The impact of environmental toxicants on gestational diabetes mellitus: Investigating the mediating role of high-density lipoprotein cholesterol

Gestational diabetes mellitus (GDM) is a significant metabolic disorder characterized by the elevated glucose level first detected during pregnancy, influencing approximately 14 % of pregnancies globally. Given the rising prevalence of environmental toxicants and their potential impact on maternal health, it is imperative to explore the relationship between environmental exposures and GDM. This study aimed to investigate the mediating role of high-density lipoprotein cholesterol (HDLC) in this context, demonstrating that exposure to environmental toxicants may influence GDM risk through some pathways. Data from the 2007-2020 waves of the National Health and Nutrition Examination Survey (NHANES) were analyzed to assess the association between exposure to 89 environmental toxicants and GDM incidence. A comprehensive evaluation was conducted to identify toxicant-GDM associations, with a particular concentration on volatile organic compounds (VOCs) and certain metals. Additionally, network pharmacology approaches were employed to predict candidate molecular targets of VOCs and elucidate protein-protein interactions (PPIs) linked to GDM pathophysiology. The Similarity Ensemble Approach (SEA) and STRING databases were utilized to construct a PPI network. The findings revealed that 29 environmental toxicants exhibited a positive association with GDM, notably among VOCs and selected metals. HDL-C emerged as a potential surrogate marker for systemic inflammation, mediating the correlation between toxicant exposure and GDM risk. Network pharmacology analysis further revealed key pathways and protein targets implicated in the relationship between environmental exposures and GDM pathogenesis. These findings highlight the critical role of environmental toxicants in shaping maternal health outcomes and GDM susceptibility. By identifying HDL-C as a mediator, this study offers novel insights into the inflammatory mechanisms driving GDM development. Public health strategies must prioritize addressing environmental toxicant exposure to reduce GDM risk and improve maternal-fetal health outcomes.