3 January 2007 and accepted in revised form 7 March 2007. The Diabetes Prevention Program Research Group

Abstract OBJECTIVE To test the hypothesis that risk of type 2 diabetes is less following reductions in body size and central adiposity. RESEARCH DESIGN AND METHODS The Diabetes Prevention Program (DPP) recruited and randomized individuals with impaired glucose tolerance to treatment with placebo, metformin, or lifestyle modification. Height, weight, waist circumference, and subcutaneous and visceral fat at L2-L3 and L4-L5 by computed tomography (CT) were measured at baseline and at 1 year. Cox proportional hazards models assessed by gender the effect of change in these variables over the first year of intervention upon development of diabetes over subsequent follow-up in a subset of 758 participants. RESULTS Lifestyle reduced visceral fat at L2-L3 (men -24.3%, women -18.2%) and at L4-L5 (men -22.4%, women -17.8%), subcutaneous fat at L2-L3 (men -15.7%, women -11.4%) and at L4-L5 (men -16.7%, women -11.9%), weight (men -8.2%, women -7.8%), body mass index (BMI, men -8.2%, women -7.8%), and waist (men -7.5%, women -6.1%). Metformin reduced weight (-2.9%) and BMI (-2.9%) in men and subcutaneous fat (-3.6% at L2-L3 and -4.7% at L4-L5), weight (-3.3%), BMI (-3.3%), and waist (-2.8%) in women. Decreased diabetes risk by lifestyle intervention was associated with reductions of body weight, BMI, and central body fat distribution after adjustment for age and self-reported ethnicity. CONCLUSIONS Reduced diabetes risk with lifestyle intervention may have been through effects upon both overall body fat and central body fat but with metformin appeared to be independent of body fat. Key Words: Body mass index, Computed tomography, Impaired glucose tolerance, Lifestyle, Metformin, Visceral fat, Waist circumference