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Endocrine-Disrupting Chemicals

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Endocrine-Disrupting Chemicals Diabetes Care 1 Daniel Ruiz,1 Marisol Becerra,2 Disparities in Environmental Jyotsna S. Jagai,3 Kerry Ard,2 and Exposures to Endocrine- Robert M. Sargis4 Disrupting Chemicals and Diabetes Risk in Vulnerable Populations https://doi.org/10.2337/dc16-2765 Burgeoning epidemiological, animal, and cellular data link environmental endocrine- disrupting chemicals (EDCs) to metabolic dysfunction. Disproportionate exposure to diabetes-associated EDCs may be an underappreciated contributor to disparities in metabolic disease risk. The burden of diabetes is not uniformly borne by American society; rather, this disease disproportionately affects certain populations, including African Americans, Latinos, and low-income individuals. The purpose of this study was to review the evidence linking unequal exposures to EDCs with racial, ethnic, and socioeconomic diabetes disparities in the U.S.; discuss social forces promoting these disparities; and explore potential interventions. Articles examining the links between chemical exposures and metabolic disease were extracted from the U.S. National REVIEW Library of Medicine for the period of 1966 to 3 December 2016. EDCs associated with diabetes in the literature were then searched for evidence of racial, ethnic, and socioeconomic exposure disparities. Among Latinos, African Americans, and low- income individuals, numerous studies have reported significantly higher exposures to diabetogenic EDCs, including polychlorinated biphenyls, organochlorine pesti- cides, multiple chemical constituents of air pollution, bisphenol A, and phthalates. This review reveals that unequal exposure to EDCs may be a novel contributor to 1Committee on Molecular Metabolism and Nu- diabetes disparities. Efforts to reduce the individual and societal burden of diabetes trition, University of Chicago, Chicago, IL should include educating clinicians on environmental exposures that may increase 2College of Food, Agriculture and Environmental disease risk, strategies to reduce those exposures, and social policies to address Sciences, School of Environment and Natural Re- sources, Ohio State University, Columbus, OH environmental inequality as a novel source of diabetes disparities. 3Environmental and Occupational Health Sci- ences Division, School of Public Health, Univer- sity of Illinois at Chicago, Chicago, IL Diabetes is a complex and devastating metabolic disease that arises from impairments 4 in insulin production and/or action with consequential derangements in global energy Division of Endocrinology, Diabetes, and Me- tabolism, Department of Medicine, University metabolism. In the U.S., diabetes is the leading cause of adult blindness, kidney failure, of Illinois at Chicago, Chicago, IL and nontraumatic amputations; moreover, it is a central driver of cardiovascular dis- Corresponding author: Robert M. Sargis, rsargis@ ease, the leading cause of death among people with diabetes. Diabetes disproportion- uic.edu. ately afflicts African Americans, Latinos, and low-income individuals. Compared with Received 27 December 2016 and accepted 23 non-Hispanic whites, the risk of developing diabetes is estimated to be 66% higher for September 2017. Hispanics and 77% higher for African Americans (1). Indeed, 17.9% of African Americans This article contains Supplementary Data online and 20.5% of Mexican Americans have diabetes compared with only 9.1% of non- at http://care.diabetesjournals.org/lookup/ Hispanic whites, and these disparities in diabetes prevalence have been amplified suppl/doi:10.2337/dc16-2765/-/DC1. over the past decade (2). Furthermore, age-adjusted diabetes mortality rates are © 2017 by the American Diabetes Association. significantly higher among Hispanics and non-Hispanic blacks than non-Hispanic whites Readers may use this article as long as the work is properly cited, the use is educational and not (3). Understanding the complete array of factors that contribute to racial and ethnic for profit, and the work is not altered. More infor- differences in the pathogenesis of metabolic disease is critical for addressing the mation is available at http://www.diabetesjournals disproportionate burden of diabetes in communities of color. .org/content/license. Diabetes Care Publish Ahead of Print, published online November 15, 2017 2 Environmental Inequality and Diabetes Risk Diabetes Care Although physical inactivity and caloric various chemical constituents of air pol- the hypothesis that PCBs are metabolic excess undoubtedly are risk factors, lution, bisphenol A (BPA), and phtha- disease risk factors. For example, residen- emerging evidence implicates environ- lates (Table 1); moreover, exposure to tial proximity to PCB-contaminated waste mental endocrine-disrupting chemicals these EDCs is higher among African Amer- sites is associated with higher diabetes (EDCs) as contributors to the diabetes ep- icans, Latinos, and low-income individuals hospitalization rates (46). Among female idemic. The Endocrine Society defines an (Supplementary Table 1). These unequal residents of Anniston, serum PCB levels EDC as an exogenous chemical or mixture exposures raise the possibility that EDCs were significantly associated with diabe- of chemicals that interferes with any as- are underappreciated contributors to di- tes (47), whereas in a separate study pect of hormone action (4). Of note, the abetes disparities. with 25 years of follow-up, women with dramatic rise in U.S. diabetes rates corre- higher PCB levels exhibited increased di- lates closely with synthetic chemical pro- PCBs abetes incidence (incidence density ratio duction (5), and these associations are Introduced in the U.S. in the 1930s for a 2.33 [95% CI 1.25–4.34]) (10). Similarly, now supported by epidemiological, ani- variety of industrial purposes, PCBs are women exposed to PCB-laced rice bran mal, and cellular data that demonstrate a class of synthetic compounds where oil during the Yucheng poisoning event that EDCs can interfere with insulin secre- various combinations of hydrogen atoms in Taiwan also had an increased risk tion and action as well as with other path- on the biphenyl (C12H10) structure are of developing diabetes (odds ratio [OR] ways that regulate glucose homeostasis. substituted with chlorine, resulting in 2.1 [95% CI 1.1–4.5]), with markedly Despite a history of environmental pollu- 209 congeners designated by a unique higher risk among those who developed tion disproportionately affecting commu- number reflecting the extent and position chloracne, a cutaneous manifestation of nities of color in the U.S. (6), the potential of their chlorination (e.g., PCB 153). Al- dioxin-like PCB exposure (OR 5.5 [95% CI contribution of environmental toxicants though banned by the U.S. Environmental 2.1–13.4]) (11). A meta-analysis that to racial and ethnic differences in diabe- Protection Agency in 1977, PCBs remain pooled data from the Nurses’ Health tes risk is underappreciated. detectable in human tissues as a result Study (NHS) with six prospective studies The issue of environmental injustice of their environmental and biologi- showed that total PCBs were associated first entered widespread consciousness in cal persistence (37). Higher PCB expo- with incident diabetes (OR 1.70 [95% CI 1982 when residents of the predomi- sures among African Americans have 1.28–2.27]) (13). Further supporting nantly African American community of been documented since the 1960s (38) these prospective links between PCB ex- Warren County, North Carolina, made (Supplementary Table 1). Ongoing human posure and diabetes are data from cohort national news by laying themselves across exposure to PCBs is due to the legacy of studies, including the Prospective Investi- a rural road to prevent encroaching trucks contamination in food, including certain gation of the Vasculature in Uppsala Se- from dumping dirt laden with polychlori- fish (39); however, additional exposure niors (PIVUS) (16) and a group followed nated biphenyls (PCBs) in their community sources include leaching from contami- for nearly 20 years (15). Finally, although (6). This media attention prompted em- nated industrial sites and indoor con- not reaching statistical significance, a pirical examination of the community’s struction materials (40,41). PCB waste is study of Swedish women suggested that claim that toxic waste facilities were being found in Superfund and toxic waste sites higher levels of PCB 153 were similarly disproportionately sited in low-income that are concentrated in neighborhoods associated with increased rates of type 2 communities and communities of color. of color (6). Although catfish consump- diabetes diagnosed after .6 years of This research has grown substantially tion has been suggested as the main con- follow-up (OR 1.6 [95% CI 0.61–4.0]) (14). since the 1980s, with the majority of evi- tributor to increased PCB levels in African Collectively, these data suggest an associ- dence showing racial and socioeconomic Americans (42), the historical siting of ation between PCBs and diabetes risk, es- disparities in exposures to myriad environ- PCB production and disposal sites in pre- pecially among women; however, some mental hazards (6). In addition to higher dominantly black communities is likely a discrepant findings exist in the literature. exposure to air pollution nationwide (7), significant additional contributor to in- In a study of Great Lakes sport fish con- unequal exposures among people of color creased contamination of locally sourced sumers, PCB 118 and total PCBs were not are also rooted in patterns
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