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

Abstract

Maternal (versus paternal) type 1 diabetes is associated with a relative reduction in type 1 diabetes risk in offspring during early life. 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. 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. 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). 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.