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Arsenic Exposure and Diabetes Mellitus in the United States

Chin-Hsiao Tseng, MD, PhD
JAMA. 2008;300(23):2728-2729. doi:10.1001/jama.2008.812
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To the Editor: Dr Navas-Acien and colleagues1 extended the observation of a diabetogenic effect of arsenic exposure from drinking water containing arsenic levels greater than 100 μg/L in Taiwan, Bangladesh, and Mexico to a fairly low exposure of approximately 0.1 μg/kg per day in the United States. This low exposure dosage is approximately 55 times lower than that observed in the arseniasis-endemic areas (assuming that a 55-kg adult drinks 3 L of water containing an arsenic level of 100 μg/L per day). The odds ratios comparing the 80th vs the 20th percentile of total urine levels of arsenic and the trend test for the tertile stratification were significant only in the models considering seafood intake (ie, with additional adjustment for arsenobetaine and blood mercury levels).

In addition to the limitations discussed by the authors, the study did not adjust for family history of diabetes, which is a strong risk factor for diabetes. It also did not consider the potential confounding of the use of hormone therapy and vitamin supplements. Estrogen2 and folate3 play important roles in the metabolism of arsenic. Furthermore, the source, forms, route, and duration of arsenic exposure were not clear in the study; therefore, urine arsenic levels might not be good surrogate markers for dosage of arsenic exposure.

There appears to be a link between an individual's methylation capacity and arsenic-related skin lesions, skin cancer, bladder cancer, and peripheral vascular disease or hypertension in persons living in arseniasis-endemic areas4 as well as those living far away from the endemic areas and with low exposure.5 Therefore, it would be interesting to know whether the methylation capacity, which can be expressed by the proportion dimethylarsinate level/total arsenic level or dimethylarsinate level/(total arsenic level − arsenobetaine level), was a risk factor for diabetes, even though total urine arsenic levels did not show significant association in some models and the evaluation for the association with levels of urine arsenite, arsenate, or methylarsonate was not feasible due to the detection limits of the assay. These additional analyses might strengthen the hypothesis of a diabetogenic effect of low-dose arsenic if consistent results were seen.

AUTHOR INFORMATION

Financial Disclosures: None reported.

REFERENCES

Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E. Arsenic exposure and prevalence of type 2 diabetes in US adults.  JAMA. 2008;300(7):814-822
PubMedCrossRef
Cohen SM, Arnold LL, Eldan M, Lewis AS, Beck BD. Methylated arsenicals: the implications of metabolism and carcinogenicity studies in rodents to human risk assessment.  Crit Rev Toxicol. 2006;36(2):99-133
PubMedCrossRef
Gamble MV, Liu X, Slavkovich V,  et al.  Folic acid supplementation lowers blood arsenic.  Am J Clin Nutr. 2007;86(4):1202-1209
PubMed
Tseng CH. Arsenic methylation, urinary arsenic metabolites and human diseases: current perspective.  J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2007;25(1):1-22
PubMed
Pu YS, Yang SM, Huang YK,  et al.  Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure.  Toxicol Appl Pharmacol. 2007;218(2):99-106
PubMedCrossRef

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Navas-Acien A, Silbergeld EK, Pastor-Barriuso R, Guallar E. Arsenic exposure and prevalence of type 2 diabetes in US adults.  JAMA. 2008;300(7):814-822
PubMedCrossRef
Cohen SM, Arnold LL, Eldan M, Lewis AS, Beck BD. Methylated arsenicals: the implications of metabolism and carcinogenicity studies in rodents to human risk assessment.  Crit Rev Toxicol. 2006;36(2):99-133
PubMedCrossRef
Gamble MV, Liu X, Slavkovich V,  et al.  Folic acid supplementation lowers blood arsenic.  Am J Clin Nutr. 2007;86(4):1202-1209
PubMed
Tseng CH. Arsenic methylation, urinary arsenic metabolites and human diseases: current perspective.  J Environ Sci Health C Environ Carcinog Ecotoxicol Rev. 2007;25(1):1-22
PubMed
Pu YS, Yang SM, Huang YK,  et al.  Urinary arsenic profile affects the risk of urothelial carcinoma even at low arsenic exposure.  Toxicol Appl Pharmacol. 2007;218(2):99-106
PubMedCrossRef
December 17, 2008
Ana Navas-Acien, MD, PhD; Eliseo Guallar, MD, DrPH
JAMA. 2008;300(23):2728-2729.
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