Obstructive Sleep Apnea and Glucose Metabolism
Obstructive Sleep Apnea and Glucose Metabolism
Many adults who are overweight have obstructive sleep apnea (OSA) which disrupts sleep and
 makes it difficult to breath during the night. OSA increases the risk for a person to become
 insulin resistant and diabetic. It is not known why OSA causes this problem, i.e., whether it
 is disrupted sleep or lack of oxygen., which can change how the body handles glucose in
 adipose tissue, muscle tissue and liver.

 The purpose of this research study is to determine the key issues and mechanisms responsible
 for dysregulated glucose metabolism in people with OSA. The investigators will do this by
 comparing glucose metabolism in people who have OSA, and those who do not, and by evaluating
 the effect of treating OSA by providing continuous positive airway pressure (CPAP) or simply
 oxygen during the night.

 The proposed study will evaluate the primary causes(s) (hypoxia, sleep fragmentation, or
 both) and pathophysiological mechanisms responsible for the OSA-associated metabolic
 abnormalities. Knowing the primary cause of Obstructive Sleep Apnea and pathophysiological
 mechanisms responsible for the OSA-associated metabolic abnormalities could help develop
 potentially novel therapeutic strategies to provide treatment for adults in improving OSA and
 associated comorbidities.
General Inclusion Criteria (for all subjects):

 -  Age: ≥30 and ≤70 years,

 -  BMI: ≥30 and ≤45 kg/m2 or body fat ≥ 30 % for women and ≥ 25 % for men,

 -  Maximum body circumference <170 cm

 -  Weight stable (≤2% change)

 -  Untrained (≤1 h of structured exercise/wk) for at least 3 months before entering the
 study

 -  No diabetes (fasting blood glucose <126 mg/dl, 2h oral glucose tolerance test (OGTT)
 glucose <200 mg/dl, HbA1c ≤6.5%)

 Sleep-related inclusion criteria:

 Subjects without OSA:

 -  AHI <5/h of sleep;

 -  Oxygen desaturation index <3/h

 -  No known sleep disorders and periodic limb movement arousal index <15/h during
 polysomnography

 -  Reported sleep duration ≥6 h per night

 -  Regular sleep schedules (i.e. bedtime between 8 pm and 12 am and wake-time between 4
 am and 8 am on all days of the week)

 Subjects with OSA

 -  AHI ≥10/h of sleep (i.e., moderate to severe OSA)

 -  Oxygen desaturation index ≥4/h;

 -  No polysomnogram finding that would trigger immediate PAP treatment as per standard
 operating protocol in our sleep medicine center (a single SaO2 <50%, SaO2 <70% for >2
 minutes, electrocardiogram pause >5 sec, or ventricular tachycardia >30 sec), because
 of the risk of a potentially adverse outcome if they are not randomized to the PAP
 group

 -  Periodic limb movement arousal index <15/h during polysomnography,

 -  Reported sleep duration ≥6 h per night,

 -  Regular night-time sleep schedules, defined as bedtime between 8 pm and 12 am and
 wake-time between 4 am and 8 am on all days of the week.

 General Exclusion Criteria (for all subjects):

 -  Current treatment for previously diagnosed OSA;

 -  Self-reported severe difficulty sleeping in unfamiliar environments;

 -  Metal implants that are incompatible with magnetic resonance imaging;

 -  Controlled substances, tobacco products, dietary supplements, or medications known or
 suspected to affect sleep, breathing, upper airway muscle physiology, or glucose
 metabolism

 -  Evidence of disease (e.g., diabetes, congestive heart failure; chronic obstructive
 pulmonary disease; hypoventilation, defined as daytime partial pressure of carbon
 dioxide (pCO2) >45 mm Hg; major neurological or neuromuscular disorders; cancer;
 uncontrolled hypertension; etc.);

 -  Contraindications to supplemental oxygen or PAP (e.g., recent trans-sphenoidal
 surgery).

 -  Unwillingness or inability to provide informed consent

 -  Study physician considers subject to be unable to safely complete the study protocol