Diabetes and Persistent Organic Pollutants

描述(申请人提供)：糖尿病与遗传和环境因素有关。虽然肥胖和缺乏运动是主要的致病因素，但暴露在环境化学物质中也可能导致风险。持久性有机污染物(POPs)，如二恶英、多氯联苯(PCBS)、对二苯基二氯乙烯(DDE)和多溴联苯醚(PBDEs)在大多数美国人口中都可检测到。最近，在几项横断面研究中，人群普遍暴露于持久性有机污染物，如二恶英、多氯联苯和DDE，与2型糖尿病有关，而在一项前瞻性研究中，多氯联苯与糖尿病有关。拟议的项目将建立在对五大湖运动鱼消费者中暴露于持久性有机污染物的老龄化队列进行了15年的研究观察的基础上，这些消费者暴露在多氯联苯和相关化合物中的风险更高。在1994至2005年间的不同时间对947名参与者进行了持久性有机污染物的测量。对471名参与者的跟踪调查显示，DDE与糖尿病事件有很强的相关性。这项新的研究将扩大混杂变量的数据，并扩大对糖尿病事件队列的跟踪，增加事件病例的数量和检测多溴二苯醚和多氯联苯的性别影响的能力；评估多次暴露和肥胖之间的效果修改；并确定DDE和糖尿病的相关性是否在暴露测量超过10年后发生糖尿病的参与者中仍然显著。将通过检测储存的血清样本中的脂联素、C反应蛋白、谷氨酸脱羧酶抗体和3-谷氨酰转移酶来研究持久性有机污染物与糖尿病风险生物标记物的相关性。拟议的研究允许在明确的队列中有效地跟进重要发现，并将为未来环境暴露对糖尿病的影响的流行病学和毒理学调查提供有希望的途径。这将是第一个关于DDE和PBDE暴露的前瞻性糖尿病研究，也将是第一个调查糖尿病风险和DDE暴露的生物标志物的研究。鉴于人类无处不在地暴露于持久性有机污染物和糖尿病发病率的增加，进一步阐明这些潜在的可改变的环境因素的作用的调查对于预防糖尿病非常重要。公共卫生相关性：项目简介本调查将研究暴露在环境污染物中对糖尿病发展的影响。正在研究的化学品是多氯联苯、二恶英、多溴联苯醚，以及杀虫剂DDT(二氯二苯基三氯乙烷)的代谢物对，对二苯基二氯乙烯(DDE)。重要的是要找出接触持久性污染物是否与糖尿病的发展有关，因为大多数人都接触到少量的这些化学物质。

DESCRIPTION (provided by applicant): Diabetes is related to both genetic and environmental factors. While obesity and physical inactivity are dominant etiologic factors, exposure to environmental chemicals may also contribute to risk. Persistent organic pollutants (POPs) such as dioxins, polychlorinated biphenyls (PCBs), p,p'-diphenyldichloroethene (DDE), and polybrominated biphenyl ethers (PBDEs) are detectable in most of the US population. Recently, general population exposures to POPs, such as dioxins, PCBs, and DDE, have been associated with type 2 diabetes in several cross sectional studies and PCBs were associated with diabetes in one prospective study. The proposed project will build upon 15 years of research observation of a POP-exposed, aging cohort of Great Lakes sport fish consumers, who are at higher risk of exposure to PCBs and related compounds. POPs were measured in 947 participants at various times between 1994 and 2005. Follow up of 471 participants shows a strong association of DDE with incident diabetes. The new study will expand data on confounding variables and extend follow up of the cohort for incident diabetes, increasing the number of incident cases and the power to detect effects of PBDEs and gender specific effects of DDE and PCBs; evaluating effect modification among multiple exposures and adiposity; and determining if the association of DDE and diabetes remains significant in participants with incident diabetes more than 10 years after exposure measurements. Associations of POPs with biomarkers of diabetes risk will be investigated by testing banked serum samples for adiponectin, C reactive protein, glutamic acid decarboxylase antibodies, and 3-glutamyl transferase. The proposed research allows for efficient follow up of important findings in a well defined cohort, and will provide insight into promising avenues for future epidemiologic and toxicologic investigations on the effect of environmental exposures on diabetes. It will be the first prospective diabetes study for DDE and PBDE exposure and will be the first study of to investigate biomarkers of diabetes risk and DDE exposure. Given the ubiquitous exposure of human populations to POPs and the increasing incidence of diabetes, investigations that further delineate the role of these potentially modifiable environmental agents are important for prevention of diabetes. PUBLIC HEALTH RELEVANCE: Project Narrative This investigation will study the effect of exposure to environmental pollutants on development of diabetes. The chemicals under study are polychlorinated biphenyls (PCBs), dioxins, polybrominated biphenyl ethers (PBDEs), and p,p'-diphenyldichloroethene (DDE), a metabolite of the pesticide DDT (dichlorodiphenyltrichloroethane). It is important to find out if exposure to persistent pollutants is related to the development of diabetes because most of the population is exposed to small amounts of these chemicals.