Associations between arsenic species in exfoliated urothelial cells and prevalence of diabetes among residents of Chihuahua, Mexico

Abstract

Background: A growing number of studies link chronic exposure to inorganic arsenic (iAs) with the risk of diabetes. Many of these studies assessed iAs exposure by measuring arsenic (As) species in urine. However, this approach has been criticized because of uncertainties associated with renal function and urine dilution in diabetic individuals.

Objectives: Our goal was to examine associations between the prevalence of diabetes and concentrations of As species in exfoliated urothelial cells (EUC) as an alternative to the measures of As in urine.

Methods: We measured concentrations of trivalent and pentavalent iAs methyl-As (MAs) and dimethyl-As (DMAs) species in EUC from 374 residents of Chihuahua, Mexico, who were exposed to iAs in drinking water. We used fasting plasma glucose, glucose tolerance tests, and self-reported diabetes diagnoses or medication to identify diabetic participants. Associations between As species in EUC and diabetes were estimated using logistic and linear regression, adjusting for age, sex, and body mass index.

Results: Interquartile-range increases in trivalent, but not pentavalent, As species in EUC were positively and significantly associated with diabetes, with ORs of 1.57 (95% CI: 1.19, 2.07) for iAsIII, 1.63 (1.24, 2.15) for MAsIII, and 1.31 (0.96, 1.84) for DMAsIII. DMAs/MAs and DMAs/iAs ratios were negatively associated with diabetes (OR = 0.62; 95% CI: 0.47, 0.83 and OR = 0.72; 95% CI: 0.55, 0.96, respectively).

Conclusions: Our data suggest that uncertainties associated with measures of As species in urine may be avoided by using As species in EUC as markers of iAs exposure and metabolism. Our results provide additional support to previous findings suggesting that trivalent As species may be responsible for associations between diabetes and chronic iAs exposure.

Figure 1

The composition of As species in EUC and urine. Data shown are mean + SD (n = 374). *p < 0.05, based on one-way ANOVA.

Figure 2

Differences in the composition of As species in EUC (A) and urine (B) collected from male and female study participants. Data shown are mean + SD (n = 252 for women; n = 122 for men). *p < 0.05 based on one-way ANOVA with Bonferroni’s posttest.

Figure 3

Association of diabetes with As species in EUC. In model 1, diabetes was classified by either FPG ≥ 126 mg/dL, 2HPG ≥ 200 mg/dL, or self-report of doctor diagnosis or use of medication for treatment of diabetes; in model 2, diabetes was classified only by FPG ≥ 126 mg/dL or 2HPG ≥ 200 mg/dL. ORs (95% CIs) are standardized to an increment of 1 IQR and adjusted for age, sex, and BMI. IQRs for each As species and species ratio are shown in Table 2. See Supplemental Material, Table S3, for numeric data. *p < 0.05.

Figure 4

Association of diabetes with As species in urine, urine creatinine, and specific gravity. Arsenic species are either unadjusted (A) or adjusted for creatinine (B) or specific gravity (C). In model 1, diabetes was classified by either FPG ≥ 126 mg/dL, 2HPG ≥ 200 mg/dL, or self-report of doctor diagnosis or use of medication for treatment of diabetes; in model 2, diabetes was classified only by FPG ≥ 126 mg/dL or 2HPG ≥ 200 mg/dL. ORs (95% CIs) are standardized to an increment of 1 IQR and adjusted for age, sex, and BMI. IQRs for each As species and species ratio are indicated in Table 2. See Supplemental Material, Table S3, for numeric data. *p < 0.05.