Pollutant-related diabetes in the Nurses' Health Study II

描述(申请人提供)：在过去的二十年里，肥胖症的患病率急剧上升，而2型糖尿病(T2D)的患病率也出现了相应的飞跃。虽然这两种疾病都有明确的遗传决定因素，但确凿的证据证明，这两种疾病也可以通过对可改变的风险因素进行生活方式和饮食干预来预防。与此同时，现在有证据表明，一些环境污染物，特别是持久性有机污染物(POPs)，也可能导致肥胖和T2D风险增加。来自动物研究的积累数据表明，一些持久性有机污染物，如多氯联苯(PCBS)和p，p‘-二氯二苯基二氯乙烯(p，p’-DDE)与体重增加和胰岛素抵抗有关。人体研究在这一领域很少见，现有的大多数研究都采用横断面设计，无法确定暴露和结果之间的因果关系或时间表。此外，我们的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)，一种主要被认为只是长期总POP暴露的标志，可能与糖尿病的风险有关。此外，已经进入环境的新持久性有机污染物，如全氟化合物(PFC)，在其对肥胖和T2D的影响方面几乎没有受到关注。为了缩小这方面的科学差距，我们的目标是评估多氯联苯、DDE、六氯苯和全氟碳化合物与1)随后的体重增加，2)新诊断的2型糖尿病的发展，以及3)胰岛素抵抗/葡萄糖代谢异常的标记物，包括空腹胰岛素、血红蛋白-A1c和总脂联素，这些指标参与了一项具有良好特征的前瞻性队列：护士健康研究(NHS)II。我们还将在该队列中探索POPs的生活方式和饮食决定因素，以及POPs与其他肥胖和糖尿病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审查AIMS。自1991年的研究基线以来，每2到4年重复收集一次关于生活方式、饮食、病史的极其丰富的数据。此外，在1994-1995年间，大约30 000名国民保健制度第二次参与者提供了血液样本，他们构成了本次调查的研究对象。在这些参与者中，我们将对2型糖尿病进行嵌套病例对照研究，预计将包括1,050例45岁或以上的2型糖尿病病例和同等数量的匹配对照组。严格的质量控制协议和流程已经并将继续应用于NHS II队列，以确保最高质量的研究数据。此外，我们还组建了一支由多学科领域的知名研究人员组成的优秀研究团队，包括环境健康、营养和 生物统计学将确保该项目的成功实施。总而言之，目前的调查将提供新的和关键的证据，不仅将极大地扩大我们对持久性有机污染物的糖尿病致病作用的认识，还将为帮助预防肥胖和T2D的公共卫生政策制定提供信息。

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.