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

描述（由申请人提供）：多氟化和全氟化化学品（pfc）具有环境持久性，在几乎每个美国人的广泛范围内都可以检测到，并且在人类和动物研究中与令人担忧的健康结果相关，包括发育毒性，癌症和甲状腺功能障碍。不太一致的证据也表明，高水平的PFCs与心脏代谢疾病的危险因素有关，包括较高的身体质量指数（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、依赖死亡率数据和/或设计较弱的限制，包括横断面和病例对照，而不是前瞻性队列研究。我们建议在一个具有2型糖尿病和心血管疾病（CVD）高风险的成年人群中，评估pfc与详细的心脏代谢风险指标的纵向关联。我们将研究1000多名参加糖尿病预防项目/糖尿病预防项目结果研究（DPPOS）的参与者，他们储存了基线和随访血浆样本供分析。这些基线糖耐量受损的参与者被随机分配到强化生活方式（ILS）干预组（n=637）或安慰剂治疗对照组（n=398），并随访15年或更长时间。至少每年对pfc潜在敏感的结局进行评估，包括：肥胖、血压、血脂、血糖和转化为2型糖尿病。该随机试验队列的使用也将允许效果修改分析，我们将调查干预效果（ILS与安慰剂）对体重变化和糖尿病风险的影响是否因PFC暴露水平而异。该项目将利用DPPOS无与伦比的资源，首次在这一高产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影响。通过增加PFC措施，我们有一个极具成本效益的机会，在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.