Pollutant-related diabetes in the Nurses' Health Study II

护士健康研究 II 中与污染物相关的糖尿病

• 批准号: 8681444
• 负责人: PHILIPPE ADAM GRANDJEAN
• 金额: $ 61.58万
• 依托单位: HARVARD SCHOOL OF PUBLIC HEALTH
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-06-14 至 2018-01-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8681444
• 关键词: Acids; Adult; Affect; Age; Animals; Attention; Biometry; Blood specimen; Body Weight; Chemical Exposure; Chemicals; Chlorinated Hydrocarbons; Data; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Diet; Dietary Factors; Dietary Intervention; Disease; Ensure; Environment; Environmental Exposure; Environmental Health; Environmental Pollutants; Epidemiologic Studies; Epidemiology; Exposure to; Fasting; Female; Food; Genetic Determinism; Glycosylated hemoglobin A; Health Policy; Hexachlorobenzene; Human; Individual; Insulin; Insulin Resistance; Investigation; Knowledge; Lead; Life; Life Style; Light; Link; Measures; Mediating; Medical History; Metabolic syndrome; Modification; Nested Case-Control Study; Newly Diagnosed; Non-Insulin-Dependent Diabetes Mellitus; Nurses' Health Study; Obesity; Oils; Outcome; Overweight; Participant; Pathogenesis; Physical activity; Plasma; Policy Making; Polychlorinated Biphenyls; Population Study; Prevalence; Process; Prospective Studies; Protocols documentation; Public Health; Quality Control; Questionnaires; Registered nurse; Relative (related person); Reporting; Research; Research Design; Research Personnel; Resistance development; Risk; Risk Factors; Rodent; Salmon; Science; Shapes; Smoking; Solid; Subgroup; Systems Biology; TimeLine; Toxicokinetics; Weight Gain; Woman; adiponectin; animal data; cohort; design; diabetes risk; environmental chemical; epidemiologic data; glucose metabolism; lifestyle intervention; middle age; modifiable risk; novel; nutrition; pollutant; prevent; prospective; public health relevance; simulation; young woman

DESCRIPTION (provided by applicant): The past two decades have witnessed a dramatic rise of obesity prevalence and a parallel leap of type 2 diabetes (T2D) prevalence. Although there are clear genetic determinants for both conditions, solid evidence proves that both conditions can also be prevented through lifestyle and dietary intervention on modifiable risk factors. Meanwhile, evidence now suggests that some environmental pollutants, especially the persistent organic pollutants (POPs), may also lead to increased risk of both obesity and T2D. Accumulating data from animal studies have linked a few POPs, such as polychlorinated biphenyls (PCBs) and p,p'- dichlorodiphenyldichloethylene (p,p'-DDE), with weight gain and insulin resistance. Human studies are rare in this field and most of the existing studies used a cross-sectional design, which cannot establish causal relationship or timeline between exposures and outcomes. Moreover, our preliminary data from epidemiologic observation and system biology simulation have suggested that hexachlorobenzene (HCB), a POP primarily deemed to be merely a marker of long-term total POP exposure, may be causally associated with risk of diabetes. In addition, new POPs that have entered the environment, such as the perfluorinated compounds (PFCs), have received little attention with respect to their effects on obesity and T2D. To narrow the gap in science in this regard, we aim to evaluate PCBs, DDE, HCB, and PFCs in relation to 1) subsequent weight gain, 2) development of newly diagnosed type 2 diabetes, and 3) markers of insulin resistance/glucose metabolism abnormalities, including fasting insulin, hemoglobin-A1c, and total adiponectin, in young and middle-aged women who participated in a well-characterized prospective cohort: The Nurses' Health Study (NHS) II. We will also explore lifestyle and dietary determinants of the POPs and potential interactions between POPs and other risk factors on obesity and diabetes in this cohort. The NHS II provides a unique and ideal opportunity for us to examine the aims. Since the study baseline in 1991, extremely rich data on lifestyle, diet, medical history have been repeatedly collected every 2 to 4 years. Moreover, in 1994-1995, blood samples were provided by approximately 30,000 NHS II participants, who comprised the study population for the current investigation. Among these participants, we will conduct a nested case-control study of type 2 diabetes, which is expected to include 1,050 incident type 2 diabetes cases at age 45 or older and the equal number of matched controls. Rigorous quality control protocol and processes have been and will be continuously applied in the NHS II cohort to ensure the highest quality of research data. In addition, we have assembled an outstanding research team comprised of well-established researchers in multi-disciplinary fields including environmental health, nutrition, and biostatistics that will ensure the successful implementation of the project. In summary, the current investigation will provide novel and critical evidence that will not only greatly expand ou knowledge of the diabetogenic effects of POPs, but also inform public health policy-making to help prevent obesity and T2D.

描述（由申请人提供）：过去二十年来，肥胖症患病率的急剧上升和2型糖尿病（T2D）患病率的平行飞跃。尽管两种情况都有明确的遗传决定因素，但稳定的证据证明，这两种情况也可以通过生活方式和饮食干预来预防可修改的危险因素。同时，现在有证据表明，某些环境污染物，尤其是持续的有机污染物（POP）也可能导致肥胖和T2D的风险增加。来自动物研究的累积数据已将几个流行音乐（例如多氯联苯（PCB）和P，P'-二氯二苯二甲基甲基乙基（P，P'-DDE）与体重增加和胰岛素耐药联系起来。人类研究在该领域很少见，大多数现有研究都使用了横截面设计，该设计无法在暴露和结果之间建立因果关系或时间表。此外，我们来自流行病学观察和系统生物学模拟的初步数据表明，六氯苯（HCB）（HCB）是一种主要被认为仅是长期总POP暴露的标志物，可能与糖尿病风险有因果关系。此外，进入环境的新流行音乐，例如全氟化化合物（PFC），对它们对肥胖和T2D的影响很少关注。为了缩小这方面的科学差异，我们旨在评估PCB，DDE，HCB和PFC相对于1）随后的体重增加，2）新诊断的2型2型糖尿病的发展，以及3）胰岛素抵抗/葡萄糖/葡萄糖代谢异常的标志参加了一项良好的前瞻性队列：护士健康研究（NHS）II。我们还将探索流行音乐的生活方式和饮食决定因素，以及该队列中肥胖和糖尿病的其他风险因素之间的潜在相互作用。 NHS II为我们提供了一个独特而理想的机会来检查目标。自1991年的研究基线以来，每2至4年一次反复收集有关生活方式，饮食，病史的极丰富数据。此外，在1994年至1995年，大约有30,000名NHS II参与者提供了血液样本，他们组成了研究人群进行当前研究。在这些参与者中，我们将对2型糖尿病进行嵌套的病例对照研究，预计将包括45岁或以上的1,050例入射2型糖尿病病例和相等数量的匹配对照。严格的质量控制方案和过程已经并且将在NHS II队列中不断应用，以确保最高质量的研究数据。此外，我们组装了一个杰出的研究团队，该团队由跨学科领域的公认研究人员组成，包括环境健康，营养和 生物统计学将确保成功实施该项目。总而言之，当前的调查将提供新颖而关键的证据，这些证据不仅将大大扩展对流行音乐的糖尿病效应的知识，而且还将告知公共卫生政策制定以帮助防止肥胖和T2D。