Relative maternal protection against type 1 diabetes: a combined analysis of five observational studies

Allen, Lowri, Taylor, Peter N. ORCID: https://orcid.org/0000-0002-3436-422X, Carlsson, Annelie, Fraser, Diane P., Hagopian, William A., Hedlund, Emma, Hill, Anita V., Jones, Angus G., Ludvigsson, Johnny, MorImer, Georgina L., Onengut-Gumuscu, Suna, Redondo, Maria J., Rich, Stephen S., Williams, Claire L, Gillespie, Kathleen M., Dayan, Colin M. and Oram, Richard A. 2026. Relative maternal protection against type 1 diabetes: a combined analysis of five observational studies. The Journal of Clinical Endocrinology & Metabolism , dgag103. 10.1210/clinem/dgag103

	PDF - Supplemental Material Available under License Creative Commons Attribution. Download (490kB)
Preview	PDF - Accepted Post-Print Version Available under License Creative Commons Attribution. Download (1MB) | Preview

Abstract

Context: Maternal (versus paternal) type 1 diabetes is associated with a relative reduction in type 1 diabetes risk in offspring during early life. Objective: To determine whether this effect extends into later life. To clarify the importance of intrauterine exposure to maternal type 1 diabetes, and baseline genetic susceptibility in this context. Methods: We compared the proportion of individuals with type 1 diabetes diagnosed age 0-88 years with affected mothers and fathers across five observational studies (n=11,475), and used random-effects meta-analyses to generate overall effect estimates. We examined this by age at diagnosis, and timing of parental diagnosis relative to offspring birth. We compared the type 1 diabetes genetic risk score (T1D-GRS2) of individuals with affected mothers and fathers. Results: Almost half as many individuals with type 1 diabetes had an affected mother versus father (OR 0.55 (95% CI 0.48, 0.64), p<0.0001). A lower proportion of individuals with affected mothers than fathers was apparent even amongst individuals diagnosed as adults (>18 years) (OR 0.63 (95% CI 0.43, 0.91), p=0.01). The lower proportion of individuals with maternal versus paternal type 1 diabetes was only observed if maternal diagnosis preceded offspring birth (OR 0.51 (95% CI 0.37, 0.70), p<0.001 versus OR 0.97 (95% CI 0.69, 1.38), p=0.87 after birth). T1D-GRS2 was similar between individuals with affected mothers and fathers (p=0.25). Conclusion: Our analyses suggest intrauterine exposure to maternal type 1 diabetes is associated with long-lasting relative protection against offspring type 1 diabetes, which is independent of genetic susceptibility as measured by T1D-GRS2.

Item Type:	Article
Date Type:	Published Online
Status:	In Press
Schools:	Schools > Medicine
Publisher:	Oxford University Press
ISSN:	0021-972X
Funders:	Wellcome Trust
Projects:	225446/Z/22/Z
Date of First Compliant Deposit:	10 March 2026
Date of Acceptance:	4 March 2026
Last Modified:	16 Mar 2026 11:13
URI:	https://orca.cardiff.ac.uk/id/eprint/182597

Actions (repository staff only)

Edit Item