Metabolomic Characteristics of Arsenic-Associated Diabetes in a Prospective Cohort in Chihuahua, Mexico

Citation

Martin, Elizabeth M.; Gonzalez-Horta, Carmen; Rager, Julia E.; Bailey, Kathryn A.; Sanchez-Ramirez, Blanca; Ballinas-Casarrubias, Lourdes; Ishida, Maria C.; Gutierrez-Torres, Daniela S.; Ceron, Roberto Hernandez; & Morales, Damian Viniegra, et al. (2015). Metabolomic Characteristics of Arsenic-Associated Diabetes in a Prospective Cohort in Chihuahua, Mexico. Toxicological Sciences, 144(2), 338-346. PMCID: PMC4372663

Abstract

BACKGROUND: 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. Objectives: To identify iAs exposure-associated metabolites with altered abundance in non-diabetic and diabetic individuals in an effort to understand the relationship between exposure, metabolomic response and disease status. METHODS: A nested study design was used to profile metabolomic shifts in urine and plasma collected from 90 diabetic and 86 non-diabetic individuals matched for varying iAs concentrations in drinking water, BMI, age and sex. Diabetes diagnosis was based on measures of fasting plasma glucose and 2-hour blood glucose. Multi-variable models were used to identify metabolites with altered abundance associated with iAs exposure among diabetic and non-diabetic individuals. RESULTS: 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). While many metabolites were altered in both diabetic and non-diabetic 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. CONCLUSION: These data highlight the broad impact of iAs exposure on the human metabolome, and demonstrate some specificity of the metabolomic response between diabetic and non-diabetic individuals. These data may provide novel insights into the mechanisms and phenotype of diabetes associated with iAs exposure.

URL

http://dx.doi.org/10.1093/toxsci/kfu318

Reference Type

Journal Article

Year Published

2015

Journal Title

Toxicological Sciences

Author(s)

Martin, Elizabeth M.
Gonzalez-Horta, Carmen
Rager, Julia E.
Bailey, Kathryn A.
Sanchez-Ramirez, Blanca
Ballinas-Casarrubias, Lourdes
Ishida, Maria C.
Gutierrez-Torres, Daniela S.
Ceron, Roberto Hernandez
Morales, Damian Viniegra
Terrazas, Francisco A. Baeza
Saunders, R. Jesse
Drobna, Zuzana
Mendez, Michelle A.
Buse, John B.
Loomis, Dana P.
Jia, Wei
Garcia-Vargas, Gonzalo G.
Del Razo, Luz M.
Styblo, Miroslav
Fry, Rebecca C.

PMCID

PMC4372663