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Perturbation of serum metabolome in relation to type 2 diabetes mellitus and urinary levels of phthalate metabolites and bisphenols
Environment International ( IF 11.8 ) Pub Date : 2021-05-06 , DOI: 10.1016/j.envint.2021.106609
Yishuang Duan 1 , Hongwen Sun 2 , Yiming Yao 2 , Liping Han 3 , Liming Chen 3
Affiliation  

Background

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.

Objectives

The purpose of the study was to investigate the roles of metabolism in the associations for exposure to PAEs and bisphenols with T2DM.

Methods

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.

Results

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.

Conclusions

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.



中文翻译:

血清代谢组的扰动与 2 型糖尿病和邻苯二甲酸酯代谢物和双酚的尿水平有关

背景

新出现的证据已经证明接触邻苯二甲酸酯 (PAE) 和双酚与 2 型糖尿病 (T2DM) 之间存在关联,但对这些关联的潜在机制知之甚少。代谢组学是识别与疾病和化学物质暴露相关的差异代谢物和代谢途径的有力工具,这可能揭示潜在的机制。然而,关于代谢在 PAE 和双酚暴露与 T2DM 关联中的作用知之甚少。

目标

该研究的目的是研究代谢在接触 PAE 和双酚与 T2DM 之间的关系中的作用。

方法

在本研究中,从我们之前研究的总研究人群中选择了年龄、性别和体重指数 (BMI) 匹配的 60 名 T2DM 病例和 60 名对照组。志愿者的空腹血液和现场尿液样本分别用于非靶向代谢组学分析和邻苯二甲酸酯代谢物 (mPAE) 和双酚的测定。使用多元线性回归模型分析尿液 mPAE 和双酚与代谢组学分析中筛选的代谢生物标志物的关联。

结果

基于非靶向代谢组学,在 T2DM 病例和对照组之间筛选了 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相关。超过一半的 mPAE 大多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 PAE 不同,没有明显的结果表明代谢在双酚暴露与 T2DM 之间的关联中的作用。

结论

结合我们之前研究中大多数尿液 mPAE 与 T2DM 之间的正相关,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(尤其是精氨酸生物合成和丙氨酸、天冬氨酸和谷氨酸代谢)和嘧啶来增加 T2DM 风险代谢。

更新日期:2021-05-06
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