Effects of Continuous Positive Airway Pressure (CPAP) on Glucose Metabolism

Obstructive sleep apnea affects approximately 2-4% of middle-aged adults in the general population and is associated with several medical conditions including hypertension and coronary artery. Research over the last decade has shown that obstructive sleep apnea may also increase the propensity for insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Positive airway pressure (PAP) is the first line therapy for the treatment of obstructive sleep apnea. While PAP therapy has several favorable effects such as improvements in daytime sleepiness and quality of life, it is not clear whether using PAP therapy can alter metabolic risk. The overall objective of this study is to examine whether treatment of obstructive sleep apnea with positive airway pressure therapy improves glucose tolerance and insulin sensitivity. The primary hypothesis of this study is that PAP therapy of obstructive sleep apnea will improve in insulin sensitivity and glucose metabolism.

Type 2 diabetes mellitus is one of the most prevalent medical conditions, affecting a staggering 246 million people worldwide. Obstructive sleep apnea is a relatively common and often undiagnosed condition in the general population. Cross-sectional studies of clinic and population-based samples suggest that up to 40% of patients with obstructive sleep apnea have type 2 diabetes and up to 75% of patients with type 2 diabetes have obstructive sleep apnea. There is increasing evidence that the pathophysiological features of intermittent hypoxia and sleep fragmentation may be responsible for altering glucose homeostasis and worsening insulin sensitivity. The mechanisms through which obstructive sleep apnea impairs glucose metabolism are largely unknown. While intermittent hypoxemia and sleep fragmentation are likely to play an essential role, the relative contribution of each in the causal pathway remains to be determined. Moreover, whether the adverse effects of intermittent hypoxia and sleep fragmentation are mediated through an increase in sympathetic nervous system activity, alterations in corticotropic function, and/or systemic inflammation is not known. Furthermore, it remains to be determined whether positive pressure therapy for obstructive sleep apnea has salutary effects on glucose metabolism. Many of the available studies examining the effects of PAP on glucose tolerance and insulin sensitivity are plagued by small sample sizes, lack of a control group, and limited data on compliance with positive pressure therapy. The current study will assess, using a community-based sample, whether treatment of obstructive sleep apnea with positive pressure therapy will improve insulin sensitivity, as assessed by the frequently sample intravenous glucose tolerance test (primary outcome measure).

Eligibility Criteria:
Inclusion Criteria:

* Ability to give informed consent
* Obstructive sleep apnea (untreated)
* Ability to comply with study-related assessments

Exclusion Criteria:

* Inability to consent or commit to the required visits
* Diabetes mellitus (fasting glucose \> 126 mg/dl)
* Use of insulin or oral hypoglycemic agent
* Weight change of 10% in last six months
* Use of oral steroids in the last six months
* Severe pulmonary disease (i.e., COPD)
* Renal or hepatic insufficiency
* Recent Myocardial Infarction (MI) or stroke (\< 3 months)
* Occupation as a commercial driver
* Active substance use
* Untreated thyroid disease
* Pregnancy
* Anemia (Hematocrit \< 30%)
* Any history of seizures or other neurologic disease
* Poor sleep hygiene or sleep disorder other than sleep apnea
* Excessive subjective sleepiness (Epworth score \> 18)