Hyperglycemic Profiles in Obstructive Sleep Apnea: Effects of PAP Therapy (HYPNOS)

This is a randomized control trial in people with diabetes and obstructive sleep apnea who will be randomly assigned for 3 months to PAP therapy along with healthy lifestyle and sleep education or healthy lifestyle and sleep education.

Research over the last decade has shown that obstructive sleep apnea (OSA) is a common condition in people with diabetes. Observational and experimental evidence also indicates that intermittent hypoxemia and recurrent arousals in OSA may alter glucose metabolism and worsen glycemic control. However, the impact of treating OSA with positive airway pressure (PAP) therapy on glycemic variability and control is not well defined. Adequately powered randomized clinical trials have yet to be performed to demonstrate whether PAP therapy for OSA in diabetics can improve glycemic variability (and control), decrease blood pressure, and reverse endothelial dysfunction. The overarching goal of this study is to determine whether PAP therapy for OSA in diabetics leads to improvements in (a) glycemic variability as assessed by self-monitoring of blood glucose and continuous monitoring of glucose; (b) glycosylated hemoglobin; (c) blood pressure; (d) endothelial function; (e) serum and urinary biomarkers; and (f) dyslipidemia.

Lifestyle guidelines developed by the American Diabetes Association for weight loss will be provided to all subjects.

Lifestyle guidelines developed by the American Diabetes Association for weight loss will be provided to all subjects.

Continuous Glucose Monitoring Metrics - change in standard deviation between baseline and three months.

Endothelial function was measured by the EndoPAT device - difference at 3 months - baseline, by group. The outcome reported is the Reactive Hyperemic Index (RHI). The RHI is a measure of endothelial vasodilator function. The RHI is the post-to-pre occlusion peripheral arterial tone signal ratio in the occluded arm relative to the other arm, which is not occluded. Persons with worse endothelial function have a lower RHI score. Consequently, a low RHI indicates more endothelial dysfunction. A value of 1.67 or less is considered abnormal vascular tone. The reported lower and upper limits in adults with type 2 diabetes is 1.1 - 4.9.

The Epworth Sleepiness Scale measures self-reported sleep propensity or daytime sleepiness. The range of the scale is 0 to 24 (integers only), with increasing values corresponding to increasing sleepiness. A cut-point of ≥ 11 is also sometimes used to differentiate those with pathological sleepiness (≥ 11) versus those without < 11. The difference between the three month final visit - the baseline visit score is reported by group

The difference from baseline to three months in self-reported in blood glucose levels before and after meals (mg/dL) (post-meal - pre-meal). Data is presented for breakfast, lunch, and dinner.

Mean Amplitude Glucose Excursion in mg/dL (difference between the peaks and troughs of glucose from continuous glucose monitoring at three months).

Continuous Glucose Monitoring Metric - change in average glucose level (mg/dL) from baseline to three months.

Inclusion Criteria: Type 2 diabetics Age > 21 and ≤ 75 years Exclusion Criteria: Inability to consent or commit to the required visits Use of insulin or other injections for diabetes Weight change of 10% in last six months Use of oral steroids in the last six months Pulmonary disease (i.e., COPD) Renal or hepatic insufficiency Recent MI or stroke (< 3 months) Sleep-related hypoventilation Obesity-hypoventilation syndrome Morbid Obesity Occupation as a commercial driver or operator of heavy machinery Active substance use Untreated thyroid disease Pregnancy Any history of seizures or other neurologic disease Poor sleep hygiene or sleep disorder other than sleep apnea Central sleep apnea Variants of obstructive sleep apnea (e.g., REM-related OSA) Participants not suitable for the study based on the clinical judgment Use of any investigational drug within the past 30 days Participating in another study

Rooney MR, Aurora RN, Wang D, Selvin E, Punjabi NM. Rationale and design of the Hyperglycemic Profiles in Obstructive Sleep Apnea (HYPNOS) trial. Contemp Clin Trials. 2021 Feb;101:106248. doi: 10.1016/j.cct.2020.106248. Epub 2020 Dec 11.