上海市300名中老年2型糖尿病患者邻苯二甲酸酯暴露的肝脏受损风险评估

陈玮华; 贾福怀; 陈婧司; 张梅如; 周小锋; 吴岷; 陈波; 厉曙光

doi:10.13213/j.cnki.jeom.2019.18809

上海市300名中老年2型糖尿病患者邻苯二甲酸酯暴露的肝脏受损风险评估

Risk assessment of liver damage related to phthalates exposure in 300 elder diabetics from Shanghai

摘要

摘要:
目的多种邻苯二甲酸酯（PAEs）被报道具有肝脏毒性。因暴露于PAEs而导致肝脏损伤的健康风险评估曾在一般人群中被报道，但在2型糖尿病（T2DM）患者中鲜见报道，而肝脏受损可加剧T2DM的发生发展。本研究旨在了解上海市社区中老年T2DM患者的PAEs暴露情况，并评估其肝脏受损的健康风险。

方法采用横断面的研究设计，收集2016年上海市黄浦区某社区医院的300名中老年T2DM患者的一次随机尿样，采用液相色谱串联质谱法对其尿中6种常见PAEs的10种代谢物进行检测，并根据肌酐校正后的代谢物浓度推算其接触PAEs的每日估计暴露量（EDI）；采用危害指数（HI）法对患者接触PAEs的累积暴露水平进行肝脏受损的健康风险评估，并采用线性回归分析一般人口学特征与PAEs的危害商（HQ）和HI的相关性。

结果 T2DM患者尿中10种PAEs代谢物的检出率除邻苯二甲酸单甲酯（MMP）、邻苯二甲酸单苄基酯（MBzP）和单（2-羧基己基）邻苯二甲酸酯（MCMHP）外，均为100%。肌酐校正后的浓度较高的为邻苯二甲酸单乙酯（MEP）、邻苯二甲酸单正丁酯（MnBP）和邻苯二甲酸单异丁酯（MiBP），其中位数分别为137.13、265.73、381.53 μg/g。MBzP的检出率（88.3%）和浓度（中位数3.70 μg/g）均为最低。6种PAEs中，邻苯二甲酸二异丁酯（DiBP）的EDI中位数12.95 μg/（kg·d）远高于其他5种PAEs。邻苯二甲酸二（2-乙基己基）酯（DEHP）、DiBP和邻苯二甲酸二正丁酯（DnBP）的HQ中位数远高于邻苯二甲酸二乙酯（DEP）和邻苯二甲酸丁基苄酯（BBP），分别为0.169 4、0.129 5和0.081 8。HI≥ 1的患者有55名（18.33%）。糖尿病家族史与DEP、DiBP和BBP的HQ呈正相关（P < 0.05）。

结论上海市社区中老年T2DM患者因接触PAEs而可能存在一定的肝脏受损风险，主要来源于DEHP。

Abstract:
Objectve Phthalates (PAEs) have been reported to have hepatotoxicity. Several studies have assessed the health risks of exposure to PAEs in general populaton, but not in patents diagnosed with type 2 diabetes mellitus (T2DM) which would be aggravated by liver damage. In this study, we aim to evaluate the levels of cumulatve exposure to PAEs in elder T2DM patents and assess the health risk of liver damage related to the exposure.

Methods A cross-sectional study was conducted. A total of 300 spot urine samples were collected from elder T2DM patents from a community health service center of Huangpu District, Shanghai in 2016. Liquid chromatography-tandem mass spectrometry was used to determine 10 metabolites of 6 kinds of PAEs in urine. Estmated daily intake (EDI) was calculated based on the creatnine-adjusted concentratons of the 10 metabolites. Hazard index (HI) as a measure of health risk assessment was used to assess the liver damage induced by cumulatve exposure to PAEs. The associatons of demographic characteristc with hazard quotent (HQ) and HI of PAEs were analyzed using linear regression.

Results Except mono-methyl phthalate (MMP), mono-benzyl phthalate (MBzP), and mono-2-carboxymethyl-hexyl phthalate (MCMHP), the detection rates of the other 7 metabolites were 100% positive in urine samples of T2DM patients. Mono-ethyl phthalate (MEP), mono-n-butyl phthalate (MnBP), and monoisobutyl phthalate (MiBP) showed highest levels, with the medians of creatnine-adjusted concentrations being 137.13, 265.73, and 381.53 μg/g, respectively. Comparatively, the positive detection rate (88.3%) and the concentraton (median:3.70 μg/g) of MBzP were the lowest. The EDI of di-isobutyl phthalate (DiBP) was much higher than those of the others, with a median of 12.95 μg/(kg·d). The HQs of di-2-ethylhexyl phthalate (DEHP), DiBP, and di-n-butyl phthalate (DnBP) were much higher than those of di-ethyl phthalate (DEP) and butyl-benzyl phthalate (BBP), with medians of 0.169 4, 0.129 5, and 0.081 8, respectvely. The partcipants (n=55) with HI≥ 1 accounted for 18.33% of total study partcipants. Having a family history of diabetes was positvely associated with the HQs of DEP, DiBP, and BBP (P < 0.05).

Conclusion The exposure to PAEs may be a risk factor of liver damage among elder T2DM patents from Shanghai, and DEHP plays a dominant role.

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