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.

而2型糖尿病被认为是一种生活方式介导的慢性疾病，而环境的重要性越来越多地认识到糖尿病的危险因素。研究表明某些人的体内平衡不平衡痕量矿物质可能会损害抗炎和抗氧化剂防御以及葡萄糖耐受性，葡萄糖耐受性共同在糖尿病的发病机理中起关键作用。此外，研究已经连接了一些重金属暴露于糖尿病的风险，尽管基本机制尚不完全清楚。尽管如此，关于微量矿物如何影响糖尿病发育的文献中，关键差距仍然存在。而且，个体痕量矿物可能对于代谢途径至关重要，它可能与其他矿物质相互作用糖尿病的代谢和进化。高级技术分析代谢物（代谢组学）使我们测量在血浆中循环的小分子代谢产物的完整特征，提供了全面的了解个人的代谢状况，这可能是痕量矿物质与糖尿病风险。在拟议的项目中，我们将研究有关事件的微量矿物质状态糖尿病和胰岛素抵抗；并将确定与糖尿病有关的代谢组学特征在一项案例研究中的痕量矿物模式，该研究是根据地理和种族差异的原因而嵌套的中风（有关）研究。问候是一个正在进行的美国国家人口的群体，该队列为30,239个非洲人美国（AA）和高加索成年人，年龄在基线时45岁及以上（2003-2007）。拟议的案例船研究将包括1,538例入射糖尿病病例和一个随机在区域内随机采样的亚事件（n = 2,666）。基线的种族性层。这项研究将有助于确定有糖尿病和/或代谢风险的美国人疾病。对于充当营养的矿物质，本研究产生的信息将对将来有用维持微量营养素的干预措施相对于预防糖尿病。对于有毒矿物质，在低到中度的接触水平下，获得的知识将成为科学基础降低糖尿病和其他代谢疾病风险的补救和预防策略。