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OSA & Type 2 Diabetes

New challenges and opportunities for respiratory care providers

Obstructive sleep apnea (OSA) is estimated to affect more than 12 million people in the United States alone, and most commonly occurs in people who are middle-aged. However, it is estimated that more than 80% of OSA patients are left untreated. Although OSA is a chronic condition, a variety of interventions can help to reduce symptoms, including the use of mandibular repositioning devices or CPAP therapy during sleep, as well as surgery and weight loss. Given the negative health consequences associated with OSA, screening for the condition and implementing effective therapy is essential for improving the lives of millions of people living with OSA.

OSA can mean more than a poor night's sleep for affected individuals. The condition is associated with a variety of adverse health issues, including hypertension, cardiovascular disease, insulin resistance, and poor glycemic control in patients with type 2 diabetes (T2D).1 This association may complicate the management of individuals with multiple comorbidities, but it also enables respiratory care providers to play a key role in improving diverse aspects of their patients' health through effective treatment of their underlying OSA. While treatment of OSA has become recognized as a target for preventing cardiovascular disease, a growing body of emerging evidence now also supports it as target for managing T2D.1 It is estimated that up to 40% of OSA patients have a known diagnosis of T2D, while the incidence of undiagnosed T2D in this population is not known.1-3 Additionally, impaired insulin sensitivity and insulin secretion have been found in non-diabetic men who have OSA.4 Consequently, there is increased urgency for providers of respiratory care to ensure that their patients with OSA are evaluated for T2D and to coordinate with endocrinologists and primary care physicians to optimize treatment for patients with both conditions.

The Role of OSA in T2D
Obesity is a known risk factor for OSA and for T2D. However, more recent studies suggest that the association between these two conditions may be independent of obesity and may result from the direct physiologic stress caused by sleep fragmentation and intermittent hypoxia.5-10 Research in animal models and in humans has identified intermittent hypoxia and sleep fragmentation as two important factors in OSA that can contribute to dysregulation of glucose metabolism. The reduced level of oxygen that occurs during OSA results in intermittent hypoxia, which appears to be associated with insulin resistance. Studies in healthy subjects have found that sleep fragmentation can also cause episodes of insulin resistance.

The Impact of OSA Treatment on T2D
A growing body of data suggests that treatment of OSA with CPAP can improve glucose metabolism. In one study, insulin sensitivity improved after two days of CPAP therapy, and this improvement was also observed following three months of therapy. The effect of the improvement was more pronounced in non-obese compared with obese patients.11 At three years of follow up, the improvement in insulin sensitivity was maintained in non-obese patients who had maintained a constant body weight.12 Improvements in glucose metabolism and glycemic control in diabetic patients with OSA have also been reported following three months of CPAP,13 and a case-controlled study found that three months of CPAP therapy reduced insulin resistance in sleepy OSA patients.14 The use of CPAP was also associated with reductions in HbA1c and blood pressure over five years in patients with both OSA and T2D, resulting in a cost-effective gain of 0.27 quality-adjusted life years per patient over the five-year period.15

It should be noted that other studies have not detected an effect of CPAP on glucose regulation, insulin sensitivity, or glycemic control.16 However, these negative findings may have resulted from an insufficient duration of CPAP treatment, as positive results have only been observed in patients using CPAP for more than four hours each night. While additional studies are needed to fully understand the association between OSA and glucose intolerance/T2D, the data generated to date suggest that effective management of OSA may lead to improved management of T2D and impaired glucose metabolism.

Screening OSA Patients for T2D
In 2008, the International Diabetes Federation Taskforce on Epidemiology and Prevention recommended "immediate actions" to increase awareness, clinical practice and research related to the association between OSA and T2D.1 One of these actions was the routine screening of OSA patients for metabolic disorders and risk factors for cardiovascular disease, with minimum testing criteria that includes waist circumference, blood pressure, fasting lipids and fasting glucose. Additional recommendations were made to screen T2D patients for OSA. Respiratory care providers must take a proactive role in ensuring that OSA patients within their practices have undergone the recommended evaluation. Care for OSA patients with existing T2D should be coordinated with patients' endocrinologist or primary care physician. OSA patients newly diagnosed with T2D, glucose intolerance or cardiovascular risk factors should be referred to an endocrinologist, cardiologist or primary care physician for further follow-up.

The finding that men with OSA may have impaired insulin sensitivity and insulin secretion even when they are not diabetic suggests that screening OSA patients for markers of metabolic disorders may allow for early detection of pre-diabetic conditions. Proactive management of these patients through changes in diet, exercise, and body weight could help to prevent progression to T2D or other metabolic disorders. The minimal screening criteria are relatively simple and inexpensive, making screening of all OSA patients feasible for most respiratory care practices. However, implementing new procedures in the clinical setting may pose logistical, procedural or personnel challenges. Care providers and practices looking to implement screening for metabolic disorders in an incremental manner could begin by screening OSA patients at highest risk for T2D or other metabolic or cardiovascular diseases, potentially by initiating screening in obese patients. Once a screening system is effectively deployed in this patient sub-population, it could be rolled out over time to encompass all patients.

Conversely, patients undergoing treatment for T2D should also be screened for OSA. Respiratory care providers play a key role in educating other physician groups about the association between OSA and T2D and the benefits that effective OSA therapy may have on managing diabetes in patients with both conditions.

CPAP in the Treatment of OSA
The preliminary data suggesting that CPAP can improve glucose metabolism are encouraging. However, adherence to CPAP therapy can be a challenge for some OSA patients. Ensuring that OSA patients are appropriately screened for markers of T2D and other comorbid conditions is necessary but not sufficient for optimizing care of patients with both T2D and OSA. Medicare defines adherence to CPAP therapy as documented use for a minimum of four hours each night for at least 70% of nights in a consecutive 30-day period.17 A recent study found that adherence to this regimen was 73% in patients receiving standard telephone call reminders on days one, seven, 14, and 30 during their first month of CPAP therapy.18 This study also found that a web-based automated messaging coaching system could increase adherence in these patients to 83%. This approach is just one of several innovative approaches that are being evaluated to improve CPAP adherence. While adherence to CPAP therapy is essential to effective disease management in all OSA patients, it may be of particular importance in OSA patients with T2D.

Conclusion
Respiratory care providers are well positioned to play an important role in the overall health of their OSA patients. Awareness of the association between OSA and T2D, screening of OSA patients for markers of T2D, and effective use of CPAP therapy in OSA patients with diabetes may help to improve both OSA and T2D outcomes. Educating physicians and patients about the association between OSA and T2D and the importance of accurate diagnosis and treatment of both conditions creates new opportunities for respiratory care providers to play a key role in making such improvements a reality.

Adam V. Benjafield is ResMed's vice president of Medical Affairs.

References
1. Shaw JE, et al. International Diabetes Federation Taskforce on E, et al. Sleep-disordered breathing and type 2 diabetes: a report from the International Diabetes Federation Taskforce on Epidemiology and Prevention. Diabetes Res Clin Pract. 2008;81(1):2-12.
2. Elmasry A, et al. Sleep-disordered breathing and glucose metabolism in hypertensive men: a population-based study. J Intern Med. 2001;249(2):153-61.
3. Meslier N, et al. Impaired glucose-insulin metabolism in males with obstructive sleep apnea syndrome. Eur Respir J. 2003;22(1):156-60.
4. Punjabi NM, Beamer BA. Alterations in Glucose Disposal in Sleep-disordered Breathing. Am J Respir Crit Care Med. 2009;179(3):235-40.
5.Punjabi NM, et al. Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study. Am J Epidemiol. 2004;160(6):521-30.
6. Braun B, et al. Women at altitude: short-term exposure to hypoxia and/or alpha(1)-adrenergic blockade reduces insulin sensitivity. J Appl Physiol. (1985) 2001;91(2):623-31.
7. Larsen JJ, et al. The effect of altitude hypoxia on glucose homeostasis in men. J Physiol. 1997;504(Pt.1):241-9.
8. Oltmanns KM, et al. Hypoxia causes glucose intolerance in humans. Am J Respir Crit Care Med. 2004;169(11):1231-7.
9.Spiegel K, et al. Impact of sleep debt on metabolic and endocrine function. Lancet. 1999;354(9188):1435-9.
10. Gottlieb DJ, et al. Association of sleep time with diabetes mellitus and impaired glucose tolerance. Arch Intern Med. 2005;165(8):863-7.
11. Harsch IA, et al. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2004;169(2):156-62.
12. Schahin SP, et al. Long-term improvement of insulin sensitivity during CPAP therapy in the obstructive sleep apnea syndrome. Med Sci Monit. 2008;14(3):CR117-21.
13. Babu AR, et al. Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea. Arch Intern Med. 2005;165(4):447-52.
14. Barcelo A, et al. Insulin resistance and daytime sleepiness in patients with sleep apnea. Thorax. 2008;63(11):946-50.
15. Guest JF, et al. Clinical outcomes and cost-effectiveness of continuous positive airway pressure to manage obstructive sleep apnea in patients with type 2 diabetes in the U.K. Diabetes Care. 2014;37(5):1263-71.
16. Lavie L. Oxidative stress - a unifying paradigm in obstructive sleep apnea and comorbidities. Prog Cardiovasc Dis. 2009;51(4):303-12.
17. Centers for Medicare & Medicaid Services, PAP Devices for the Treatment of OSA (L11528, L11528, L11518, L171), U.S. Department of Health and Human Services (revision effective date 1/1/2014).
18. Munafo D HW, et al. A web based automated messaging program for CPAP adherence coaching reduced the coaching labor required while yielding similar adherence and efficacy to standard of care coaching. Am J Respir Crit Care Med. 2014;189:A6570.

 

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Why is a cough assist used as an illustration for an OSA and diabetes article? The cough assist is used for airway clearance in individuals with a diminished peak cough flow, i.e. neuromuscular disease. There is no connection to OSA and treatment with positive airway pressure devices.

David TroxellSeptember 23, 2014




     

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