Effects of Continuous Positive Airway Pressure (CPAP) Treatment on Glucose Control in Patients With Type 2 Diabetes

Study Overview
=================
Brief Summary
-----------------
The overall goal of the proposed protocol is to rigorously test the hypothesis that CPAP treatment has beneficial effects on glycemic control in patients with both type 2 diabetes (T2DM) and obstructive sleep apnea (OSA). If our hypothesis were to be proven, this would imply that CPAP treatment of OSA in patients with T2DM is an essential component of their glycemic control. The proposed work is thus expected to provide additional preventive and therapeutic approaches in the management of millions of patients with T2DM.

Official Title
-----------------
Effects of Continuous Positive Airway Pressure (CPAP) Treatment on Glucose Control in Patients With Type 2 Diabetes

Conditions
-----------------
Obstructive Sleep Apnea, Type 2 Diabetes

Intervention / Treatment
-----------------
* Device: active CPAP Therapy
* Device: sham CPAP therapy


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Male and female subjects with type 2 diabetes on a stable medication regimen (no change in diabetic medications in the previous 3 months) will be eligible. Exclusion Criteria: Subjects on insulin will be excluded. Subjects with unstable cardiopulmonary disease, painful neuropathy, significant psychiatric illness, cognitive impairment and pregnancy will be excluded. Shift workers Subjects having traveled across >2 time zones less than one month prior to the study Diagnosis of a sleep disorder other than OSA by screening polysomnography Previous treatment with positive airway pressure or supplemental oxygen Requirement of supplemental oxygen or bi-level positive airway pressure for OSA treatment during titration Claustrophobia or other conditions of CPAP intolerance, Presence of active infection.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active CPAP therapy<br>7 days of treatment in the laboratory with active CPAP therapy. | Device: active CPAP Therapy<br>* 7 days of active CPAP therapy<br>|
| Sham Comparator: Sham CPAP therapy<br>7 days of sham CPAP therapy in the laboratory. | Device: sham CPAP therapy<br>* 7 days of sham CPAP therapy<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change From Baseline to End of 7-day Intervention in Mean Plasma Glucose Derived From 24 Hour Blood Sampling | 24 hour blood sampling will be performed at baseline and at the end of the 7-day intervention. Glucose levels will be measured on each sample. Mean glucose level for all baseline samples will be calculated for each participant. Mean glucose levels for all samples collected at the end of the intervention will be calculated. Change in mean glucose level from baseline to end of intervention will be calculated for each participant. | after 1 week of CPAP therapy in the laboratory | 
| Change From Baseline in Mean Glucose From Continuous Interstitial Glucose Monitoring Over 36-40 Hours | Continuous Glucose monitoring will provide interstitial glucose levels for 36-40 hours at baseline and after one week of active or sham CPAP therapy. The mean glucose level of all samples collected at baseline will be calculated for each participant. The mean glucose level of all samples collected at the end of the 7-day intervention will be calculated for each participant. For each participant, we will calculate the change in mean glucose level from baseline till end of the intervention. | change in mean interstitial glucose after 1 week of active or sham CPAP therapy in the laboratory | 
| Change in Mean Serum Insulin Derived From 24 Hour Blood Sampling | Serum insulin levels will be measured on each sample collected during 24-h sampling at baseline and at the end of the 7-day intervention. Mean insulin level over 24 hours will be calculated for each participant at baseline and at the end of the intervention. For each participant, we will calculate the change in mean insulin level from baseline. | after 1 week of therapy in the laboratory | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in Mean Plasma Cortisol Level From 24-h Sampling | The mean plasma cortisol level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean cortisol level from baseline to end of intervention will be calculated. | after 1 week of active CPAP therapy in the laboratory | 
| 24-hr Profile of Plasma Growth Hormone | The mean plasma growth hormone level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean cortisol level from baseline to end of intervention will be calculated. | after 1 week of active CPAP therapy in the laboratory | 
| Change in 24-h Mean Level of Plasma Norepinephrine | The mean plasma norepinephrine level will be calculated for all samples collected at baseline and for all samples collected at the end of the intervention in participants randomized to the active CPAP arm. The goal of the analysis of cortisol, growth hormone and norepinephrine levels was to explore putative mechanisms underlying the effects of active CPAP therapy. Examining putative hormonal mechanisms underlying changes in glucose levels in the sham CPAP arm was not part of our aims. For each participant, the change in mean norepinephine level from baseline to end of intervention will be calculated. | after 1 week of active CPAP therapy in the laboratory |