Persistent Organic Pollutants, Endogenous Hormones and Diabetes in Latinos

 描述（由申请人提供）：糖尿病目前影响5580万人，占美国人口的8.3%，西班牙裔的患病率特别高，为11.8%。几项研究表明，糖尿病与持久性有机污染物（POP），包括有机氯农药，多氯联苯（PCB）和溴化阻燃剂（BFR）有着重要的联系。这些暴露可能增加糖尿病风险的生物学途径尚未阐明，尽管有证据表明可能涉及炎症和内分泌机制。在墨西哥和其他选定的拉丁美洲国家，氯化农药的使用持续时间更长，在美国，西班牙裔的使用水平高于其他族裔群体。拟议的研究将建立在西班牙裔社区健康研究/拉丁美洲人研究（HCHS/SOL）的基础上，这是一项正在进行的队列研究，共有16,415名多种族西班牙裔人，分布在美国4个城市：芝加哥、圣地亚哥、纽约和迈阿密。将选择2，850名年龄在45-74岁之间的男性和绝经后女性的基线血液样本，用于测量9种有机氯农药，11种BFR和37种PCB，以及内源性甲状腺和类固醇激素以及与暴露和/或糖尿病相关的炎症措施。将检查POP水平、内源性激素和炎症指标与人口统计学因素（包括年龄、性别、西班牙裔背景组和在美国居住年限）以及基线糖尿病、糖尿病前期和胰岛素抵抗的关系。将检查持久性有机污染物的基线水平、炎症和内源性激素的测量与随后的糖尿病、糖尿病前期和胰岛素抵抗的发展之间的关系，这些关系在6年随访时确定。将使用相互作用术语和分层，按性别、年龄、体重指数、种族、移民状况、激素、饮食和炎症标志物对POP与糖尿病、糖尿病前期和胰岛素抵抗的关联进行修改。潜在的中间标记物，如激素和炎症的措施的影响将与调解分析探讨。HCHS/SOL研究是美国对不同背景的西班牙裔群体进行的最大的前瞻性研究。这一人群在接触和疾病方面的差异很大，因此很适合研究持久性有机污染物可能影响一种日益流行和代价高昂的疾病的生物途径。在这个模型中提出的假设，以后可以外推到其他持久性较低和更难以研究的常见暴露。结果不仅在确定病因因素方面很重要，而且在设计适当的干预策略方面也很重要。

 DESCRIPTION (provided by applicant): Diabetes currently affects 55.8 million people, or 8.3% of the U.S. population, with prevalence in Hispanics particularly high at 11.8%. Several studies have shown significant associations of diabetes with persistent organic pollutants (POPs), including organochlorine pesticides, polychlorinated biphenyls (PCBs), and brominated flame retardants (BFRs). The biologic pathways by which these exposures could increase risk of diabetes have not been elucidated, although there is evidence that inflammatory and endocrine mechanisms may be involved. Use of chlorinated pesticides continued longer in Mexico and other selected Latin American countries and levels are higher in Hispanics in the US than in other ethnic groups. The proposed study will build upon the Hispanic Community Health Study/Study of Latinos (HCHS/SOL), an ongoing cohort of 16,415 multiethnic Hispanics in 4 cities in the US: Chicago, San Diego, New York and Miami. Baseline bloods samples from 2,850 men and postmenopausal women age 45-74 will be selected for measurements of 9 organochlorine pesticides, 11 BFRs, and 37 PCBs, as well as endogenous thyroid and steroid hormones and measures of inflammation that have been related to the exposures and/or diabetes. Relationships of levels of POPs, endogenous hormones and measures of inflammation with demographic factors (including age, gender Hispanic background group and years of residence in the US), and baseline diabetes, pre-diabetes and insulin resistance will be examined. Associations of baseline levels of POPs, measures of inflammation and endogenous hormones with subsequent development of diabetes, pre-diabetes and insulin resistance determined at the six year follow-up will be examined. Modification of associations of POPs with diabetes, pre-diabetes and insulin resistance by gender, age, body mass index, ethnicity, immigration status, hormones, diet and inflammation markers will be examined with interaction terms and stratification. Effects of potential intermediate markers such as hormones and measures of inflammation will be explored with mediation analysis. The HCHS/SOL Study is the largest prospective study in the United States of Hispanic groups of diverse background. The wide variation in both exposures and disease in this population renders it ideal in which to examine biologic pathways by which POPs could be affecting an increasingly prevalent and costly disease. Hypotheses developed in this model can later be extrapolated to other common exposures that are less persistent and more difficult to study. Results could be important not only in identifying etiologic factors, but also in designing appropriate intervention strategies.