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

PFC 与肥胖、糖尿病和代谢综合征的纵向关联

• 批准号: 9025801
• 负责人: Edward Schurr Horton
• 金额: $ 35.64万
• 依托单位: HARVARD PILGRIM HEALTH CARE, INC.
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-03-01 至 2020-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9025801
• 关键词: Adult; American; Animals; Behavior; Behavioral Genetics; Beta Cell; Blood Pressure; Body Weight Changes; Body mass index; Cardiovascular Diseases; Cell physiology; Chemical Actions; Chemical Exposure; Chemicals; Cholesterol; Cohort Studies; Control Groups; Data; Development; Diabetes Mellitus; Disease; Enrollment; Exposure to; Fasting; Functional disorder; Glucose; Glycosylated hemoglobin A; Grant; Health; Human; Hyperlipidemia; Hypertension; Individual; Insulin; Insulin Resistance; Intervention; LDL Cholesterol Lipoproteins; Life Style; Link; Lipids; Literature; Malignant neoplasm of thyroid; Measurement; Measures; Medical; Metabolic; Metabolic Diseases; Metabolic syndrome; Modification; Non-Insulin-Dependent Diabetes Mellitus; Obesity; Outcome; Outcome Measure; Outcome Study; Participant; Placebos; Plasma; Policies; Population; Production; Productivity; Randomized; Research; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Time; Weight; age related; cardiometabolic risk; cardiovascular disorder risk; case control; clinical practice; cohort; cost effective; design; developmental toxicity; diabetes prevention program; diabetes risk; disorder risk; environmental chemical; environmental chemical exposure; follow-up; high risk; impaired glucose tolerance; insulin secretion; intervention effect; lifestyle intervention; longitudinal design; mortality; prospective; randomized trial; trend; waist circumference

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.

描述（由申请人提供）：多氟和全氟化学品 (PFC) 具有环境持久性，几乎在每个美国人体内都能检测到，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。不太一致的证据也将较高水平的 PFC 与心脏代谢疾病的危险因素联系起来，包括较高的体重指数 (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/或较弱的设计（包括横断面和病例对照而不是前瞻性队列研究）的限制。我们建议在大量特征明确的2型糖尿病和心血管疾病（CVD）高风险成人人群中评估PFC与详细心脏代谢风险测量的纵向关联。我们将研究参加糖尿病预防计划/糖尿病预防计划结果研究 (DPPOS) 的 1000 多名参与者，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)，并进行了 15 年或更长时间的随访。至少每年都会对可能对 PFC 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。使用该随机试验队列还可以进行效果修改分析，其中我们将调查干预措施（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，在这个高产群体中首次评估合成化学品对肥胖、糖尿病和其他 CVD 风险的影响。通过添加 PFC 措施，我们有一个极具成本效益的机会，可以在短短 5 年的资助周期内进行 15 年以上的分析。