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, ?-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.
Many people with obesity have obstructive sleep apnea (OSA). OSA is a major risk factor for diabetes. However, it is not known why OSA increases the risk for diabetes. This research will elucidate the mechanisms responsible for abnormal sugar metabolism in people with OSA. It will evaluate how people with OSA and people without OSA respond to sugar and insulin (a hormone that regulates blood sugar concentration) and how giving oxygen at night or positive airway pressure (PAP) affects this. The results from this study may lead to better treatments for people with OSA.
