UAB DRC P&F Supplement For Emerging Physician Scientist

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Project Summary Childhood T2D has increased in severity and frequency over the last four decades, and adolescents with T2D experience on average a reduction in 15 years off of their life expectancy. Mounting evidence suggests that the incidence of T2D in adolescents, its aggressive course, and adverse impact on longevity depends on multiple mechanisms beyond that which genetics and social/lifestyle determinants of health can help explain. Epigenetics is emerging as an important mechanism to consider. Prior studies have identified methylation changes to CpG sites to estimate an overall age of a cell type, and patterns of epigenetic methylation linked to longevity in humans, termed the epigenetic clock. The acceleration of epigenetic age, and its deviation from chronological age, has been shown to lead to increase in comorbidity and all-cause mortality. There is little or no data regarding epigenetic age acceleration in adolescents with T2D and the role of the epigenetic clock in the shortened lifespan of these patients. For the first time, we will; (1) Calculate epigenetic age and quantify the difference between epigenetic age and chronological age in African American adolescents with T2D compared to BMI, age, and gender matched adolescents, and (2) Investigate possible mechanisms for epigenetic age acceleration in subjects with T2D by testing associations between epigenetic age and potential T2D risk factors (i.e., BMI, glycemic control, fasting LDL, TG, total cholesterol, and inflammatory biomarkers). We hypothesize that adolescents with T2D will have an accelerated epigenetic age compared to their matched non-diabetic counterparts, and that elevated BMI, high TG, low HDL, increased HbA1C, and systemic inflammation will be associated with accelerated epigenetic aging. Pilot data from our cross-sectional study would allow us to inform larger studies of epigenetic age as a biomarker for assessing efficacy of interventions and for the basis of larger epigenome-wide association studies to identify loci of interest involved in T2D which may mediate epigenetic age acceleration.