Abstract
Iron overload due to environmental or genetic causes have been associated diabetes. We hypothesized that prenatal iron exposure is associated with higher risk of childhood type 1 diabetes. In the Norwegian Mother and Child cohort study (n = 94,209 pregnancies, n = 373 developed type 1 diabetes) the incidence of type 1 diabetes was higher in children exposed to maternal iron supplementation than unexposed (36.8/100,000/year compared to 28.6/100,000/year, adjusted hazard ratio 1.33, 95%CI: 1.06-1.67). Cord plasma biomarkers of high iron status were non-significantly associated with higher risk of type 1 diabetes (ferritin OR = 1.05 [95%CI: 0.99-1.13] per 50 mg/L increase; soluble transferrin receptor: OR = 0.91 [95%CI: 0.81-1.01] per 0.5 mg/L increase). Maternal but not fetal HFE genotypes causing high/intermediate iron stores were associated with offspring diabetes (odds ratio: 1.45, 95%CI: 1.04, 2.02). Maternal anaemia or non-iron dietary supplements did not significantly predict type 1 diabetes. Perinatal iron exposures were not associated with cord blood DNA genome-wide methylation, but fetal HFE genotype was associated with differential fetal methylation near HFE. Maternal cytokines in mid-pregnancy of the pro-inflammatory M1 pathway differed by maternal iron supplements and HFE genotype. Our results suggest that exposure to iron during pregnancy may be a risk factor for type 1 diabetes in the offspring.
| Original language | English |
|---|---|
| Article number | 9067 |
| Journal | Scientific Reports |
| Volume | 8 |
| DOIs | |
| Publication status | Published - 13 Jun 2018 |
Bibliographical note
Acknowledgements: We are grateful to all the participating families in Norway who take part in this on-going cohort study. We thank Dr. Maria Vistnes at Diakonhjemmet Hospital, Oslo, Norway for help with cytokine assays, PM Ueland and Ø Midttun at BEVITAL, Bergen, Norway, for neopterin and KTR assay, and Kathleen Gillespie at Bristol University, UK for confirmatory HLA genotyping. The Norwegian Mother and Child Cohort Study is supported by the Norwegian Ministry of Health and Care Services and the Ministry of Education and Research, NIH/NIEHS (contract no N01-ES-75558), NIH/NINDS (grant no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1). The sub-study was funded by a research grant from the Research Council of Norway. The Norwegian Childhood Diabetes Registry is financed by the South-Eastern Norway Regional Health Authority. Dr London was supported by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences. Dr Størdal was supported by an unrestricted grant from Oak Foundation, Geneva, Switzerland.
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- Prenatal iron exposure and childhood type 1 diabetes
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