Arsenic, metabolism and metabolic syndrome in the Strong Heart Study

强心研究中的砷、代谢和代谢综合征

• 批准号: 9259459
• 负责人: Miranda Jones Spratlen
• 金额: $ 3.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2018-02-15
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9259459
• 关键词: Academia; Accounting; Adult; Affect; American Indians; Arizona; Arsenic; Attenuated; Biochemical; Blood Pressure; Carbon; Cardiovascular Diseases; Cholesterol; Choline; Chronic Disease; Coronary heart disease; Data; Development; Diabetes Mellitus; Dietary intake; Drug Metabolic Detoxication; Early Intervention; Excretory function; Exposure to; Family; Family Study; Folic Acid; Food; Frequencies; Genetic; Health; Heart; High Prevalence; Incidence; Individual; Intake; Knowledge; Malignant Neoplasms; Measures; Mediation; Metabolic; Metabolic syndrome; Metabolism; Methylation; Non-Insulin-Dependent Diabetes Mellitus; North Dakota; Nutrient; Nutritive Value; Oklahoma; Opitz trigonocephaly syndrome; Outcome; Participant; Pathway interactions; Play; Population; Prevention strategy; Preventive Intervention; Prospective Studies; Public Health; Questionnaires; Research; Riboflavin; Risk; Risk Factors; Role; South Dakota; Stroke; Syndrome; Time; Toxic effect; Triglycerides; Visit; Vitamin B 12; Vitamin B Complex; Vitamin B6; Vitamins; base; career; cohort; diabetogenic; drinking water; fasting glucose; high risk population; improved; interest; metabolomics; modifiable risk; non-genetic; prevent; prospective; skills training; vitamin metabolism; waist circumference

PROJECT SUMMARY/ABSTRACT Metabolic syndrome (MetS) is a rising public health threat now affecting a quarter of the world adult population and a third of the US adult population. The implications of this health condition are significant: those afflicted with MetS are twice as likely to die from and three times as likely to develop coronary heart disease or stroke, compared to those without it. People with MetS are also at a five times greater risk of developing Type 2 diabetes. As a result of its global burden, substantial effort has been made to identify risk factors for both diabetes and MetS in attempts to target prevention and early intervention. Inorganic arsenic exposure has been associated with numerous health outcomes, including cancer, cardiovascular disease, diabetes, and MetS. Evidence suggests that methylation of inorganic arsenic to dimethylated arsenic (DMA) facilitates its excretion and detoxification; this is supported by findings that higher %DMA has been associated with lower arsenic-related health effects, particularly cancer and cardiovascular disease. Arsenic metabolism profiles, however, present differently for metabolic-related outcomes, with lower %DMA being associated with diabetes, BMI and MetS, including in prospective studies. One-carbon metabolism (OCM), an essential biochemical cycle dependent on B-vitamins and other nutrients such as choline, appears to play a role in both arsenic metabolism and metabolic outcomes. Little is known, however, on the interplay between OCM and arsenic metabolism for MetS development, especially in US populations. In our proposed research, we aim to fill in these important gaps in research using existing data from the Strong Heart Family Study, a prospective family- based cohort developed to investigate genetic and non-genetic factors for cardiovascular disease, diabetes, and their risk factors in American Indians. First, we plan to evaluate the association of arsenic exposure and arsenic metabolism with incident MetS in this population. Second, we will separately evaluate the associations between intake of OCM vitamins (choline, folate (B9) and vitamins B12, B6, and B2) with arsenic metabolism as well as with incident MetS. We will then assess the influence of OCM in the relationship between arsenic exposure and metabolism with MetS by evaluating the change in the magnitude and significance of the association between arsenic metabolism and MetS after accounting for measures of OCM. Lastly, we will attempt to better characterize mechanistic pathways in the diabetogenic effects of arsenic exposure and metabolism through metabolomic data. Improved understanding of modifiable risk factors for MetS, such as arsenic exposure and nutrient-regulated OCM, are essential to identifying high risk populations and developing early preventative interventions

项目概要/摘要 代谢综合征 (MetS) 是一种日益严重的公共卫生威胁，目前影响着世界四分之一的成年人口 以及美国成年人口的三分之一。这种健康状况的影响是重大的：那些受影响的人 患有 MetS 的人死于冠心病或中风的可能性是普通人的两倍，患冠心病或中风的可能性是普通人的三倍， 与没有它的人相比。患有 MetS 的人患 2 型糖尿病的风险也高出五倍 糖尿病。由于其全球负担，已做出大量努力来确定这两种疾病的风险因素 糖尿病和 MetS 试图以预防和早期干预为目标。无机砷暴露 与许多健康结果相关，包括癌症、心血管疾病、糖尿病和 气象局。有证据表明，无机砷甲基化为二甲基化砷（DMA）有利于其 排泄和解毒；较高的 %DMA 与较低的 DMA 相关的研究结果支持了这一点 砷相关的健康影响，特别是癌症和心血管疾病。砷代谢概况， 然而，代谢相关结果的表现有所不同，较低的 DMA 百分比与糖尿病相关， BMI 和 MetS，包括前瞻性研究。一碳代谢（OCM），一种重要的生化物质 循环依赖于 B 族维生素和胆碱等其他营养物质，似乎在砷和砷中都发挥着作用 代谢和代谢结果。然而，人们对 OCM 和砷之间的相互作用知之甚少。 新陈代谢对 MetS 发展的影响，尤其是在美国人群中。在我们提出的研究中，我们的目标是填补 使用“强心家庭研究”的现有数据进行的研究中存在这些重要差距，该研究是一项未来的家庭- 开发的队列旨在研究心血管疾病、糖尿病、 以及美洲印第安人的危险因素。首先，我们计划评估砷暴露与 该人群中砷代谢与代谢综合征事件的关系。其次，我们将分别评估协会 OCM 维生素（胆碱、叶酸 (B9) 和维生素 B12、B6 和 B2）的摄入与砷代谢之间的关系 以及 MetS 事件。然后我们将评估 OCM 对砷与砷之间关系的影响。 通过评估 MetS 的量级和显着性变化来暴露和代谢 考虑 OCM 测量后砷代谢与 MetS 之间的关联。最后，我们将 尝试更好地描述砷暴露导致糖尿病的机制途径 通过代谢组数据进行新陈代谢。更好地了解 MetS 的可改变风险因素，例如 砷暴露和营养调节的 OCM 对于识别高风险人群和发展至关重要 早期预防性干预