RESUMEN
BACKGROUND: Exposure to arsenic (As) concentrations in drinking water > 150 µg/L has been associated with risk of diabetes and cardiovascular disease, but little is known about the effects of lower exposures. OBJECTIVE: 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. METHODS: 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. RESULTS: After multivariable adjustment, concentrations in the second quartile of water As (25.5 to < 47.9 µg/L) and concentrations of total speciated urinary As (< 55.8 µg/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. CONCLUSIONS: 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. CITATION: 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.
Asunto(s)
Arsénico/toxicidad , Enfermedades Cardiovasculares/sangre , Diabetes Mellitus/sangre , Adulto , Estudios Transversales , Femenino , Humanos , Modelos Lineales , Masculino , México , Persona de Mediana Edad , Contaminantes Químicos del Agua/toxicidadRESUMEN
Inorganic arsenic (iAs) and fluoride (F-) are naturally occurring drinking water contaminants. However, co-exposure to these contaminants and its effects on human health are understudied. The goal of this study was examined exposures to iAs and F- in Chihuahua, Mexico, where exposure to iAs in drinking water has been associated with adverse health effects. All 1119 eligible Chihuahua residents (>18 years) provided a sample of drinking water and spot urine samples. iAs and F- concentrations in water samples ranged from 0.1 to 419.8 µg As/L and from 0.05 to 11.8 mg F-/L. Urinary arsenic (U-tAs) and urinary F- (U-F-) levels ranged from 0.5 to 467.9 ng As/mL and from 0.1 to 14.4 µg F-/mL. A strong positive correlation was found between iAs and F- concentrations in drinking water (rs = 0.741). Similarly, U-tAs levels correlated positively with U-F- concentrations (rs = 0.633). These results show that Chihuahua residents exposed to high iAs concentrations in drinking water are also exposed to high levels of F-, raising questions about possible contribution of F- exposure to the adverse effects that have so far been attributed only to iAs exposure. Thus, investigation of possible interactions between iAs and F- exposures and its related health risks deserves immediate attention.
Asunto(s)
Arsénico/orina , Agua Potable/análisis , Fluoruros/orina , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Agua Subterránea/análisis , Humanos , Masculino , México , Persona de Mediana Edad , Fosfatos , Adulto JovenRESUMEN
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.
Asunto(s)
Arsénico/toxicidad , Diabetes Mellitus/epidemiología , Metabolómica , Adolescente , Adulto , Anciano , Diabetes Mellitus/sangre , Diabetes Mellitus/inducido químicamente , Diabetes Mellitus/orina , Femenino , Humanos , Masculino , México , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Adulto JovenRESUMEN
BACKGROUND: A growing number of studies link chronic exposure to inorganic arsenic (iAs) with the risk of diabetes. Many of these studies assessed iAs exposure by measuring arsenic (As) species in urine. However, this approach has been criticized because of uncertainties associated with renal function and urine dilution in diabetic individuals. OBJECTIVES: Our goal was to examine associations between the prevalence of diabetes and concentrations of As species in exfoliated urothelial cells (EUC) as an alternative to the measures of As in urine. METHODS: We measured concentrations of trivalent and pentavalent iAs methyl-As (MAs) and dimethyl-As (DMAs) species in EUC from 374 residents of Chihuahua, Mexico, who were exposed to iAs in drinking water. We used fasting plasma glucose, glucose tolerance tests, and self-reported diabetes diagnoses or medication to identify diabetic participants. Associations between As species in EUC and diabetes were estimated using logistic and linear regression, adjusting for age, sex, and body mass index. RESULTS: Interquartile-range increases in trivalent, but not pentavalent, As species in EUC were positively and significantly associated with diabetes, with ORs of 1.57 (95% CI: 1.19, 2.07) for iAsIII, 1.63 (1.24, 2.15) for MAsIII, and 1.31 (0.96, 1.84) for DMAsIII. DMAs/MAs and DMAs/iAs ratios were negatively associated with diabetes (OR = 0.62; 95% CI: 0.47, 0.83 and OR = 0.72; 95% CI: 0.55, 0.96, respectively). CONCLUSIONS: Our data suggest that uncertainties associated with measures of As species in urine may be avoided by using As species in EUC as markers of iAs exposure and metabolism. Our results provide additional support to previous findings suggesting that trivalent As species may be responsible for associations between diabetes and chronic iAs exposure.