274-OR: Gestational Diabetes, Epigenetic Age Acceleration, and Insulin Sensitivity and Secretion in the Exploring Perinatal Outcomes among Children Study

Objectives: Epigenetic age acceleration (EAA) occurs when DNA methylation-predicted age is older than chronological age. EAA is associated with glucose intolerance in adults. In-utero exposure to gestational diabetes (GDM) is associated with glucose intolerance in offspring. It is not known if GDM predicts EAA in offspring or if offspring EAA is associated with insulin sensitivity and secretion. Methods: We examined the association between exposure to GDM in-utero and EAA, computed at average age 10.5 years, and EAA and measures of insulin sensitivity (HOMA-2S) and secretion (HOMA-2β) at average age 10.5 and 16.7 years in 209 girls and 209 boys in the Colorado EPOCH (Exploring Perinatal Outcomes Among Children) cohort. We calculated EAA using the Horvath, Hannum, and Levine calculators. Separate general linear mixed models adjusted associations for chronologic age and sex. Results: Exposure to GDM was associated with EAA using the Hannum (beta-coefficient 1.39, p=0.009) and Levine (1.92, p=0.024) but not the Horvath calculator (-0.01, p=0.69). EAA by the Hannum calculator predicted lower insulin sensitivity and higher insulin secretion (Table). Conclusions: We conclude that GDM predicts offspring EAA, and EAA is associated with decreased insulin sensitivity and increased insulin secretion. Associations are dependent upon the EAA calculator used. Disclosure C. Kim: None. K. K. Harrall: None. D. H. Glueck: None. B. Needham: None. D. Dabelea: None. Funding National Institutes of Health (R01DK076648, R01GM121081, R01DK068001307, M01RR00069, 5UG3OD023248)