OSA AND GLUCOSE METABOLISM

OSA 和葡萄糖代谢

基本信息

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
项目类别：
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

项目摘要

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) 会导致间歇性缺氧和睡眠碎片化。常见于肥胖人群，是糖尿病前期和 2 型糖尿病的主要危险因素。我们应用的目标是检查导致血糖异常的机制我们将使用“深度代谢表型分析”方法（高胰岛素血症）。血糖正常钳夹技术与稳定同位素和放射性标记示踪剂输注相结合，动态正电子发射断层扫描、脂肪和肌肉组织活检、胰岛素改良的静脉内葡萄糖耐量试验，以及双系统详细的身体成分分析能量 X 射线吸收测定法、磁共振和光谱成像）来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率，以及可能损害胰岛素清除率的全身和细胞因素葡萄糖调节）导致 OSA 患者葡萄糖代谢失调。此外，我们将通过以下方式检查缺氧与睡眠碎片化的相对影响比较夜间补充氧气治疗的代谢反应，与气道正压通气 (PAP) 相比，它可以消除缺氧，但不能消除睡眠碎片。消除缺氧和睡眠碎片。