Diabetes care · 2026
Genetic Susceptibility in Relative Maternal Protection From Type 1 Diabetes.
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Slack Sarah D, Venkatesh Neha, Ridoux Shane E, Hohsfield Kirk R, Vanderlinden Lauren A, Norris Jill M, Johnson Randi K
Аннотация
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.
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.