Fat Metabolism and Digestion in Obstructive Sleep Apnea and Chronic Obstructive Pulmonary Disease
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 62
- 试验地点
- 1
- 主要终点
- Endogenous Glucose Production
研究概览
简要总结
Obstructive sleep apnea (OSA) is the most common type of sleep apnea and is caused by an obstruction of the upper airways. The obstruction results in periods of intermittent hypoxia and re-oxygenation, which lead to increased oxidative stress, increased inflammation, endothelial dysfunction, and insulin resistance. Chronic obstructive pulmonary disease (COPD) is a lung disease that leads to poor airflow. This disease leads to systemic hypoxia, reduced oxidative capacity, and increased inflammation. The direct cause of OSA and COPD is unclear, but OSA and COPD may be linked to other comorbid conditions such as obesity and type II diabetes. Upon onset of OSA and COPD, metabolic disturbances associated with obesity and type II diabetes can be exacerbated.
Obesity is a condition characterized by an increase in visceral fat, elevated plasma levels of free fatty acids, inflammation, and insulin resistance. Although the effects of body fat distribution have not been studied in these patients, an increase in both subcutaneous and abdominal fat mass in non-OSA older women was shown to increase morbidity and mortality. Fat/adipose tissue is an active tissue capable of secreting proinflammatory cytokines such as tumor necrosis factor (TNF)-alpha and interleukin (IL)-6, reactive oxygen species and adipokines. Particularly, abdominal fat is a prominent source of pro-inflammatory cytokines, which contributes to a low grade, chronic inflammatory state in these patients. Additionally, an increased inflammatory state is associated with reduced lean body mass, and together with elevated circulating free fatty acids may increase the occurrence of lipotoxicity and insulin resistance. Thus, increased fat deposition is associated with a poor prognosis in OSA and COPD patients and therefore it is of clinical and scientific importance to understand the changes in fat metabolism and digestion as a result of OSA and COPD.
It is therefore our hypothesis that fat synthesis and insulin resistance is increased and whole body protein synthesis is decreased in OSA and COPD patients, leading to a poor prognosis.
详细描述
This research study involves 3 visits for subjects and healthy controls. The first visit is the screening visit and includes review of the informed consent and a DXA scan and the second and third visit for the study days. For the first test day, 3 hours of the subjects time will be for urine and blood sample collection, and to stable isotope administration (deuterated water, isotopically labeled amino acids). Subjects are allowed to go home after and eat normally. On the second study day, subjects will arrive early that morning. For the duration of the study, subjects have to lie in the bed (except for bathroom privileges). They can watch tv or bring and use a book/tablet. The research nurse or study staff will be present in the human subject area to assist the subject if necessary. Subjects are not allowed to eat or drink during the second test day, except for the test drink (meal) and water. One IV catheter will be placed in a vein of the arm/hand for blood draws. The hand will be placed in a hot box during blood collection. Another IV catheter will be placed in the contra-lateral forearm for a primed and continuous infusion of isotopes (isotopically labeled amino acids and glycerol). Each day, a total of 80-100 ml of blood will be obtained. Stable isotopes will be ingested and infused on the first test day and added to the test drinks and infused on the second day. On the second test day, subjects will fill out questionnaires. After completion of the study, we will provide the subject with a meal.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Cross Sectional
入排标准
- 年龄范围
- 30 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- 未提供
排除标准
- 未提供
结局指标
主要结局
Endogenous Glucose Production
时间窗: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion
Determine whole body glucose production in subjects
Citrulline Rate of appearance
时间窗: Postabsorptive state during 2 hours
plasma enrichment of citrulline
Adipose tissue de novo lipogenesis
时间窗: pre and 4 hours post meal
changes in adipose tissue de novo lipogenesis before and after a meal
Net whole-body protein synthesis
时间窗: 0, 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210 min post-meal
change in whole-body protein synthesis rate after intake of meal
Hepatic triglyceride synthesis
时间窗: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion
changes in hepatic triglyceride synthesis before and after a meal
Glucose disposal
时间窗: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion
Determine whole body glucose uptake in subjects
Hepatic de novo lipogenesis
时间窗: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion
changes in hepatic de novo lipogenesis before and after a meal
Arginine turnover rate
时间窗: postabsorptive state during 3 hours
Arginine enrichment in plasma
Tryptophan turnover rate
时间窗: Postabsorptive state during 3 hours
Tryptophan enrichment in plasma
Adipose tissue triglyceride synthesis
时间窗: pre and 4 hours post meal
changes in adipose tissue triglyceride synthesis before and after a meal
Adipose tissue lipolysis - glycerol rate of appearance
时间窗: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion
changes in adipose tissue lipolysis before and after a meal. plasma enrichment of glycerol.
Rate of appearance of ingested glucose
时间窗: Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion
determine changes in appearance of glucose rate in subjects
Glycine rate of appearance
时间窗: Postabsorptive state during 3 hours
glycine enrichment in plasma
Taurine turnover rate
时间窗: postabsorptive state during 3 hours
enrichment of taurine in
Whole body collagen breakdown rate
时间窗: Postabsorptive state during 3 hours
Hydroxyproline enrichment in plasma
Myofibrillar protein breakdown rate
时间窗: 0,15,30,45,60,75,90,105,120,150,180,210 min post-meal
3methylhistidine enrichment in plasma
次要结局
- Fat digestion and absorption(Pre meal ingestion and 15, 30, 45, 60, 75, 90, 105, 120, 150, 180, 210, 240, 270, and 300 min post meal ingestion)
- Protein digestion after feeding(0,15,30,45,60,75,90,105,120,150,180,210, min post-meal)
- Body composition(1 day)
- Physical activity questionnaire(1 day)
- Insulin response to feeding(pre and up to 5 hours post meal)
研究者
Marielle PKJ Engelen, PhD
Associate Professor
Texas A&M University