What We Know and What Can Be Done? By Gary D. Foster, Ph.D, Temple University School of Medicine There is increasing attention to the causes, consequences, and treatment of obstructive sleep apnea (OSA). OSA is a condition that millions of Americans suffer from, many without knowing it. This article describes risk factors and treatment for OSA with a focus on its relationship to type 2 diabetes.
Obstructive Sleep Apnea
Defintion: Sleep apnea is characterized by the cessation of airflow during sleep.1 There are three main types: obstructive, central, and mixed, and OSA is the most common. OSA is repetitive episodes of partial (hypopnea) or complete (apnea) upper airway obstruction during sleep, resulting in a reduction or stoppage of airflow.1,2 The severity of OSA is based on the number of apneas and hyopneas per hour - the apnea-hypopnea index (AHI). An AHI of 5.0-14.9 is mild, 15.0-29.9 is moderate, and 30.0 or more is severe3,4 OSA diagnosis is based upon medical and family history, a full physical exam, and results from an overnight sleep study (polysomnography) - (References: 1,2,5)
Prevalence.: Approximately 9% of women and 24% of men have OSA, with higher rates in those who are overweight, of a minority race, and older in age. A large percentage of these cases are undiagnosed and are not being treated. (References: 6)
Symptoms.:The signs of OSA include: daytime sleepiness, not explained by other factors; loud snoring; gasping for breath (apneic episodes); recurrent awakenings from sleep; unrefreshing sleep; morning headaches; memory problems; an inability to focus; feeling irritable, depressed, or experiencing mood swings; and a dry throat upon waking up. (References: 1,2,7)
Risk Factors: Obesity is the strongest risk factor for OSA.7,8,9 Obesity increases the risk of OSA because excess weight deposits extra fat around the thorax, reducing chest compliance and functional capacity, while increasing oxygen demand. In addition, extra soft fat tissue builds up around the wall of the esophagus, narrowing the airway. The increased fat composition also makes the airway more collapsible. (References:7,10)
Men are more likely than women to have OSA, and are more severely impacted by other risk factors. For example, a weight gain (about 20 pounds) in women increases their risk of having moderate-to-severe OSA by 2.5 times, compared to increasing a man's risk by five-fold. Conversely, men experience greater improvements in OSA with weight loss than women.10 Sex differences in the anatomical and functional properties of the upper airway or the possibility of a hormonal influence (as postmenopausal women have a higher OSA prevalence than premenopausal) may explain the higher rates of OSA among men.9 In addition to increased risk due to weight and sex, OSA rates are greater in older adults, those who have a family history of OSA, those who are African American, Hispanic, or Pacific Islander, and those who currently smoke and use alcohol. (References: 7,9)
Consequences: OSA confers multiple consequences, including difficulty concentrating, depression, irritability, sexual dysfunction, and falling asleep at work or while driving. OSA is also associated with hypertension, heart attack, congestive heart failure, cardiac arrhythmia, and stroke. (References: 11)
The Link Between OSA and Type 2 Diabetes
OSA is associated with impaired fasting glucose, glucose intolerance, and type 2 diabetes, even after accounting age, sex, waist circumference, and obesity. 9,12 A recent comprehensive literature review, comprised of 83 studies, found that among all of the sleep disorders, OSA has the strongest association with type 2 diabetes. It is possible that the relationship goes in both directions. Poor sleep quality and intermittent hypoxemia from OSA may serve as the catalyst for glucose dysregulation. Over time these abnormalities may accelerate weight gain, which increases the severity of OSA. (References: 12)
The Sleep AHEAD study we conducted found that 86% of obese patients with type diabetes had undiagnosed OSA; 33.4% had mild OSA, 30.5% had moderate, and 22% had severe.8 For type 2 diabetes patients who have untreated OSA, a recent study showed a clear relationship between the severity of OSA and glucose control. Compared to those without OSA, the adjusted mean HbA1c was 1.5% higher in those with mild OSA, 1.9% higher in those with moderate OSA, and 3.69% higher in severe OSA patients. (References: 13) These two studies suggest that many patients with type 2 diabetes have undiagnosed OSA and that, if untreated, OSA has adverse effects on glycemic control.
Treatment of OSA
There are various treatments for OSA including continuous positive airway pressure (CPAP), oral appliances, surgery and weight loss. Our focus here will be on CPAP because of its superior efficacy and weight loss because of the benefits it confers beyond the improvement of OSA among patients with type 2 diabetes.
CPAP: CPAP is the principal and most effective treatment for OSA. CPAP is a portable breathing device that is used in the comfort of the patient's home. CPAP treatment is common for patients with moderate to severe OSA and involves sleeping with a mask over your mouth and nose. The mask gently blows air into the throat, providing pressure to keep the throat and windpipe open during sleep. References: 8, 14) While CPAP is effective in reducing or even eliminating apneas and hyopneas, adherence rates are about 50%. Patients often do not wear the mask for the correct number of hours per night or at the correct pressure level, so the benefits are diminished. Adherence may be enhanced by trying different types and sizes of masks and actively problem-solving barriers to adherence.
Weight Loss: Despite the strong association between obesity and OSA most existing studies on the effect of weight loss on OSA had been limited by small sample sizes, short durations, predominantly male samples, and a lack of a comparison group. The Sleep AHEAD study, published in 2009, was the first and largest, one-year randomized controlled trial to investigate the effect of weight loss on OSA in obese patients with type 2 diabetes. The four center trial recruited 264 participants, with an average age of 62.1 years, 59.1% female, 18.6% African American, 73% European American, with an average BMI of 36.7 kg/m2 and an HbA1c of 7.2%. (References 3)
The participants were randomly assigned to a diabetes and support education (DSE) group or the intensive lifestyle intervention (ILI). The DSE group met three times over the year and discussed diet, physical activity, and social support. The ILI group participated in a behavioral weight loss program specifically for obese patients with type 2 diabetes. The program included: portion controlled diets (utilizing meal replacements, frozen food entrees, and snack bars), prescribed energy intake (1200-1800 calories, dependent upon baseline weight) and a physical activity recommendation of 175 minutes per week of moderate to intense physical activity, such as brisk walking.
Sleep AHEAD found that ILI was more effective than DSE in reducing the severity of OSA. After one year, the ILI group had lost significantly more weight than the DSE group (10.8kg versus 0.6kg). Likewise, OSA improved among the ILI group, with AHI levels decreasing from 22.9 to 18.3, while AHI levels worsen in DSE, increasing from 23.5 to 28.3. Remission of OSA was three times more likely in the ILI group and more than twice as many ILI patients showed improvement in OSA severity than DSE participants.
Patients who lost 10% or more of their initial weight showed the greatest reductions in AHI. Additionally, the DSE group, which maintained a stable weight, saw a mean increase in AHI of 4 events per hour over the year, demonstrating a rapid natural progression of OSA when left untreated. Overall, Sleep AHEAD found that each kilogram of weight loss was associated with a decrease in AHI of 0.6 events per hour, and if left untreated OSA will rapidly progress.3 Other smaller studies have shown similar results in patients without diabetes.References: 15, 16)
In addition to its effects on improving OSA, weight loss has many other benefits that are important. These include improvements in blood pressure, lipid profiles, and glycemic control.10 Studies are now underway to compare the effects of CPAP, weight loss, and their combination on OSA and related metabolic consequences.
Conclusion
Numerous studies, both large population-based and clinical, have concretely established relationships between obstructive sleep apnea, type 2 diabetes, and obesity. As the obesity epidemic continues, the prevalence of OSA and type 2 diabetes will increase. Many patients with type 2 diabetes have OSA and don't know it. Given the adverse consequences of untreated OSA (hypertension, stroke, motor vehicle accidents, poor glycemic control), clinicians should increase patients awareness of the signs and symptoms of OSA and refer for sleep studies when appropriate. Once diagnosed, patients should be encouraged to adhere to CPAP treatment, given its high degree of efficacy. Weight loss can be expected to improve OSA as well as the conditions that that often accompany obesity, OSA, and diabetes and OSA (insulin resistance, hypertension and dyslipidemia).
References:
1. Guilleminault, C, Tilkian, A, & Dement, WC. (1976). The Sleep apnea syndromes. Ann. Rev. Med., 27, 465-484.
2. The Report of an American academy of sleep medicine task force: sleep-related breathing disorders in adults: recommendations for syndrome definition and measurement techniques in clinical research. (1999). SLEEP, 22(5), 667-689.
3. Foster, GD, Borradaile , KE, Sanders, MH, Millman, R, & Zammit, G., et al. (2009). A Randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes. Arch Intern Med, 169(17), 1619-1626.
4. Punjabi, NM, Shahar, E, Redline, S, Gottlieb, DJ, & Givelber, R., et al. (2004). Sleep-disordered breathing, glucose intolerance, and insulin resistance: the sleep heart health study. Am J Epidemiol, 160(6), 521-530.
5. Tasali, E, Mokhlesi, B, & Van Cauter, E. (2008). Obstructive sleep apnea and type 2 diabetes: interacting epidemics. Chest, 133, 496-506.
6. Young , T. (2009). Rationale, design, and findings from the Wisconsin sleep cohort study: toward understanding the total societal burden of sleep-disordered breathing. Sleep Med Clin, 4, 37-46.
7. The National heart lung and blood institute diseases and conditions index: sleep apnea. (2009, May). Retrieved from http://www.nhlbi.nih.gov/health/dci/Diseases/SleepApnea/SleepApnea_WhatIs.html
8. Foster, GD, Sanders, MH, Millman, R, Zammit, G, & Borradaile, KE., et al. (2009). Obstructive sleep apnea among obese patients with type 2 diabetes. Diabetes Cares, 32(6), 1017-1019.
9. Punjabi, NM. (2008). The Epidemiology of adult obstructive sleep apnea. Proc Am Thorac Soc, 5, 136-143. 10. Romero-Corral , A, Caples, SM, Lopez-Jimenez, F, & Somers, VK. (2010). Interactions between obesity and obstructive sleep apnea: implications for treatment. Chest, 137, 711-719.
11. National sleep foundation. sleep apnea and sleep. (n.d.). Retrieved from http://www.sleepfoundation.org/article/sleep-related-problems/obstructive-sleep-apnea-and-sleep
12. Punjabi, NM. (2009). Do sleep disorders and associated treatments impact glucose metabolism?. Drugs, 69(Suppl 2), 13-27.
13. Aronsohn, RS, Whitmore, H, Van Cauter, E, & Tasali, E. (2010). Impact of untreated obstructive sleep apnea on glucose control in type 2 diabetes. Am J Respir Crit Care Med, 181, 507-513.
14. McDaid, C, Duree, KH, Griffin, SC, Weatherly, HL, & Stradling, JR., et al. (2009). A Systematic review of continuous positive airway pressure for obstructive sleep apnoea-hypopnoea syndrome. Sleep Medicine Reviews, 13, 427-436.
15. Tuomilehto, HP, Seppä, JM, Partinen, MM, Peltonen, M, & Gylling H., et al. (2009). Lifestyle Intervention with Weight Reduction. Am J Crit Care Med, 179, 320-327.
16. Johansson, K, Neovius, M, Lagerros, YT, Harlid, R, & Rösser, S., et al. (2009). Effect of a very lose energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomized controlled trial. BMJ, 399, b4609.
About the Author: In addition to being a member of the DiabetesCare.net Healthcare Advisory Board, Gary D. Foster, PhD., is Professor of Medicine and Public Health and the Director of the Center for Obesity Research and Education at Temple University.
Dr. Foster's research interests include the prevention and treatment of obesity. He studies a variety of treatment approaches including behavior therapy, pharmacotherapy, and surgery. He evaluates obesity prevention strategies in schools and communities. His current research studies include: the effects of weight loss on sleep apnea, the safety and efficacy of low and high-carbohydrate diets, and the prevention of obesity in school and community settings.
He has authored or coauthored more than 125 scientific publications and 3 books on the etiology and treatment of obesity.
Dr. Foster has been a frequent presenter at national and international scientific meetings. He also has considerable clinical experience treating overweight patients in individual and group settings for over 20 years. Dr. Foster has received numerous awards and honors including: Outstanding Contributions to Health Psychology from the American Psychological Association, an Honorary Membership from the American Dietetic Association and he served as President of the Obesity Society (2008). His research on the school-based prevention of obesity (Pediatrics, 2008) was cited by the American Heart Association as one of the top 10 advances in cardiovascular research in 2008.
