Genetic Risk, Adherence to Healthy Lifestyle, and Type 2 Diabetes: The Dongfeng-Tongji Cohort Study

Abstract

Background: Genetic and lifestyle factors both contribute to diabetes development, but whether healthy lifestyle could reduce diabetes risk among individuals with different genetic profile is unknown. Methods: A prospective cohort study with 19,005 participants from the Dongfeng-Tongji Cohort were performed. Adherence to a healthy lifestyle was determined on the basis of six factors: non-smoker, non-drinker, healthy diet, body mass index of 18.5 to 23.9 kg/m2, waist circumference <85 cm for men and <80 cm for women, and higher level of physical exercise. Hazard ratios (HRs) of combined healthy lifestyle factors on 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 an association with diabetes risk among 7,344 individuals, estimated using Logistic regression. Findings: Of 19,005 individuals, 10,438 (54.9%) were female, and the mean (SD) age was 63.2 (7.7) years. During a median follow-up of 4.6 years 1,555 incident diabetes (8.2%) were ascertained. The risk of diabetes escalated with the increment of genetic risk score. Per SD of simple and weighted GRS increase was respectively significantly associated with 1.42 and 1.45 fold higher diabetes risk. Compared with poor lifestyle (0 to 2 healthy lifestyle factors), individuals with intermediate (3 or 4 healthy lifestyle factors) or ideal lifestyle (5 or 6 healthy lifestyle factors) had 23% (HR, 0.77; 95% CI, 0.69-0.87) and 46% (HR, 0.54; 95% CI, 0.45-0.65) decreased risk of incident diabetes, respectively. The association of lifestyle factors with diabetes risk was independent of genetic risk stratums. Among individuals at the high genetic risk group, intermediate and ideal lifestyle was associated with 29% lower (OR, 0.71; 95% CI: 0.58-0.86) and 49% lower (OR, 0.51; 95% CI: 0.38-0.69) risk of diabetes. Interpretation: Genetic and 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, independent of genetic risk. Funding Statement: This work was supported by the grant from the National Natural Science Foundation (grant NSFC-81522040, 81473051, and 81230069); the Program for HUST Academic Frontier Youth Team; National Key RD the 111 Project (No. B12004); the Program for Changjiang Scholars; Innovative Research Team in University of Ministry of Education of China (No. IRT1246); China Postdoctoral Science Funding (2018M630869); and China Medical Board (No. 12-113). Declaration of Interests: No potential conflicts of interest relevant to this article were reported. Ethics Approval Statement: The present study has been approved by the Ethics and Human Subject Committee of the School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, and Dongfeng General Hospital, the Dongfeng Motor Corporation (DMC). All study participants provided written informed consents.