Impact of exposure to metallic elements on gestational diabetes mellitus: Insights from human investigations

Metal elements play a crucial role in maternal and fetal health. Gestational diabetes mellitus (GDM) is diagnosed when any degree of glucose intolerance is identified for the first time in a pregnant individual, resulting in varying degrees of hyperglycemia that can cause short- or long-term complications for both the mother and fetus. GDM has a multifactorial etiology, including genetic and environmental factors. The increase in the global prevalence of GDM is believed to be related to maternal exposure to environmental trace elements. The latest progress in population-level association studies has investigated the relationship between maternal metal content and GDM, especially the effect of exogenous metal exposure on the incidence of GDM. This review comprehensively and qualitatively elucidates the relationship between GDM risk and metal content across a range of maternal and neonatal biospecimens, including maternal peripheral blood, urine, nails, hair, placenta, umbilical cord blood, and meconium. Specifically, we identified various exacerbating and mitigating effects of metal exposure on the risk of developing GDM. Furthermore, the role of metal elements in the occurrence and progression of GDM and their potential mechanisms of action were analyzed and discussed. In this review, we provide new perspectives for understanding the relationship between environmental metals and GDM, and have important applications and public health implications for inhibiting environmental metal exposure and preventing GDM.