Mediation analysis for the relationship between urinary phthalate metabolites and type 2 diabetes via oxidative stress in a population in Jeddah, Saudi Arabia
Mediation analysis for the relationship between urinary phthalate metabolites and type 2 diabetes via oxidative stress in a population in Jeddah, Saudi Arabia
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DOI：
10.1016/j.envint.2019.01.082
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发表时间：
2019-05-01
影响因子：
11.8
通讯作者：
Kannan, Kurunthachalam
中科院分区：
文献类型：
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作者：
Li, Adela Jing;Martinez-Moral, Maria-Pilar;Kannan, Kurunthachalam
人体暴露于邻苯二甲酸酯是普遍存在的，并已受到相当大的关注，因为它们与不良健康结果，包括2型糖尿病（T2 DM）。然而，早期将邻苯二甲酸酯暴露与T2 DM联系起来的研究结果不明确。此外，将邻苯二甲酸酯暴露与氧化应激，然后与T2 DM相关联的研究很少。在这项糖尿病病例对照研究中，分析了从沙特阿拉伯吉达收集的101名年龄在28-68岁的个体的尿液样本，以确定20种邻苯二甲酸酯代谢物（PhM）和7种氧化应激生物标志物（OSB）。非条件Logistic回归用于估计参与者中糖尿病与尿PhM和OSB之间相关性的比值比，按年龄，性别，国籍，吸烟状况，职业和尿肌酐分层。发现12种PhM和5种OSB的检出率高于50%，几何平均浓度分别为0.61-100和0.35-10.7 ng/mL（1.04-171和0.61-18.6 μ g/g肌酐）。糖尿病患者几乎所有暴露量均显著高于对照组。12种PhM与较高的尿中8-羟基-2 '-脱氧鸟苷（8-OHdG）和8-异前列腺素F-2 α（8-PGF（2 α））浓度呈正相关。与第一四分位数相比，第三和/或第四分位数的PhM和OSB尿液浓度的个体患糖尿病的几率分别增加了3.7倍和7.3倍。PhM/OSB与糖尿病的相关性顺序为：mEP近似于mBP > mEHP > mCPP > mECPP近似于mEOHP近似于mEHHP近似于mIBP近似于mMP > mCMHP近似于mBzP和8-OHdG > 8-PGF（2 α）近似于15-PGF（2 α）。邻苯二甲酸酯暴露与发生T2 DM风险之间的关系部分由邻苯二甲酸酯诱导的氧化应激介导，尤其是8-OHdG。我们的研究表明，人体暴露于邻苯二甲酸酯与氧化应激增加有关，氧化应激可介导T2 DM的发生。
Human exposure to phthalates is ubiquitous and has received considerable attention due to their association with adverse health outcomes, including type 2 diabetes mellitus (T2DM). Nevertheless, earlier studies that link phthalate exposure to T2DM yielded ambiguous results. Furthermore, studies that associate phthalate exposure with oxidative stress and then with T2DM are scant. In this diabetic case-control study, urine samples collected from 101 individuals aged 28-68 years from Jeddah, Saudi Arabia, were analyzed to determine 20 phthalate metabolites (PhMs) and seven oxidative stress biomarkers (OSBs). Unconditional logistic regression was used to estimate odds ratios for the association between diabetes and urinary PhMs and OSBs in participants, stratified by age, gender, nationality, smoking status, occupation, and urinary creatinine. Twelve PhMs and five OSBs were found at detection rates above 50%, with geometric mean concentrations of 0.61-100 and 0.35-10.7 ng/mL (1.04-171 and 0.61-18.6 mu g/g creatinine), respectively. Almost all exposures were significantly higher in diabetic cases than in controls. The 12 PhMs were positively associated with higher urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F-2 alpha (8-PGF(2 alpha)). Individuals in the 3rd and/or 4th quartile(s) for urinary concentrations of PhMs and OSBs showed 3.7- and 7.3-fold increase, respectively, in the odds of having diabetes compared with those in the 1st quartile. The rank order of association of PhMs/OSBs with diabetes followed the order of: mEP approximate to mBP > mEHP > mCPP > mECPP approximate to mEOHP approximate to mEHHP approximate to mIBP approximate to mMP > mCMHP approximate to mBzP and 8-OHdG > 8-PGF(2 alpha) approximate to 15-PGF(2 alpha). The relationship between phthalate exposure and risk of developing T2DM was mediated in part by phthalate-induced oxidative stress, especially 8-OHdG. Our study suggests that human exposure to phthalates is associated with increased oxidative stress which mediates the development of T2DM.