307-OR: Interaction of Diabetes Genetic Risk and Successful Lifestyle Modification in the Diabetes Prevention Program

Intensive lifestyle intervention (ILS) targeting diet, physical activity (PA), and weight loss is efficacious for diabetes mellitus (DM) prevention, but not all high-risk individuals benefit. We tested whether DM genetic risk helps identify persons for whom ILS had a greater influence on DM risk. We studied 823 individuals in the ILS arm of the Diabetes Prevention Program with genetic and lifestyle data who were free of DM at one year after study enrollment. We estimated the associations of a DM genetic risk score (GRS) based on 67 loci from a recent genome-wide association study and achievement of three ILS goals at one year (7% weight loss, 150 minutes/week of self-reported moderate to strenuous leisure-time PA, and a goal for self-reported daily total fat intake) with incident DM using multivariable proportional hazards regression, including multiplicative interaction terms (i.e., on rate ratios) between GRS and each ILS goal. We used multivariable Poisson regression to estimate absolute risk reduction (ARR) in DM from ILS goal achievement across tertiles of the GRS, including tests for additive interaction (i.e., on rate differences) between GRS and each ILS goal. The GRS, and achieving each ILS goal and achieving all three ILS goals were associated with incident DM (all p