The Role of Diet in Diabetes Associated with Arsenic Exposure

描述（由申请人提供）：无机砷（iAs）是一种常见的饮用水污染物，也是一种可疑的环境致糖尿病物质。目前的共识是，长期暴露于饮用水中高水平的iAs会增加糖尿病的风险。然而，这种关联的因果关系、低水平iAs暴露的影响以及生活方式因素（如饮食）在调节与iAs暴露相关的糖尿病风险中的作用仍存在不确定性。我们的初步数据和来自其他实验室的结果表明，膳食摄入的各种营养素，特别是甲基的捐助者调节iAs代谢，从而可能会影响iAs暴露的不良后果，包括糖尿病的发展。这个探索性项目的目标是利用先前建立的奇瓦瓦州居民队列（n = 1，165）暴露于饮用水中广泛的iAs浓度中收集的数据和样本（血浆和DNA）来表征甲基组供体（叶酸、钴胺素和胆碱）的膳食摄入量、iAs代谢和糖尿病风险之间的关联。将使用先前通过食物频率问卷（FFQ）和血浆中的营养生物标志物（将在拟议项目中测量）收集的数据评估膳食摄入量。将使用从血液中分离的DNA分析参与一个碳（甲基）代谢的基因多态性，这些基因也已知会影响iAs代谢或毒性。血浆中的营养生物标志物和FFQ数据将用于识别与iAs暴露或代谢（通过先前确定的iAs代谢物的尿液特征表征）相互作用以影响糖尿病风险的膳食甲基供体。我们还将确定是否有任何检查的遗传多态性修改iAs代谢和/或发展糖尿病的风险。这个探索性的项目将是第一个研究饮食的作用， 特别是膳食甲基供体在与iAs暴露相关的糖尿病发展中的作用。这项研究将确定可能降低暴露于饮用水中iAs的人群患糖尿病风险的饮食因素，从而为未来的干预研究提供重要线索，并最终预防或治疗这种疾病。

DESCRIPTION (provided by applicant): Inorganic arsenic (iAs) is a common drinking water contaminant and one of the suspected environmental diabetogens. A consensus exists that chronic exposures to high levels of iAs in drinking water increase risk of diabetes mellitus. However, uncertainties remain about causality of this association, effects of low-level iAs exposures, and the role of lifestyle factors such as diet in modulating the risk of diabetes associated with iAs exposure. Our preliminary data and results from other laboratories suggest that dietary intake of various nutrients, and specifically donors of methyl groups modulate iAs metabolism, and thus may affect the adverse outcomes of iAs exposure, including development of diabetes. The goal of this exploratory project is to characterize the associations between dietary intakes of the methyl group donors (folate, cobalamin, and choline), iAs metabolism, and risk of diabetes using data and samples (plasma and DNA) collected in a previously established cohort of Chihuahua residents (n = 1,165) exposed to a wide range of iAs concentrations in drinking water. The dietary intakes will be evaluated using data previously collected by food frequency questionnaire (FFQ) and nutrient biomarkers in plasma (to be measured in the proposed project). Polymorphisms of genes involved in one carbon (the methyl group) metabolism that are also known to affect iAs metabolism or toxicity will be analyzed using DNA isolated from blood. Nutrient biomarkers in plasma and FFQ data will be used to identify dietary methyl group donors that interact with iAs exposure or metabolism (characterized by previously determined urinary profiles of iAs metabolites) to affect the risk of diabetes. We will also determine if any of the examined genetic polymorphisms modify iAs metabolism and/or the risk of developing diabetes. This exploratory project will be the first to examine the role of diet, and specifically dietary methyl group donors in development of diabetes associated with iAs exposure. This research will identify dietary factors that may decrease risk of diabetes in populations exposed to iAs in drinking water, thus providing important clues for future intervention studies, and ultimately for prevention or treatment of this disease.