Genetic Susceptibility in Relative Maternal Protection From Type 1 Diabetes

IF 22.6 1区医学 Q1 ENDOCRINOLOGY & METABOLISM

Diabetes Care Pub Date : 2026-10-01 DOI:10.2337/dc26-1524

Sarah D. Slack, Neha Venkatesh, Shane E. Ridoux, Kirk R. Hohsfield, Lauren A. Vanderlinden, Jill M. Norris, Randi K. Johnson

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引用次数: 0

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.

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1型糖尿病母亲保护的遗传易感性

1型糖尿病母亲的后代患1型糖尿病的几率是父亲的一半。我们研究了在1型糖尿病妊娠期间选择性失去具有高遗传风险的胎儿是否解释了这种相对保护。研究设计与方法：在“青少年糖尿病的环境决定因素”（The Environmental Determinants of Diabetes In The Young， TEDDY）队列中6942名活产婴儿中，我们比较了家庭成员患有1型糖尿病的遗传易感性，并检验了这是否解释了母亲对糖尿病或其临床前阶段的保护。结果1型糖尿病遗传风险评分2延长（GRS2x）在母亲（P = 0.36）或兄弟姐妹（P = 0.27）与父亲患有1型糖尿病的儿童之间没有差异。GRS2x调节（糖尿病：危险比[HR] 0.50, P = 0.01; IA: HR 0.38, P = 0.006）观察到母体对1型糖尿病和胰岛自身免疫（IA）的相对保护作用，但在IA向糖尿病进展过程中没有调节。这种保护作用在6岁后减弱。结论：宫内暴露于1型糖尿病对儿童早期IA有相对的保护作用，不能用遗传易感性差异来解释。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Diabetes Care 医学-内分泌学与代谢

CiteScore

27.80

自引率

4.90%

发文量

449

审稿时长

1 months

期刊介绍： The journal's overarching mission can be captured by the simple word "Care," reflecting its commitment to enhancing patient well-being. Diabetes Care aims to support better patient care by addressing the comprehensive needs of healthcare professionals dedicated to managing diabetes. Diabetes Care serves as a valuable resource for healthcare practitioners, aiming to advance knowledge, foster research, and improve diabetes management. The journal publishes original research across various categories, including Clinical Care, Education, Nutrition, Psychosocial Research, Epidemiology, Health Services Research, Emerging Treatments and Technologies, Pathophysiology, Complications, and Cardiovascular and Metabolic Risk. Additionally, Diabetes Care features ADA statements, consensus reports, review articles, letters to the editor, and health/medical news, appealing to a diverse audience of physicians, researchers, psychologists, educators, and other healthcare professionals.