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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


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.


Reference Type

Journal Article

Year Published


Journal Title

Toxicological Sciences


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.