Hubei Key Laboratory of Environmental and Health Effects of Persistent Toxic Substances, Institute of Environment and Health, Jianghan University, Wuhan, China; Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin, China.
Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin, China.
Environ Int. 2021 Oct;155:106609. doi: 10.1016/j.envint.2021.106609. Epub 2021 May 6.
Emerging 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.
The purpose of the study was to investigate the roles of metabolism in the associations for exposure to PAEs and bisphenols with T2DM.
In 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.
Based 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.
Combined 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.
新兴证据证明了邻苯二甲酸酯（PAEs）和双酚暴露与 2 型糖尿病（T2DM）之间存在关联，但这些关联的潜在机制尚不清楚。代谢组学是一种识别与疾病和化学暴露相关的差异代谢物和代谢途径的有力工具，它可能揭示潜在的机制。然而，对于代谢在 PAE 和双酚暴露与 T2DM 关联中的作用知之甚少。
本研究旨在探讨代谢在 PAE 和双酚暴露与 T2DM 关联中的作用。
本研究从我们之前的研究中选择了 60 例 T2DM 病例和 60 例匹配年龄、性别和体重指数（BMI）的对照，采集志愿者的空腹血和尿样，用于非靶向代谢组学分析和邻苯二甲酸代谢物（mPAEs）和双酚的测定。采用多元线性回归模型分析尿 mPAEs 和双酚与代谢组学分析中筛选出的代谢生物标志物的关联。
基于非靶向代谢组学，在 T2DM 病例和对照之间筛选出 19 个血清代谢生物标志物，主要与半乳糖代谢、氨基酸代谢和嘧啶代谢有关。大多数 mPAEs 与上调的代谢生物标志物呈正相关，与下调的生物标志物呈负相关。与 PAEs 不同，代谢在双酚暴露与 T2DM 之间的关联中没有明显的作用结果。
结合我们之前的研究中大多数尿 mPAEs 与 T2DM 之间的正相关关系，我们的研究结果表明，PAE 暴露可能通过干扰半乳糖代谢、氨基酸代谢（特别是精氨酸生物合成和丙氨酸、天冬氨酸和谷氨酸代谢）和嘧啶代谢，导致 T2DM 风险增加。
