Arsenic, metabolism and metabolic syndrome in the Strong Heart Study

项目总结/摘要 代谢综合征（MetS）是一种日益严重的公共卫生威胁，目前影响着全球四分之一的成年人口 占美国成年人口的三分之一。这种健康状况的影响是重大的： 患有代谢综合征的人死于冠心病或中风的可能性是常人的两倍，患冠心病或中风的可能性是常人的三倍， 与没有代谢综合征的人相比，代谢综合征患者患2型糖尿病的风险也高出5倍。 糖尿病由于其全球负担，人们已做出大量努力来确定两者的风险因素 糖尿病和代谢综合征，试图以预防和早期干预为目标。无机砷暴露 与许多健康结果有关，包括癌症，心血管疾病，糖尿病， MetS。有证据表明，无机砷甲基化为二甲基砷（DMA）有助于其 排泄和解毒;这一点得到了研究结果的支持，即较高的DMA %与较低的 与砷有关的健康影响，特别是癌症和心血管疾病。砷代谢概况， 然而，对于代谢相关的结果呈现不同，较低的%DMA与糖尿病相关， BMI和MetS，包括前瞻性研究。一碳代谢（OCM），一种重要的生物化学 循环依赖于B族维生素和其他营养素，如胆碱，似乎在砷都发挥作用 代谢和代谢结果。然而，对OCM和砷之间的相互作用知之甚少 代谢的MetS发展，特别是在美国人口。在我们提议的研究中，我们的目标是填补 这些研究中的重要空白使用了来自强心家庭研究的现有数据，一个前瞻性的家庭- 基于队列研究，旨在研究心血管疾病、糖尿病 和他们的危险因素。首先，我们计划评估砷暴露与 砷代谢与MetS的关系。第二，我们将分别对协会进行评估 摄入OCM维生素（胆碱，叶酸（B 9）和维生素B12，B6和B2）与砷代谢之间的关系， 以及事故MetS。然后，我们将评估OCM在砷与 通过评估MetS的幅度和意义的变化来评估MetS的暴露和代谢 考虑OCM措施后，砷代谢和MetS之间的关联。最后，我们将 试图更好地描述砷暴露致糖尿病效应的机制途径， 通过代谢组学数据进行代谢。更好地理解代谢综合征的可改变风险因素，例如 砷暴露和营养调控的OCM，是必不可少的，以确定高风险人群和发展 早期预防干预

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