Non-esterified Fatty Acids and Cardiometabolic Disease in Older Adults

非酯化脂肪酸与老年人的心脏代谢疾病

• 批准号: 9522069
• 负责人: LUC DJOUSSE
• 金额: $ 76万
• 依托单位: BRIGHAM AND WOMEN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-15 至 2020-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9522069
• 关键词: Accounting; Address; Age; Aging; Agonist; American; Atrial Fibrillation; Basic Science; Behavior Therapy; Biological; Biology; Cardiovascular Diseases; Cardiovascular system; Cholesterol; Clinical; Cohort Studies; Data; Data Repository and Coordinating Center; Development; Diabetes Mellitus; Diabetes prevention; Diagnosis; Disease; Drug Targeting; Elderly; Epidemiology; Event; Fasting; Fatty Acids; Future; Glucose; Healthcare; Heart failure; Hepatic; Hour; Individual; Intervention; Knowledge; Life Style; Lifestyle Therapy; Lipolysis; Measurement; Measures; Metabolic; Metformin; Morbidity - disease rate; Muscle; Myocardial Infarction; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; OGTT; Oral; Outcomes Research; Pathogenesis; Pathway interactions; Pattern; Peripheral; Pharmacology; Pharmacotherapy; Phenotype; Play; Population; Population Sciences; Predisposition; Prevalence; Prevention; Prospective Studies; Quality of life; Research; Resources; Risk; Role; Serum; Shapes; Specimen; Stroke; Testing; Tissues; Translational Research; United States National Institutes of Health; Work; adjudicate; adverse outcome; base; cardiometabolic risk; cardiometabolism; cardiovascular health; cohort; cost; design; diabetes management; diabetes prevention program; diabetes risk; disability; disorder risk; drug development; fatty acid metabolism; glucose production; glucose transport; high risk; improved; insight; insulin sensitivity; insulin signaling; lifestyle intervention; mortality; new therapeutic target; novel; prevent; prospective; randomized trial; receptor; success

Abstract Non-esterified fatty acids (NEFAs) play a central role in the development of type 2 diabetes and cardiovascular diseases (CVD). Although total fasting NEFAs have been associated with higher risks of diabetes, CVD, and mortality, no previous cohort study has examined of the associations of NEFAs measured after oral glucose challenge with cardiometabolic disease, despite their much stronger association with insulin sensitivity. Further, total NEFAs consist of >40 different fatty acids, and which subset of individual NEFAs or patterns of NEFAs confer the greatest risk of cardiometabolic disorders is currently unknown. In addition, although a large randomized trial has demonstrated the efficacy of metformin therapy and lifestyle intervention on diabetes risk, it is unclear what effects these have on individual NEFAs and whether reduction of serum NEFAs may account for their efficacy. These questions assume particular relevance in older adults, the group at greatest risk for cardiometabolic disorders. Our central hypothesis is that higher post-load NEFAs and atherogenic NEFA patterns can identify subjects at higher risk of cardiometabolic diseases and such abnormality can be favorably influenced by metformin therapy and/or lifestyle intervention. We will use prospective data from the Cardiovascular Health Study to examine the associations of post-glucose challenge NEFAs on the risk of cardiometabolic diseases (Aim 1) and evaluate associations of individual NEFAs (using an unbiased approach) and patterns of NEFAs (using current knowledge to derive NEFA patterns) with incident diabetes, atrial fibrillation, heart failure, and mortality (aim 2). Using data from the Diabetes Prevention Program, we will examine the effects of metformin therapy and lifestyle intervention on serum NEFAs collected 3 years apart. Our findings will shape our understanding of the role of NEFAs in diabetes and cardiovascular disease, and, given recent advances in NEFA receptor agonists, could identify potential drug targets for prevention of diabetes and its cardiovascular complications. Finally, our findings have the potential to harness low-cost and sustainable lifestyle interventions to address derangements in NEFA metabolism in elders, and extend some of the most important findings from our previous work in new directions in basic, translational, and population science.

抽象的 非酯化脂肪酸（NEFA）在2型糖尿病和心血管的发展中起着核心作用 疾病（CVD）。尽管总禁食的NEFA与糖尿病，CVD和 死亡率，先前的队列研究没有研究过口服葡萄糖后测得的NEFA的关联 尽管心脏代谢疾病与胰岛素敏感性相关得多，但对心脏代谢疾病的挑战。 此外，总NEFA由> 40种不同的脂肪酸组成，单个NEFA或模式的哪个子集 NEFAS赋予心脏代谢疾病的最大风险目前尚不清楚。此外，虽然很大 随机试验证明了二甲双胍治疗和生活方式干预对糖尿病风险的功效， 目前尚不清楚这些对单个NEFA的影响以及血清NEFA的减少是否可能说明 因为他们的功效。这些问题在老年人中具有特别相关，该小组面临的风险最大 心脏代谢疾病。我们的中心假设是较高的载荷后NEFA和动脉粥样硬化NEFA 模式可以识别出较高的心脏代谢疾病风险的受试者，这种异常可能是有利的 受二甲双胍治疗和/或生活方式干预的影响。我们将使用来自 心血管健康研究以检查葡萄糖后挑战NEFA的关联 心脏代谢疾病（AIM 1）并评估单个NEFA的关联（使用公正的方法） NEFA的模式（使用当前知识来得出NEFA模式），患有糖尿病，心房 纤颤，心力衰竭和死亡率（AIM 2）。使用来自糖尿病预防计划的数据，我们将 检查二甲双胍治疗和生活方式干预对相距3年收集的血清NEFA的影响。 我们的发现将影响我们对NEFA在糖尿病和心血管疾病中的作用的理解，以及 鉴于NEFA受体激动剂的最新进展，可以识别预防潜在的药物靶标 糖尿病及其心血管并发症。最后，我们的发现有可能利用低成本和 可持续的生活方式干预措施以解决长老中NEFA代谢的危险，并扩展一些 我们以前在基本，翻译和人口新方向上的工作中最重要的发现 科学。