METABOLIC ALTERATIONS IN CACHECTIC PATIENTS WITH CHRONIC OBSTRUCTIVE PULMONARY D

慢性阻塞性肺疾病患者的代谢变化

• 批准号: 7950695
• 负责人: FAROOK JAHOOR
• 金额: $ 0.41万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7950695
• 关键词: Acidosis; Affect; Alanine; Biochemical; Body Weight decreased; Branched-Chain Amino Acids; C-reactive protein; Cachexia; Catabolism; Chronic; Chronic Obstructive Airway Disease; Clinical Research; Computer Retrieval of Information on Scientific Projects Database; Disease; Exercise Tolerance; Exposure to; Fatty acid glycerol esters; Functional disorder; Funding; Future; Gluconeogenesis; Glucose; Glutamates; Glutathione; Grant; Hyperglycemia; Hyperinsulinism; Hypoxemia; Inflammation; Institution; Insulin; Interleukin-6; Lead; Lung; Malignant Neoplasms; Measurement; Metabolic; Methods; Muscle; Patients; Peripheral; Plasma; Play; Production; Protein Biosynthesis; Proteins; Pulmonary Function Test/Forced Expiratory Volume 1; Pyruvate; Pyruvates; Quality of life; Research; Research Personnel; Resources; Role; Secondary to; Severity of illness; Source; Syndrome; Tracer; United States National Institutes of Health; Walking; airway obstruction; cigarette smoking; cytokine; glucose metabolism; glucose production; inflammatory marker; mortality; muscle form; muscle strength; oxidation; stable isotope

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Chronic obstructive pulmonary disease (COPD) is a disease caused by exposure to cigarette smoke and is characterized by airflow limitation resulting from airway obstruction and inflammation. Although COPD primarily affects the lung, it has significant consequences in the whole body, including weight loss and peripheral muscle dysfunction. Because of a preferential loss of muscle mass over fat, weight loss in COPD can be characterized as cachexia and is associated with poor quality of life, impaired exercise tolerance, and increased mortality. Multiple factors associated with cachexia in other diseases such as cancer and acquired syndrome may also play a role in COPD. These include increased levels of proinflammatory cytokines, hypoxemia, acidosis, and inactivity. While the exact mechanisms underlying cachexia in COPD remain unclear, most studies attribute it to the inflammation that occurs in this disease. This inflammation may lead to changes in both protein and glucose metabolism. The purpose of this study is to use stable isotope and biochemical methods to determine differences in protein synthesis and breakdown, glucose production and clearance, and conversion of glucose to produce pyruvate and lactate in patients with COPD with weight loss compared with patients with COPD without weight loss. Results from this study will increase our understanding of the mechanisms of cachexia in patients with COPD and may identify potential targets for future therapy. As compared with patients with COPD without cachexia, patients with COPD and cachexia will have: Hypothesis Increased net protein loss secondary to increased protein catabolism and decreased protein synthesis. Hypothesis Hyperinsulinemia and hyperglycemia secondary to increased gluconeogenesis and decreased glucose clearance. Hypothesis Increased lactate production because of increased pyruvate availability secondary to decreased pyruvate oxidation and decreased conversion to alanine. Hypothesis Increased levels of inflammatory markers and increased severity of illness. SPECIFIC AIMS Stable isotope tracer and biochemical methods will be used to study and compare two groups of subjects: patients with COPD without cachexia and patients with COPD and cachexia. The following measurements will be made in the postabsorptive state: Specific Aim Whole body protein breakdown, synthesis, and catabolism and plasma concentrations of the branched chain amino acids Specific Aim Endogenous glucose flux, total glucose production, glucose clearance, and plasma insulin levels Specific Aim Pyruvate flux, pyruvate oxidation, the rate of conversion of pyruvate to alanine, lactate flux, and plasma glutamate and alanine concentrations Specific Aim Plasma concentrations of TNF-a, IL-6, C-reactive protein, and glutathione; and FEV1, BODE score, 6 minute walk distance, and muscle strength using dynamometry

该子项目是利用该技术的众多研究子项目之一 资源由 NIH/NCRR 资助的中心拨款提供。子项目及 研究者 (PI) 可能已从 NIH 的另一个来源获得主要资金， 因此可以在其他 CRISP 条目中表示。列出的机构是 对于中心来说，它不一定是研究者的机构。 慢性阻塞性肺疾病（COPD）是一种由接触香烟烟雾引起的疾病，其特征是气道阻塞和炎症导致气流受限。 尽管慢性阻塞性肺病主要影响肺部，但它也会对全身产生重大影响，包括体重减轻和外周肌肉功能障碍。 由于肌肉质量比脂肪优先减少，慢性阻塞性肺病患者的体重减轻可被描述为恶病质，并与生活质量差、运动耐量受损和死亡率增加有关。 与癌症和获得性综合征等其他疾病中的恶病质相关的多种因素也可能在慢性阻塞性肺病中发挥作用。 这些包括促炎细胞因子水平升高、低氧血症、酸中毒和缺乏活动。 虽然慢性阻塞性肺病恶病质的确切机制尚不清楚，但大多数研究将其归因于这种疾病中发生的炎症。 这种炎症可能会导致蛋白质和葡萄糖代谢的变化。 本研究的目的是使用稳定同位素和生化方法来确定体重减轻的慢性阻塞性肺病患者与体重减轻的慢性阻塞性肺病患者相比，蛋白质合成和分解、葡萄糖产生和清除以及葡萄糖转化为丙酮酸和乳酸的差异。损失。 这项研究的结果将增加我们对慢性阻塞性肺病患者恶病质机制的理解，并可能确定未来治疗的潜在目标。 与没有恶病质的慢性阻塞性肺病患者相比，患有恶病质的慢性阻塞性肺病患者会出现： 假设 蛋白质分解代谢增加和蛋白质合成减少继发净蛋白质损失增加。 假设高胰岛素血症和高血糖继发于糖异生增加和葡萄糖清除率降低。 假设由于丙酮酸氧化减少和丙氨酸转化减少继发丙酮酸可用性增加，因此乳酸产量增加。 假设炎症标志物水平升高，疾病严重程度增加。 具体目标 将使用稳定同位素示踪剂和生化方法来研究和比较两组受试者：没有恶病质的慢性阻塞性肺病患者和患有恶病质的慢性阻塞性肺病患者。 以下测量将在吸收后状态下进行： 具体目标 全身蛋白质分解、合成和分解代谢以及支链氨基酸的血浆浓度 具体目标 内源性葡萄糖通量、总葡萄糖产生、葡萄糖清除率和血浆胰岛素水平 具体目标 丙酮酸通量、丙酮酸氧化、丙酮酸转化为丙氨酸的速率、乳酸通量以及血浆谷氨酸和丙氨酸浓度 具体目标 TNF-a、IL-6、C 反应蛋白和谷胱甘肽的血浆浓度；以及 FEV1、BODE 评分、6 分钟步行距离以及使用测力法的肌肉力量