Adipose Dysfunction, Imaging, Physiology, and Outcomes With Sodium Glucose Cotransporter 2 Inhibitor (SGLT2i) for Sleep Apnea: The ADIPOSA Study

Participants will undergo standard measurements including height, weight, waist circumference, hip circumference, and neck circumference by MRI to quantify fat and lean tissue composition in the neck and body. Volumetric imaging datasets of the body will be derived by MRI using validated and readily available protocols with rapid scan time to perform precise measurements of total and regional body composition to quantify fat and lean tissue composition in the neck and body. MRI imaging using a 6-minute dual-echo Dixon Vibe protocol, providing water and fat separated volumetric data set covering neck to knees, and a single-slice multi-echo Dixon acquisition for proton density fat fraction (PDFF) assessment in the liver.

Volumetric imaging datasets of the body derived by MRI using validated and readily available protocols with rapid scan time to perform precise measurements of total and regional body composition to quantify fat and lean tissue composition in the neck and body, including MRI imaging using a 6-minute dual-echo Dixon Vibe protocol, providing water and fat separated volumetric data set covering neck to knees, and a single-slice multi-echo Dixon acquisition for proton density fat fraction (PDFF) assessment in the liver.

Mathematical modeling to determine the patient's ventilatory drive in response to changes in ventilation induced by upper airway obstruction (i.e., apnea/hypopnea). Pharyngeal collapsibility, calculated as the level of ventilation during sleep at normal or eupneic ventilatory drive (Vpassive) and is a valid proxy for critical closing pressure (Pcrit) and a reflection of the impact of the anatomic traits of sleep apnea.

Change in neck circumference measured by tape measure. Measuring the change in the evening to morning neck circumference which is a validated measure of caudal to rostral fluid shift. Higher neck circumference indicates an increase in probability of sleep apnea.

Percent of time with O2 saturation < 90% (T90) recorded during the aPSG

Total arousal index (ArI) was defined as the total number of arousals recorded during the aPSG per hour of sleep.

The Insomnia Severity Index has seven questions. The seven answers are added up to get a total score. Total scores scale:

0-7 = No clinically significant insomnia 8-14 = Subthreshold insomnia 15-21 = Clinical insomnia (moderate severity) 22-28 = Clinical insomnia (severe)

This questionnaire contains 19 self-rated questions that are combined to form seven "component" scores, each of which has a range of 0-3 points. In all cases, a score of 0 indicates no difficulty in that area, while a score of 3 indicates severe difficulty. The seven component scores are then added to yield one global score, with a range of 0-21 points, with 0 indicating no difficulty and 21 indicating severe difficulties in all areas.

The seven component domains are: 1. Subjective sleep quality, 2. Sleep latency, 3. Sleep duration, 4. Habitual sleep efficiency, 5. Step disturbances, 6. Use of sleeping medication, and 7. Daytime dysfunction.

The 5 questions reduced MEQ is a self-assessment questionnaire. Responses to the questions are combined to form a composite score that indicates the degree to which the respondent favors morning versus evening. In Total Score (0-25) higher scores indicate morningness, lower scores indicate eveningness.

Regulatory Satisfaction Alertness Timing Efficiency Duration (RU-SATED) questionnaire. This is a multidimensional metric for sleep health with 6 questions. RU-SATED stands for: regularity of sleep, satisfaction with sleep, alertness during the day, timing of sleep, efficiency of sleep, and duration of sleep. Each question is scored 0, 1, or 2 based on rarely/never, sometimes, usually always responses. The scores are summed, and a higher score indicates better sleep health.

The questionnaire is divided into two sections. The first section assesses sleep duration in hours as a weighted average of work night hours and weekend night hours. Sleep deprivation is determined from the reported hours of sleep as follows: ≥7 hours = no sleep deprivation; <7 but ≥5 hours = mild to moderate sleep deprivation; <5 hours = severe sleep deprivation. The second section assesses the circadian timing of sleep by asking questions related to circadian-sleep mismatch; a higher score indicates worse circadian sleep timing.

The snoring, tiredness, observed apnea, high BP, BMI, age, neck circumference, and gender (STOP-Bang) questionnaire. The Total Sore 0-8 with higher scores indicating higher risks for obstructive sleep apnea. Affirmative answers get a "1" and the sum of the eight question scores is stratified into low risk for OSA (0-2), moderate risk (3-4), and high risk (5-8).

This is a disease specific quality of life index for OSA in adults. Categories and domains include daily functioning, social interactions, emotional functioning, and symptoms. The scaling of items ranges from "not at all" to "all the time," a seven point scale.

This is a validated scale to assess perceived hypersomnia. Patients are asked to score on a scale of 0 to 3 the likelihood that they would "doze-off" in different scenarios ranging from passes activities to active situations. The low score is zero in the high score is 24. The score of greater than 10 is considered clinically significant hypersomnia.

Height measured in cm.

Weight will be recorded to the nearest 0.1 kg using calibrated scales. Weight will be measured in a fasting state with an empty bladder, without shoes and only wearing light clothing.

Body mass index (BMI) is a value derived from the mass (weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and height in metres.

Waist circumference measured in cm.

Hip circumference measured in cm.

The amount of time spent sleep walking in naturalistic settings will be measured using the ActiGraph which will be worn on the non-dominant wrist for 24-hours each day for seven consecutive days.

24-hour ambulatory blood pressure monitoring using a blood pressure monitoring device to measure average systolic blood pressure

24-hour ambulatory blood pressure monitoring using a blood pressure monitoring device to measure average diastolic blood pressure

24-hour ambulatory blood pressure monitoring using a blood pressure monitoring device measure blood pressure variability over 24 hour monitoring session.

Comparing average BP during wakefulness to average BP during major sleep episode in 24 hours monitoring session

Mathematical modeling to determine the patient's ventilatory drive (or desired ventilation, Vdrive) in response to changes in ventilation induced by upper airway obstruction (i.e., apnea/hypopnea). The Vdrive signal is fit to the ventilation (VE) signals when the airway is expected to be patent (VE = Vdrive). Recorded during the sleep study. Measures of Vdrive allow determinations of Loop gain (LG), measured by the increase in ventilatory drive that occurs following a unit reduction in ventilation due to apneas/hypopneas.

Mathematical modeling to determine the patient's ventilatory drive (or desired ventilation, Vdrive) in response to changes in ventilation induced by upper airway obstruction (i.e., apnea/hypopnea). The Vdrive signal is fit to the ventilation (VE) signals when the airway is expected to be patent (VE = Vdrive). Recorded during the sleep study. Measures of Vdrive allow determinations of Arousal threshold (ArTH), quantified as the level of "ventilatory drive" just before arousal from sleep.

Mathematical modeling to determine the patient's ventilatory drive (or desired ventilation, Vdrive) in response to changes in ventilation induced by upper airway obstruction (i.e., apnea/hypopnea). The Vdrive signal is fit to the ventilation (VE) signals when the airway is expected to be patent (VE = Vdrive). Recorded during the sleep study. Measures of Vdrive allow determinations of Pharyngeal muscle compensation (Mresp), assessed by the increase in ventilation achieved during sleep per unit increase in the ventilatory drive. The analysis is automated using custom MATLAB software.