Rationale: Approximately 15-20% of adults have obstructive sleep apnea (OSA), and evidence indicates that the prevalence of OSA is perhaps twice as high among Veterans. OSA has been clearly linked to increased mortality and multiple morbidities, and undoubtedly contributes to the high prevalence of health problems among Veterans. Current treatments for OSA are not well tolerated, often have limited efficacy, and often do not result in improvements in health. The investigators' recent research demonstrated that 12 weeks of moderate exercise training elicited a reduction of OSA of \~25%, as well as significant improvement in mood, fatigue, quality of life, and cardiovascular health. Interestingly, as with other health benefits of exercise, the investigators' research is consistent with other research showing that exercise can reduce OSA independent of changes in body weight. These studies raise the exciting possibility that exercise training combined with modest weight loss could elicit a chronic reduction in OSA of 50% or more.

Objectives: The investigators' Objective is to compare the effects of 16 weeks of exercise training alone, weight loss alone, and exercise + weight loss on OSA severity and associated morbidity.

Methods: Following extensive screening and baseline assessment, N=90 overweight/obese Veterans (ages 18-60 years) with mild to severe OSA will be randomized to one of three 16-week treatments. (1) Exercise Alone (n=30) will involve training 4 days per week under supervision of a clinical exercise physiologist. It will include aerobic exercise (treadmill, cycling, elliptical) that will gradually increase to 30-45 min on 4 days/wk, as well as resistance exercise (15 min) on 2 days/week. (2) Weight Loss Alone (n=30) will involve a structured meal plan (including some meal replacement with shakes or bars), and weekly counseling designed to elicit a reduction in body weight of 10%. (3) Exercise + Weight Loss (n=30) will involve the same exercise and weight loss interventions as in the other treatments. Outside of the interventions, participants will be asked to maintain their usual exercise and diet habits, as verified, respectively, with actigraphic recording and a 24-hr food recall. Before and after the treatments, participants will undergo 5 days/nights of home-based actigraphic and diary-assessed sleep, and one night of laboratory polysomnographic recording of sleep, including OSA severity. Comorbidity measures will include pre- to post-treatment changes in blood pressure, glucose, insulin, lipids, hemoglobin a1c, body weight/composition, and inflammation (e.g., CRP, IL-6). Also measured will be monthly changes in self-reports of sleep quality, functional outcomes of sleepiness (FOSQ), and snoring symptoms. A 3-month follow-up will include home assessment of OSA, as well as sleep quality, FOSQ, and snoring. Mediation analysis will explore whether improvements in OSA are mediated by changes in percent of deep sleep, body weight, trunk body fat percent, trunk total mass, respiratory muscle strength, and upper airway obstruction assessed in the laboratory.

Implications for Future Research. Demonstration of a reduction of OSA by 50% would result in extensive subsequent studies. These would likely include studies of dose-response effects; comparisons of different modes of exercise; studies of the feasibility of telemedicine approaches to the interventions; comparative efficacy studies vs. PAP; further mechanistic studies, for example, of upper airway collapsibility and composition (e.g, via MRI); and studies of other positive health outcomes, such as extensive heart imaging.