This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Cross-sectional studies indicate that sleep disordered breathing (SDB) occurs commonly in individuals with diabetes, hypertension, and obesity. Small, uncontrolled clinical studies of sleep apnea patients suggest that some indices of metabolic syndrome, systemic inflammation, and thrombosis may improve with sleep apnea treatment. However, to date, there have been no rigorously conducted studies to assess the extent to which the physiological stressors associated with SDB may be causally implicated in metabolic syndrome, and whether treatment of SDB improves indices of insulin resistance. We propose a rigorous controlled assessment of the effect of continuous positive airway pressure (CPAP) therapy on indices of metabolic syndrome, inflammatory status, and markers of endothelial function.
The specific aims and hypotheses are extensive and detailed in the protocol but include improvement in indices of metabolic syndrome, inflammation, sympathetic nervous system over-activity, endothelial function, and blood pressure after 2 months of CPAP therapy. This is a single-center, randomized, blinded, cross-over study. Subjects must have moderate to severe SDB and impaired glucose tolerance and not be on current treatment for either condition. Following a two-week run-in period and a one-month wash-out period, subjects will be randomized to receive either CPAP or sham-CPAP therapy for 8 weeks. (Sham-CPAP therapy will be delivered by altering the CPAP system to deliver less pressure and acts as a placebo.) Then there is a one-month wash-out period and subjects will for 8 weeks receive the alternative therapy (sham-CPAP or CPAP) to what they first received. Study procedures done on the GCRC will include overnight measures of sleep and breathing, oral glucose tolerance tests, blood and urine samples, blood pressure, brachial ultrasound, sleep and quality of life questionnaires, anthropometry, and abdominal CT scans. A future plan for year 3.5 of the study adds euglycemic hyperinsulinemic clamp studies for a subset of subjects to validate the increase in insulin sensitivity in CPAP-treated participants. 84 subjects will be enrolled in the two-week CPAP run-in study. 50 of those subjects will be randomized to continue with the rest of the study procedures, and assuming a 15% dropout rate, complete data on 42 subjects is expected.
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