ArticleBMC medicine2022
Epigenetic and transcriptomic alterations in offspring born to women with type 1 diabetes (the EPICOM study).
Article in BMC medicine, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 7 citations in OpenAlex.
- Relative maternal protection against type 1 diabetes: A combined analysis of 5 observational studies.The Journal of clinical endocrinology and metabolism · 2026Article
- Review
- Infants exposed to maternal type 1 diabetes: intrauterine epigenetic modifications and neurological development.Frontiers in endocrinology · 2026Article
- Blood methylome signatures in children exposed to maternal type 1 diabetes are linked to protection against islet autoimmunity.Nature metabolism · 2025Article
- Circulating amino acids and cardiometabolic risk profile in offspring of women with type 1 diabetes: cross-sectional case-control study.Scientific reports · 2025Article
- The good, the bad, and the unknown nature of decreased GD3 synthase expression.Frontiers in molecular neuroscience · 2024Article
- An unwelcome inheritance: childhood obesity after diabetes in pregnancy.Diabetologia · 2023Review
- Lysosomal acid lipase deficiency: A rare inherited dyslipidemia but potential ubiquitous factor in the development of atherosclerosis and fatty liver disease.Frontiers in genetics · 2022Review
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundOffspring born to women with pregestational type 1 diabetes (T1DM) are exposed to an intrauterine hyperglycemic milieu and has an increased risk of metabolic disease later in life. In this present study, we hypothesize that in utero exposure to T1DM alters offspring DNA methylation and gene expression, thereby altering their risk of future disease.
methodsFollow-up study using data from the Epigenetic, Genetic and Environmental Effects on Growth, Metabolism and Cognitive Functions in Offspring of Women with Type 1 Diabetes (EPICOM) collected between 2012 and 2013.
settingExploratory sub-study using data from the nationwide EPICOM study.
participantsAdolescent offspring born to women with T1DM (n=20) and controls (n=20) matched on age, sex, and postal code.
main outcome measuresThis study investigates DNA methylation using the 450K-Illumina Infinium assay and RNA expression (RNA sequencing) of leucocytes from peripheral blood samples.
resultsWe identified 9 hypomethylated and 5 hypermethylated positions (p < 0.005, |ΔM-value| > 1) and 38 up- and 1 downregulated genes (p < 0.005, log2FC ≥ 0.3) in adolescent offspring born to women with T1DM compared to controls. None of these findings remained significant after correction for multiple testing. However, we identified differences in gene co-expression networks, which could be of biological significance, using weighted gene correlation network analysis. Interestingly, one of these modules was significantly associated with offspring born to women with T1DM. Functional enrichment analysis, using the identified changes in methylation and gene expression as input, revealed enrichment in disease ontologies related to diabetes, carbohydrate and glucose metabolism, pathways including MAPK1/MAPK3 and MAPK family signaling, and genes related to T1DM, obesity, atherosclerosis, and vascular pathologies. Lastly, by integrating the DNA methylation and RNA expression data, we identified six genes where relevant methylation changes corresponded with RNA expression (CIITA, TPM1, PXN, ST8SIA1, LIPA, DAXX).
conclusionsThese findings suggest the possibility for intrauterine exposure to maternal T1DM to impact later in life methylation and gene expression in the offspring, a profile that may be linked to the increased risk of vascular and metabolic disease later in life.
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