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

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

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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破碎。这是在肥胖患者中常见，是糖尿病前和2型糖尿病的主要危险因素。我们应用的目的是检查负责异常葡萄糖的机制 OSA的代谢。我们将使用“深层代谢表型”方法（高胰岛素 - 葡萄糖夹具技术与稳定的同位素和无线电标记的示踪剂输注，动态正电子发射断层扫描，脂肪和肌肉组织活检，胰岛素 - 修饰的静脉葡萄糖耐受性测试和详细的身体成分分析，并具有双重能量X射线绝对测定法以及磁共振和光谱成像）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， Hepati和肝外胰岛素清除率以及可能损害的全身和细胞因素葡萄糖调节）负责OSA患者的葡萄糖代谢失调。在此外，我们将检查缺氧与睡眠碎片的相对影响比较夜间补充氧对治疗的代谢反应，这消除缺氧但没有睡眠碎片，与正气道压力（PAP）相比消除了缺氧和睡眠碎裂。