Evaluation of the Association Between Arsenic and Diabetes

A National Toxicology Program Workshop Review

Elizabeth A. Maull; Habibul Ahsan; Joshua Edwards; Matthew P. Longnecker; Ana Navas-Acien; Jingbo Pi; Ellen K. Silbergeld; Miroslav Styblo; Chin-Hsiao Tseng; Kristina A. Thayer; Dana Loomis

Disclosures

Environ Health Perspect. 2012;120(12):1658-1670. 

In This Article

Abstract and Introduction

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.

Introduction

Diabetes, both type 1 and type 2 (T2D), is a major threat to public health in the United States and abroad [Centers for Disease Control and Prevention (CDC) 2011; Danaei et al. 2011; World Health Organization (WHO) 2011]. Based on data from the 2005–2008 National Health and Nutrition Examination Survey (NHANES), approximately 25.6 million, or 11.3%, of all persons in the United States ≥ 20 years of age have diagnosed or undiagnosed diabetes, resulting in estimated direct medical costs and indirect costs (disability, work loss, premature death) of $174 billion in 2007 alone (CDC 2011). Another 35% of persons ≥ 20 years of age are prediabetic (American Diabetes Association 2011; Knowler et al. 2002). Diabetes is now being diagnosed in individuals earlier in life [National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) 2011]. Although approximately 70% of T2D is attributed to being overweight or obese (Eyre et al. 2004), 30% of T2D cases are not attributable to obesity. Given the number of persons impacted by T2D—346 million worldwide (WHO 2011)—and its long-term consequences in terms of morbidity, mortality, and economic costs, there is considerable interest in understanding the contribution of nontraditional risk factors to the diabetes epidemic, including environmental chemicals.

Research addressing the role of environmental chemicals in diabetes manifestation has rapidly expanded. The February 2011 Diabetes Strategic Plan (NIDDK 2011) acknowledged the need to understand the role of environmental exposures as part of future research and prevention strategies. To help develop such a research strategy, the National Institute of Environmental Health Sciences/National Toxicology Program (NIEHS/NTP) organized a state-of-the-science workshop in January 2011 entitled Role of Environmental Chemicals in the Development of Diabetes and Obesity (NTP 2011b). The objective of this workshop was to assess the literature for evidence of associations between diabetes and/or obesity with chemicals, including arsenic, persistent organic pollutants, maternal smoking during pregnancy, bisphenol A, phthalates and organotins, and nonpersistent pesticides (Thayer et al. 2012). This report is derived from discussions on arsenic that occurred at the workshop.

The arsenic evaluation focused on diabetes only, as studies have not assessed obesity as a primary health outcome. Our review focused on the a) consistency, strength/weaknesses, and biological plausibility of findings, b) identification of the most useful and relevant end points in experimental animals and mechanistic studies, and c) identification of data gaps and areas for future evaluation/research.

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