Accelerated Epigenetic Aging in Diabetes: Socio-Biological Pathways of Health Inequity.

Abstract

Type 2 diabetes mellitus (T2DM) is an aging-related disease with greater incidence in older African Americans (AAs) than whites, but studies on racial disparity in epigenetic aging pathways are scarce; specifically, socio-biological aging processes are not well characterized. We investigated biological aging acceleration (aging accel) with development of T2DM and additionally, insulin resistance (IR) of nondiabetic women at baseline in cross-section. We estimated the extent to which social adversity explained AAs' greater aging accel and, together with accelerated aging, mediated their greater burden of glucometabolic outcomes. Clinical and social determinants of health (SDOH) variables and genome-wide DNA methylation data were extracted from the Women's Health Initiative with > 1,500 postmenopausal non-diabetic women. Diabetic outcome was followed for a mean of 19 years, and baseline IR was measured using fasting serum samples. Aging accel metrics were calculated with Levine's clock, and mediation effects of SDOH and aging accel was estimated via Multiple Mediation analyses. Greater aging accel was observed in T2DM, albeit with only univariate significance and IR and in AAs rather than whites. SDOH was associated with greater aging accel, but its impact on greater accelerated aging in AAs varied and in combination, was minimal. Although aging accel has greater influence than SDOH on the racial difference in glucometabolic outcomes, these parameters jointly mediated to only a limited extent T2DM/IR pathways by race. Our mediation findings are exploratory and hypothesis-generating and thus, our results warrant validation studies to better understand socio-glucometabolic pathways shared by epigenetic aging processes and to inform early risk stratification among at-risk older women for disease prevention and reduced racial health inequity.