Diabetes Research Group, Cardiff University, University Hospital of Wales, Cardiff, UK.
Diabetes Research Group, Cardiff University, University Hospital of Wales, Cardiff, UK.
Lancet Diabetes Endocrinol. 2023 Oct;11(10):755-767. doi: 10.1016/S2213-8587(23)00190-0. Epub 2023 Sep 1.
Type 1 diabetes is around twice as common in the offspring of men with type 1 diabetes than in the offspring of women with type 1 diabetes, but the reasons for this difference are unclear. This Review summarises the evidence on the rate of transmission of type 1 diabetes to the offspring of affected fathers compared with affected mothers. The findings of nine major studies are presented, describing the magnitude of the effect observed and the relative strengths and weaknesses of these studies. This Review also explores possible underlying mechanisms for this effect, such as genetic mechanisms (eg, the selective loss of fetuses with high-risk genes in mothers with type 1 diabetes, preferential transmission of susceptibility genes from fathers, and parent-of-origin effects influencing gene expression), environmental exposures (eg, exposure to maternal hyperglycaemia, exogenous insulin exposure, and transplacental antibody transfer), and maternal microchimerism. Understanding why type 1 diabetes is more common in the offspring of men versus women with type 1 diabetes will help in the identification of individuals at high risk of the disease and can pave the way in the development of interventions that mimic the protective elements of maternal type 1 diabetes to reduce the risk of disease in individuals at high risk.
1 型糖尿病在 1 型糖尿病男性患者的子女中较为常见，其发病率约为女性患者子女的两倍，但造成这种差异的原因尚不清楚。本综述总结了有关与 1 型糖尿病母亲相比，1 型糖尿病父亲将疾病遗传给子女的发生率的证据。本文呈现了 9 项主要研究的结果，描述了所观察到的效应的幅度，以及这些研究的相对优势和局限性。本综述还探讨了这种效应的潜在机制，如遗传机制（例如，1 型糖尿病母亲中高风险基因的胎儿选择性丢失、易感基因从父亲优先传递、以及影响基因表达的母源来源效应）、环境暴露（例如，暴露于母体高血糖、外源性胰岛素暴露和胎盘抗体转移）和母体微嵌合体。了解为什么 1 型糖尿病在 1 型糖尿病男性患者的子女中更为常见，有助于确定疾病高危个体，并为开发模仿母体 1 型糖尿病的保护因素的干预措施铺平道路，从而降低高危个体的疾病风险。
