Obstructive Sleep Apnea (OSA) and Metabolic Syndrome: Role of Oxidative Stress

The metabolic syndrome has been defined as insulin resistance, central obesity, systemic hypertension and dyslipidemia and is associated with increased cardiovascular (CV) risk. Obstructive Sleep Apnea-Hypopnea (OSAH) is also associated with increased CV risk and insulin resistance. Since OSAH is associated with oxidative stress and pro-inflammatory processes, both of which are associated with insulin resistance, it follows that oxidative stress and inflammation may mediate the linkage between OSAH, insulin resistance and ultimately, the metabolic syndrome. The overall goal of this research is to test the hypothesis that oxidative stress and inflammation link OSAH to insulin resistance as well as other CV risk-promoting conditions reflecting the metabolic syndrome (e.g. hyperlipidemia). We will specifically test if the individual sleep consequences of OSAH, including sleep fragmentation and intermittent sleep hypoxia, promote oxidative stress and inflammation which in turn promote insulin resistance and other features of the metabolic syndrome. Aim 1a: To determine the effect of sleep fragmentation on oxidative stress and inflammation and features of the metabolic syndrome including insulin resistance, dyslipidemia, obesity, and hypertension. Aim 1b: To assess the interaction between pre-existing metabolic syndrome and the overweight condition without metabolic syndrome, with regard to the effects of sleep fragmentation on the study variables, we will contrast the effect of experimentally-induced sleep fragmentation in non-OSAH/overweight individuals with the metabolic syndrome, non-OSAH/overweight individuals without metabolic syndrome and a control group of non-OSAH/normal weight without metabolic syndrome. Aim: 2: To evaluate the effect of intermittent sleep hypoxia on oxidative stress and inflammation and explore the relationships between these two processes and insulin resistance, lipid profile, heart period variability and plasma cortisol. Aim: 3: Using microarray data from peripheral monocytes, we will explore if specific gene expression patterns after the study conditions are associated with alterations consistent with metabolic syndrome. Aim: 4: This exploratory aim is to collect preliminary data regarding the correlation among genetic variations (polymorphisms), gene expression patterns (microarray) and resultant protein production (proteomics). These data will be used for hypothesis development.