Ministry of Education Key Laboratory of Pollution Processes and Environmental Criteria, College of Environmental Science and Engineering, Nankai University, Tianjin, China.
Tianjin Medical University Metabolic Diseases Hospital, Tianjin, China.
Environ Int. 2017 Dec;109:53-63. doi: 10.1016/j.envint.2017.09.002. Epub 2017 Sep 19.
Epidemiologic studies have revealed higher concentrations of the metabolites of phthalic acid esters (mPAEs) in patients with type 2 diabetes. On the other hand, oxidative stress, adiponectin, and inflammatory cytokines play important roles in the pathogenesis of diabetes and its complications. However, little information is known about the association between exposure to PAEs and these physiological parameters. Hence, paired urine and blood samples were collected from a total of 329 volunteers, and 11 main mPAEs and malondialdehyde (MDA), as a biomarker of oxidative stress, were measured in the urine samples. Serum adiponectin and tumor necrosis factor-α (TNF-α), a biomarker of inflammation, were also measured. Multivariable linear regression was used to assess the association between urinary mPAEs and these physiological parameters in the total subjects and subjects stratified by age, sex, and body mass index (BMI) to elucidate their possible interactions. All 11 mPAEs were detected in the urine with detection rates of 42.9%-100% and geometric means of 0.30-54.52ng/mL (0.44-79.93μg/g creatinine). The mPAEs were all positively associated with MDA levels. There were significant positive associations between monomethyl phthalate (mMP) and TNF-α, and inverse associations between mMP and adiponectin levels. In the stratified analysis, there were age-, sex-, and BMI-specific differences for these associations. The positive associations between mPAEs and MDA were insignificant in some subgroups, especially in the larger age group. However, in the larger BMI group, summed metabolites of di-(2-ethylhexyl) phthalate (∑DEHP) and mono(2-ethylhexyl) phthalate were positively associated with TNF-α, and the concentrations of ∑DEHP were negatively associated with adiponectin. Our findings suggested that PAE exposure is associated with oxidative stress, adiponectin, and inflammatory cytokines in diabetic patients; further studies on toxicology and a comparison with general population are needed.
流行病学研究表明，2 型糖尿病患者体内邻苯二甲酸酯代谢物（mPAEs）浓度较高。另一方面，氧化应激、脂联素和炎症细胞因子在糖尿病及其并发症的发病机制中起着重要作用。然而，对于接触 PAEs 与这些生理参数之间的关系，我们知之甚少。因此，共采集了 329 名志愿者的配对尿液和血液样本，并测量了尿液样本中的 11 种主要 mPAEs 和丙二醛（MDA），MDA 是氧化应激的生物标志物。还测量了血清脂联素和肿瘤坏死因子-α（TNF-α），这是炎症的生物标志物。多变量线性回归用于评估所有受试者和按年龄、性别和体重指数（BMI）分层的受试者的尿液 mPAEs 与这些生理参数之间的关系，以阐明它们可能的相互作用。所有 11 种 mPAEs 均在尿液中检出，检出率为 42.9%-100%，几何平均值为 0.30-54.52ng/mL（0.44-79.93μg/g 肌酐）。mPAEs 均与 MDA 水平呈正相关。单甲基邻苯二甲酸酯（mMP）与 TNF-α之间存在显著的正相关，与脂联素水平之间存在负相关。在分层分析中，这些关联存在年龄、性别和 BMI 特异性差异。在一些亚组中，mPAEs 与 MDA 之间的正相关关系不显著，尤其是在较大的年龄组中。然而，在较大的 BMI 组中，邻苯二甲酸二（2-乙基己基）酯（∑DEHP）和单（2-乙基己基）邻苯二甲酸酯的总和代谢物与 TNF-α呈正相关，∑DEHP 的浓度与脂联素呈负相关。我们的研究结果表明，PAE 暴露与糖尿病患者的氧化应激、脂联素和炎症细胞因子有关；需要进一步进行毒理学研究并与一般人群进行比较。
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