Abstract Body:
Background: Epigenetic age acceleration (AA) has been associated with diabetes, but associations differ across DNA methylation (DNAm) based epigenetic clocks and populations. We examined whether epigenetic age acceleration (EAA) estimated from several epigenetic clocks was associated with the prevalence of diabetes and glucose metabolism markers among Hispanic/Latino adults in the United States.

Methods: Genome-wide DNAm was profiled in a random sample of 1,000 participants from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and was used to estimate EAA derived from four well-known epigenetic clocks (Horvath, Hannum, PhenoAge, GrimAge). Using a cross-sectional study design, we investigated the associations between each EAA measure and diabetes status at baseline, as well as their associations with glucose metabolism markers [fasting blood glucose (FBG), glycosylated hemoglobin (HbA1c), 2-h post-prandial blood glucose (2hBG), and homeostatic model assessment of insulin resistance (HOMA-IR)]. Survey-weighted Poisson regression models with robust variance were used to estimate prevalence ratios (PRs) for the associations between each EAA measure and diabetes status, adjusting for sex, education, age, smoking status, alcohol use, physical activity, diet, sleep duration, and cell type proportions. Survey-weighted multivariate linear regression models were used to estimate associations between each EAA measure and log-transformed glucose metabolism marker.

Results: Five-year increases in EAA were associated with higher prevalence of diabetes for PhenoAA [PR: 1.37 (1.19, 1.57)] and GrimAA [PR: 1.43 (1.06, 1.91)]. Estimates also indicated a higher prevalence of diabetes for HannumAA [PR: 1.22 (0.99, 1.50)] and HovarthAA [PR: 1.13 (0.94, 1.35)]; however, these associations were not statistically significant. In linear regression models, increases in EAA were associated with higher glucose metabolism markers. For example, 5- year increases in PhenoAA were associated with higher levels of FBG [β: 0.02 (0.01, 0.03)] and HbA1c [β: 0.02 (0.01, 0.03)]. Increases in HannumAA, PhenoAA, and GrimAA were associated with higher HOMA-IR (p <0.05).

Conclusion: Among a population-based sample of Hispanic/Latino adults, EAA was associated with a higher prevalence of diabetes and higher glucose metabolism markers. Further research on the longitudinal association EAA and diabetes is needed to identify individuals at greater risk for developing diabetes.