Vol. 18 • Issue 7
• Page 33
Research shows that patients with untreated obstructive sleep apnea (OSA) are predisposed to cardiovascular death.1 Coexisting diabetes and insulin resistance have not been thoroughly explored in OSA. Research suggests that they should be.
OSA is a partial or complete narrowing of the pharynx due to sleep-induced relaxation of upper airway muscle tone. Apneic and hypopneic episodes during sleep are evidenced by airflow cessation, oxygen desaturation and interrupted sleep.2
Increased patient morbidity and mortality have been linked to coexisting diabetes, insulin resistance and OSA. Additionally, insulin resistance leads to diminished insulin-mediated glucose clearance and is associated with metabolic syndrome.3 Continuous positive airway pressure (CPAP) can promptly improve insulin sensitivity in patients with OSA.4,5
These facts prompt a clinically significant question: Does CPAP influence insulin sensitivity in adult patients who have OSA with or without a diagnosis of type 2 diabetes?
Background
Metabolic syndrome is associated with insulin resistance.3 Insulin resistance in OSA may be due to stimulation of sympathetic pathways by the arousals, hypoxia and disruptive sleep that impair glucose tolerance.6
The association between increased morbidity and mortality in patients with coexisting diabetes and insulin resistance as a result of OSA has been demonstrated but not thoroughly researched. OSA corresponds to stress that advances insulin resistance in obese and nonobese patients, as indicated by insulin resistance index and increased fasting serum insulin level based on the Homeostasis Model Assessment Method.3 Therefore, it is essential to evaluate all patients with OSA for insulin resistance.
Review of Literature
We performed a comprehensive literature search of CINAHL, Medline, EBSCO Host, Proquest and Cochrane for reviews investigating the effects of CPAP on insulin resistance. We specifically sought studies published between January 1994 and February 2009. We selected randomized, controlled studies, with evaluation before and after application of CPAP for sleep apnea. From a total of 3,664 studies published, 47 fit the eligibility criteria for inclusion in our review.
Findings
Twenty-six of the 47 studies were randomized, controlled trials that were considered appropriate. Trials that included special patient populations with neuromuscular diseases or cerebral malformations or subjects with central sleep apnea were not reviewed.
We examined only studies whose participants had undergone a diagnostic test or intervention to support the diagnosis of OSA. Our electronic searches were complemented with a systematic search of the reference lists of all eligible studies and relevant review articles.
The findings of these studies suggest that CPAP has an independent positive effect on insulin resistance. Minimum CPAP oxygen saturations were a significant determinant of fasting insulin levels and preinsulin and postinsulin resistance levels. Most researchers believed that this phenomenon may be related to microawakenings or hypoxia-related nocturnal increases in sympathetic system and hypothalamic-pituitary-adrenal axis activities.7 Researchers believed that hyperinsulinemia was related to hypoxia and hypercapnea during OSA caused by an overly stimulated sympathetic nervous system.
The mechanism believed responsible for increased insulin resistance is a stress response activated by chemoreceptors in the carotids, the aortic arch and the medulla of the brain stem in the presence of hypoxia.8 The corollary of these events is the release of catecholamines, epinephrine, norepinephrine and cortisol. Based on this assumption, OSA plays a role in obesity by impeding glucose management with insulin.
Another general hypothesis would be that increased adrenergic activity with excess catecholamine production contributes to insulin resistance and arises as a consequence of increased sympathetic nerve activity in OSA.9 OSA either directly increases risk factors for metabolic syndrome, or OSA and metabolic syndrome share a common risk factor, such as obesity and sedentary lifestyle.10
We found further support in a study showing that increases in the apnea-hyponea index were associated with worsening insulin resistance independent of obesity, and increased rates of OSA were associated with increased rates of impaired glucose tolerance.11,12
A study of nonhypertensive, nondiabetic, nonobese Korean men showed changing patterns of glucose and insulin levels at 1 hour and 2 hours after the ingestion of 75 g of glucose. These levels were appreciably different between habitual snorers and nonhabitual snorers, but no significant difference in blood glucose and insulin levels occurred.13
OSA is related to hyperinsulinemia, which may be correlated to primary insulin resistance mediated by increased catecholamine secretion.14 As a result, successful CPAP treatment of OSA may reduce insulin resistance in both diabetic and nondiabetic patients.4
OSA demonstrates pathophysiologic mechanisms that may be a factor in the development of insulin resistance, consisting of autonomic activation, alterations in neuroendocrine function and direct effects of hypoxemia on glucose regulation.15 In contrast, among obese white people with untreated OSA, CPAP did not modify insulin resistance or change metabolic profile after 6 weeks.16 Short CPAP treatment regimes (2 nights) demonstrated no significant changes in insulin resistance. But after longer CPAP treatment of 3 months, insulin sensitivity was significantly improved in both diabetic and nondiabetic patients.4 In healthy subjects, transitory hypoxia (30 minutes) can impair glucose tolerance and is associated with insulin resistance. These findings support that OSA is independently associated with insulin resistance and improvement is achieved with CPAP.3,9
Studies also show that patients with OSA who are at risk for metabolic syndrome would benefit from CPAP treatment because it improves insulin resistance.17 Longer CPAP use (3 weeks or more) produces greater reduction in fasting insulin levels and a reduction in OSA symptoms.18
he use of stable CPAP at a pressure level to re-establish patency of the upper airway has been the foundation of treatment for OSA since the 1980s.19 CPAP has demonstrated prompt improvement in insulin sensitivity.4,5 It follows, then, that CPAP may be effective in inhibiting OSA-related insulin resistance in adults with or without diabetes.
Putting It Into Practice
All NPs should recognize risk factors for OSA. Patients with fatty deposits around the neck, neck circumference greater than 17 inches, self-reported daytime tiredness, or loud or heroic snoring should be screened for OSA with sleep studies.
Patients with OSA are at increased risk for insulin resistance, and patients with known OSA and diabetes are at risk for complications as a result of nonadherence to CPAP therapy.
Question patients with OSA about consistent and accurate use of CPAP. Examination of capillary blood glucose results and trends may assist in distinguishing between nonadherence to CPAP use and nonadherence to dietary or medication therapy.
The use of CPAP can produce improvement in insulin resistance, and in patients with diabetes it may result in diminished mortality and morbidity related to end-stage organ disease.
References
1. Ross SD, et al. Systematic review and meta-analysis of the literature regarding the diagnosis of sleep apnea. Sleep. 2000;23(4):519-532.
2. Carter R, Watenpaugh DE. Obesity and obstructive sleep apnea. Or is it OSA and obesity? Pathophysiology. 2008;15(2):71-77.
3. Ip MS, et al. Obstructive sleep apnea is independently associated with insulin resistance. Am J Resp Crit Care Med. 2002;165(5):670-676.
4. Harsch IA, et al. Continuous positive airway pressure treatment rapidly improves insulin sensitivity in patients with obstructive sleep apnea syndrome. Am J Resp Crit Care Med. 2004;169(2):156-162.
5. Pallayova M, et al. Beneficial effects of severe sleep apnea therapy on nocturnal glucose control in persons with type 2 diabetes mellitus. Diabetes Res Clin Pract. 2008;81(1):e8-e11.
6. West SD, Nicoll, et al. Effect of CPAP on insulin resistance and HbA1Cin men with obstructive sleep apnea and type 2 diabetes. Thorax. 2007;62(11):969-974.
7. Vgontzas AN, et al. Sleep apnea and daytime sleepiness and fatigue: relation to visceral obesity, insulin resistance, and hypercytokinemia. J Clin Endocrinol Metab. 2000;85(3):1151-1158.
8. Chasens ER, et al. Insulin resistance and obstructive sleep apnea: is increased sympathetic stimulation the link? Biol Res Nurs. 2003;5(2):87-96.
9. Gibson GJ. Sleep apnoea, diabetes and insulin resistance. Practical Diabetes International. 2006;23(4):147-148.
10. Coughlin SR, et al. Obstructive sleep apnoea is independently associated with an increased prevalence of metabolic syndrome. Eur Heart J. 2004;25(9):735-741.
11. Punjabi NM, et al. Sleep disordered breathing and insulin resistance in middle-aged and overweight men. Am J Respir Crit Care Med. 2002;165(5):677-682.
12. Meslier N, et al. Impaired glucose insulin metabolism in males with obstructive sleep apnoea syndrome. Eur Resp J. 2003;22:156-160.
13. Shin C, et al. Association of habitual snoring with glucose and insulin metabolism in nonobese Korean adult men. Am J Resp Crit Care Med. 2005;171(3):287-291.
14. Brooks B, et al. Obstructive sleep apnea in obese noninsulin dependent diabetic patients: effect of continuous positive airway pressure treatment on insulin responsiveness. J Clin Endocrioln Metab. 1994;79(6):1681-1685.
15. Lam JC, Ip MS. An update on obstructive sleep apnea and the metabolic syndrome. Curr Opin Pulm Med. 2007;13(6):484-489.
16. Coughlin SR, et al. Cardiovascular and metabolic effects of CPAP in obese males with OSA. Eur Resp J. 2007;29(4):720-727.
17. Barcelo A, et al. Insulin resistance and daytime sleepiness in patients with sleep apnoea. Thorax. 2008;63(11):946-950.
18. Lindberg E, et al. CPAP treatment of a population based sample - what are the benefits and the treatment compliance? Sleep Medicine. 2006;7(7):553-560.
19. Pevernagie D, et al. Treatment of obstructive sleep disordered breathing with positive airway pressure systems. Eur Resp Rev. 2007;16(106):125-131.
Susan Eley is a family nurse practitioner with a PhD who is a member of the nurse practitioner faculty at Indiana State University in Terre Haute. Jules Sybert is a student in the family nurse practitioner program at Indiana State University. Lea Hall is a family nurse practitioner who is a member of the Indiana State University NP faculty.
|