OSA AND GLUCOSE METABOLISM

OSA 和葡萄糖代谢

• 批准号: 9424214
• 负责人: Bettina Mittendorfer
• 金额: $ 75万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-15 至 2022-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9424214
• 关键词: Adipose tissue; Affect; Age; Apnea; Arousal; Beta Cell; Biopsy; Blood; Blood Circulation; Blood Glucose; Body Composition; Body fat; Cell physiology; Cellular Stress; Closure by clamp; Data; Diabetes Mellitus; Dual-Energy X-Ray Absorptiometry; Euglycemic Clamping; Extrahepatic; Fatty acid glycerol esters; Functional disorder; Gastrocnemius Muscle; Glucose; Glucose Intolerance; Goals; Health; Hepatic; Hormones; Hypoxemia; Hypoxia; Impairment; In Situ; Individual; Inferior; Inflammation; Infusion procedures; Insulin; Insulin Resistance; Kinetics; Label; Lead; Link; Liver; Magnetic Resonance Spectroscopy; Mediating; Metabolic; Metabolism; Muscle; Muscle Cells; Non-Insulin-Dependent Diabetes Mellitus; Nonesterified Fatty Acids; Obesity; Obstructive Sleep Apnea; Outcome; Oxygen; Placebos; Plant Roots; Plasma; Positron-Emission Tomography; Prediabetes syndrome; Procedures; Race; Radio; Randomized; Rattus; Research; Risk Factors; Rodent; Severities; Signal Transduction; Site; Sleep; Sleep Fragmentations; Soleus Muscle; Stress; Techniques; Testing; Time; Tissues; Tracer; adipokines; cytokine; diabetes risk; glucose disposal; glucose metabolism; glucose production; glucose transport; glucose uptake; improved; indexing; inflammatory marker; insulin secretion; insulin sensitivity; insulin signaling; intravenous glucose tolerance test; mathematical model; metabolic phenotype; pressure; response; sex; spectroscopic imaging; stable isotope; sugar; tissue oxygenation; treatment response

Obstructive sleep apnea (OSA) causes intermittent hypoxia and sleep fragmentation. It is common in people with obesity and is a major risk factor for prediabetes and type 2 diabetes. The goal of our application is to examine the mechanisms responsible for abnormal glucose metabolism in OSA. We will use a “deep metabolic phenotyping” approach (hyperinsulinemic- euglycemic clamp technique combined with stable isotope- and radio-labelled tracer infusions, dynamic positron emission tomography, adipose and muscle tissue biopsies, the insulin- modified intravenous glucose tolerance test, and detailed body composition analysis with dual- energy X-ray absorptiometry, and magnetic resonance and spectroscopy imaging) to determine the key tissues and metabolic mechanisms (multi-organ insulin sensitivity, β-cell function, hepatic and extra-hepatic insulin clearance, and systemic and cellular factors that can impair glucoregulation) responsible for dysregulated glucose metabolism in people with OSA. In addition, we will examine the relative impact of hypoxia versus sleep fragmentation by comparing the metabolic response to treatment with night-time supplemental oxygen, which eliminates hypoxia but not sleep fragmentation, versus positive airway pressure (PAP), which eliminates both hypoxia and sleep fragmentation.

阻塞性睡眠呼吸暂停(OSA)会导致间歇性低氧和睡眠碎片。它是 在肥胖者中很常见，是糖尿病前期和2型糖尿病的主要危险因素。 我们的应用程序的目标是检查导致血糖异常的机制 阻塞性睡眠呼吸暂停综合征的新陈代谢。我们将使用“深层代谢表型”方法(高胰岛素血症- 正血糖钳夹技术结合稳定的同位素和放射性标记示踪剂输注， 动态正电子发射断层扫描，脂肪和肌肉组织活检，胰岛素- 改良的静脉葡萄糖耐量试验，以及详细的身体成分分析 能量X射线吸收法、磁共振和光谱成像)以确定 关键组织和代谢机制(多器官胰岛素敏感性、β细胞功能、 肝脏和肝外胰岛素清除，以及可能损害的全身和细胞因素 糖调节)是阻塞性睡眠呼吸暂停综合征患者糖代谢失调的原因。在……里面 此外，我们将通过以下方式检查低氧与睡眠碎片的相对影响 比较夜间补充氧气治疗的代谢反应，这是 消除低氧，但不能消除睡眠碎片，而不是气道正压(PAP)，后者 消除缺氧和睡眠碎片。