Atherogenic index of plasma in early pregnancy: associations with gestational diabetes mellitus and preeclampsia and its mediating role

Gestational diabetes mellitus (GDM) and preeclampsia (PE) are severe complications that significantly impact maternal and fetal well-being. Although their clinical association is well-established, the role of dyslipidemia remains unclear. The objective of this investigation was to characterize a readily available lipid indicator that functions as both an early predictor and a mediator of the link between GDM and PE, thereby supporting timely clinical intervention. A total of 1858 singleton pregnant women recruited from Eastern and Western China were included in this study. Fasting serum lipid profiles were collected during the first trimester (between the 10th and 14th weeks). Lasso regression and the Boruta algorithm were used to identify an optimized lipid-derived predictor for PE. Additionally, association and mediation modeling were implemented to evaluate the contribution of the selected lipid marker to the GDM-PE association. The mean age of all participants was 30 (27, 33) years. The atherogenic index of plasma (AIP), total cholesterol (TC), and high-density lipoprotein cholesterol (HDL-C) were the only lipid-related variables identified at the intersection of Lasso and Boruta analyses as candidate predictors for PE. In the GDM with PE group, AIP was significantly higher than in other subgroups, whereas TC and HDL-C were not. A high first-trimester AIP emerged as an independent risk factor for both GDM (adjusted odds ratio [aOR]: 1.74; 95% confidence interval [CI]: 1.33 to 2.27, P < 0.001) and PE (aOR: 2.38; 95% CI: 1.10 to 5.15, P = 0.028). Restricted cubic splines (RCS) analysis revealed a significant nonlinear association between AIP and the risk of GDM, and a linear association with PE. Crucially, mediation analysis demonstrated that AIP significantly mediated the association between GDM and PE, accounting for 31.45% of the total effect (P = 0.012), a proportion exceeding that of other lipid parameters such as triglyceride (TG) (29.58%). These results demonstrate that early-pregnancy AIP predicts a greater susceptibility to both GDM and PE, while functioning as a critical mediator of their pathological interrelationship. These observations highlight AIP as a highly accessible and cost-effective indicator for stratifying PE risk, offering a practical strategy to mitigate severe obstetric complications and enhance global maternal health outcomes.