Pollutant-related diabetes in the Nurses' Health Study II

描述（由申请人提供）：在过去的二十年里，肥胖患病率急剧上升，2型糖尿病（T2D）患病率也出现了平行的飞跃。虽然这两种疾病都有明确的遗传决定因素，但确凿的证据表明，这两种疾病也可以通过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，尤其是持久性有机污染物（POPs），也可能导致肥胖和糖尿病的风险增加。从动物研究中积累的数据表明，一些持久性有机污染物，如多氯联苯（PCBs）和p，p'-二氯二苯二乙烯（p,p'- dde）与体重增加和胰岛素抵抗有关。该领域的人体研究很少，现有的研究大多采用横断面设计，无法建立暴露与结果之间的因果关系或时间轴。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暴露的标记物，可能与糖尿病风险有因果关系。此外，已进入环境的新的持久性有机污染物，如全氟化合物（pfc），在其对肥胖和糖尿病的影响方面很少受到关注。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、HCB和PFCs与以下因素的关系：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/葡萄糖代谢异常标志物，包括空腹胰岛素、血红蛋白a1c和总脂联素，这些指标参加了一个特征明确的前瞻性队列：护士健康研究（NHS） II。我们还将探讨该队列中持久性有机污染物的生活方式和饮食决定因素，以及持久性有机污染物与其他肥胖和糖尿病风险因素之间的潜在相互作用。NHS II为我们研究这些目标提供了一个独特而理想的机会。从1991年的研究基线开始，每2到4年就反复收集非常丰富的生活方式、饮食、病史数据。此外，1994-1995年，约有30,000名NHS II参与者提供了血液样本，他们构成了当前调查的研究人群。在这些参与者中，我们将进行2型糖尿病的巢式病例对照研究，预计将包括1050例45岁或以上的2型糖尿病病例和相同数量的匹配对照。严格的质量控制协议和流程已经并将继续在NHS II队列中应用，以确保研究数据的最高质量。此外，我们还组建了一支杰出的研究团队，由环境健康、营养和营养等多学科领域的知名研究人员组成

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.