Chlorinated persistent organic pollutants, obesity, and type 2 diabetes.
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.
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.
Duk-Hee
DH
Lee
Miquel
M
Porta
David R
DR
Jacobs
Laura N
LN
Vandenberg
D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D004195:Disease Models, Animal; D004785:Environmental Pollutants / Q000009:adverse effects*; D006801:Humans; D006843:Hydrocarbons, Chlorinated / Q000009:adverse effects; D009765:Obesity / Q000453:epidemiology* / Q000209:etiology / Q000503:physiopathology; D009930:Organic Chemicals / Q000009:adverse effects*; D010575:Pesticides / Q000009:adverse effects; D011078:Polychlorinated Biphenyls / Q000009:adverse effects; D012307:Risk Factors
D004785:Environmental Pollutants; D006843:Hydrocarbons, Chlorinated; D009930:Organic Chemicals; D010575:Pesticides; D011078:Polychlorinated Biphenyls