Abstract
BACKGROUND: Type 1 diabetes is believed to be associated with early genetic and environmental stressors. Epigenetic age acceleration (EAA) is also associated with environmental stressors and the pathogenesis of many chronic diseases. This study explored longitudinal changes in EAA among individuals at high risk for type 1 diabetes. METHODS: DNA methylation was measured longitudinally in subjects from the Diabetes Autoimmunity Study in the Young cohort, 2547 children born 1993-2006 at high risk for type 1 diabetes. Data were collected before and after islet autoimmunity (IA) seroconversion, a preclinical type 1 diabetes stage. EAA was estimated from DNA methylation using an epigenetic clock appropriate for pediatric blood samples. A linear mixed model was used to test for differences in EAA between 85 type 1 diabetes cases and 85 controls, before and after IA seroconversion. RESULTS: Change in EAA significantly differed between cases and controls (p=0.02). EAA significantly decreased in cases, from pre-IA to post-IA seroconversion by 0.367 units (95% CI -0.64 to 0.09, p=0.01), but not in controls (0.045, 95% CI 0.23 to 0.32, p=0.75). CONCLUSION: These results suggest that EAA occurs in children who develop type 1 diabetes prior to IA seroconversion, highlighting the potential role of early environmental stressors in disease pathogenesis.