Posttransplant diabetes mellitus (PTDM) is a prevalent complication of liver transplantation and is associated with cardiometabolic complications. We studied the consequences of genetic effects of liver donors and recipients on PTDM outcomes, focusing on the diverse genetic pathways related to insulin that play a role in the development of PTDM. One thousand one hundred fifteen liver transplant recipients without a pretransplant diagnosis of type 2 diabetes mellitus (T2D) and their paired donors recruited from 2 transplant centers had polygenic risk scores (PRS) for T2D, insulin secretion, and insulin sensitivity calculated. Among recipients in the highest T2D-PRS quintile, donor T2D-PRS did not contribute significantly to PTDM. However, in recipients with the lowest T2D genetic risk, donor livers with the highest T2D-PRS contributed to the development of PTDM (OR [95% CI] = 3.79 [1.10-13.1], P = .035). Recipient risk was linked to factors associated with insulin secretion (OR [95% CI] = 0.85 [0.74-0.98], P = .02), while donor livers contributed to PTDM via gene pathways involved in insulin sensitivity (OR [95% CI] = 0.86 [0.75-0.99], P = .03). Recipient and donor PRS independently and collectively serve as predictors of PTDM onset. The genetically influenced biological pathways in recipients primarily pertain to insulin secretion, whereas the genetic makeup of donors exerts an influence on insulin sensitivity.

中文翻译：

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供体和受体遗传学：对移植后糖尿病发展的影响


移植后糖尿病（PTDM）是肝移植的常见并发症，与心脏代谢并发症相关。我们研究了肝脏捐献者和接受者的遗传效应对 PTDM 结局的影响，重点关注与胰岛素相关的多种遗传途径，这些途径在 PTDM 的发展中发挥着作用。对 1115 名移植前未诊断为 2 型糖尿病 (T2D) 的肝移植受者及其从 2 个移植中心招募的配对供体进行了 T2D 多基因风险评分 (PRS)、胰岛素分泌和胰岛素敏感性计算。在 T2D-PRS 最高五分位数的受者中，T2D-PRS 捐赠者对 PTDM 没有显着影响。然而，在 T2D 遗传风险最低的受者中，T2D-PRS 最高的供体肝脏促进了 PTDM 的发展（OR [95% CI] = 3.79 [1.10-13.1]，P = .035）。受体风险与胰岛素分泌相关因素相关（OR [95% CI] = 0.85 [0.74-0.98]，P = .02），而供体肝脏通过涉及胰岛素敏感性的基因途径导致 PTDM（OR [95% CI] ] = 0.86 [0.75-0.99]，P = .03）。受者和供者 PRS 独立或共同充当 PTDM 发病的预测因素。受体中受遗传影响的生物途径主要与胰岛素分泌有关，而捐赠者的遗传组成则对胰岛素敏感性产生影响。