School of Public Health, Seoul National University, Seoul, Republic of Korea.
Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.
Environ Int. 2021 Jan;146:106227. doi: 10.1016/j.envint.2020.106227. Epub 2020 Nov 2.
Phthalates and bisphenol A (BPA) have been suspected as risk factors for obesity and diabetes mellitus (DM) among humans. However, associations between phthalates and environmental phenols are often inconsistent across different populations. In this study, we recruited the adult population (n = 3782) of the Korean National Environmental Health Survey (KoNEHS) 2015-2017 (Cycle 3) and assessed the associations between urinary biomarkers of phthalate, BPA, and paraben exposure with obesity and DM. A potential collider issue with the use of urinary creatinine (Cr) or specific gravity (SG) exists when adjusting urinary dilution; therefore, a covariate-adjusted standardization (CAS) was employed for adjustment, and the results were compared. In the present population, the direction of the association often varied depending on the choices made to adjust urinary dilution. When using CAS, the direction of association resembled those of previously reported experimental observations. With Cr or SG adjustment, ORs for obesity decreased in the highest quartiles of monocarboxyoctyl phthalate (MCOP) [OR (95% CI) = Cr: 0.71 (0.54, 0.93); SG: 0.68 (0.52, 0.90)], monocarboxy-isononyl phthalate (MCNP) [OR (95% CI) = Cr: 0.67 (0.52, 0.87); SG: 0.68 (0.52, 0.89)], and mono(3-carboxylpropyl) phthalate (MCPP) in the urine [OR (95% CI) = Cr: 0.60 (0.47, 0.76); SG: 0.61 (0.48, 0.77)]; however, with CAS, these negative associations disappeared. Instead, mono-benzyl phthalate (MBzP) [OR (95% CI) = 1.31 (1.03, 1.66)], BPA [OR (95% CI) = 1.62 (1.27, 2.06)], or ethyl paraben (EtP) [OR (95% CI) = 1.51 (1.19, 1.91)] concentrations in the highest quartile showed positive associations with a higher risk of obesity. On the other hand, for DM, an overall decrease in ORs was observed for phthalate metabolites and BPA following SG adjustment and disappeared with CAS adjustment. In addition, the highest quartiles of BPA, methyl paraben (MeP), and ethyl paraben (EtP) showed a significantly higher risk of DM than those in the lowest quartiles following CAS [OR (95% CI) = BPA: 1.65 (1.06, 2.59); MeP: 1.68 (1.08, 2.60); and EtP: 2.74 (1.77, 4.24), respectively]. The present observations outline the importance of using an appropriate adjustment method for urinary dilution in association studies on obesity and DM. In addition, several phthalates, BPA, and parabens were identified as potential chemical risk factors for these outcomes. Further studies are warranted in other populations to confirm these observations.
邻苯二甲酸酯和双酚 A(BPA)已被怀疑是人类肥胖和糖尿病(DM)的危险因素。然而,邻苯二甲酸酯和环境酚类物质之间的关联在不同人群中往往不一致。在这项研究中,我们招募了韩国国家环境健康调查(KoNEHS)2015-2017 年(第 3 周期)的成年人群(n=3782),评估了尿中邻苯二甲酸酯、BPA 和对羟基苯甲酸酯暴露的生物标志物与肥胖和 DM 的关联。当调整尿稀释度时,使用尿肌酐(Cr)或比重(SG)可能存在潜在的共发事件问题;因此,采用了协变量调整标准化(CAS)进行调整,并比较了结果。在本人群中,关联的方向往往取决于调整尿稀释度时的选择。使用 CAS 时,关联的方向类似于先前报道的实验观察结果。使用 Cr 或 SG 调整后,单羧酸辛基邻苯二甲酸酯(MCOP)[OR(95%CI)=Cr:0.71(0.54,0.93);SG:0.68(0.52,0.90)]、单羧酸异壬基邻苯二甲酸酯(MCNP)[OR(95%CI)=Cr:0.67(0.52,0.87);SG:0.68(0.52,0.89)]和单(3-羧基丙基)邻苯二甲酸酯(MCPP)[OR(95%CI)=Cr:0.60(0.47,0.76);SG:0.61(0.48,0.77)]在尿液中的最高四分位数与肥胖的风险增加呈负相关;然而,使用 CAS,这些负相关消失了。相反,单苄基邻苯二甲酸酯(MBzP)[OR(95%CI)=1.31(1.03,1.66)]、BPA[OR(95%CI)=1.62(1.27,2.06)]或乙基对羟基苯甲酸酯(EtP)[OR(95%CI)=1.51(1.19,1.91)]在最高四分位数的浓度与肥胖的高风险呈正相关。另一方面,对于 DM,在 SG 调整后,邻苯二甲酸代谢物和 BPA 的 OR 总体呈下降趋势,而在 CAS 调整后则消失。此外,BPA、甲基对羟基苯甲酸酯(MeP)和乙基对羟基苯甲酸酯(EtP)的最高四分位数与最低四分位数相比,患 DM 的风险显著增加[OR(95%CI)=BPA:1.65(1.06,2.59);MeP:1.68(1.08,2.60);EtP:2.74(1.77,4.24)]。本研究结果概述了在肥胖和 DM 相关研究中使用适当的尿稀释度调整方法的重要性。此外,还确定了几种邻苯二甲酸酯、BPA 和对羟基苯甲酸酯可能是这些结果的潜在化学危险因素。需要在其他人群中进一步研究以证实这些观察结果。
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