Martin Elizabeth, González-Horta Carmen, Rager Julia, Bailey Kathryn A, Sánchez-Ramírez Blanca, Ballinas-Casarrubias Lourdes, Ishida María C, Gutiérrez-Torres Daniela S, Hernández Cerón Roberto, Viniegra Morales Damián, Baeza Terrazas Francisco A, Saunders R Jesse, Drobná Zuzana, Mendez Michelle A, Buse John B, Loomis Dana, Jia Wei, García-Vargas Gonzalo G, Del Razo Luz M, Stýblo Miroslav, Fry Rebecca
*Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, Programa de Maestría en Ciencias en Biotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, México, Colegio de Médicos Cirujanos y Homeópatas del Estado de Chihuahua, A.C., Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, International Agency for Research of Cancer, Monographs Section, IARC/WHO, Lyon Cedex, France, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii, Facultad de Medicina, Universidad Juárez del Estado de Durango, Gómez Palacio, Durango, México and Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México.
*Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina, Chapel Hill, North Carolina, Programa de Maestría en Ciencias en Biotecnología, Facultad de Ciencias Químicas, Universidad Autónoma de Chihuahua, Chihuahua, México, Colegio de Médicos Cirujanos y Homeópatas del Estado de Chihuahua, A.C., Department of Nutrition, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, Department of Medicine, School of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, International Agency for Research of Cancer, Monographs Section, IARC/WHO, Lyon Cedex, France, University of Hawaii Cancer Center, University of Hawaii, Honolulu, Hawaii, Facultad de Medicina, Universidad Juárez del Estado de Durango, Gómez Palacio, Durango, México and Departamento de Toxicología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, México DF, México
Toxicol Sci. 2015 Apr;144(2):338-46. doi: 10.1093/toxsci/kfu318. Epub 2015 Jan 9.
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.
长期接触无机砷（iAs）与糖尿病风险增加有关，但具体的疾病表型和潜在机制尚不清楚。在本研究中，我们试图识别非糖尿病和糖尿病个体中丰度发生变化的与iAs暴露相关的代谢物，以了解暴露、代谢组学反应和疾病状态之间的关系。采用嵌套研究设计，对从90名糖尿病患者和86名非糖尿病患者收集的尿液和血浆中的代谢组学变化进行分析，这些患者在饮用水中的iAs浓度、体重指数、年龄和性别方面相匹配。糖尿病诊断基于空腹血糖和2小时血糖测量。使用多变量模型来识别糖尿病和非糖尿病个体中与iAs暴露相关的丰度发生变化的代谢物。总共鉴定出132种代谢物在尿液或血浆中因iAs暴露而发生变化，以尿液中iAs代谢物总和（U-tAs）为特征。虽然许多代谢物在糖尿病和非糖尿病受试者中均发生了变化，但糖尿病个体对iAs暴露表现出独特的反应，有59种代谢物发生了变化，包括那些在三羧酸循环和氨基酸代谢中起作用的代谢物。综上所述，这些数据突出了iAs暴露对人类代谢组的广泛影响，并证明了糖尿病和非糖尿病个体之间代谢组学反应的一些特异性。这些数据可能为与iAs暴露相关的糖尿病的机制和表型提供新的见解。
