Relative maternal protection against type 1 diabetes: A combined analysis of 5 observational studies

Maternal (vs 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 aged 0 to 88 years of age with affected mothers and fathers across 5 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 vs father (odds ratio [OR], 0.55; 95% CI, 0.48-0.64; P < .0001). A lower proportion of individuals with affected mothers than fathers was apparent even among individuals diagnosed as adults (>18 years) (OR, 0.63; 95% CI, 0.43-0.91; P = .01). The lower proportion of individuals with maternal vs paternal type 1 diabetes was only observed if maternal diagnosis preceded offspring birth (OR, 0.51; 95% CI, 0.37-0.70; P < .001 vs OR 0.97; 95% CI, 0.69-1.38; P = .87 after birth). T1D-GRS2 was similar between individuals with affected mothers and fathers (P = .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.