The Association of Arsenic Exposure and Arsenic Metabolism With the Metabolic Syndrome and Its Individual Components: Prospective Evidence From the Strong Heart Family Study

Abstract

Inorganic arsenic exposure is ubiquitous and both exposure and inter-individual differences in its metabolism have been associated with cardiometabolic risk. The association between arsenic exposure and arsenic metabolism with metabolic syndrome and its individual components, however, is relatively unknown. We used poisson regression with robust variance to evaluate the association between baseline arsenic exposure (urine arsenic levels) and metabolism (relative percentage of arsenic species over their sum) with incident metabolic syndrome and its individual components (elevated waist circumference, elevated triglycerides, reduced HDL, hypertension, elevated fasting plasma glucose) in 1,047 participants from the Strong Heart Family Study, a prospective family-based cohort in American Indian communities (baseline visits in 1998-1999 and 2001-2003, follow-up visits in 2001-2003 and 2006-2009). 32% of participants developed metabolic syndrome over follow-up. An IQR increase in arsenic exposure was associated with 1.19 (95% CI: 1.01, 1.41) greater risk for elevated fasting plasma glucose but not with other individual components or overall metabolic syndrome. Arsenic metabolism, specifically lower MMA% and higher DMA% was associated with higher risk of overall metabolic syndrome and elevated waist circumference, but not with any other component. These findings support there is a contrasting and independent association between arsenic exposure and arsenic metabolism with metabolic outcomes which may contribute to overall diabetes risk.

Demographic predictors of urinary arsenic in a low-income predominantly Hispanic pregnancy cohort in Los Angeles

“…Arsenic methylation capacity has been related to As toxicity. In support of this, numerous observational studies have observed that a higher proportion of MMA and/or a lower proportion of DMA in urine is associated with increased risk for many adverse health effects [33], although the opposite has also been observed for certain outcomes such as diabetes and metabolic syndrome [51,52]. In the current study, when compared with non-Hispanic women, foreign-born Hispanic women had significantly higher %DMA in their urine and a corresponding trend toward lower %iAs.…”

“…It is possible that such variants are more common in Hispanic women and may be protective against some adverse health effects of As exposure. Differences in diet or nutritional status could also play a role, as certain dietary factors (especially folate) have been related to an increased As methylation capacity [52,[56][57][58][59]. However, it is also possible that the %As metabolites do not reflect As metabolism, but rather organic arsenicals from dietary sources, in this population, as some foods, such as rice and seafood, can be sources of specific As species, such as iAs and DMA [60][61][62].…”

State of the science review of the health effects of inorganic arsenic: Perspectives for future research

“…Also, folic acid consumption increases the biotransformation of i As leading to excretion of DMA in urine, and the reduction of MMA concentration in the blood . A more recent study pointed out that a low MMA/DMA ratio resulting from As metabolism is associated with elevated risk of overall metabolic syndrome that contribute to the risk of diabetes …”

“…This carcinogen disrupts the bioactivity of cellular immune system causing a reduction of CD4+ cells in epidermal keratinocytes, and inducing skin carcinogenesis . Using ATO as a test compound and HaCaT keratinocytes as a test system, Udensi et al pointed out that low concentrations of arsenic modulate gene expression in the immune system. While many biomarkers such as cytokines are up‐regulated, other signaling molecules are down‐regulated.…”

Targeted Degradation of Glucose Transporters Protects against Arsenic Toxicity

“…Implications for human disease. In addition to its well-established role as a carcinogen, a large body of epidemiologic evidence indicates a strong association between arsenic exposure and the risk for diabetes (3,4), a conclusion supported by a comprehensive meta-analysis of the literature by the National Toxicology Program (2). However, the underlying molecular basis for this association remains unknown.…”