Effects of Continuous Positive Airway Pressure (CPAP) on Glucose Metabolism (SOMNOS)

Sleep, Obesity, and Metabolism in Normal and Overweight Subjects: Effects of CPAP on Glucose Metabolism

Obstructive sleep apnea affects approximately 2-4% of middle-aged adults in the general population and is associated with several medical conditions including hypertension and coronary artery. Research over the last decade has shown that obstructive sleep apnea may also increase the propensity for insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Positive airway pressure (PAP) is the first line therapy for the treatment of obstructive sleep apnea. While PAP therapy has several favorable effects such as improvements in daytime sleepiness and quality of life, it is not clear whether using PAP therapy can alter metabolic risk. The overall objective of this study is to examine whether treatment of obstructive sleep apnea with positive airway pressure therapy improves glucose tolerance and insulin sensitivity. The primary hypothesis of this study is that PAP therapy of obstructive sleep apnea will improve in insulin sensitivity and glucose metabolism.

Study Overview

• Status: Completed
• Conditions: Obstructive Sleep Apnea; Sleep Apnea; Sleep-disordered Breathing
• Intervention / Treatment: Device: Positive Pressure Therapy (PAP); Behavioral: LifeStyle Counseling

Detailed Description

Type 2 diabetes mellitus is one of the most prevalent medical conditions, affecting a staggering 246 million people worldwide. Obstructive sleep apnea is a relatively common and often undiagnosed condition in the general population. Cross-sectional studies of clinic and population-based samples suggest that up to 40% of patients with obstructive sleep apnea have type 2 diabetes and up to 75% of patients with type 2 diabetes have obstructive sleep apnea. There is increasing evidence that the pathophysiological features of intermittent hypoxia and sleep fragmentation may be responsible for altering glucose homeostasis and worsening insulin sensitivity. The mechanisms through which obstructive sleep apnea impairs glucose metabolism are largely unknown. While intermittent hypoxemia and sleep fragmentation are likely to play an essential role, the relative contribution of each in the causal pathway remains to be determined. Moreover, whether the adverse effects of intermittent hypoxia and sleep fragmentation are mediated through an increase in sympathetic nervous system activity, alterations in corticotropic function, and/or systemic inflammation is not known. Furthermore, it remains to be determined whether positive pressure therapy for obstructive sleep apnea has salutary effects on glucose metabolism. Many of the available studies examining the effects of PAP on glucose tolerance and insulin sensitivity are plagued by small sample sizes, lack of a control group, and limited data on compliance with positive pressure therapy. The current study will assess, using a community-based sample, whether treatment of obstructive sleep apnea with positive pressure therapy will improve insulin sensitivity, as assessed by the frequently sample intravenous glucose tolerance test (primary outcome measure).

• Study Type: Interventional
• Enrollment (Actual): 111
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224
      • Johns Hopkins Bayview Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Ability to give informed consent
• Obstructive sleep apnea (untreated)
• Ability to comply with study-related assessments

Exclusion Criteria:

• Inability to consent or commit to the required visits
• Diabetes mellitus (fasting glucose > 126 mg/dl)
• Use of insulin or oral hypoglycemic agent
• Weight change of 10% in last six months
• Use of oral steroids in the last six months
• Severe pulmonary disease (i.e., COPD)
• Renal or hepatic insufficiency
• Recent Myocardial Infarction (MI) or stroke (< 3 months)
• Occupation as a commercial driver
• Active substance use
• Untreated thyroid disease
• Pregnancy
• Anemia (Hematocrit < 30%)
• Any history of seizures or other neurologic disease
• Poor sleep hygiene or sleep disorder other than sleep apnea
• Excessive subjective sleepiness (Epworth score > 18)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Positive pressure therapy (PAP); Positive airway pressure(PAP) therapy is the standard of care for patients with obstructive sleep apnea. During sleep, a mask is worn over the nose and connected to the PAP machine.	Device: Positive Pressure Therapy (PAP); Positive pressure therapy is the standard of care for managing obstructive sleep apnea. It entails wearing a mask that is connected to the PAP device which deliver pressure to the upper airway during sleep.; Other Names: CPAP
Sham Comparator: Lifestyle counseling	Behavioral: LifeStyle Counseling; Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.; Other Names: Dietary and Lifestyle Counseling

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Insulin Sensitivity (SI)	Insulin sensitivity will be determined with the insulin-modified frequently sampled intravenous glucose tolerance test (IVGTT) before and 2-months after study intervention. This test requires administration of a weight-adjusted dose of D50W as an IV bolus at time "zero". After the glucose bolus, blood samples are drawn at the scheduled times for 3-hours. At the 20-minute mark, a weight-adjusted dose of regular insulin is administered. The resulting serum is analyzed for glucose and insulin and the "minimal model" (MINMOD) will be used to derive insulin sensitivity. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.	Baseline
Insulin Sensitivity (SI)	Insulin sensitivity will be determined with the insulin-modified frequently sampled intravenous glucose tolerance test (IVGTT) before and 2-months after study intervention. This test requires administration of a weight-adjusted dose of D50W as an IV bolus at time "zero". After the glucose bolus, blood samples are drawn at the scheduled times for 3-hours. At the 20-minute mark, a weight-adjusted dose of regular insulin is administered. The resulting serum is analyzed for glucose and insulin and the "minimal model" (MINMOD) will be used to derive insulin sensitivity. A low SI signifies low insulin sensitivity and high SI represents high insulin sensitivity.	2 months after intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Glucose Effectiveness (SG)	Glucose effectiveness is the ability for glucose to move intracellularly in the absence of insulin. It is a parameter that results from the MINMOD analysis of the serum glucose and insulin levels derived from the frequently sampled intravenous glucose tolerance test. Low SG indicates a lower predisposition for glucose disposal independent of any effects of insulin.	Baseline
Glucose Effectiveness (SG)	Glucose effectiveness is the ability for glucose to move intracellularly in the absence of insulin. It is a parameter that results from the MINMOD analysis of the serum glucose and insulin levels derived from the frequently sampled intravenous glucose tolerance test. Low SG indicates a lower predisposition for glucose disposal independent of any effects of insulin.	2 months after intervention
Disposition Index (DI)	The disposition index is the mathematical product of insulin sensitivity (SI) and acute insulin response to glucose (AIRG) both of which are derived from the MINMOD analysis of the frequently sampled intravenous glucose tolerance test data. A low DI is indicative of a higher risk of developing diabetes.	Baseline
Disposition Index (DI)	The disposition index is the mathematical product of insulin sensitivity (SI) and acute insulin response to glucose (AIRG) both of which are derived from the MINMOD analysis of the frequently sampled intravenous glucose tolerance test data.	2 months after intervention
Acute Insulin Response to Glucose (AIRG)	The acute insulin response to glucose (AIRG) value is derived from the MINMOD analysis of the glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test. A low AIRG indicates decreased ability of the pancreas to secrete insulin.	Baseline
Acute Insulin Response to Glucose (AIRG)	The acute insulin response to glucose (AIRG) value is derived from the MINMOD analysis of the glucose and insulin levels obtained during the frequently sampled intravenous glucose tolerance test. A low AIRG indicates decreased ability of the pancreas to secrete insulin.	2 months after intervention
Endothelial Function	Endothelial function will be assessed using peripheral arterial tonometry using the Endo-PAT device. Using the EndoPat device, the relative vasoconstriction of occluded versus non-occluded arms was derived and provided the relative hyperemic index.	Baseline
Endothelial Function	Endothelial function will be assessed using peripheral arterial tonometry using the Endo-PAT device. Using the EndoPat device, the relative vasoconstriction of occluded versus non-occluded arms was derived and provided the relative hyperemic index.	2 month after intervention
Area Under the Curve Assessed by Oral Glucose Tolerance Test	Results of the oral glucose tolerance test will be analyzed using indices derived from the serial glucose and insulin levels over the 2 hour period. This will be the area under the glucose/ insulin curves	Baseline
Area Under the Curve Assessed by Oral Glucose Tolerance Test (OGTT)	Results of the oral glucose tolerance test will be analyzed using indices derived from the serial glucose and insulin levels over a 2 hour period 2 months post intervention. This will be the area under the glucose/ insulin curves	2 month after intervention

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Naresh M Punjabi, MD, PhD, Johns Hopkins University

Publications and helpful links

General Publications

• Young T, Peppard PE, Gottlieb DJ. Epidemiology of obstructive sleep apnea: a population health perspective. Am J Respir Crit Care Med. 2002 May 1;165(9):1217-39. doi: 10.1164/rccm.2109080.
• Tasali E, Mokhlesi B, Van Cauter E. Obstructive sleep apnea and type 2 diabetes: interacting epidemics. Chest. 2008 Feb;133(2):496-506. doi: 10.1378/chest.07-0828.
• Punjabi NM, Ahmed MM, Polotsky VY, Beamer BA, O'Donnell CP. Sleep-disordered breathing, glucose intolerance, and insulin resistance. Respir Physiol Neurobiol. 2003 Jul 16;136(2-3):167-78. doi: 10.1016/s1569-9048(03)00079-x.
• Punjabi NM; Workshop Participants. Do sleep disorders and associated treatments impact glucose metabolism? Drugs. 2009;69 Suppl 2:13-27. doi: 10.2165/11531150-000000000-00000.
• Aurora RN, Swartz R, Punjabi NM. Misclassification of OSA severity with automated scoring of home sleep recordings. Chest. 2015 Mar;147(3):719-727. doi: 10.1378/chest.14-0929.

Study record dates

Study Major Dates

• Study Start (Actual): September 1, 2011
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: December 29, 2011
• First Submitted That Met QC Criteria: December 30, 2011
• First Posted (Estimate): January 2, 2012

Study Record Updates

• Last Update Posted (Actual): October 19, 2017
• Last Update Submitted That Met QC Criteria: October 18, 2017
• Last Verified: October 1, 2017

More Information

Terms related to this study

• Keywords: Obstructive sleep apnea; Type 2 diabetes; Sleep Apnea; Insulin sensitivity; Sleep-disordered breathing; Glucose tolerance
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Respiratory Tract Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Respiratory Aspiration; Apnea
• Other Study ID Numbers: NA_00036672; 2R01HL075078 (U.S. NIH Grant/Contract)