The purpose of this study is to determine if the treatment of Obstructive sleep apnea (OSA) by hypoglossal nerve stimulation (HGNS) will alter glucose metabolism. The study team will also determine if the treatment of Obstructive sleep apnea (OSA) by (hypoglossal nerve stimulation) HGNS will alter predictors of cardiovascular outcomes.

Obstructive sleep apnea (OSA) is a highly prevalent sleep disorder in the general population. It is estimated that 80 percent of those who have OSA remain undiagnosed, and thus do not receive therapy. Strong evidence from epidemiologic and clinical studies suggests that untreated OSA is an independent risk factor for cardiometabolic disease, particularly among those with moderate-to-severe OSA. Animal and human models have revealed that intermittent hypoxia and sleep fragmentation (i.e., main features of OSA) result in insulin resistance, glucose intolerance and pancreatic beta-cell dysfunction, hypertension and dyslipidemia. Continuous positive airway pressure (CPAP) is the established first-line treatment for OSA. However, only 50% of patients with OSA are adherent to CPAP therapy. Notably, a key limitation of prior CPAP trials on cardiometabolic outcomes is low treatment adherence.

A randomized controlled trial conducted at the University of Chicago demonstrated that 8 hours of nightly CPAP reduces glucose response during oral glucose tolerance testing and improves insulin sensitivity in individuals with OSA and prediabetes. In 2014, following the pivotal Safe and Timely Antithrombotic Removal - Ticagrelor trial (STAR), the Food and Drug Administration (FDA) approved hypoglossal nerve stimulation (HNS) as an alternative therapy for OSA. Five-year outcomes from STAR have confirmed durable efficacy, tolerance, and safety for HNS. From improved tolerance and adherence, it is theorized that HNS may be more effective than CPAP at ameliorating cardiovascular and diabetes risk. Yet, there is no literature on the cardiometabolic outcomes of treating OSA with HNS.

The study team's long-term goal is to understand the metabolic and cardiovascular effects of OSA and how current therapies can mitigate risk and improve outcomes. The overall objective of this study is to determine the cardiometabolic impact of HNS therapy in patients with moderate-to-severe OSA who are intolerant to CPAP. It is hypothesized by the investigator that effective HNS treatment will improve glucose metabolism and markers of cardiovascular disease.

Inclusion Criteria:

• Overweight or obese males and females BMI 25 kg/m2 to 40 kg/m2
• Age 18 years and older
• Diagnosed with obstructive sleep apnea by Apnea-Hypopnea Index >15 events/hr using 4% oxygen desaturation criteria and < 25% central events/hr on prior sleep testing Data can be derived from home sleep testing or in-lab polysomnogram
• Not able to use positive airway pressure >4 hours for 5 nights/week or unwilling to use positive airway pressure

Exclusion Criteria:

• Insulin-dependent Diabetes
• Inability to undergo in-lab polysomnography or home sleep testing
• Central Nervous System (CNS) disease with impairment of cognitive function (dementia) and/or muscle paresis, such as stroke
• Currently pregnant, trying to get pregnant or nursing
• age < 18 years
• Regular and adherent CPAP use per clinical guidelines
• Current night shift or rotating shift work
• Diagnosis of another sleep disorder (e.g. periodic limb movement disorder)
• Current systemic steroid use
• Predominantly central sleep apnea or requiring oxygen or bi-level positive airway pressure or advanced positive airway pressure modalities
• Protected patient: under guardianship, curatorship or other legal protection, deprived of liberty by judicial or administrative decision, including hospitalized without consent

The subjects will be recruited from the Sleep Surgery Clinic of the Duchossois Center for Advanced Medicine (DCAM) in Hyde Park and Sleep Surgery Clinic of UChicago Medicine - Orland Park and Hinsdale.. We will take advantage of the electronic medical records (EMR) to identify potential candidates using databases (EPIC-based) from the University of Chicago and Ingalls. Participants will be identified by an initial screening of patients scheduled in EPIC for drug induced sleep endoscopy (DISE).