Abstract：
BACKGROUND: Organochlorine pesticides (OCPs), polybrominated diphenyl ethers (PBDEs), and polychlorinated biphenyls (PCBs) are persistent organic pollutants (POPs) that can negatively impact metabolic health through pathways including endocrine disruption. Few studies have evaluated diabetes risk associated with PBDEs. Little is known about the joint effect of exposure to POP mixtures on diabetes risk.
OBJECTIVE: We investigated the relationship between POPs, individually and as mixtures, and diabetes development over 18 years (1999-2016) in midlife women.
METHODS: We measured lipid-standardized serum concentrations of 34 PCBs, 19 OCPs, and 14 PBDEs in 1040 midlife women aged 45-56 years from the Study of Women\'s Health Across the Nation. We tested the association between POPs measured in 1999/2000 and incident diabetes using Cox proportional hazards models. We evaluated diabetes risk associated with the overall POP mixture using Quantile-Based G-Computation (QBGC).
RESULTS: For most mixture components, single pollutant and mixtures analyses indicated null associations with diabetes risk, however results were inconsistent. After adjustment, hazard ratios (HRs) of developing diabetes (95% CI) associated with upper exposure tertiles (T2/T3) compared with the first tertile (T1), were 1.7 (1.0, 2.8) at T2 and 1.5 (0.84, 2.7) at T3 for hexachlorobenzene and 1.9 (1.1, 3.3) at T2 and 1.6 (0.88, 2.9) at T3 for PCB 123. A doubling of PBDE 47 was associated with 1.11 (1.00, 1.24) times the risk of T2D. QBGC identified no association for the overall joint effect of the POP mixture on diabetes (HR = 1.04 [0.53, 2.07]).
CONCLUSIONS: Exposure to a mixture of PCBs, OCPs, and PBDEs was not associated with incident diabetes in midlife U.S. women, although some individual POPs demonstrated significant yet inconsistent associations with diabetes. Non-linear and non-monotonic dose-response dynamics deserve further exploration. More research is needed on the diabetogenic effects of PBDEs.
OBJECTIVE: We investigated the relationship between POPs, individually and as mixtures, and diabetes development over 18 years (1999-2016) in midlife women.
METHODS: We measured lipid-standardized serum concentrations of 34 PCBs, 19 OCPs, and 14 PBDEs in 1040 midlife women aged 45-56 years from the Study of Women\'s Health Across the Nation. We tested the association between POPs measured in 1999/2000 and incident diabetes using Cox proportional hazards models. We evaluated diabetes risk associated with the overall POP mixture using Quantile-Based G-Computation (QBGC).
RESULTS: For most mixture components, single pollutant and mixtures analyses indicated null associations with diabetes risk, however results were inconsistent. After adjustment, hazard ratios (HRs) of developing diabetes (95% CI) associated with upper exposure tertiles (T2/T3) compared with the first tertile (T1), were 1.7 (1.0, 2.8) at T2 and 1.5 (0.84, 2.7) at T3 for hexachlorobenzene and 1.9 (1.1, 3.3) at T2 and 1.6 (0.88, 2.9) at T3 for PCB 123. A doubling of PBDE 47 was associated with 1.11 (1.00, 1.24) times the risk of T2D. QBGC identified no association for the overall joint effect of the POP mixture on diabetes (HR = 1.04 [0.53, 2.07]).
CONCLUSIONS: Exposure to a mixture of PCBs, OCPs, and PBDEs was not associated with incident diabetes in midlife U.S. women, although some individual POPs demonstrated significant yet inconsistent associations with diabetes. Non-linear and non-monotonic dose-response dynamics deserve further exploration. More research is needed on the diabetogenic effects of PBDEs.
摘要：
背景：有机氯农药（OCPs），多溴联苯醚（PBDEs），多氯联苯（PCBs）是持久性有机污染物（POPs），可通过内分泌干扰等途径对代谢健康产生负面影响。很少有研究评估与多溴二苯醚相关的糖尿病风险。关于暴露于POP混合物对糖尿病风险的联合影响知之甚少。
目的：我们调查了持久性有机污染物之间的关系，单独和作为混合物，和糖尿病发展超过18年（1999-2016年）的中年女性方法：我们测量了34多氯联苯的脂质标准化血清浓度，19个OCP，以及来自全国妇女健康研究的1,040名45-56岁的中年妇女中的14种多溴二苯醚。我们使用Cox比例风险模型测试了1999/2000年测量的POPs与糖尿病发病率之间的关联。我们使用基于分位数的G计算（QBGC）评估了与整体POP混合物相关的糖尿病风险。
结果：对于大多数混合物成分，单一污染物和混合物分析表明与糖尿病风险无关联，然而结果不一致。调整后,与第一三位数(T1)相比，与上暴露三位数(T2/T3)相关的发展为糖尿病(95%CI)的风险比(HR)，六氯苯的T2为1.7（1.0、2.8），T3为1.5（0.84、2.7），多氯联苯123的T2为1.9（1.1、3.3），T3为1.6（0.88、2.9）。PBDE47加倍与T2D风险的1.11（1.00，1.24）倍相关。QBGC确定POP混合物对糖尿病的整体联合作用没有关联(HR=1.04[0.53,2.07])。
结论：暴露于多氯联苯的混合物，OCPs,PBDEs与美国中年女性的糖尿病事件无关，尽管某些POPs与糖尿病有显著但不一致的关联.非线性和非单调剂量反应动力学值得进一步探索。需要对多溴二苯醚的致糖尿病作用进行更多的研究。
目的：我们调查了持久性有机污染物之间的关系，单独和作为混合物，和糖尿病发展超过18年（1999-2016年）的中年女性方法：我们测量了34多氯联苯的脂质标准化血清浓度，19个OCP，以及来自全国妇女健康研究的1,040名45-56岁的中年妇女中的14种多溴二苯醚。我们使用Cox比例风险模型测试了1999/2000年测量的POPs与糖尿病发病率之间的关联。我们使用基于分位数的G计算（QBGC）评估了与整体POP混合物相关的糖尿病风险。
结果：对于大多数混合物成分，单一污染物和混合物分析表明与糖尿病风险无关联，然而结果不一致。调整后,与第一三位数(T1)相比，与上暴露三位数(T2/T3)相关的发展为糖尿病(95%CI)的风险比(HR)，六氯苯的T2为1.7（1.0、2.8），T3为1.5（0.84、2.7），多氯联苯123的T2为1.9（1.1、3.3），T3为1.6（0.88、2.9）。PBDE47加倍与T2D风险的1.11（1.00，1.24）倍相关。QBGC确定POP混合物对糖尿病的整体联合作用没有关联(HR=1.04[0.53,2.07])。
结论：暴露于多氯联苯的混合物，OCPs,PBDEs与美国中年女性的糖尿病事件无关，尽管某些POPs与糖尿病有显著但不一致的关联.非线性和非单调剂量反应动力学值得进一步探索。需要对多溴二苯醚的致糖尿病作用进行更多的研究。
