The Metabolic Syndrome (Met. Syn.) has been defined as insulin resistance (I.R.), central obesity, systemic hypertension and dyslipidemia and is associated with increased cardio/cerebrovascular (CV) risk. I.R. may mediate much of this risk. Obstructive Sleep Apnea-Hypopnea (OSAH) is also associated with augmented CV risk and I.R. and plausibly, the CV risk of OSAH is mediated through I.R. Since OSAH is associated with both Oxidative Stress (O.S.) and pro-inflammatory processes, and O.S. is associated with I.Ro, it follows that O.S. and inflammation may link OSAH to I.R. and the Met. Syn. The Overall Goal of this research is to test the hypothesis that O.S and Inflammation link OSAH to I.R. as well as other CV risk-promoting conditions reflecting Met. Syn. We will specifically test if individual sleep consequences of OSAH, including Sleep Fragmentation and Intermittent Sleep Hypoxia, promote O.S. and Inflammation which in turn promote I.R. and other features of the Met. Syn. We propose:
Specific Aim : la: To determine the effect of Sleep Fragmentation on O.S. and Inflammation and to explore the relationships between O.S. and Inflammation and I.R., dyslipidemia, sympathovagal tone and plasma cortisol, we will measure the following study variables: I.R., lipid profile, circulating & exhaled biomarkers of O.S., pro-inflammatory cytokines, plasma cortisol, & heart period variability before and after 2 consecutive nights with experimentally induced Sleep Fragmentation in normal subjects.
Aim lb: To assess interaction between i) pre-existing Met. Syn., and ii) the overweight condition without Met. Syn., with regard to the effects of Sleep Fragmentation on the study variables, we will contrast the effect of experimentallyinduced sleep disruption in: non-OSAH/overweight individuals/(+)Met. Syn., non-OSAH/overweight individuals/(-)Met. Syn. and a control group of non-OSAH/normal weight/(-)Met. Syn.;
Aim : 2: To evaluate the effect of Intermittent Sleep Hypoxia on O.S. and Inflammation and explore the relationships between O.S. and Inflammation and I.R., dyslipidemia, sympathovagal tone and plasma cortisol. OSAH patients on chronic positive airway pressure (PAP) therapy will have biomarkers of O.S., Inflammation and the other above study variables, measured under two conditions in random order: i) before and after 2 consecutive nights using PAP therapy but with experimentally induced Sleep Fragmentation (fragmentation+normoxia), ii) before and after 2 nights without PAP (fragmentation+hypoxia) to evaluate for an independent Intermittent Sleep Hypoxia effect.;
Aim : 3: Using microarray data from peripheral monocytes, we will explore if specific gene expression profiles after the study conditions are associated with alterations consistent with Met. Syn.
| Rodway, George W; Hoffman, Leslie A; Tasota, Frederick J et al. (2008) Inducing hypoxemia in healthy humans: a method for intermittently lowering arterial blood oxygenation during physiological studies. Wilderness Environ Med 19:218-20 |
| Sanders, Mark H; Montserrat, Josep M; Farre, Ramon et al. (2008) Positive pressure therapy: a perspective on evidence-based outcomes and methods of application. Proc Am Thorac Soc 5:161-72 |
| Rodway, George W; Sethi, Jigme M; Hoffman, Leslie A et al. (2007) Hemodynamic and molecular response to intermittent hypoxia (IH) versus continuous hypoxia (CH) in normal humans. Transl Res 149:76-84 |
