Association Between Variants in Arsenic (+3 Oxidation State) Methyltranserase (AS3MT) and Urinary Metabolites of Inorganic Arsenic: Role of Exposure Level.

Variants in AS3MT, the gene encoding arsenic (+3 oxidation state) methyltranserase, have been shown to influence patterns of inorganic arsenic (iAs) metabolism. Several studies have suggested that capacity to metabolize iAs may vary depending on levels of iAs exposure. However, it is not known whether the influence of variants in AS3MT on iAs metabolism also vary by level of exposure. We investigated, in a population of Mexican adults exposed to drinking water As, whether associations between 7 candidate variants in AS3MT and urinary iAs metabolites were consistent with prior studies, and whether these associations varied depending on the level of exposure. Overall, associations between urinary iAs metabolites and AS3MT variants were consistent with the literature. Referent genotypes, defined as the genotype previously associated with a higher percentage of urinary dimethylated As (DMAs%), were associated with significant increases in the DMAs% and ratio of DMAs to monomethylated As (MAs), and significant reductions in MAs% and iAs%. For 3 variants, associations between genotypes and iAs metabolism were significantly stronger among subjects exposed to water As >50 versus ≤50 ppb (water As X genotype interaction P < .05). In contrast, for 1 variant (rs17881215), associations were significantly stronger at exposures ≤50 ppb. Results suggest that iAs exposure may influence the extent to which several AS3MT variants affect iAs metabolism. The variants most strongly associated with iAs metabolism-and perhaps with susceptibility to iAs-associated disease-may vary in settings with exposure level.

Chronic Exposure to Arsenic and Markers of Cardiometabolic Risk: A Cross-Sectional Study in Chihuahua, Mexico.

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.

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

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.

Associations between arsenic species in exfoliated urothelial cells and prevalence of diabetes among residents of Chihuahua, Mexico.

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.

Calorimetría indirecta: diez años de experiencia en el hospital Español

Introducción: los requerimientos energéticos en el enfermo se precisan bien por medio de la calorimetría indirecta. La magnitud del catabolismo puede deducirse mediante la escala metabólica de Cerra (EMC) y el índice catabólico de Bistrian (IC). El consumo de oxígeno, la producción de CO2 y la excreción de nitrógeno determinan el coeficiente respiratorio no proteico (QRnoP) para deducir la proporción de grasa y glucosa utilizada como sustrato energético. Material y métodos: en los últimos 10 años se estudiaron 710 sujetos, con diferentes patologías. Los análisis efectuados fueron: 1. Relación entre GBE medido y edad. 2. Relación entre GBE obtenido mediante calorimetría indirecta y la fórmula de Harris-Benedict. 3. Coeficiente respiratorio no proteico en los diversos grupos. 4. Cambios del GBE, QRnop y utilización energética de proteínas en función del grado de estrés. 5. Correlación entre el APACHE II, FBE y QRnoP. Resultados: El GBE mostró una progresiva disminución con la edad. Hubo un incremento moderado en el postoperatorio inmediato de 172 kcl. El GBE de 24 horas fue de 936 kcal en cirugía mayor por sólo 813 kcal en cirugí menor. En los 710 enfermos se observó que la fórmula de Harris-Benedict sobreestimó el GBE> El QRnop se acerca a uno en enfermos neurológicos, sépticos y pancréaticos. Hubo una correlación entre el grado de estrés, el GBE, el QRnoP y el porcentaje de proteínas utilizadas como energético. Esto fue más notable en enfermos con APACHE II mayor de 15 puntos. Sin embargo, por arriba de 20 puntos el GBE disminuye. Comentarios: la calorimetría indirecta es un método útil para precisar el GBE. En nuestro estudio hubo una buena correlación entre el estrés y el GBE. Dar requerimientos energéticos por debajo de lo necesario, no produce resultados satisfactorios; y dar de más genera alteracines y aumenta el costo.

Gasto basal energetico en le paciente quirurgico / Energetic basal consumption in the surgical patient

La estimacion de las demandas metabolicas esta sujeta a una gran variabilidad derivada de la talla, peso, edad, actividad fisica, la ADE y el aumento de las demandas metabolicas del proceso patologico. La calorimetria indirecta efectuada con los dos modernos monitores metabolicos ( en este estudio se utilizo el MGM TWO, Medidor INc.) dan una buena estimacion con la superficie corporal. En el enfermo quirurgico se utilizo el indice catabolico de Bistrian para estimar la magnitud del estres. Se efectuaron 171 observaciones en 85 sujetos que muestran datos significativos en los siguientes aspectos: confiabilidad del GBE medido y expresado como indice de superficie; relacion de la edad con el GBE; influencia del postoperatorio y la sepsis sobre el GBE y el IC; relacion del aporte calorico nitrogenado sobre el balance nitrogenado en funcion del IC; utilizacion proteica y grado de estres; y accion dinamica especifica del aporte calorico administrado. En este estudio el aumento del GBE fue de 4// con aportes caloricos bajos y hasta 14// con aportes caloricos de 100// o mas sobre el GBE. En enfermos no septicos el suministro de un aporte calorico mayor al 100// del GBE no se observo aumento de la ADE; esto debe ser tenido en cuenta y relacionado con el pobre ahorro proteico que se logra con aportes caloricos altos. El nulo efecto de la ADE con aportes mayores del 100// sobre el GBE sugiere la dificultad para metabolizar la excesiva provision de substractos y sus posibles consecuencias adversas.

Gasto basal energético en cirugía / Basal metabolic energy expenditure during surgery

La estimación de las demandas metabólicas está sujeta a una gran variabilidad derivada de la talla,el peso,la edad,la actividad física,la ADE y el aumento de demandas metabólicas del proceso patológico.La calorimetría indirecta,efectuada con los modernos monitores metabólicos(en este estudio se utilizó el MGMTWO, Medicor Inc.) dan una buena estimación del GBE.En el presenteestudio se muestra la utilidad del GBE medido y expresado en índice de superficie.En el enfermo quirúrgico se utilizó el indice catabólico de Bristrian para estimar la magnitud del estrés. Se efectuaron 171 observaciones en 85 sujetos,que muestran datos significativos en los siguientes aspectos:confiabilidad del GBE medido y expresado por índice de superficie; relación de la edad con el GBE; influencia del postoperatorio y la sepsis sobre el GBE y el IC; relación del aporte calórico nitrogenado sobre el balance nitrogenado en función del IC; utilización proteica y grado de estrés, y acción dinámica específica del aporte calórico administrado.

Gasto basal energético en cirugía / Basal energy expenditure in surgery

La estimación de las demandas metabólicas está sujeta a una gran variabilidad derivada de la talla, el peso, la edad, actividad física, la ADE y el aumento de demandas metabólicas del proceso patologico. La calorimetría indirecta, efectuada con los modernos monitores metabólicos (en este estudo se utilizó el MGM TWO, medicor inc.) dan una buena estimación del GBE. En el presente estudio se muestra la utilidad del GBE medido y expresado en índice de superficie, en el enfermo quirúrgico. Se utilizó el índice catabólico de Bistrian para estimar la magnitud del estres. Se efectuaron 171 observaciones en 85 sujetos, que muestran datos significativos en los siguientes aspectos: confiabilidad del GBE medido y expresado por índice de superficie, relación de la edad con el GBE; influencia del postoperatorio y la sepsis sobre el GBE y el IC; relación del aporte calórico nitrogenado sobre el balance nitrogenado en función del IC; utilización proteica y grado de estres; y acción dinámica específica del aporte calórico administrado