Metallome-Wide Association Study of Maternal-Fetus Interface Metabolism Dysfunction in Gestational Diabetes Mellitus

摘要

A broad set of elements has been linked to gestational diabetes mellitus (GDM); the previous study also acknowledged some metabolic biomarkers in meconium can provide the biology of GDM. This work was to assess a set of elements' associations with GDM and infer the causality by using the maternal-fetus interface surrogating sample of meconium. We conducted a case-control study nested on the cross-sectional retrospection of 1359 recruitments from the Xiamen Maternity and Child Care Hospital. The ICP-MS and ICP-OES was used to characterize the meconium metallome of 23 elements. The associations for some GDM-related elements, GDM-oriented metabolic biomarkers and GDM incidence were assessed by using redundancy analysis and Correlation-Adjusted corRelation. Mediation analysis was in further used to test the metabolic biomarker mediation between the elements and GDM incidence. The significant associations of eight elements with GDM incidence were observed, the risk elements are Al, As, Ba, Cd, Hg, and Sn and the preventive elements are Ca and V. Among them, As, Cd, Ba, and Ca can also explain the variation of GDM-oriented metabolites. 69% of the total variance of GDM incidence can be explained by all investigated factors and the elements had an independent predictive power of 16%. The investigated elements can also explain 39.5%, 26.58%, and 23.78% of the total variance of argininosuccinic acid, oxotrihydroxyleukotriene B4 and taurodeoxycholic acid, respectively, which are the top three metabolic determinants and can explain about 45% of the total GDM incidence. From more to less, the associations of Cd, Ba, Ca and As with GDM incidence have been mediated by the metabolic biomarkers. Ba, As and Cd aggravate GDM occurrence while Ca play the preventive role; the metabolic biomarker involved lipid metabolism and ALANO pathways may imply the elements' biological action on GDM. Notably the toxic effect of Ba and the beneficial effect of Ca on GDM have not been attended before.