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: 10365944
• 负责人: Simin Liu
• 金额: $ 46.94万
• 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/10365944
• 关键词: Age; Arsenic; Attention; Biological; Blood; Cadmium; Cardiometabolic Disease; China; Chinese; Chromium; Clinical; Cobalt; Cohort Studies; Collection; Copper; Cross-Sectional Studies; Data; Diagnosis; 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; 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; diagnostic criteria; 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.

项目总结 2型糖尿病(T2D)是我们这个时代的一种流行病，在全球范围内困扰着4亿多人。鉴定 迫切需要新的可预防的风险因素，因为既有的风险因素并不能完全解释 提高T2D速率。重金属在t2d风险中的病因学作用已得到相当大的关注。 全世界。在美国，国家毒理学计划最近建议对此进行进一步研究 在全面回顾了环境因素与T2D之间的关系之后，提出了这一主题。近期 将重金属与T2D风险联系起来的数据虽然诱人，但主要来自易受影响的横断面研究 颠倒因果关系。此外，很少有研究调查暴露于多种金属对T2D的作用 风险，以至于几乎没有证据表明多种金属的独立和联合影响。另外， 建议将必需金属作为有益的补充剂，以减轻有毒金属对糖尿病的影响， 但是，抵消有毒金属影响所需的最优必需金属水平并不是很清楚。 因此，迫切需要大规模和高质量的前瞻性研究来进一步研究重金属的风险。 T2D的因素，以及必需金属可能的缓解作用。我们的研究团队在美国国立卫生研究院的支持下， 建立了以人群为基础的前瞻性金昌金属队列研究。这项正在进行的研究包括： 2011-13年度对42,122名参与者进行了面谈，2014-16年度进行了第一次后续访问，第二次后续访问 访问始于2017年。在基线和随后的访问中，受试者完成了1)体检；2) 临床化验；3)面谈；4)采集血液和尿液样本。广泛的试点 已经在这一人群中开展了与金属暴露相关的T2D风险的研究。有了这样的 从这个庞大的基于预期人口的队列中获得大量数据，我们现在处于一个独特的位置 进行嵌套式病例对照研究，以全面调查接触重金属是否会增加T2D 风险。选定重金属的基线血清和尿液水平将从2,200次T2D事件中进行测量 病例和他们各自年龄性别匹配的2200名对照，当时没有T2D和前驱糖尿病 当相应的病例被诊断为T2D时。研究的具体目标包括：1)确定 基线有毒金属水平是否与T2D风险独立或联合相关；2)确定 基本金属的失衡基线水平(缺乏或过量暴露)是独立的或联合的 与T2D风险相关；以及3)确定有毒金属对糖尿病的影响是否可以通过以下方法缓解 必需金属，如果是的话，人体内可降低毒性的T2D风险的最佳必需金属水平 金属。金昌金属队列研究是唯一一项专门为 研究金属暴露对心脏代谢性疾病的影响。研究结果将阐明 在与美国和中国相关的水平上，将金属暴露作为T2D的可修改风险因素，并将有助于 制定干预策略以改善人类人群的心脏代谢结果。

项目成果

The relationship between urinary selenium levels and risk of gestational diabetes mellitus: A nested case-control study.

• DOI: 10.3389/fpubh.2023.1145113
• 发表时间: 2023
• 期刊: FRONTIERS IN PUBLIC HEALTH
• 影响因子: 5.2
• 作者: Liu, Yuanxia;Chen, Hongmei;Zhang, Mengtian;Zhu, Gangjiao;Yang, Yan;Li, Yuanyuan;Lu, Wei;Zhang, Hongling
• 通讯作者: Zhang, Hongling

Ending the epidemics of cardiovascular diseases: time is now to integrate both population and individual strategies for prevention.

结束心血管疾病的流行：现在是整合人口和个人预防策略的时候了。

• DOI: 10.1016/j.scib.2018.05.031
• 发表时间: 2018
• 期刊: Science bulletin
• 影响因子: 18.9
• 作者: Huang,Mengna;Liu,Simin
• 通讯作者: Liu,Simin

Dose-response analysis of environmental exposure to multiple metals and their joint effects with fasting plasma glucose among occupational workers.

• DOI: 10.1016/j.chemosphere.2017.08.002
• 发表时间: 2017-11
• 期刊: Chemosphere
• 影响因子: 8.8
• 作者: A. Yang;Simin Liu;Z. Cheng;H. Pu;N. Cheng;Jiao Ding;Juansheng Li;Hai-Yan Li;Xiaobin Hu;X. Ren;Kehu Yang;T. Zheng;Yana Bai

Altered cord blood mitochondrial DNA content and prenatal exposure to arsenic metabolites in low-arsenic areas.

低砷地区脐带血线粒体 DNA 含量和产前砷代谢物暴露发生改变。

• DOI: 10.21203/rs.3.rs-3414865/v1
• 发表时间: 2023
• 期刊: Research square
• 作者: Qiu,Feng;Zhang,Hongling;Wang,Xin;Jia,Zhenxian;He,Yujie;Wu,Yi;Li,Zhangpeng;Zheng,Tongzhang;Xia,Wei;Xu,Shunqing;Li,Yuanyuan
• 通讯作者: Li,Yuanyuan

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• DOI: 10.1002/art.40923
• 发表时间: 2019
• 期刊: Arthritis & rheumatology (Hoboken, N.J.)
• 作者: Kim,AlfredHJ;Strand,Vibeke;Atkinson,JohnP
• 通讯作者: Atkinson,JohnP