Association between Organophosphate Ester Exposure and Insulin Resistance with Glycometabolic Disorders among Older Chinese Adults 60–69 Years of Age: Evidence from the China BAPE Study

作者：Enmin Ding, Fuchang Deng, Jianlong Fang, Tiantian Li, Minmin Hou, Juan Liu, Ke Miao, Wenyan Yan, Kwok Lung Fan, Wanying Shi, Yuanzheng Fu, Yuanyuan Liu, Haoran Dong, Li Dong, Changming Ding, Xiaohui Liu, Krystal J. Godri Pollitt, John S. Ji, Yali Shi, Yaqi Cai, Song Tang, Xiaoming Shi · 发表于：Environmental Health Perspectives · 年份：2023 · DOI：10.1289/ehp11896 · 被引用次数：57 · 研究领域：Pesticide Exposure and Toxicity、Metabolomics and Mass Spectrometry Studies、Toxic Organic Pollutants Impact

BACKGROUND: Organophosphate esters (OPEs) are common endocrine-disrupting chemicals, and OPE exposure may be associated with type 2 diabetes (T2D). However, greater knowledge regarding the biomolecular intermediators underlying the impact of OPEs on T2D in humans are needed to understand biological etiology. OBJECTIVES: We explored the associations between OPE exposure and glycometabolic markers among older Chinese adults 60-69 years of age to elucidate the underlying mechanisms using a multi-omics approach. METHODS: This was a longitudinal panel study comprising 76 healthy participants 60-69 years of age who lived in Jinan city of northern China. The study was conducted once every month for 5 months, from September 2018 to January 2019. We measured a total of 17 OPEs in the blood, 11 OPE metabolites in urine, and 4 glycometabolic markers (fasting plasma glucose, glycated serum protein, fasting insulin, and homeostatic model assessment for insulin resistance). The blood transcriptome and serum/urine metabolome were also evaluated. The associations between individual OPEs and glycometabolic markers were explored. An adverse outcome pathway (AOP) was established to determine the biomolecules mediating the associations. RESULTS: Exposure to five OPEs and OPE metabolites (trimethylolpropane phosphate, triphenyl phosphate, tri-iso-butyl phosphate, dibutyl phosphate, and diphenyl phosphate) was associated with increased levels of glycometabolic markers. The mixture effect analysis ...