Abstract P362: Association of DNA Methylation Age With Risk of Type 2 diabetes: The Atherosclerosis Risk in Communities (ARIC) Study

Abstract

Introduction: It has been proposed that DNA methylation patterns can be used to characterize rate of aging, but it is not known whether methylation age associates with aging-related diseases and conditions independently of chronological age and other risk factors. Hypothesis: There is a positive association between age acceleration (defined as the difference between DNA methylation age and chronological age) and risk of type 2 diabetes (T2D). Methods: We estimated DNA methylation age in African American men and women of the Atherosclerosis Risk in Communities Study using two published predictors. Incident T2D was identified from follow-up visits and telephone interviews. Logistic and Cox proportional hazards regression models were used to estimate the association of age acceleration with incident T2D, modeling age acceleration both continuously and categorically in three percentile groups (0-25th, 25-75th, 75-100th). Regression models were adjusted for chronological age, sex, white blood cell distribution, education, smoking, alcohol, sport index, body mass index, waist to hip ratio, blood pressure, antihypertensive and lipid-lowering medication, HDL and LDL cholesterol, and triglycerides. Results: After adjustment for chronological age, sex, and white blood cell type proportions, those with greater age acceleration were more likely to have prevalent T2D (p-trend ≤ 0.003 across percentile categories of age acceleration for both DNA methylation predictors). Among 1,547 participants who were free of T2D at baseline (mean age: 56 years, range: 47-70), there were 170 incident cases of T2D over a mean 5.4 years of follow-up. T2D incidence was not associated with age acceleration in either crude or risk factor-adjusted models. In the fully-adjusted logistic regression models, odds ratios (95% confidence intervals) for T2D across the percentile categories of age acceleration were 1 (ref.), 0.92 (0.58, 1.45), and 1.42 (0.84, 2.40); and 1 (ref.), 0.87 (0.55, 1.39), and 0.93 (0.52, 1.64), respectively, for the two DNA methylation age predictors. Conclusion: In conclusion, DNA methylation age acceleration, proposed as a marker of the rate of aging, was associated cross-sectionally with prevalent diabetes, but did not predict risk of T2D independently of chronological age. Additional prospective studies are needed to explore relationships with development of other chronic conditions in order to determine if DNA methylation age can serve as a useful proxy for rate of aging.