Diabetes, Sleep Apnea
Conditions
Keywords
CPAP, diabetes, sleep apnea
Brief summary
Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits. The objective of this study is to determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA.
Detailed description
Although obstructive sleep apnea (OSA) is associated with impaired glucose tolerance and diabetes, it remains unclear whether OSA treatment with continuous positive airway pressure (CPAP) has metabolic benefits. To determine the effect of 8-hour nightly CPAP treatment on glucose metabolism in individuals with prediabetes and OSA. In a randomized, controlled parallel group study, 39 participants were randomized (2:1) to receive either 8-hour nightly CPAP (n=26) or oral placebo (n=13). Sleep was polysomnographically recorded in the laboratory on each night. CPAP adherence was ensured by continuous supervision. Participants continued their daily daytime routine activities outside the laboratory. Glucose metabolism was assessed at baseline and after 2-weeks of assigned treatment using both the oral and intravenous glucose tolerance tests (OGTT and ivGTT, respectively). The primary outcome was the overall glucose response as quantified by the area under the curve for glucose during 2-hour oral glucose tolerance testing.
Interventions
DEVICECPAP mask
The subjects who are randomized to CPAP treatment will undergo an overnight CPAP titration in the laboratory, which will be performed manually by a registered technician according to American Academy of Sleep Medicine (AASM) guidelines .Subjects will be admitted in the early evening and will receive positive airway pressure education, hands on demonstration, careful mask fitting and acclimatization prior to titration. The goal during the titration will be to determine the optimal CPAP pressure setting that eliminates obstructive respiratory events, restore oxygen saturations and sleep continuity. \_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_\_
DRUGPlacebo
oral placebo tablet
Sponsors
University of Chicago
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Overweight or obese adults (age ≥45 yrs and BMI ≥25 kg/m2) * prediabetes and OSA (AHI ≥ 5) * regular life styles and schedules (no shift work in the past 6 months, no travel across time zones during the past 4 weeks) * habitual bedtimes of at least 6 hours but not exceeding 9 hours will be eligible. * not to take any medications during the study period with the exception of antihypertensives and lipid lowering agents * not on hormone replacement therapy. * have sedentary activities and no competitive athletes or subjects with high exercise levels.
Exclusion criteria
* previous or current treatment with supplemental oxygen * requirement of supplemental oxygen or bi-level positive airway pressure for OSA treatment during titration * presence of active infection, psychiatric disease or history of other significant illness (e.g., myocardial infarction, congestive heart failure, stroke, arrhythmia, chronic kidney or liver disease0 * clinical depression as evidenced by a score \>16 in CES-D scale * smoking, or routine alcohol use (more than 2 drinks per day), or excessive caffeine intake (\>300mg per day)
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Area Under the Curve (AUC) Glucose at Week 2 | Baseline and Week 2 | The area under the glucose time curve, between 0 and 120 minutes of the OGTT, was calculated for each patient using the trapezoidal rule . Change = Week 2 - Baseline. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline in Insulin Sensitivity (SI) at Week 2 | Baseline and Week 2 | SI is estimated from modeling of the insulin and glucose values during the intravenous glucose tolerance test (ivGTT). Change = Week 2 - Baseline. |
| Change From Baseline in 24-hr Systolic Blood Pressure (mmHg) at Week 2 | Baseline and Week 2 | The average systolic blood pressure measured over a 24-hr period was calculated for each patient. Change = Week 2 - Baseline. |
| Change From Baseline in 24-hr Diastolic Blood Pressure (mmHg) at Week 2 | Baseline and Week 2 | The average diastolic blood pressure over a 24-hr period was calculated for each patient. Change = Week 2 - Baseline |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Continuous Positive Airway Pressure 2 weeks of continuous positive airway pressure (CPAP) treatment which includes wearing the CPAP mask for 8 hours each night | 26 |
| Placebo 2 weeks of oral administration of a placebo tablet 30min before bedtime | 13 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | CPAP intolerance | 2 | 0 |
| Overall Study | Withdrawal by Subject | 3 | 1 |
Baseline characteristics
| Characteristic | Continuous Positive Airway Pressure | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 53.8 years STANDARD_DEVIATION 6.2 | 55.2 years STANDARD_DEVIATION 8.4 | 54.3 years STANDARD_DEVIATION 6.9 |
| Region of Enrollment United States | 26 participants | 13 participants | 39 participants |
| Sex: Female, Male Female | 10 Participants | 3 Participants | 13 Participants |
| Sex: Female, Male Male | 16 Participants | 10 Participants | 26 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 26 | 0 / 13 |
| serious Total, serious adverse events | 0 / 26 | 0 / 13 |
Outcome results
Primary
Change From Baseline in Area Under the Curve (AUC) Glucose at Week 2
The area under the glucose time curve, between 0 and 120 minutes of the OGTT, was calculated for each patient using the trapezoidal rule . Change = Week 2 - Baseline.
Time frame: Baseline and Week 2
Population: One patient in the Placebo group who withdrew prior to any testing was excluded from the analysis.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Continuous Positive Airway Pressure | Change From Baseline in Area Under the Curve (AUC) Glucose at Week 2 | -794.2 (mg/dL)*min |
| Placebo | Change From Baseline in Area Under the Curve (AUC) Glucose at Week 2 | 482.7 (mg/dL)*min |
p-value: 0.03Mixed Models Analysis
Secondary
Change From Baseline in 24-hr Diastolic Blood Pressure (mmHg) at Week 2
The average diastolic blood pressure over a 24-hr period was calculated for each patient. Change = Week 2 - Baseline
Time frame: Baseline and Week 2
Population: Patients were excluded from the analysis if they were missing blood pressure data at both Baseline and Week 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Continuous Positive Airway Pressure | Change From Baseline in 24-hr Diastolic Blood Pressure (mmHg) at Week 2 | -2.6 mmHg |
| Placebo | Change From Baseline in 24-hr Diastolic Blood Pressure (mmHg) at Week 2 | 4.5 mmHg |
p-value: <0.001Mixed Models Analysis
Secondary
Change From Baseline in 24-hr Systolic Blood Pressure (mmHg) at Week 2
The average systolic blood pressure measured over a 24-hr period was calculated for each patient. Change = Week 2 - Baseline.
Time frame: Baseline and Week 2
Population: Patients were excluded from the analysis if they were missing blood pressure data at both Baseline and Week 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Continuous Positive Airway Pressure | Change From Baseline in 24-hr Systolic Blood Pressure (mmHg) at Week 2 | -1.9 mmHg |
| Placebo | Change From Baseline in 24-hr Systolic Blood Pressure (mmHg) at Week 2 | 7.6 mmHg |
p-value: 0.009Mixed Models Analysis
Secondary
Change From Baseline in Insulin Sensitivity (SI) at Week 2
SI is estimated from modeling of the insulin and glucose values during the intravenous glucose tolerance test (ivGTT). Change = Week 2 - Baseline.
Time frame: Baseline and Week 2
Population: One patient from each group was excluded from the analysis since they were missing SI data at both Baseline and Week 2.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Continuous Positive Airway Pressure | Change From Baseline in Insulin Sensitivity (SI) at Week 2 | 0.31 [mU/L]^-1·[min]^-1 |
| Placebo | Change From Baseline in Insulin Sensitivity (SI) at Week 2 | -0.46 [mU/L]^-1·[min]^-1 |
p-value: 0.04Mixed Models Analysis