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Trace mineral levels, metabolomics, and diabetes risk

微量矿物质水平、代谢组学和糖尿病风险

基本信息

批准号：
9984764
负责人：
Ka Kahe
金额：
$ 74.13万
依托单位：
COLUMBIA UNIVERSITY HEALTH SCIENCES
依托单位国家：
美国
项目类别：
财政年份：
2019
资助国家：
美国
起止时间：
2019-07-01 至 2021-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9984764
关键词：
Adult Affect African American American Anti-inflammatory Antioxidants Arsenic Beta Cell Cadmium Calcium Caucasians Chronic Disease Cohort Studies Data Development Diabetes Mellitus Diabetes prevention Elements Environmental Risk Factor Evolution Foundations Future Heavy Metals Homeostasis Incidence Individual Insulin Insulin Resistance Intervention Knowledge Life Style Link Literature Magnesium Measures Mediating Mercury Metabolic Metabolic Diseases Metabolic Pathway Metabolism Metal exposure Micronutrients Minerals Non-Insulin-Dependent Diabetes Mellitus Nutrient Nutritional Oxidants Participant Pathogenesis Pattern Physiological Processes Plasma Play Population Prevention strategy Race Reasons for Geographic And Racial Differences in Stroke Research Role Sampling Secretory Cell Selenium Serum Specimen Techniques Trace Elements Urine aged base cofactor cohort diabetes risk follow-up glucose tolerance insulin sensitivity metabolomics population based prospective remediation sex small molecule

项目摘要

Whereas type 2 diabetes is considered a lifestyle-mediated chronic disease, the importance of environmental risk factors of diabetes is increasingly recognized. Studies indicate that imbalanced homeostasis of certain trace minerals may damage anti-inflammatory and anti-oxidant defense as well as glucose tolerance, which together play pivotal roles in the pathogenesis of diabetes. In addition, studies have linked some heavy metal exposure to the risk of diabetes, though the underlying mechanisms are not completely clear. Despite this, a critical gap remains in the literature on how trace minerals affect diabetes development. Moreover, while an individual trace mineral may be essential for a metabolic pathway, it may interact with other minerals in the metabolism and evolution of diabetes. The advanced techniques profiling metabolite (metabolomics) enable us to measure the full profile of small molecule metabolites circulating in plasma, providing a comprehensive understanding of an individual’s metabolic status that may underlie the associations of trace minerals with diabetes risk. In the proposed project, we will examine trace mineral status in relation to the incidence of diabetes, and insulin resistance; and will identify metabolomic signatures associated with diabetes-related trace mineral patterns in a case-cohort study nested in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study. REGARDS is an ongoing US national population-based cohort of 30,239 African American (AA) and Caucasian adults, aged 45 and older at baseline (2003-2007). The proposed case-cohort study will include 1,538 incident diabetes cases and a sub-cohort (n=2,666) randomly sampled within region- race-sex stratum at baseline. This research will help to identify Americans at risk for diabetes and/or metabolic disorders. For minerals that function as nutrients, information generated from this study will be useful for future interventions to maintain a homeostasis of micronutrients with respect to diabetes prevention. For the toxic minerals, at low-to-moderate exposure level, knowledge gained will serve as a scientific foundation for remediation and prevention strategies to reduce the risk of diabetes and other metabolic disorders.

虽然2型糖尿病被认为是一种生活方式介导的慢性疾病，但环境因素的重要性糖尿病的危险因素越来越被认识。研究表明，不平衡的稳态的某些微量矿物质可能会破坏抗炎和抗氧化防御以及葡萄糖耐量，在糖尿病的发病机制中起关键作用。此外，研究表明，一些重金属暴露于糖尿病的风险，虽然潜在的机制还不完全清楚。尽管如此，A 关于微量矿物质如何影响糖尿病发展的文献中仍然存在关键空白。此外，虽然A 个别微量矿物质可能是必不可少的代谢途径，它可能与其他矿物质相互作用，代谢和糖尿病的演变。代谢物分析（代谢组学）的先进技术使我们能够测量血浆中循环的小分子代谢物的完整概况，提供全面的了解一个人的代谢状态，可能是微量矿物质与糖尿病风险在拟议的项目中，我们将研究微量矿物质状况与糖尿病和胰岛素抵抗;并将确定与糖尿病相关的代谢组学特征在一项病例队列研究中的微量矿物质模式嵌套在地理和种族差异的原因中，卒中（REGARDS）研究。REGARDS是一项正在进行的美国全国人群队列研究，共有30，239名非洲人参加。基线时年龄≥ 45岁的美国（AA）和高加索成人（2003-2007年）。拟定病例队列研究将包括1，538例新发糖尿病病例和一个在区域内随机抽样的子队列（n= 2，666）- 基线时的种族-性别分层。这项研究将有助于确定美国人患糖尿病和/或代谢性疾病的风险。紊乱对于具有营养功能的矿物质，这项研究产生的信息将对未来有用。在预防糖尿病方面，维持微量营养素体内平衡的干预措施。的有毒矿物，在低至中度接触水平，所获得的知识将作为科学基础，补救和预防策略，以降低糖尿病和其他代谢紊乱的风险。