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Exposure to Arsenic in Drinking Water Is Associated With Increased Prevalence of Diabetes: A Cross-Sectional Study in the Zimapán and Lagunera Regions in Mexico

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Exposure to Arsenic in Drinking Water Is Associated With Increased Prevalence of Diabetes: A Cross-Sectional Study in the Zimapán and Lagunera Regions in Mexico

Luz M Del Razo et al. Environ Health.

Abstract

Background: Human exposures to inorganic arsenic (iAs) have been linked to an increased risk of diabetes mellitus. Recent laboratory studies showed that methylated trivalent metabolites of iAs may play key roles in the diabetogenic effects of iAs. Our study examined associations between chronic exposure to iAs in drinking water, metabolism of iAs, and prevalence of diabetes in arsenicosis-endemic areas of Mexico.

Methods: We used fasting blood glucose (FBG), fasting plasma insulin (FPI), oral glucose tolerance test (OGTT), glycated hemoglobin (HbA1c), and insulin resistance (HOMA-IR) to characterize diabetic individuals. Arsenic levels in drinking water and urine were determined to estimate exposure to iAs. Urinary concentrations of iAs and its trivalent and pentavalent methylated metabolites were measured to assess iAs metabolism. Associations between diabetes and iAs exposure or urinary metabolites of iAs were estimated by logistic regression with adjustment for age, sex, hypertension and obesity.

Results: The prevalence of diabetes was positively associated with iAs in drinking water (OR 1.13 per 10 ppb, p < 0.01) and with the concentration of dimethylarsinite (DMAsIII) in urine (OR 1.24 per inter-quartile range, p = 0.05). Notably, FPI and HOMA-IR were negatively associated with iAs exposure (β -2.08 and -1.64, respectively, p < 0.01), suggesting that the mechanisms of iAs-induced diabetes differ from those underlying type-2 diabetes, which is typically characterized by insulin resistance.

Conclusions: Our study confirms a previously reported, but frequently questioned, association between exposure to iAs and diabetes, and is the first to link the risk of diabetes to the production of one of the most toxic metabolites of iAs, DMAsIII.

Figures

Figure 1
Figure 1
Effect of the storage time and temperature on DMAsIII oxidation in human urine. Spot urines from two subjects were spiked with iododimethylarsine (DMAsIIII) at final concentrations of 15 ppb As (a) or 100 ppb As (b). DMAsIII contents were determined in urines immediately after spiking (Control) and after 6 and 24 hours after spiking in urines stored either on ice (0°C) or in dry ice (-78°C). Mean ± SD are shown for n = 3.
Figure 2
Figure 2
Correlation between sums of As species in urines of eighteen Zimapán residents analyzed in both Cinvestav-IPN and in Universidad Juárez del Estado de Durango (UJED): R = 0.997, p < 0.01).
Figure 3
Figure 3
Correlations between logarithmically transformed concentrations of iAs in drinking water and tAs in urines collected from subjects in Zimapán and Lagunera: ● tAs in ng/mL (full line); ○ tAs in μg/mg of creatinine (dashed line).

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