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


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

In This Article

Identification of Relevant Studies

A PubMed (National Library of Medicine, Washington, DC, USA) search strategy, first conducted on 24 August 2009 and then run weekly until 15 December 2010, was developed to identify human, animal, and mechanistic studies (including in vitro assays) on arsenic exposures related to diabetes and obesity using MeSH (Medical Subject Headings)-based and keyword strategies [for search terms, see Supplemental Material, p. 2 (http://dx.doi.org/10.1289/ehp.1104579)]. A total of 108 publications were identified from the search, and 38 of those presented original data concerning both arsenic exposure and diabetes (or diabetes-related end points and/or mechanisms) and were considered relevant (see Supplemental Material, Figure S1). An additional 38 studies were identified during the course of the initial primary literature review and discussions with workshop participants, including two studies that had been submitted but not yet accepted for publication (Del Razo et al. 2011; Paul et al. 2011), for a total of 76 studies considered as the final primary literature. Two of these studies included more than one type of data, human and animal (Wang et al. 2009) or animal and in vitro (Yen et al. 2007).

One goal of the review was to assess the scientific literature using the descriptors "sufficient," "limited," or "insufficient" to classify existing evidence, with NTP definitions utilized for the NTP Report on Carcinogens as a framework for "sufficient" and "limited" (NTP 2011a). "Sufficient" evidence for human studies indicates a causal relationship between exposure to the agent, substance, or mixture and an outcome based on evidence of a dose–response and other characteristics such as consistency and coherence among different studies, adequate control for other covariates, biological plausibility, and adequate identification of sources of potential bias. "Limited" evidence indicates that causal interpretation is credible but that alternative explanations, such as chance, bias, or confounding factors could not adequately be excluded. The term "insufficient" is used when there is low confidence in the body of evidence to reach a conclusion on the association between exposure to a substance and health outcome(s) or when no data are available.

Epidemiological studies were classified as a) occupational studies; b) population-based studies in areas with relatively high environmental arsenic exposure (≥ 150 μg/L in drinking water); c) population-based studies in areas with lower arsenic exposure (< 150 μg/L in drinking water) excluding NHANES studies; and d) NHANES studies. The cut points used for drinking-water arsenic were selected to distinguish between high-exposure studies in areas with unusually high exposures via drinking water (e.g., in areas of Taiwan and Bangladesh) and low-to-moderate exposure studies.