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      Evaluation of the Association between Arsenic and Diabetes: A National Toxicology Program Workshop Review

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          Abstract

          Background: Diabetes affects an estimated 346 million persons globally, and total deaths from diabetes are projected to increase > 50% in the next decade. Understanding the role of environmental chemicals in the development or progression of diabetes is an emerging issue in environmental health. In 2011, the National Toxicology Program (NTP) organized a workshop to assess the literature for evidence of associations between certain chemicals, including inorganic arsenic, and diabetes and/or obesity to help develop a focused research agenda. This review is derived from discussions at that workshop.

          Objectives: Our objectives were to assess the consistency, strength/weaknesses, and biological plausibility of findings in the scientific literature regarding arsenic and diabetes and to identify data gaps and areas for future evaluation or research. The extent of the existing literature was insufficient to consider obesity as an outcome.

          Data Sources, Extraction, and Synthesis: Studies related to arsenic and diabetes or obesity were identified through PubMed and supplemented with relevant studies identified by reviewing the reference lists in the primary literature or review articles.

          Conclusions: Existing human data provide limited to sufficient support for an association between arsenic and diabetes in populations with relatively high exposure levels (≥ 150 µg arsenic/L in drinking water). The evidence is insufficient to conclude that arsenic is associated with diabetes in lower exposure (< 150 µg arsenic/L drinking water), although recent studies with better measures of outcome and exposure support an association. The animal literature as a whole was inconclusive; however, studies using better measures of diabetes-relevant end points support a link between arsenic and diabetes.

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          Most cited references134

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          Quantifying biases in causal models: classical confounding vs collider-stratification bias.

          It has long been known that stratifying on variables affected by the study exposure can create selection bias. More recently it has been shown that stratifying on a variable that precedes exposure and disease can induce confounding, even if there is no confounding in the unstratified (crude) estimate. This paper examines the relative magnitudes of these biases under some simple causal models in which the stratification variable is graphically depicted as a collider (a variable directly affected by two or more other variables in the graph). The results suggest that bias from stratifying on variables affected by exposure and disease may often be comparable in size with bias from classical confounding (bias from failing to stratify on a common cause of exposure and disease), whereas other biases from collider stratification may tend to be much smaller.
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            Scientific Opinion on Arsenic in Food

            (2009)
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              Role of Environmental Chemicals in Diabetes and Obesity: A National Toxicology Program Workshop Review

              Background: There has been increasing interest in the concept that exposures to environmental chemicals may be contributing factors to the epidemics of diabetes and obesity. On 11–13 January 2011, the National Institute of Environmental Health Sciences (NIEHS) Division of the National Toxicology Program (NTP) organized a workshop to evaluate the current state of the science on these topics of increasing public health concern. Objective: The main objective of the workshop was to develop recommendations for a research agenda after completing a critical analysis of the literature for humans and experimental animals exposed to certain environmental chemicals. The environmental exposures considered at the workshop were arsenic, persistent organic pollutants, maternal smoking/nicotine, organotins, phthalates, bisphenol A, and pesticides. High-throughput screening data from Toxicology in the 21st Century (Tox21) were also considered as a way to evaluate potential cellular pathways and generate -hypotheses for testing which and how certain chemicals might perturb biological processes related to diabetes and obesity. Conclusions: Overall, the review of the existing literature identified linkages between several of the environmental exposures and type 2 diabetes. There was also support for the “developmental obesogen” hypothesis, which suggests that chemical exposures may increase the risk of obesity by altering the differentiation of adipocytes or the development of neural circuits that regulate feeding behavior. The effects may be most apparent when the developmental exposure is combined with consumption of a high-calorie, high-carbohydrate, or high-fat diet later in life. Research on environmental chemical exposures and type 1 diabetes was very limited. This lack of research was considered a critical data gap. In this workshop review, we outline the major themes that emerged from the workshop and discuss activities that NIEHS/NTP is undertaking to address research recommendations. This review also serves as an introduction to an upcoming series of articles that review the literature regarding specific exposures and outcomes in more detail.
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                Author and article information

                Journal
                Environ Health Perspect
                Environ. Health Perspect
                EHP
                Environmental Health Perspectives
                National Institute of Environmental Health Sciences
                0091-6765
                1552-9924
                10 August 2012
                December 2012
                : 120
                : 12
                : 1658-1670
                Affiliations
                [1 ]Biomolecular Screening Branch, Division of the National Toxicology Program, National Institute of Environmental Sciences (NIEHS), National Institutes of Health (NIH), Department of Health and Human Services (DHHS), Research Triangle Park, North Carolina, USA
                [2 ]Departments of Health Studies, Medicine, and Human Genetics, University of Chicago Cancer Research Center, Chicago, Illinois, USA
                [3 ]Department of Pharmacology, Midwestern University, Downers Grove, Illinois, USA
                [4 ]Epidemiology Branch, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA
                [5 ]Department of Environmental Health Sciences, and
                [6 ]Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA
                [7 ]Institute for Chemical Safety Sciences, The Hamner Institutes for Health Sciences, Research Triangle Park, North Carolina, USA
                [8 ]Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA
                [9 ]National Taiwan University College of Medicine, Taipei, Taiwan
                [10 ]Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
                [11 ]Office of Health Assessment and Translation, Division of the National Toxicology Program, NIEHS, NIH, DHHS, Research Triangle Park, North Carolina, USA
                [12 ]Department of Epidemiology, University of Nebraska Medical Center College of Public Health, Omaha, Nebraska, USA
                Author notes
                Address correspondence to D. Loomis, Department of Epidemiology, University of Nebraska Medical Center, 984395 Nebraska Medical Center, Omaha, NE 68198-4395 USA. Telephone: (402) 559-3976. Fax: (402) 552-3683. E-mail: dana.loomis@ 123456unmc.edu

                This review is based on deliberations that occurred at an 11–13 January 2011 workshop [Role of Environmental Chemicals in the Development of Diabetes and Obesity ( http://ntp.niehs.nih.gov/go/36433)] sponsored by the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP), U.S. Environmental Protection Agency (EPA), and the Food and Drug Administration National Center for Toxicological Research (FDA/NCTR). D. Loomis served as chair and E. Maull served as rapporteur for the arsenic breakout group. Other members of the arsenic breakout group included H. Ahsan, G. Cooper, J. Edwards, M.P. Longnecker, A. Navas-Acien, J. Pi, E. Silbergeld, M. Styblo, and C.-H. Tseng. K. Thayer was the primary author of the background literature review document prepared prior to the workshop.

                Article
                ehp.1104579
                10.1289/ehp.1104579
                3548281
                22889723
                05ec048d-9a6a-443c-8c62-a162d9cce2c4
                Copyright @ 2012

                This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, properly cited.

                History
                : 04 October 2011
                : 10 August 2012
                Categories
                Review

                Public health
                animal,arsenic toxicity,cell line,chemically induced/epidemiology,cultured cell,diabetes,environmental epidemiology,glucose,insulin,metabolism,obesity

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