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Metabolomic characteristics of arsenic-associated diabetes in a prospective cohort in Chihuahua, Mexico.

ABSTRACT: Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 nondiabetic individuals matched for varying iAs concentrations in drinking water, body mass index, age, and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-h blood glucose. Multivariable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and nondiabetic individuals. A total of 132 metabolites were identified to shift in urine or plasma in response to iAs exposure characterized by the sum of iAs metabolites in urine (U-tAs). Although many metabolites were altered in both diabetic and nondiabetic 35 subjects, diabetic individuals displayed a unique response to iAs exposure with 59 altered metabolites including those that play a role in tricarboxylic acid cycle and amino acid metabolism. Taken together, these data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and nondiabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure.

SUBMITTER: Martin E

PROVIDER: S-EPMC4372663 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature

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Metabolomic characteristics of arsenic-associated diabetes in a prospective cohort in Chihuahua, Mexico.

Martin Elizabeth E González-Horta Carmen C Rager Julia J Bailey Kathryn A KA Sánchez-Ramírez Blanca B Ballinas-Casarrubias Lourdes L Ishida María C MC Gutiérrez-Torres Daniela S DS Hernández Cerón Roberto R Viniegra Morales Damián D Baeza Terrazas Francisco A FA Saunders R Jesse RJ Drobná Zuzana Z Mendez Michelle A MA Buse John B JB Loomis Dana D Jia Wei W García-Vargas Gonzalo G GG Del Razo Luz M LM Stýblo Miroslav M Fry Rebecca R

Toxicological sciences : an official journal of the Society of Toxicology 20150109 2

Chronic exposure to inorganic arsenic (iAs) has been linked to an increased risk of diabetes, yet the specific disease phenotype and underlying mechanisms are poorly understood. In the present study we set out to identify iAs exposure-associated metabolites with altered abundance in nondiabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response, and disease status. A nested study design was used to profile metabolomic shifts in urine and p ...[more]

PMID: 25577196

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Project description:Exposure to arsenic (As) concentrations in drinking water > 150 ?g/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures.This study aimed to examine whether moderate As exposure, or indicators of individual As metabolism at these levels of exposure, are associated with cardiometabolic risk.We analyzed cross-sectional associations between arsenic exposure and multiple markers of cardiometabolic risk using drinking-water As measurements and urinary As species data obtained from 1,160 adults in Chihuahua, Mexico, who were recruited in 2008-2013. Fasting blood glucose and lipid levels, the results of an oral glucose tolerance test, and blood pressure were used to characterize cardiometabolic risk. Multivariable logistic, multinomial, and linear regression were used to assess associations between cardiometabolic outcomes and water As or the sum of inorganic and methylated As species in urine.After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 ?g/L) and concentrations of total speciated urinary As (< 55.8 ?g/L) below the median were significantly associated with elevated triglycerides, high total cholesterol, and diabetes. However, moderate water and urinary As levels were also positively associated with HDL cholesterol. Associations between arsenic exposure and both dysglycemia and triglyceridemia were higher among individuals with higher proportions of dimethylarsenic in urine.Moderate exposure to As may increase cardiometabolic risk, particularly in individuals with high proportions of urinary dimethylarsenic. In this cohort, As exposure was associated with several markers of increased cardiometabolic risk (diabetes, triglyceridemia, and cholesterolemia), but exposure was also associated with higher rather than lower HDL cholesterol.Mendez MA, González-Horta C, Sánchez-Ramírez B, Ballinas-Casarrubias L, Hernández Cerón R, Viniegra Morales D, Baeza Terrazas FA, Ishida MC, Gutiérrez-Torres DS, Saunders RJ, Drobná Z, Fry RC, Buse JB, Loomis D, García-Vargas GG, Del Razo LM, Stýblo M. 2016. Chronic exposure to arsenic and markers of cardiometabolic risk: a cross-sectional study in Chihuahua, Mexico. Environ Health Perspect 124:104-111; http://dx.doi.org/10.1289/ehp.1408742.

Project description:BACKGROUND:Exposure to inorganic arsenic (iAs) via drinking water is a serious global health threat. Various factors influence susceptibility to iAs-associated health outcomes, including differences in iAs metabolism. Previous studies have shown that obesity is associated with iAs metabolism. It has been hypothesized that this association can be explained by confounding from nutritional factors involved in one-carbon metabolism, such as folate or other B vitamins, whose intake may differ across BMI categories and is known be associated with iAs metabolism. However, no studies have explored whether this association is confounded by nutritional factors. METHODS:We investigated the relationship between body mass index (BMI) and the distribution of urinary arsenic species in a cross-sectional cohort of 1166 adults living in Chihuahua, Mexico from 2008 to 2013. Nutrient intake related to one-carbon metabolism, including folate, vitamin B2, and vitamin B12, was assessed using a food frequency questionnaire developed for Mexican populations. Multivariable linear regression was used to estimate the association between BMI and the distribution of urinary arsenic metabolites. Effect modification by drinking water iAs level and sex was also examined. RESULTS:After adjusting for potential confounders, including age, educational attainment, smoking, alcohol consumption, seafood consumption, water iAs, and sex, BMI was negatively associated with the proportion of urinary inorganic arsenic (%U-iAs) and urinary monomethylated arsenic (%U-MMAs) and positively associated with urinary dimethylated arsenic (%U-DMAs). This relationship was not influenced by additional adjustment for folate, vitamin B2, or vitamin B12 intake. Additionally, there was significant effect modification by both drinking water iAs level and sex. CONCLUSIONS:This study provides further evidence for an association between BMI and arsenic metabolism. However, contrary to previous hypotheses, these results suggest that this association is not confounded by the intake of micronutrients involved in one-carbon metabolism.

Dataset Information

Metabolomic characteristics of arsenic-associated diabetes in a prospective cohort in Chihuahua, Mexico.

Publications

Metabolomic characteristics of arsenic-associated diabetes in a prospective cohort in Chihuahua, Mexico.

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