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

描述（由申请人提供）：多氟和全氟化学品（PFC）具有环境持久性，几乎在每个美国人的广泛范围内均可检测到，并且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较高水平的PFC与心脏代谢疾病的风险因素联系起来，包括较高的体重指数（BMI），胆固醇和代谢综合征以及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（包括横断面和病例对照研究，而不是前瞻性队列研究）的限制。我们建议在一个大的，特征良好的成年人谁是发展2型糖尿病和心血管疾病（CVD）的高风险人群中，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计划/糖尿病预防计划结局研究（DPPOS）的受试者，这些受试者储存了可用于分析的基线和随访血浆样本。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），并已随访15年或更长时间。至少每年评估一次对PFC潜在敏感的结果，包括：肥胖、血压、血脂、糖尿病和转化为2型糖尿病。使用该随机试验队列还将允许进行效应修正分析，其中我们将研究PFC暴露水平对体重变化和糖尿病风险的干预效应（ILS与安慰剂）是否不同。该项目将利用DPPOS无与伦比的资源，首次在这个高产群体中评估合成化学品对肥胖，糖尿病和其他CVD风险的贡献。通过增加PFC措施，我们有一个非常具有成本效益的机会，在短短5年的赠款周期内进行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.