Ying Xiang, Wu Quanfeng, Li Xiaohan, Bi Yan, Gao Li, Yu Shushu, Xu Xiaona, Li Xiaotian, Wang Yanlin, Hua Renyi
Division of Fetal Medicine, Prenatal Diagnosis Department, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.
Shanghai Key Laboratory of Embryo Original Disease, Shanghai 200030, China.
Healthcare (Basel). 2025 May 7;13(9):1085. doi: 10.3390/healthcare13091085.
Pre-eclampsia (PE) is a serious pregnancy complication defined by the onset of hypertension and multi-organ dysfunction occurring after 20 weeks of gestation. Studies have indicated the correlation between diabetes mellitus (DM) and PE, but the causal relationship remains unclear.
The two-sample Mendelian randomization (MR) approach, including the inverse variance weighted random effects (IVW-RE) model and the traditional sensitivity model, was employed to assess the causal effects of pre-pregnancy type 1 diabetes (T1D) and type 2 diabetes (T2D) on PE using summary-level data obtained from genome-wide association studies. Additionally, diabetes-related factors, such as glycated hemoglobin (HbA1c) levels, fasting insulin levels, and body mass index (BMI), were evaluated for their potential causal effects on the risk of PE. Pleiotropy-robust and multivariable Mendelian randomization (MVMR) methods were further used because of the intricate associations among the traits. Insulin and metformin use was also assessed for their causal role in PE risk.
Our findings show that genetically predicted T1D (OR = 1.06, 95% CI: 1.03-1.09, < 0.001), T2D (OR = 1.09, 95% CI: 1.04-1.14, < 0.001), and BMI (OR = 1.64, 95% CI 1.49 to 1.80, < 0.001) had causal effects on the incidence of PE, while the effects of HbA1c (OR = 0.77, 95% CI 0.59 to 1.02, = 0.064) and fasting insulin levels (OR = 1.35, 95% CI 0.89 to 2.05, = 0.153) on the occurrence of PE were not significant. The results were verified by MVMR analysis. Additionally, insulin use increased the risk of pre-eclampsia (OR = 1.11, 95% CI 1.05-1.17, < 0.001).
Our findings demonstrate a causal relationship between pre-pregnancy diabetes (DM) and obesity and the risk of PE from a genetic epidemiological perspective. Adverse maternal factors, including DM and obesity prior to pregnancy, should be considered in mechanistic studies of PE. In addition, comprehensive interventions for risk factors such as pre-pregnancy DM and obesity should be emphasized in clinical practice.
子痫前期（PE）是一种严重的妊娠并发症，定义为妊娠20周后出现高血压和多器官功能障碍。研究表明糖尿病（DM）与PE之间存在相关性，但因果关系仍不明确。
采用两样本孟德尔随机化（MR）方法，包括逆方差加权随机效应（IVW-RE）模型和传统敏感性模型，利用全基因组关联研究获得的汇总水平数据，评估孕前1型糖尿病（T1D）和2型糖尿病（T2D）对PE的因果效应。此外，还评估了糖化血红蛋白（HbA1c）水平、空腹胰岛素水平和体重指数（BMI）等糖尿病相关因素对PE风险的潜在因果效应。由于这些性状之间存在复杂的关联，因此进一步使用了多效性稳健和多变量孟德尔随机化（MVMR）方法。还评估了胰岛素和二甲双胍的使用对PE风险的因果作用。
我们的研究结果表明，基因预测的T1D（OR = 1.06，95%CI：1.03 - 1.09，< 0.001）、T2D（OR = 1.09，95%CI：1.04 - 1.14，< 0.001）和BMI（OR = 1.64，95%CI 1.49至1.80，< 0.001）对PE的发生率有因果效应，而HbA1c（OR = 0.77，95%CI 0.59至1.02，= 0.064）和空腹胰岛素水平（OR = 1.35，95%CI 0.89至2.05，= 0.153）对PE发生的影响不显著。MVMR分析验证了结果。此外，使用胰岛素会增加子痫前期的风险（OR = 1.11，95%CI 1.05 - 1.17，< 0.001）。
我们的研究结果从遗传流行病学角度证明了孕前糖尿病（DM）和肥胖与PE风险之间存在因果关系。在PE的机制研究中应考虑包括孕前DM和肥胖在内的不良母体因素。此外，在临床实践中应强调对孕前DM和肥胖等危险因素的综合干预。
