Diabetes, Sleep Apnea
Conditions
Brief summary
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.
Detailed description
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.
Interventions
DEVICEREMStar Positive Airway Pressure
Positive airway pressure therapy is the standard of care for managing obstructive sleep apnea
BEHAVIORALLifeStyle Counseling
Lifestyle guidelines developed by the American Diabetes Association for weight loss will be provided to all subjects.
Sponsors
National Heart, Lung, and Blood Institute (NHLBI)
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Continuous Glucose Monitoring System Standard Deviation | Baseline and 3 months | Continuous Glucose Monitoring Metrics - change in standard deviation between baseline and three months. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Endothelial Dysfunction as Assessed by the Reactive Hyperemic Index | Baseline and 3 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. |
| Heart Rate Variability | 3 months | — |
| Change in the Epworth Sleepiness Scale | Baseline and 3 months | 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 |
| Change in Post-Pre Meal Blood Glucose Levels | Baseline and 3 months | 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 Difference in Systolic Blood Pressure | Baseline and 3 months | Mean difference between 3 months and baseline systolic blood pressures (in mmHg) by group. |
| Continuous Glucose Monitoring System Mean Amplitude Glucose Excursion | 3 months | 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 System Standard Deviation | 3 months | The standard deviation of the glucose from continuous glucose monitoring at three months. |
| Change in Continuous Glucose Monitoring System Mean Glucose | Baseline and 3 months | Continuous Glucose Monitoring Metric - change in average glucose level (mg/dL) from baseline to three months. |
| Change in Glycosylated Hemoglobin A1c Level | Baseline and 3 months | Change in point-of-care hemoglobin A1c (%) after three months. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| REMStar Positive Airway Pressure Positive pressure therapy is the standard of care for managing obstructive sleep apnea.
REMStar Positive Airway Pressure: Positive airway pressure therapy is the standard of care for managing obstructive sleep apnea | 92 |
| LifeStyle Counseling Lifestyle guidelines developed by the American Diabetes Association for weight loss will be provided to all subjects.
LifeStyle Counseling: Lifestyle guidelines developed by the American Diabetes Association for weight loss will be provided to all subjects. | 92 |
| Total | 184 |
Baseline characteristics
| Characteristic | REMStar Positive Airway Pressure | LifeStyle Counseling | Total |
|---|---|---|---|
| Age, Continuous | 58.4 years STANDARD_DEVIATION 8.6 | 60.8 years STANDARD_DEVIATION 9.6 | 59.6 years STANDARD_DEVIATION 9.1 |
| Body Mass Index (BMI) | 33.8 kg/m^2 STANDARD_DEVIATION 5.5 | 33.7 kg/m^2 STANDARD_DEVIATION 5.8 | 33.8 kg/m^2 STANDARD_DEVIATION 5.6 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 10 Participants | 5 Participants | 15 Participants |
| Race (NIH/OMB) Black or African American | 29 Participants | 34 Participants | 63 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 3 Participants | 3 Participants |
| Race (NIH/OMB) White | 53 Participants | 50 Participants | 103 Participants |
| Sex: Female, Male Female | 40 Participants | 50 Participants | 90 Participants |
| Sex: Female, Male Male | 52 Participants | 42 Participants | 94 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 92 | 0 / 92 |
| other Total, other adverse events | 0 / 92 | 0 / 92 |
| serious Total, serious adverse events | 1 / 92 | 0 / 92 |
Outcome results
Primary
Change in Continuous Glucose Monitoring System Standard Deviation
Continuous Glucose Monitoring Metrics - change in standard deviation between baseline and three months.
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Change in Continuous Glucose Monitoring System Standard Deviation | 0.8 mg/dL | Standard Deviation 6.7 |
| LifeStyle Counseling | Change in Continuous Glucose Monitoring System Standard Deviation | 1.1 mg/dL | Standard Deviation 8.6 |
Secondary
Change in Continuous Glucose Monitoring System Mean Glucose
Continuous Glucose Monitoring Metric - change in average glucose level (mg/dL) from baseline to three months.
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Change in Continuous Glucose Monitoring System Mean Glucose | 4.3 mg/dL | Standard Deviation 25.3 |
| LifeStyle Counseling | Change in Continuous Glucose Monitoring System Mean Glucose | 9.5 mg/dL | Standard Deviation 29.3 |
Secondary
Change in Endothelial Dysfunction as Assessed by the Reactive Hyperemic Index
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.
Time frame: Baseline and 3 months
Population: Missing data is due to participants who did not complete the procedure at three months.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Change in Endothelial Dysfunction as Assessed by the Reactive Hyperemic Index | -0.0014 ratio | Standard Deviation 0.65 |
| LifeStyle Counseling | Change in Endothelial Dysfunction as Assessed by the Reactive Hyperemic Index | 0.0024 ratio | Standard Deviation 0.69 |
Secondary
Change in Glycosylated Hemoglobin A1c Level
Change in point-of-care hemoglobin A1c (%) after three months.
Time frame: Baseline and 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Change in Glycosylated Hemoglobin A1c Level | 0.2 percentage of glycosylated hemoglobin | Standard Deviation 0.7 |
| LifeStyle Counseling | Change in Glycosylated Hemoglobin A1c Level | 0.2 percentage of glycosylated hemoglobin | Standard Deviation 0.9 |
Secondary
Change in Post-Pre Meal Blood Glucose Levels
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.
Time frame: Baseline and 3 months
Population: One participant in the REMStar Positive Airway Pressure arm was missing data on the three month visit.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| REMStar Positive Airway Pressure | Change in Post-Pre Meal Blood Glucose Levels | Change post-pre breakfast | -9.9 mg/dL | Standard Error 4.8 |
| REMStar Positive Airway Pressure | Change in Post-Pre Meal Blood Glucose Levels | Change post-pre lunch | 1.0 mg/dL | Standard Error 5.4 |
| REMStar Positive Airway Pressure | Change in Post-Pre Meal Blood Glucose Levels | Change post-pre dinner | -3.0 mg/dL | Standard Error 5.1 |
| LifeStyle Counseling | Change in Post-Pre Meal Blood Glucose Levels | Change post-pre breakfast | -1.3 mg/dL | Standard Error 4.8 |
| LifeStyle Counseling | Change in Post-Pre Meal Blood Glucose Levels | Change post-pre lunch | -6.1 mg/dL | Standard Error 5.4 |
| LifeStyle Counseling | Change in Post-Pre Meal Blood Glucose Levels | Change post-pre dinner | 3.7 mg/dL | Standard Error 5.1 |
Secondary
Change in the Epworth Sleepiness Scale
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
Time frame: Baseline and 3 months
Population: Missing data points were due to participants not completing the survey at three months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Change in the Epworth Sleepiness Scale | -2.5 units on a scale | Standard Deviation 4.3 |
| LifeStyle Counseling | Change in the Epworth Sleepiness Scale | -1.3 units on a scale | Standard Deviation 3.1 |
Secondary
Continuous Glucose Monitoring System Mean Amplitude Glucose Excursion
Mean Amplitude Glucose Excursion in mg/dL (difference between the peaks and troughs of glucose from continuous glucose monitoring at three months).
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Continuous Glucose Monitoring System Mean Amplitude Glucose Excursion | 69.5 mg/dL | Standard Deviation 20.5 |
| LifeStyle Counseling | Continuous Glucose Monitoring System Mean Amplitude Glucose Excursion | 71.4 mg/dL | Standard Deviation 20.4 |
Secondary
Continuous Glucose Monitoring System Standard Deviation
The standard deviation of the glucose from continuous glucose monitoring at three months.
Time frame: 3 months
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Continuous Glucose Monitoring System Standard Deviation | 38.7 mg/dL | Standard Deviation 11.3 |
| LifeStyle Counseling | Continuous Glucose Monitoring System Standard Deviation | 39.2 mg/dL | Standard Deviation 10.8 |
Secondary
Heart Rate Variability
Time frame: 3 months
Population: No data was collected
Secondary
Mean Difference in Systolic Blood Pressure
Mean difference between 3 months and baseline systolic blood pressures (in mmHg) by group.
Time frame: Baseline and 3 months
Population: Missing data is due to participants who did not have their blood pressure taken at three month timepoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| REMStar Positive Airway Pressure | Mean Difference in Systolic Blood Pressure | -7.3 mmHg | Standard Error 6.1 |
| LifeStyle Counseling | Mean Difference in Systolic Blood Pressure | 7.4 mmHg | Standard Error 5.8 |