Persistent organic pollutants (POPs) are lipophilic compounds that travel with lipids and accumulate mainly in adipose tissue. Recent human evidence links low-dose POPs to an increased risk of type 2 diabetes (T2D). Because humans are contaminated by POP mixtures and POPs possibly have nonmonotonic dose-response relations with T2D, critical methodological issues arise in evaluating human findings. This review summarizes epidemiological results on chlorinated POPs and T2D, and relevant experimental evidence. It also discusses how features of POPs can affect inferences in humans. The evidence as a whole suggests that, rather than a few individual POPs, background exposure to POP mixtures-including organochlorine pesticides and polychlorinated biphenyls-can increase T2D risk in humans. Inconsistent statistical significance for individual POPs may arise due to distributional differences in POP mixtures among populations. Differences in the observed shape of the dose-response curves among human studies may reflect an inverted U-shaped association secondary to mitochondrial dysfunction or endocrine disruption. Finally, we examine the relationship between POPs and obesity. There is evidence in animal studies that low-dose POP mixtures are obesogenic. However, relationships between POPs and obesity in humans have been inconsistent. Adipose tissue plays a dual role of promoting T2D and providing a relatively safe place to store POPs. Large prospective studies with serial measurements of a broad range of POPs, adiposity, and clinically relevant biomarkers are needed to disentangle the interrelationships among POPs, obesity, and the development of T2D. Also needed are laboratory experiments that more closely mimic real-world POP doses, mixtures, and exposure duration in humans.

中文翻译：

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氯化持久性有机污染物、肥胖症和 2 型糖尿病。

持久性有机污染物 (POPs) 是亲脂性化合物，与脂质一起传播并主要积聚在脂肪组织中。最近的人类证据将低剂量持久性有机污染物与 2 型糖尿病 (T2D) 的风险增加联系起来。由于人类受到持久性有机污染物混合物的污染，而且持久性有机污染物可能与 T2D 具有非单调的剂量反应关系，因此在评估人类发现时出现了关键的方法学问题。本综述总结了氯化持久性有机污染物和 T2D 的流行病学结果，以及相关的实验证据。它还讨论了持久性有机污染物的特征如何影响人类的推理。整体证据表明，背景暴露于 POP 混合物（包括有机氯杀虫剂和多氯联苯）会增加人类 T2D 风险，而不是个别 POPs。由于种群间持久性有机污染物混合物的分布差异，个体持久性有机污染物的统计显着性可能不一致。在人体研究中观察到的剂量反应曲线形状的差异可能反映了继发于线粒体功能障碍或内分泌紊乱的倒 U 形关联。最后，我们研究了持久性有机污染物与肥胖之间的关系。动物研究中有证据表明低剂量持久性有机污染物混合物会导致肥胖。然而，持久性有机污染物与人类肥胖之间的关系并不一致。脂肪组织在促进 T2D 和提供一个相对安全的地方来储存持久性有机污染物方面发挥着双重作用。需要对广泛的持久性有机污染物、肥胖和临床相关生物标志物进行连续测量的大型前瞻性研究，以理清持久性有机污染物、肥胖、以及T2D的发展。还需要更接近模拟真实世界持久性有机污染物剂量、混合物和人体暴露持续时间的实验室实验。