Evaluation of the Association between Persistent Organic Pollutants (POPs) and Diabetes in Epidemiological Studies: A National Toxicology Program Workshop Review

Abstract

Background: Diabetes is a major threat to public health in the United States and worldwide. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health.Objective: We assessed the epidemiologic literature for evidence of associations between persistent organic pollutants (POPs) and type 2 diabetes.Methods: Using a PubMed search and reference lists from relevant studies or review articles, we identified 72 epidemiological studies that investigated associations of persistent organic pollutants (POPs) with diabetes. We evaluated these studies for consistency, strengths and weaknesses of study design (including power and statistical methods), clinical diagnosis, exposure assessment, study population characteristics, and identification of data gaps and areas for future research.Conclusions: Heterogeneity of the studies precluded conducting a meta-analysis, but the overall evidence is sufficient for a positive association of some organochlorine POPs with type 2 diabetes. Collectively, these data are not sufficient to establish causality. Initial data mining revealed that the strongest positive correlation of diabetes with POPs occurred with organochlorine compounds, such as trans-nonachlor, dichlorodiphenyldichloroethylene (DDE), polychlorinated biphenyls (PCBs), and dioxins and dioxin-like chemicals. There is less indication of an association between other nonorganochlorine POPs, such as perfluoroalkyl acids and brominated compounds, and type 2 diabetes. Experimental data are needed to confirm the causality of these POPs, which will shed new light on the pathogenesis of diabetes. This new information should be considered by governmental bodies involved in the regulation of environmental contaminants.

Dose-Dependent Metabolic Reprogramming and Differential Gene Expression in TCDD-Elicited Hepatic Fibrosis

“…In humans TCDD has a longer half-life which, in addition to lifetime exposure, sustains AhR activation and may be a potential link between metabolic disease and persistent environmental contaminant exposure (Taylor et al, 2013). However, as exposure duration increased glucose tolerance improved, contrary to expectations (Taylor et al, 2013). No changes in insulin levels were observed, consistent with a previous report (Takuma et al, 2015), suggesting insulin signaling is not responsible for improved tolerance.…”

“…In humans TCDD has a longer half-life which, in addition to lifetime exposure, sustains AhR activation and may be a potential link between metabolic disease and persistent environmental contaminant exposure (Taylor et al, 2013). However, as exposure duration increased glucose tolerance improved, contrary to expectations (Taylor et al, 2013).…”

From the Cover: Coagulation-Driven Hepatic Fibrosis Requires Protease Activated Receptor-1 (PAR-1) in a Mouse Model of TCDD-Elicited Steatohepatitis

“…Several factors, including genetics, diet, lifestyle, and age, have been implicated in the development of NAFLD and associated metabolic disorders including diabetes, dyslipidemia, and cardiovascular disease (Pitsavos et al, 2006;. Recent studies also suggest exposure to environmental contaminants including persistent organic pollutants and organochlorines contributes to metabolic disease development (Cave et al, 2010;Lee et al, 2006Lee et al, , 2007Taylor et al, 2013). For example,2,3,7,, the prototypical aryl hydrocarbon receptor (AhR) ligand, has been shown to contribute to the progression of NAFLD spectrum from simple, reversible steatosis, to steatohepatitis and early signs of fibrosis in mice (Kopec et al, 2013;Nault et al, 2015a;Pierre et al, 2014).…”

Persistent Organic Pollutants (POPs): A Primer for Practicing Clinicians

“…POPs may induce obesogenic effects and also induce a pro-inflammatory state that can lead to the metabolic syndrome and diabetes [29,32,33]. These effects may also be age/period of development specific [34].…”