We assessed the risk of T2D in people consuming arsenic contaminated drinking water in Bangladesh. The findings suggest an association between chronic arsenic exposure through drinking water and T2D. Risks are generally higher with longer duration of arsenic exposure. The risk of T2D is highest among those who were exposed to the highest concentration of arsenic (>250μg/L) for more than 10 years.
More females than males participated in this study. This is because data was collected during the morning when many of the males were out of the home for their daily work. The overall prevalence of T2D is higher in this study than that reported previously in rural Bangladesh [25
]. The prevalence of T2D is also higher in the low arsenic area of Kaligonj relative to rural areas of Bangladesh. This may be due to increased risk of T2D even at the lower concentration of inorganic arsenic in drinking water [15
Studies in Taiwan, Bangladesh, and Mexico have all shown an association between high levels of inorganic arsenic in drinking water and increased risk of T2D [5
]. These studies are limited by the use of ecologic measures of arsenic in drinking water rather than individual measurements of arsenic exposure through drinking water. Data from the studies in Taiwan and Bangladesh were pooled earlier in a meta-analysis [9
] that examined extreme arsenic exposure categories (village drinking water levels or living in a high-vs-low-arsenic area); the pooled relative risk for diabetes associated with high versus low arsenic areas was 2.52 (95% CI: 1.69 – 3.75).
Only a limited number of studies have examined the association of low or moderate exposure to inorganic arsenic with diabetes risk [29
]. An early ecological study in Utah, USA found no association between arsenic levels in drinking water and diabetes mortality after controlling for age and sex [30
]. A cross-sectional study in Wisconsin, USA that examined the association between arsenic in drinking water and nine self reported chronic diseases found that compared to those with an arsenic exposure <2μg/L, those exposed to 2μg/L -10μg/L and >10μg/L of arsenic in drinking water had an adjusted odds ratio of 1.35 (95% CI, 0.78-2.33) and 1.02 (95% CI, 0.49-2.15), respectively [29
]. Wang et al., in a previous study found that hair arsenic levels were associated with elevated plasma glucose levels and with the prevalence of the metabolic syndrome in 660 participants exposed to relatively low arsenic levels in drinking water in Taiwan [31
]. Chen JW et al in another study from Taiwan reported a two-fold increased risk of T2D among subjects with total urinary As (U-As) >75 μg/g creatinine as compared with individuals whose U-As was <
35 μg/g creatinine after adjustment for potential confounders [12
]. However, Chen Y et al observed no association between chronic arsenic exposure and diabetes mellitus in Bangladesh and they reported a prevalence of diabetes of 2.1%, low BMI (<20kg/m2) in 49% and exposure to <300μg/L of arsenic in 90% of the participants [14
]. On the other hand, our study reports diabetes in 9%, low BMI (<20kg/m2
) in 55% and exposure to <300μg/L of arsenic in 77% of the participants. The low prevalence of diabetes among arsenic exposed people in the Chen Y et al study might be due to the use of glycated hemoglobin (HbA1
C) and glucosuria to identify diabetic individuals, rather than fasting blood glucose and 2-hour blood glucose that were used to identify diabetics in another study [28
]. Inaccuracies in BMI determination may have contributed to an underestimation of association with T2D risk in our study. Despite the participants in this study might not be representative to the general population; however the participants staying at home were more appropriate for the study, as their exposure to arsenic concentration was determined from the well water they had been consuming.
The mechanism by which arsenic causes T2D is still largely undefined.
Animal model experimentation suggests that arsenic impairs pancreatic β cell function, particularly affecting insulin synthesis and secretion [32
]. The molecular mechanism for this effect may be via adverse effects on insulin signal transduction and the inhibition of gene transcription factors [34
]. A few non-specific mechanisms such as oxidative stress, inflammation or apoptosis may also increase the risk of developing diabetes [32
Important strengths of this study include the use of a large population sample, the direct measurement of arsenic in the subjects’ drinking water, and the adjustment for relevant diabetes risk factors such as age, sex, education, body mass index (BMI) and family history of diabetes. While the public health and research implications of this study are important, some caveats must also be considered. One limitation of this study is that biomarkers of arsenic exposure were not measured. Also, we excluded people with chronic medical conditions which may be related to arsenic exposure, although this would tend to bias towards the null and therefore indicates robustness of our results.
Other limitations include the use of a glucometer to measure fasting glucose as this may give inaccurate results. Validity of this glucometer has not been tested earlier. Therefore, there may be misclassification of T2D. Use of field screening tests to diagnose T2D in relation to explore association with chronic arsenic exposure has been a concern. A few previous studies reported an association between T2D and chronic arsenic exposure using field screening tests such as glucometer for blood, and glucometric strips for glucosuria [28
]. Laboratory facilities are still rare or unavailable in rural Bangladesh and portable blood glucose devices are suggested for screening rather than diagnosis for diabetes mellitus [38
]. Nevertheless, interviewers were unaware of the arsenic concentration levels of the subjects’ usual drinking water. Therefore, this misclassification is likely to be non-differential, and hence may underestimate the risk. It would also have been desirable to have directly measured individual exposure data over time, as the available water samples reflected only a particular point in time and not the historical exposure. In the absence of any reliable information on past exposure, it was essential to assume that arsenic concentrations from the tube wells had been relatively constant over time. The historical consistency of arsenic concentration is of particular concern with shallow ground water, which might be subject to greater fluctuation than water from a deeper well. However, we assume that any fluctuation of arsenic concentrations is likely to affect the study participants equally. Duration of tube well water use was also obtained from the participants. In the absence of any good documentation of water use, we had to rely on the individual’s recall. The study is cross-sectional and temporality between drinking water arsenic and development of T2D cannot be ensured. Prospective epidemiologic studies in populations exposed to a wide range of inorganic arsenic are needed to confirm this association.
Also many other factors need to be considered in any population studies as diabetes risk increases with age, obesity and individual’s physical activity [39
]. Another limitation in this study is that we did not adjust for physical activity. However, we adjusted for obesity in the final model. Furthermore, obesity and physical activity would not be an issue in the rural population in Bangladesh as obesity is much lower [40
] and physical activity may be higher in this context.