Arsenic in Drinking Water and Diabetes Incidence
Background: Established causes of diabetes do not fully explain the present epidemic. High-level arsenic exposure has been implicated in diabetes risk, but the effect of low-level arsenic exposure in drinking water remains unclear.
Objective: We sought to determine whether long-term exposure to low-level arsenic in drinking water in Denmark is associated with an increased risk of diabetes using a large prospective cohort.
Methods: During 1993–1997, we recruited 57,053 persons. We followed each cohort member for diabetes occurrence from enrollment until 31 December 2006. We traced and geocoded residential addresses of the cohort members and used a geographic information system to link addresses with water-supply areas. We estimated individual exposure to arsenic using all addresses from 1 January 1971 until the censoring date. Cox proportional hazards models were used to model the association between arsenic exposure and diabetes incidence, separately for two definitions of diabetes: all cases and a more strict definition in which cases of diabetes based solely on blood glucose results were excluded.
Results: Over a mean follow-up period of 9.7 years for 52,931 eligible participants, there were a total of 4,304 (8.1%) diabetes cases, and 3,035 (5.8%) cases of diabetes based on the more strict definition. The adjusted incidence rate ratios (IRRs) per 1-μg/L increment in arsenic levels in drinking water were as follows: IRR = 1.03 (95% CI: 1.01, 1.06) and IRR = 1.02 (95% CI: 0.99, 1.05) for all and strict diabetes cases, respectively.
Conclusions: Long-term exposure to low-level arsenic in drinking water may contribute to the development of diabetes.
The prevalence and incidence of diabetes is rapidly increasing in all countries, including Denmark, presenting a major public health threat [Carstensen et al. 2008; Danaei et al. 2011; World Health Organization (WHO) 2011]. Established risk factors are mainly related to lifestyle and include older populations, obesity, and physical inactivity and are in part related to a family history of diabetes and genetic polymorphisms. However, these factors do not fully explain the present diabetes epidemic. Given that almost 400 million persons had diagnosed diabetes worldwide in 2008 (Danaei et al. 2011; WHO 2011) and the severe, long-term consequences of this disease in terms of morbidity, mortality, and economic costs, there is an increased need to understand the effects of nontraditional risk factors such as environmental chemicals.
Arsenic occurs in both organic and inorganic environmental forms (Eyre et al. 2004; Mandal and Suzuki 2002). Organic arsenic is found primarily in food, whereas inorganic arsenic is mostly found in aquifers (Eyre et al. 2004; Mandal and Suzuki 2002) where it accumulates by natural processes such as weathering and erosion (Smedley 2008). Globally, exposure to inorganic arsenic via groundwater used for drinking is associated with most health risks (Smedley and Kinniburg 2005). In Denmark, all drinking water from tap water is derived from groundwater (Dansk Vand og Spildevandsforening 2010); this tap water is very clean and not chlorinated and is bottled-water quality at the tap (Thomsen et al. 2004). It is the standard in Denmark to use tap water for cooking, coffee, tea, and drinking. Thus, the consequences of a possible relationship between low-level groundwater arsenic exposure and population health are serious.
Arsenic exposure has been implicated in the diabetes epidemic. Mechanisms remain unclear, but based on in vitrostudies, they are thought to include the disruption of several pathways related to pancreatic β-cell function and insulin sensitivity, including oxidative stress, glucose uptake and transport, gluconeogenesis, adipocyte differentiation, and calcium ion signaling (Díaz-Villaseñor et al. 2007; Druwe and Vaillancourt 2010; Tseng 2004). Two recent systematic reviews and a meta-analysis of epidemiological studies addressing the association between arsenic exposure in drinking water and diabetes risk have concluded that the positive association of diabetes with high-level inorganic arsenic exposure was consistent but also that the evidence regarding low-level exposure, defined as < 50 ppb (equivalent to 50 μg/L), remains unclear and that a threshold might exist (Maull et al. 2012; Navas-Acien et al. 2006; Wang et al. 2013). The role of low-level arsenic in diabetes risk needs to be elucidated, and the need for future research including large prospective studies in areas of low arsenic exposure using individual arsenic exposures has been recommended (Maull et al. 2012).
The Danish Diet, Cancer and Health (DCH) cohort is a large prospective study, with detailed information on potential confounders collected at baseline, and the Danish National Diabetes Register (NDR) (Carstensen et al. 2008, 2011) allows for the objective ascertainment of diabetes on a national scale. By combining geocoded past and present residential addresses of cohort participants—obtained from the Danish Civil Registration System (CRS) (Pedersen 2011)—with geographic information on water supply areas, the estimation of individual arsenic exposure of all cohort participants was made possible.
The purpose of this large population-based prospective study was to determine whether individual long-term exposure to low-level inorganic arsenic in drinking water is associated with an increased risk of diabetes.
Abstract and Introduction
Abstract
Background: Established causes of diabetes do not fully explain the present epidemic. High-level arsenic exposure has been implicated in diabetes risk, but the effect of low-level arsenic exposure in drinking water remains unclear.
Objective: We sought to determine whether long-term exposure to low-level arsenic in drinking water in Denmark is associated with an increased risk of diabetes using a large prospective cohort.
Methods: During 1993–1997, we recruited 57,053 persons. We followed each cohort member for diabetes occurrence from enrollment until 31 December 2006. We traced and geocoded residential addresses of the cohort members and used a geographic information system to link addresses with water-supply areas. We estimated individual exposure to arsenic using all addresses from 1 January 1971 until the censoring date. Cox proportional hazards models were used to model the association between arsenic exposure and diabetes incidence, separately for two definitions of diabetes: all cases and a more strict definition in which cases of diabetes based solely on blood glucose results were excluded.
Results: Over a mean follow-up period of 9.7 years for 52,931 eligible participants, there were a total of 4,304 (8.1%) diabetes cases, and 3,035 (5.8%) cases of diabetes based on the more strict definition. The adjusted incidence rate ratios (IRRs) per 1-μg/L increment in arsenic levels in drinking water were as follows: IRR = 1.03 (95% CI: 1.01, 1.06) and IRR = 1.02 (95% CI: 0.99, 1.05) for all and strict diabetes cases, respectively.
Conclusions: Long-term exposure to low-level arsenic in drinking water may contribute to the development of diabetes.
Introduction
The prevalence and incidence of diabetes is rapidly increasing in all countries, including Denmark, presenting a major public health threat [Carstensen et al. 2008; Danaei et al. 2011; World Health Organization (WHO) 2011]. Established risk factors are mainly related to lifestyle and include older populations, obesity, and physical inactivity and are in part related to a family history of diabetes and genetic polymorphisms. However, these factors do not fully explain the present diabetes epidemic. Given that almost 400 million persons had diagnosed diabetes worldwide in 2008 (Danaei et al. 2011; WHO 2011) and the severe, long-term consequences of this disease in terms of morbidity, mortality, and economic costs, there is an increased need to understand the effects of nontraditional risk factors such as environmental chemicals.
Arsenic occurs in both organic and inorganic environmental forms (Eyre et al. 2004; Mandal and Suzuki 2002). Organic arsenic is found primarily in food, whereas inorganic arsenic is mostly found in aquifers (Eyre et al. 2004; Mandal and Suzuki 2002) where it accumulates by natural processes such as weathering and erosion (Smedley 2008). Globally, exposure to inorganic arsenic via groundwater used for drinking is associated with most health risks (Smedley and Kinniburg 2005). In Denmark, all drinking water from tap water is derived from groundwater (Dansk Vand og Spildevandsforening 2010); this tap water is very clean and not chlorinated and is bottled-water quality at the tap (Thomsen et al. 2004). It is the standard in Denmark to use tap water for cooking, coffee, tea, and drinking. Thus, the consequences of a possible relationship between low-level groundwater arsenic exposure and population health are serious.
Arsenic exposure has been implicated in the diabetes epidemic. Mechanisms remain unclear, but based on in vitrostudies, they are thought to include the disruption of several pathways related to pancreatic β-cell function and insulin sensitivity, including oxidative stress, glucose uptake and transport, gluconeogenesis, adipocyte differentiation, and calcium ion signaling (Díaz-Villaseñor et al. 2007; Druwe and Vaillancourt 2010; Tseng 2004). Two recent systematic reviews and a meta-analysis of epidemiological studies addressing the association between arsenic exposure in drinking water and diabetes risk have concluded that the positive association of diabetes with high-level inorganic arsenic exposure was consistent but also that the evidence regarding low-level exposure, defined as < 50 ppb (equivalent to 50 μg/L), remains unclear and that a threshold might exist (Maull et al. 2012; Navas-Acien et al. 2006; Wang et al. 2013). The role of low-level arsenic in diabetes risk needs to be elucidated, and the need for future research including large prospective studies in areas of low arsenic exposure using individual arsenic exposures has been recommended (Maull et al. 2012).
The Danish Diet, Cancer and Health (DCH) cohort is a large prospective study, with detailed information on potential confounders collected at baseline, and the Danish National Diabetes Register (NDR) (Carstensen et al. 2008, 2011) allows for the objective ascertainment of diabetes on a national scale. By combining geocoded past and present residential addresses of cohort participants—obtained from the Danish Civil Registration System (CRS) (Pedersen 2011)—with geographic information on water supply areas, the estimation of individual arsenic exposure of all cohort participants was made possible.
The purpose of this large population-based prospective study was to determine whether individual long-term exposure to low-level inorganic arsenic in drinking water is associated with an increased risk of diabetes.
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