Perturbation of serum metabolome in relation to type 2 diabetes mellitus and urinary levels of phthalate metabolites and bisphenols

Abstract

BackgroundEmerging evidence has proved the associations between exposure to phthalates (PAEs) and bisphenols and type 2 diabetes mellitus (T2DM), but the underlying mechanisms for these associations are poorly understood. Metabolomics is a powerful tool to identify differential metabolites and metabolic pathways related to diseases and chemical exposure, which may reveal underlying mechanisms. However, little is known about the roles of metabolism in the associations for PAE and bisphenol exposure with T2DM. ObjectivesThe purpose of the study was to investigate the roles of metabolism in the associations for exposure to PAEs and bisphenols with T2DM. MethodsIn this study, 60 T2DM cases and 60 controls, who were matched in age, sex, and body mass index (BMI), were selected from the total study population in our previous studies. Fasting blood and spot urine samples of the volunteers were used for non-targeted metabolomics analysis and determination of phthalate metabolites (mPAEs) and bisphenols, respectively. The associations of urinary mPAEs and bisphenols with screened metabolic biomarkers in metabolomics analysis were analyzed using multiple linear regression models. ResultsBased on non-targeted metabolomics, 19 serum metabolic biomarkers were screened between T2DM cases and controls, mostly related to galactose metabolism, amino acid metabolism, and pyrimidine metabolism. More than half of mPAEs were mostly positively associated with up-regulated metabolic biomarkers and negatively associated with down-regulated biomarkers. Different from PAEs, no evident results suggested the roles of metabolism in the associations between bisphenol exposure and T2DM. ConclusionsCombined with the positive associations between most urinary mPAEs and T2DM in our previous study, our findings indicated that PAE exposure may contribute to T2DM risk through disturbing galactose metabolism, amino acid metabolism (especially arginine biosynthesis and alanine, aspartate and glutamate metabolism), and pyrimidine metabolism.