Abstract
OBJECTIVE
Type 1 diabetes is half as common in offspring of mothers versus fathers with type 1 diabetes. We investigated whether selective loss of fetuses with high genetic risk during type 1 diabetes pregnancy explains this relative protection.
RESEARCH DESIGN AND METHODS
In 6,942 live births in The Environmental Determinants of Diabetes in the Young (TEDDY) cohort, we compared genetic susceptibility by family member with type 1 diabetes and tested whether it explained maternal protection from diabetes or its preclinical stages.
RESULTS
The type 1 diabetes Genetic Risk Score 2 extended (GRS2x) did not differ between children with mothers (P = 0.36) or siblings (P = 0.27) versus fathers with type 1 diabetes. Relative maternal protection from type 1 diabetes and islet autoimmunity (IA) was observed with GRS2x adjustment (diabetes: hazard ratio [HR] 0.50, P = 0.01; IA: HR 0.38, P = 0.006) and without adjustment but not during progression from IA to diabetes. This protection waned after age 6 years.
CONCLUSIONS
Intrauterine exposure to type 1 diabetes offers relative protection from IA during early childhood and is not explained by genetic susceptibility differences.