Large study finds distinctive DNA methylation patterns in toddlers exposed in utero to maternal type 1 diabetes, with signatures tied to lower risk of islet autoimmunity
Children born to mothers with type 1 diabetes appear to carry a protective epigenetic imprint that lowers their chances of developing early islet autoimmunity, the presymptomatic stage that often precedes type 1 diabetes.
The open access paper in Nature Metabolism, published on 6 November 2025, reports specific DNA methylation changes in blood that map to known type 1 diabetes risk genes and immune pathways.
Researchers analysed blood from 1,752 children enrolled in the BABYDIAB, BABYDIET and POInT cohorts at a median age of about two years.
They compared 790 children whose mothers had type 1 diabetes with 962 whose mothers did not.
The team found differential methylation at multiple loci, including the HOXA gene cluster and 15 susceptibility genes for type 1 diabetes.
Many signals fell within the HLA region on chromosome 6, a major genetic determinant of risk.
The group distilled a methylation propensity score from 34 CpG sites linked to susceptibility loci.
In children whose mothers did not have type 1 diabetes, each unit increase in this score was associated with lower odds of developing islet autoimmunity, and the association held in an independent validation cohort.
The authors argue that the intrauterine environment of maternal type 1 diabetes can modulate a child’s immune programming in ways that influence disease risk.
The work builds on long observed epidemiology.
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Offspring of mothers with type 1 diabetes are less likely to develop the condition than offspring of affected fathers, despite similar genetic loads.
The new data point to epigenetic mechanisms as a plausible explanation for that relative protection.
Helmholtz Munich, which led the study with European partners, said the methylation changes were concentrated in immune related regions and corresponded with altered expression of susceptibility genes.
The centre added that the approach may help refine risk prediction by combining methylation scores with existing genetic models.
Why it matters
If replicated and extended, these signatures could sharpen early risk stratification and open lines of research into tolerising pathways that reduce autoimmune attack on pancreatic beta cells.
For families affected by type 1 diabetes, the findings offer a mechanistic clue to a protective maternal effect that clinicians have reported for decades.
Reference: Ott R, Zapardiel-Gonzalo J, Kreitmaier P, et al. Blood methylome signatures in children exposed to maternal type 1 diabetes are linked to protection against islet autoimmunity. Nature Metabolism. Published 6 November 2025.
