A nested case-control study of exposure to toxic metals, essential metals and their interaction on the risk of type 2 diabetes

一项巢式病例对照研究，探讨有毒金属、必需金属的暴露及其相互作用对 2 型糖尿病风险的影响

• 批准号: 9892009
• 负责人: Simin Liu
• 金额: $ 52.51万
• 依托单位: BROWN UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-03-15 至 2023-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9892009
• 关键词: Age; Arsenic; Attention; Biological; Blood; Cadmium; China; Chinese People; Chromium; Clinical; Cobalt; Cohort Studies; Collection; Copper; Cross-Sectional Studies; Data; Diagnosis; Diagnostic; Dietary Intervention; Disease; Educational workshop; Environmental Exposure; Environmental Risk Factor; Epidemic; Etiology; Exposure to; Gender; Grant; Heavy Metals; Human; Individual; Institution; International; Intervention; Interview; Joints; Laboratories; Lead; Link; Magnesium; Manganese; Measures; Mercury; Metabolism; Metal exposure; Metals; Molybdenum; Morbidity - disease rate; National Toxicology Program; Nested Case-Control Study; Nickel; Non-Insulin-Dependent Diabetes Mellitus; Outcome; Participant; Persons; Physical Examination; Pilot Projects; Population; Positioning Attribute; Prediabetes syndrome; Prevention; Preventive Intervention; Process; Prospective Studies; Prospective cohort study; Public Health; Reporting; Research; Resources; Risk; Risk Factors; Role; Sampling; Selenium; Serum; Testing; Time; Toxic effect; Trace metal; Tungsten; United States National Institutes of Health; Urine; Vanadium; Visit; Work; Zinc; aged; burden of illness; cardiometabolic risk; cardiometabolism; cohort; cost; cost efficient; design; diabetes risk; diabetic; follow-up; high risk; improved; modifiable risk; novel; population based; preservation; prevent; prospective; sex; toxic metal

PROJECT SUMMARY Type 2 diabetes (T2D) is an epidemic of our time afflicting more than 400 million people globally. Identification of novel preventable risk factors is urgent because established risk factors do not fully account for the rapid increase in T2D rates. The etiologic role of heavy metals in T2D risk has gained considerable attention worldwide. In the U.S., the National Toxicological Program recently recommended further research on this topic following a comprehensively review of the relationship between environmental factors and T2D. Recent data linking heavy metals to T2D risk, while tantalizing, come mainly from cross-sectional studies susceptible to reverse causation. Moreover, few studies have investigated the role of exposures to multiple metals on T2D risk, such that there is little evidence of the independent and joint effects of multiple metals. Separately, essential metals are recommended as beneficial supplements to mitigate the diabetic effects of toxic metals, but the optimal levels of essential metals required to counteract the toxic metal effects are not well understood. Thus, large and high-quality prospective studies are urgently needed to further investigate heavy metals as risk factors for T2D, and the possible mitigating role of essential metals. Our research team, with support from NIH, has built the population-based prospective Jinchang Metal Cohort Study. This on-going study includes in- person interviews of 42,122 participants in 2011-13, a first follow-up visit in 2014-16, and a second follow-up visit started in 2017. At the baseline and subsequent visits, subjects completed 1) physical examinations; 2) clinical laboratory tests; 3) in-person interviews; and 4) collections of blood and urine samples. Extensive pilot work on T2D risk associated with metal exposure has already been conducted in this population. With such extensive data available from this large prospective population-based cohort, we are now in a unique position to conduct a nested case-control study to comprehensively investigate if heavy metal exposures increase T2D risk. Baseline serum and urine levels of selected heavy metals will be measured from 2,200 incident T2D cases and their individually age-sex-matched 2,200 controls who were T2D- and prediabetes-free at the time when the corresponding cases were diagnosed with T2D. The study specific aims include: 1) Determine whether baseline toxic metal levels are independently or jointly associated with T2D risk; 2) Determine whether imbalanced baseline levels (deficiency or overexposure) of essential metals are independently or jointly associated with T2D risk; and 3) Determine whether diabetic effects of toxic metals can be mitigated by essential metals and, if so, the optimal body levels of essential metals that could reduce T2D risk from toxic metals. The Jinchang Metal Cohort Study is the only large prospectively study specifically designed to investigate the impact of metal exposures on cardiometabolic diseases. The study results will clarify the role of metals exposure as a modifiable risk factor for T2D at levels relevant to both the US and China, and will help to establish intervention strategies to improve cardiometabolic outcomes in human populations.

项目摘要 2型糖尿病（T2D）是我们时间遭受全球超过4亿人的流行病的流行。鉴别 新颖的可预防风险因素是紧急的，因为既定的危险因素并不能完全解释 T2D率的增加。重金属在T2D风险中的病因学作用引起了人们的关注 全世界。在美国，国家毒理计划最近建议对此进行进一步的研究 在对环境因素与T2D之间的关系进行全面审查之后，主题。最近的 将重金属与T2D风险联系起来的数据，虽然诱人，主要来自横断面研究 逆转因果关系。此外，很少有研究研究了对T2D的多种金属暴露的作用 风险，几乎没有证据表明多种金属的独立和关节作用。分别地， 建议将基本金属作为有益的补充剂来减轻有毒金属的糖尿病作用， 但是，对抵消有毒金属效应所需的最佳基本金属水平尚不清楚。 因此，迫切需要进行大型和高质量的前瞻性研究，以进一步研究重金属作为风险 T2D的因素，以及基本金属的可能减轻作用。我们的研究团队在NIH的支持下 已经建立了基于人群的前瞻性金金属队列研究。这项正在进行的研究包括 2011 - 13年的42,122名参与者的人访谈，2014-16的第一次随访和第二次随访 访问始于2017年。在基线和随后的访问时，受试者完成了1）体格检查； 2） 临床实验室测试； 3）面对面访谈； 4）血液和尿液样本的收集。广泛的飞行员 该人群已经进行了与金属暴露有关的T2D风险的工作。这样 我们现在处于独特的位置，可从这个大型潜在人群的同类群体获得广泛的数据 进行嵌套的病例对照研究，以全面研究重金属暴露是否增加T2D 风险。基线血清和所选重金属的尿液水平将从2200事件中测量T2D 案例及其单独年龄匹配的2200个对照，当时不含T2D和糖尿病前期 当相应病例被诊断为T2D时。该研究的具体目的包括：1）确定 基线毒性金属水平是独立或与T2D风险共同相关的； 2）确定是否 必需金属的基线水平不平衡（缺陷或过度暴露）是独立或共同的 与T2D风险相关； 3）确定是否可以通过 必需的金属，如果是的，则可能会降低有毒风险的最佳物体基本金属水平 金属。 Jinchang金属队列研究是唯一专门设计的大型前瞻性研究 研究金属暴露对心脏代谢疾病的影响。研究结果将阐明 金属暴露是与美国和中国相关的T2D的可修改危险因素，并将有助于 建立干预策略，以改善人群中的心脏代谢结果。