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

Obstructive Sleep Apnea Clinical Trial

— SOMNOS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01503164
• Other study ID #: NA_00036672
• Secondary ID: 2R01HL075078
• Status: Completed
• Phase: N/A
• First received: December 29, 2011
• Last updated: October 18, 2017
• Start date: September 2011
• Est. completion date: December 2013

Study information

• Verified date: October 2017
• Source: Johns Hopkins University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 111
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: No
• Gender: All
• Age group: 21 Years to 75 Years

Eligibility

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)

Related Conditions & MeSH terms

• Apnea
• Obstructive Sleep Apnea
• Respiratory Aspiration
• Sleep Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive
• Sleep-disordered Breathing

Intervention

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.

Behavioral:
• LifeStyle Counseling
Subjects randomized to the lifestyle (and nutritional) counseling arm will be given advice on a balanced dietary and exercise plan.

Locations

Country	Name	City	State
United States	Johns Hopkins Bayview Medical Center	Baltimore	Maryland

Sponsors (2)

Lead Sponsor	Collaborator
Johns Hopkins University	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (4)

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

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. Review. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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
Primary	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	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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