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病因，但接触环境中的化学物质也可能导致风险。持久性有机污染物（POPs），如二恶英，多氯联苯（PCBs）， p,p'-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以检测到。最近，在几项横断面研究中，一般人群暴露于持久性有机污染物（如二恶英、多氯联苯和二恶英）与2型糖尿病有关，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15年的研究观察基础上，研究对象是接触持久性有机污染物的五大湖运动鱼消费者，他们接触多氯联苯和相关化合物的风险更高。在1994年至2005年期间的不同时间，对947名参与者的持久性有机污染物进行了测量。对471名参与者的随访显示，DDE与偶发糖尿病有很强的关联。这项新研究将扩大混杂变量的数据，并扩大对糖尿病发病队列的随访，增加发病病例的数量和检测多溴二苯醚影响的能力，以及多溴二苯醚和多氯联苯的性别特异性影响；多重暴露与肥胖的效应修正评价并确定DDE与糖尿病的关联在接触测量后10年以上的糖尿病患者中是否仍然显著。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-谷氨酰基转移酶，调查持久性有机污染物与糖尿病风险生物标志物之间的关联。拟议的研究允许在一个明确的队列中有效地跟踪重要发现，并将为未来关于环境暴露对糖尿病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和多溴二苯醚暴露的前瞻性糖尿病研究，也是第一个研究糖尿病风险和DDE暴露的生物标志物的研究。鉴于人类普遍暴露于持久性有机污染物和糖尿病发病率的增加，进一步确定这些潜在可改变的环境因素的作用的调查对预防糖尿病很重要。这项调查将研究暴露于环境污染物对糖尿病发展的影响。所研究的化学品是多氯联苯、二恶英、多溴联苯醚和农药DDT（二氯二苯三氯乙烷）的代谢物对，对'-二苯二氯乙烯（DDE）。重要的是要弄清楚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过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.