MON-561 Epigenetic Age Acceleration in African American Adolescents with Type 2 Diabetes

Abstract Disclosure: C. Foster: None. A. Patki: None. H. Tiwari: None. B. Hidalgo: None. Background: Type 2 diabetes (T2D) results from insulin resistance and relative insulin deficiency (1). Adolescent-onset T2D differs from adult-onset T2D, notably in faster progression to insulin dependence (2). Early-onset T2D is linked to significant long-term morbidity, reducing life expectancy by up to 15 years (3). African Americans (AAs) are disproportionately affected by T2D and obesity, pointing to a higher disease burden, compared to non-Hispanic Whites (4, 5). While genetic factors contribute to T2D, epigenetic mechanisms offer additional insights, especially as they can reflect exposures and disease risks. However, limited data exists on how the onset of T2D earlier in the lifespan could impact epigenetic aging. This study aims to assess epigenetic age acceleration in adolescents with obesity and T2D in a population of African American adolescents. Methods: We conducted a cross-sectional study with adolescent patients (ages 12-18) diagnosed with T2D + obesity (T2D+o), obesity only (BMI > 95th percentile) controls (oc), and controls without T2D or obesity (BMI < 95th percentile) (nwc). Anthropometric and laboratory data were collected at a single visit. DNA methylation was assessed using the Illumina Infinium EPIC 850K array. Epigenetic age was calculated using GrimAge, PhenoAge, Hannum, Horvath, and PedsBe clocks. Analysis of variance (ANOVA) was used to assess differences among the groups, and epigenetic age acceleration was calculated by regressing DNA methylation age (DNAm age) against chronological age. Results: The study included 19 adolescents with T2D+o, 42 oc, and 17 nwc. The group with T2D+o had a mean age of 15 (1.9) and a mean BMI of 2.4 (0.3). The group with oc had a mean age of 15 (1.9) and a mean BMI of 2.5 (0.3). The group with nwc had a mean age of 15 (1.5) and a mean BMI of 0.3 (1.1). Notably, the T2D+o and oc groups showed significant epigenetic age acceleration using the GrimAge clock compared to the nwc controls. However, no epigenetic age acceleration differences were observed using the Hannum, Horvath, PhenoAge, or PedsBe clocks. Conclusions: Our findings suggest that epigenetic age acceleration is observed in adolescents with T2D+obesity. This indicates that biological aging effects may be present in adolescents with a new onset of this disease. Larger and follow-up studies are needed to validate these findings in other adolescent populations with early-onset T2D. Presentation: Monday, July 14, 2025