OSA AND GLUCOSE METABOLISM

阻塞性睡眠呼吸暂停（OSA）会导致间歇性缺氧和睡眠碎片。是 在肥胖人群中很常见，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（高胰岛素血症- 正葡萄糖钳夹技术结合稳定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和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 葡萄糖调节）负责OSA患者的葡萄糖代谢失调。在 此外，我们还将通过以下方法研究缺氧与睡眠片段的相对影响： 比较夜间补充供氧治疗的代谢反应， 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，而气道正压通气（PAP）可以消除缺氧，但不能消除睡眠碎片。 消除缺氧和睡眠碎片。

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.