Genetic Risk, a Healthy Lifestyle, and Type 2 Diabetes: the Dongfeng-Tongji Cohort Study

Abstract Objective The objective of this study is to examine whether healthy lifestyle could reduce diabetes risk among individuals with different genetic profiles. Design A prospective cohort study with a median follow-up of 4.6 years from the Dongfeng-Tongji cohort was performed. Participants A total of 19 005 individuals without diabetes at baseline participated in the study. Main Variable Measure A healthy lifestyle was determined based on 6 factors: nonsmoker, nondrinker, healthy diet, body mass index of 18.5 to 23.9 kg/m2, waist circumference less than 85 cm for men and less than 80 cm for women, and higher level of physical activity. Associations of combined lifestyle factors and incident diabetes were estimated using Cox proportional hazard regression. A polygenic risk score of 88 single-nucleotide polymorphisms previously associated with diabetes was constructed to test for association with diabetes risk among 7344 individuals, using logistic regression. Results A total of 1555 incident diabetes were ascertained. Per SD increment of simple and weighted genetic risk score was associated with a 1.39- and 1.34-fold higher diabetes risk, respectively. Compared with poor lifestyle, intermediate and ideal lifestyle were reduced to a 23% and 46% risk of incident diabetes, respectively. Association of lifestyle with diabetes risk was independent of genetic risk. Even among individuals with high genetic risk, intermediate and ideal lifestyle were separately associated with a 29% and 49% lower risk of diabetes. Conclusion Genetic and combined lifestyle factors were independently associated with diabetes risk. A healthy lifestyle could lower diabetes risk across different genetic risk categories, emphasizing the benefit of entire populations adhering to a healthy lifestyle.