Metabolic biomarkers linking urinary arsenic species to gestational diabetes mellitus: A cross-sectional study in Chinese pregnant women

Environmental arsenic (As) exposure has been associated with gestational diabetes mellitus (GDM) risk. Our recent study found that GDM was positively associated with urinary As3+ level while negatively correlated to As5+. However, the mechanisms underlying the association between arsenic species and GDM remain largely unknown. In the present study, through the measurement of urinary arsenic species and metabolome analysis in 399 pregnant women, we aimed to identify the metabolic biomarkers that may link arsenic exposure to GDM based on a novel systems epidemiology strategy termed meet-in-metabolite-analysis (MIMA). The metabolomics analysis revealed that 20 and 16 urinary metabolites were relevant to arsenic exposure and GDM, respectively. Among them, 12 metabolites were identified to be both arsenic- and GDM-related, which are mainly involved in purine metabolism, one-carbon metabolism (OCM) and glycometabolism. Moreover, it was further showed that the regulation of thiosulfate (AOR: 2.52; 95 % CI: 1.33, 4.77) and phosphoroselenoic acid (AOR: 2.35; 95 % CI: 1.31, 4.22) could significantly contribute to the negative association between As5+ and GDM. Considering the biological functions of these metabolites, it is suggested that As5+ may reduce GDM risk by disturbing OCM in the pregnant women. These data will provide novel insights into the mechanism of action of environmental arsenic exposure on GDM incidence from the aspect of metabolism disorder.

Automated summary

Recent research has found a positive correlation between urinary As3+ level and gestational diabetes mellitus (GDM), while a negative correlation with As5+. In this study, through metabolome analysis and measurement of urinary arsenic species in 399 pregnant women, a novel strategy called meet-in-metabolite-analysis (MIMA) was used to identify metabolic biomarkers that link arsenic exposure to GDM. The analysis revealed 20 metabolites relevant to arsenic exposure and 16 relevant to GDM, with 12 identified as being related to both arsenic and GDM, primarily involved in purine metabolism, one-carbon metabolism, and glycometabolism. Further research showed that the regulation of thiosulfate and phosphoroselenoic acid significantly contributed to the negative association between As5+ and GDM. It is suggested that As5+ may reduce GDM risk by disrupting one-carbon metabolism in pregnant women. These findings provide new insights into the mechanism of environmental arsenic exposure on GDM incidence from a metabolic disorder perspective.