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: 9230371
• 负责人: Emily Oken
• 金额: $ 35.2万
• 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/9230371
• 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; Control Groups; Data; Development; Diabetes Mellitus; Disease; Enrollment; Exposure to; Fasting; Functional disorder; Glucose; Glycosylated hemoglobin A; Grant; Health; Human; Hyperlipidemia; Hypertension; Individual; Industrialization; Insulin; Insulin Resistance; Intervention; LDL Cholesterol Lipoproteins; Life Style; Link; Lipids; Literature; Malignant Neoplasms; 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; Prospective cohort study; Randomized; Research; Resources; Risk; Risk Factors; Role; Sample Size; Sampling; Thyroid Gland; Time; Weight; age related; blood lipid; 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; public health relevance; 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）：多氟化和全氟化化学物质（PFC）在环境上是持久性的，几乎在每个美国人中都可以在广泛的范围内检测到，并且与人类和动物研究中令人担忧的健康结果有关，包括发育性毒性，癌症，癌症，癌症，甲状腺功能障碍。不太一致的证据还将较高水平的PFC与心脏代谢疾病的危险因素联系起来，包括更高的体重指数（BMI），胆固醇和代谢综合征以及2型糖尿病。但是，许多先前的研究受到少量样本量，对死亡率数据的依赖以及/或包括横截面和病例控制的弱设计而不是前瞻性队列研究的限制。我们建议评估PFC的纵向关联，并在大型，充分表现的成年人中使用详细的心脏代谢风险度量，他们患有2型糖尿病和心血管疾病（CVD）的高风险。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（DPPO）的1000多名参与者，他们存储了基线和随访血浆样本可用于分析。这些患有基线受损葡萄糖耐受性的参与者被随机分为密集的生活方式（ILS）干预措施（n = 637）或安慰剂处理的对照组（n = 398），并遵循15年或更长时间。至少每年对PFC敏感的结果进行了评估，包括：肥胖，血压，脂质，血糖，以及转化为2型糖尿病。这种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，我们将研究干预效果（ILS与安慰剂）对体重变化的影响是否会因PFC暴露水平而有所不同。该项目将利用DPPO的无与伦比的资源来评估这一高生产力的队列中的首次，合成化学对肥胖，糖尿病和其他CVD风险的贡献。通过添加PFC措施，我们有一个极具成本效益的机会，可以在仅5年的赠款周期内进行15年以上的分析。