Longitudinal Association of PFCs with Obesity, Diabetes, and Metabolic Syndrome

描述(申请人提供)：多氟和全氟化化学品(PFC)对环境具有持久性，几乎每个美国人都能在广泛的范围内检测到，并与人类和动物研究中令人担忧的健康结果有关，包括发育毒性、癌症和甲状腺功能障碍。不太一致的证据也将高水平的PFC与心脏代谢性疾病的风险因素联系起来，包括高体重指数(BMI)、胆固醇、代谢综合征以及2型糖尿病。然而，许多先前的研究受到样本量小、对死亡率数据的依赖和/或包括横断面和病例对照在内的较弱设计的限制，而不是前瞻性队列研究。我们建议在一大群具有良好特征的成人人群中评估PFC与详细的心脏代谢风险测量的纵向相关性，这些成人是发展成2型糖尿病和心血管疾病(CVD)的高危人群。我们将研究1000多名参加糖尿病预防计划/糖尿病预防计划结果研究(DPPOS)的参与者，他们存储了可供分析的基线和后续血浆样本。这些基线糖耐量受损的参与者被随机分为强化生活方式(ILS)干预组(n=637)或安慰剂对照组(n=398)，并已跟踪观察15年或更长时间。至少每年，对PFC可能敏感的结果进行评估，包括：肥胖、血压、血脂、血糖和转化为2型糖尿病。这个随机试验队列的使用还将允许进行效果修改分析，在该分析中，我们将调查在体重变化和糖尿病风险方面的干预效果(ILS与安慰剂)是否因PFC暴露水平而不同。该项目将利用DPPOS无与伦比的资源，有史以来第一次在这个高生产率的队列中评估合成化学品对肥胖、糖尿病和其他心血管疾病风险的贡献。通过增加PFC措施，我们有一个极具成本效益的机会，可以在短短5年的拨款周期内进行15年以上的分析。

DESCRIPTION (provided by applicant): Polyfluorinated and perfluorinated chemicals (PFCs) are environmentally persistent, detectible across a wide range in almost every American, and linked to worrisome health outcomes in human and animal studies including developmental toxicities, cancers, and thyroid dysfunction. Less consistent evidence also links higher levels of PFCs with risk factors for cardiometabolic disease including higher body mass index (BMI), cholesterol, and metabolic syndrome as well as type 2 diabetes mellitus. However, many prior studies were limited by small sample sizes, reliance on mortality data, and/or weaker designs including cross sectional and case-control rather than prospective cohort studies. We propose to evaluate longitudinal associations of PFCs with detailed cardio-metabolic risk measures in a large, well-characterized population of adults who are at high risk for developing type 2 diabetes and cardiovascular disease (CVD). We will study over 1000 participants enrolled in the Diabetes Prevention Program/Diabetes Prevention Program Outcomes Study (DPPOS) who have stored baseline and follow-up plasma samples available for analysis. These participants with baseline impaired glucose tolerance were randomized to an intensive lifestyle (ILS) intervention (n=637) or to a placebo-treated control group (n=398), and have been followed for 15 years or more. At least annually, outcomes potentially sensitive to PFCs have been assessed including: adiposity, blood pressure, lipids, glycemia, and conversion to type 2 diabetes. The use of this randomized trial cohort will also allow for effect modification analysis in which we will investigate whether intervention effects (ILS vs. placebo) on weight change and diabetes risk differ by PFC exposure level. This project will leverage the unparalleled resources of the DPPOS to assess, for the first time ever within this highly productive cohort, the contribution of synthetic chemicas to adiposity, diabetes, and other CVD risks. By adding PFC measures, we have an exceptionally cost-effective opportunity to conduct 15+ years of analysis over just a 5-year grant cycle.