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Causal Associations Between Pre-Pregnancy Diabetes Mellitus and Pre-Eclampsia Risk: Insights from a Mendelian

Xiang Ying1,2, Quanfeng Wu3,4, Xiaohan Li1,2

  • 1Division of Fetal Medicine, Prenatal Diagnosis Department, International Peace Maternity and Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China.

Healthcare (Basel, Switzerland)
|May 14, 2025
PubMed

Insights

Pre-pregnancy diabetes mellitus (DM) and obesity causally increase pre-eclampsia (PE) risk. Managing these conditions before pregnancy is crucial for reducing PE incidence.

Area of Science:

  • Reproductive Medicine
  • Genetics
  • Epidemiology

Background:

  • Pre-eclampsia (PE) is a severe pregnancy complication characterized by hypertension and multi-organ dysfunction after 20 weeks of gestation.
  • The link between diabetes mellitus (DM) and PE is recognized, but a causal relationship requires further investigation.

Purpose of the Study:

  • To investigate the causal effects of pre-pregnancy type 1 diabetes (T1D) and type 2 diabetes (T2D) on the risk of developing PE.
  • To evaluate the causal impact of diabetes-related factors (HbA1c, fasting insulin, BMI, insulin use) on PE incidence.

Main Methods:

  • Utilized a two-sample Mendelian randomization (MR) approach with summary-level data from genome-wide association studies.
  • Employed inverse variance weighted random effects (IVW-RE), pleiotropy-robust, and multivariable Mendelian randomization (MVMR) methods.
  • Assessed causal effects of T1D, T2D, HbA1c, fasting insulin, BMI, and insulin/metformin use on PE risk.

Main Results:

  • Genetically predicted T1D (OR=1.06), T2D (OR=1.09), and BMI (OR=1.64) showed significant causal effects on PE incidence.
  • HbA1c and fasting insulin levels did not demonstrate a significant causal effect on PE occurrence.
  • Insulin use was associated with an increased risk of pre-eclampsia (OR=1.11).

Conclusions:

  • Established a genetic epidemiological basis for a causal relationship between pre-pregnancy diabetes and obesity and PE risk.
  • Highlights the importance of considering pre-pregnancy DM and obesity as adverse maternal factors in PE pathogenesis.
  • Emphasizes the need for comprehensive interventions targeting pre-pregnancy DM and obesity in clinical practice to mitigate PE risk.
Abstract

Keywords:
Mendelian randomizationdiabetes mellituspre-eclampsia

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