Endocrine Reviews 35: 557–601, 2014

 

Chlorinated Persistent Organic Pollutants, Obesity, and Type 2 Diabetes

Duk-Hee Lee, Miquel Porta, David R. Jacobs Jr., and Laura N. Vandenberg

Department of Preventive Medicine (D.-H.L.), School of Medicine, Kyungpook National University, Daegu 700-422, Korea;BK21 Plus KNU Biomedical Convergence Program, Department of Biomedical Science (D.-H.L.), Kyungpook National University, Korea; Hospital del Mar Institute of Medical Research (M.P.), School of Medicine, Universitat Autonoma de Barcelona, and Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona 08193, Spain; Division of Epidemiology (D.R.J.), School of Public Health, University of Minnesota, Minneapolis, Minnesota 55455; Department of Nutrition (D.R.J.), University of Oslo, 0313 Oslo, Norway; and University of Massachusetts–Amherst (L.N.V.),
School of Public Health, Division of Environmental Health Sciences, Amherst, Massachusetts 01003

Persistent organic pollutants (POPs) are lipophilic compounds that travel with lipids and accumulate mainly in
adipose tissue. Recenthumanevidence 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 doseresponse curvesamonghumanstudies 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.