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

基本信息

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
项目类别：
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

项目摘要

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

该副本是利用众多研究子项目之一由NIH/NCRR资助的中心赠款提供的资源。子弹和调查员（PI）可能已经从其他NIH来源获得了主要资金，因此可以在其他清晰的条目中代表。列出的机构是对于中心，这不一定是调查员的机构。慢性阻塞性肺疾病（COPD）是暴露于香烟烟雾的疾病，其特征是气道阻塞和炎症引起的气流限制。尽管COPD主要影响肺部，但它对整个身体产生了重大影响，包括体重减轻和周围肌肉功能障碍。由于肌肉质量比脂肪的优先损失，因此COPD的体重减轻可以被描述为恶病质，并且与生活质量差，运动耐受性受损和死亡率增加有关。与其他疾病（例如癌症和获得综合征）中的卡氏症相关的多个因素也可能在COPD中起作用。这些包括促炎细胞因子，低氧血症，酸中毒和无活跃的水平增加。尽管COPD中的恶病质的确切机制尚不清楚，但大多数研究将其归因于该疾病中发生的炎症。这种炎症可能导致蛋白质和葡萄糖代谢的变化。这项研究的目的是使用稳定的同位素和生化方法来确定蛋白质合成和分解，葡萄糖产生和清除率的差异，以及葡萄糖的转化率与COPD患者相比，体重减轻患者的COPD患者中产生丙酮酸和乳酸患者。这项研究的结果将提高我们对COPD患者恶病质机制的理解，并可能确定未来治疗的潜在靶标。与没有恶病质的COPD患者相比，患有COPD和恶病质的患者将患有：假设增加了蛋白质分解代谢增加和蛋白质合成减少的净蛋白损失。假设高胰岛素血症和高血糖继发于增加糖异生和葡萄糖清除率降低。假设由于丙酮酸氧化降低并降低向丙氨酸的转化而增加了丙酮酸的可用性增加。假设增加了炎症标记水平和疾病严重程度的增加。具体目标稳定的同位素示踪剂和生化方法将用于研究和比较两组受试者：没有卡氏病的COPD患者和COPD和Cachexia患者。以下测量将以释放状态进行：分支链氨基酸的特定目标全身蛋白质分解，合成，分解代谢和血浆浓度特定的目标内源性葡萄糖通量，总葡萄糖产生，葡萄糖清除和血浆胰岛素水平特定的目标丙酮酸通量，丙酮酸氧化，丙酮酸转化为丙氨酸，乳酸通量和血浆谷氨酸和丙氨酸浓度的速率 TNF-A，IL-6，C反应蛋白和谷胱甘肽的特定目标血浆浓度；和FEV1，Bode评分，步行6分钟，肌肉强度使用元计