DNA Methylation Biomarkers Predict Offspring Metabolic Risk From Mothers With Hyperglycemia in Pregnancy.

Assaf, Johnny; Khurana, Ishant; Abou Zaki, Ram; Tam, Claudia H T; Correa, Ilana; Maxwell, Scott; Kinnberg, Julie; Christiansen, Malou et al. · Diabetes · 2025

basic_science · Level V

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Abstract

Maternal hyperglycemia is linked to 19 cord blood DNA methylation biomarkers that predict offspring metabolic dysfunction. These methylation changes, associated with maternal glycemic status, improved the prediction of β-cell dysfunction at 7, 11, and 18 years of age compared with clinical factors alone. Validation in human β-cells and pancreatic ductal epithelial cells confirmed that hyperglycemia influences methylation-dependent gene expression. These findings highlight the role of epigenetic modifications at birth as early indicators of diabetes risk, suggesting that in utero hyperglycemic exposure may mediate long-term metabolic outcomes in offspring.

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