The association between obesity and OSA is complex; metabolism and the endocrine system both play a role.
Obesity is a growing problem in the United States. As defined by the US National Institutes of Health, a person with a body mass index (BMI) of 25 to 29.9 is considered overweight and those with higher BMIs are considered obese. Approximately two thirds of the US population is at least overweight, and half these individuals are obese.1 Obesity is also the greatest risk factor for obstructive sleep apnea (OSA). While approximately 2% to 4% of the population is estimated to have OSA, the prevalence increases to 20% to 40% in the obese population.2 The main symptoms of OSA (excessive daytime sleepiness [EDS] and fatigue) are known to contribute to overeating and being sedentary. Tiredness can cause people to eat for stimulation. These habits, over time, can result in obesity, which worsens sleep apnea, leading to a progression in severity for both conditions. Endocrine dysfunction that exacerbates hypertension, cardiac problems, and insulin resistance is also seen in obesity and OSA.
Predictors of OSA
Despite the strong association between obesity and OSA, BMI does not consistently correlate with the severity of OSA as measured by the apnea-hypopnea index (AHI).3 One explanation may be that BMI measures only weight and height and does not include any measure of body composition (muscle versus adipose tissue). BMI considers the ratio of height to weight, but not the distribution of weight on the patients body. Common indicators of OSA in the general population, such as snoring and EDS, do not predict OSA in the obese population. Several factors have been investigated as predictors of OSA severity: Physiologically, airway collapsibility is associated with OSA severity.3 Anatomically, decreased area in the oropharynx at the end of expiration is associated with OSA severity, based on an ongoing study4 of 13 morbidly obese women. Dixon et al5 studied 99 patients with BMIs of 35 or more. They collected data on a wide range of factors associated with obesity and OSA, including self-reported symptoms (snoring, observed sleep apnea, nocturnal choking, morning headaches, EDS, and poor sleep quality); biochemical markers of metabolic syndrome; weight, height, neck, waist, and hip circumferences; and lung-volume test results. The study found that the single best predictor of an AHI of 15 or more was neck circumference of 43 cm or more. Other studies2 have shown that neck circumference and waist-hip ratio are also predictors of OSA. Other significant predictors were BMI of more than 45, age, male gender, observed sleep apnea, glycosylated hemoglobin levels of 6% or more, and fasting plasma insulin concentration of 28 or more mmol/L. The authors proposed a 6-point scale that assigned a point to each of these variables. Significant sleep apnea was defined as an AHI of 15 or more. In the study, all patients with significant sleep apnea had a score of at least 2. The relationship between apnea severity and metabolic parameters also indicates the widespread impact of OSA and resulting sleep disruption.
Among the risk factors for OSA, obesity is probably the most important. Muscles associated with breathing must overcome the additional workload imposed by the presence of adipose tissue around the ribs, diaphragm, and abdomen. Centrally distributed fat deposition is also proposed as a cause of increased pressure on the thorax and lungs. This leads to decreased lung volume and the expenditure of greater effort for respiration.6
Obesity may also induce alterations in the airway that create a propensity for collapse during sleep. Tomographic images have shown that obesity causes increased fatty deposits in the pharyngeal area.5 These deposits encroach on the airway, altering its shape. Rodenstein et al7 used MRI to investigate differences between obese subjects and nonobese controls. Coronal sections of awake OSA patients showed elliptical airways with long axes that were oriented anteroposteriorly; controls had airways that were oriented transversely. Another study by Schafer et al8 of 85 males at risk for OSA did not find a significant correlation between parapharyngeal fat deposits and AHI of 10 or more. The authors stated that differences between their conclusions and those of others might be due to the large sample size of their study and/or to differences in the techniques performed to measure pharyngeal fat deposits. Differences in the criteria used to define clinically significant AHI might also have contributed to the differing conclusions, since many studies use an AHI of 15 or more. The study group was only male, so gender differences could also account for contradictory results.
During sleep, and especially rapideye-movement sleep, support for the airway is compromised due to muscle atonia. A narrowing in the upper airway due to fat deposits and/or decreased rigidity of the tissue due to the presence of adipose tissue may predispose patients to sleep apnea. Therefore, distribution of fat in obese patients may be a better predictor than BMI. Other consequences of obesity that are related to OSA include increased respiratory resistance, increased carbon dioxide production, increased oxygen consumption, reduced lung volumes with consequent hypoxia, and decreased overall respiratory-system compliance.9,10
Beyond the symptoms of fatigue, there are physiologic mechanisms whereby OSA may contribute to obesity. Patients recently diagnosed with OSA often report recent weight gain. In patients with OSA, weight gain may be related to diet and lifestyle; in addition, it may be related to endocrine dysfunction. Leptin is a protein produced by adipose tissue that circulates in the blood and acts on the hypothalamus to inhibit eating.11 It is associated with suppressed appetite and increased energy expenditure (hence, a propensity for weight loss). Obese individuals have high leptin levels, and it is presumed that their obesity may persist because of a resistance to the appetite-suppressing and metabolism-increasing effects of leptin.12 Male patients with OSA have leptin levels approximately 50% higher than those of similarly obese males without OSA.13 A study14 investigating the effect of treating sleep apnea on leptin levels found that patients with successfully treated sleep apnea had significant reductions in leptin, whereas patients with unsuccessful resolution of sleep apnea had increased leptin levels. These observations were independent of BMI. Therefore, it is likely that sleep apnea contributes to leptin resistance. This resistance also exists with obesity alone, and may be compounded in patients with obesity and OSA. One proposed mechanism is that OSA results in increased sympathetic activity that has detrimental effects on multiple endocrine functions, including the processing of leptin.15 This may be a feed-forward mechanism in which OSA and obesity are individually detrimental to each other.
OSA may also impair endocrine functions such as glucose tolerance. Patients with OSA tend to have higher levels of fasting blood glucose, insulin, and glycosylated hemoglobin, independent of body weight.16 In some studies,17,18 the severity of OSA has been correlated with the degree of insulin resistance, though the data have been inconsistent. A hypoxia-induced hormonal stress reaction may decrease tissue insulin sensitivity. Upper-body obesity is associated with both insulin resistance and sleep apnea, so the distribution of fat that contributes to the severity of both conditions is a confounding factor. Data on the improvement of glucose tolerance after continuous positive airway pressure (CPAP) therapy have been inconsistent.19 A recent study20 investigated glycemic control in relation to 1 to 3 months of CPAP therapy. Before and after 30 to 90 days of CPAP therapy, 24 participants with OSA underwent 72 hours of continuous glucose monitoring. CPAP use history over the study period was obtained by downloading data from the CPAP machines. Glucose-tolerance parameters improved in participants who used CPAP for more than 4 hours per night, and the level of improvement correlated with number of days of CPAP use (r=0.76, P=.006). No such relationship was observed in participants using CPAP for less than 4 hours per night. Variability of CPAP use in previous studies may provide an explanation for inconsistent data in this area.
Key factors of metabolic syndrome are also affected by OSA. While obesity appears to be the main risk factor for metabolic syndrome, OSA has been shown to exacerbate markers of metabolic syndrome (obesity, triglyceride levels, high-density lipoprotein cholesterol, blood pressure, and fasting glucose levels) independently. Independent of the effects of obesity, OSA has been shown to exacerbate these conditions and it may, thereby, influence obesity and metabolic syndrome.
The relationship between obesity and OSA is further reinforced by studies of the effects of weight loss on OSA. In a population-based prospective study21 of 690 subjects, a 10% weight gain was associated with a sixfold increase in the odds of developing sleep apnea. The same study also showed that a 10% weight loss predicted a 26% decrease in AHI. In work on the effects of weight loss on sleep-disordered breathing, consistent improvements have been shown. A meta-analysis22 on bariatric surgery reported significant weight loss as a result of surgery and resolution of OSA in 85.7% of patients. Reduction in AHIs and normalization of sleep architecture occurred, in varying amounts, with weight loss. Weight loss and decreases in visceral body fat have also resulted from CPAP therapy.23 This relationship may be related to changes in lifestyle and energy levels, which may lead to healthier lifestyle choices.
Obesity is a serious national health issue affecting approximately one third of the population. The pathological changes that occur as a result of obesity are significant and affect multiple functions including the respiratory, endocrine, and cardiovascular systems. Excess adipose tissue characteristic of obesity may contribute to OSA by encroaching on organs (causing airway narrowing and decreases in lung volume). Endocrine systems are affected by changes in leptin levels that result from excess adipose tissue. This may further affect breathing centers and cardiovascular health. Other problems associated with obesity include disorders of glucose metabolism. All of these problems are exacerbated by OSA and the resulting disruption of sleep architecture. Fortunately, normalization of these parameters has been demonstrated following weight loss. Treatment of OSA has also been shown to facilitate weight loss. Just as obesity and OSA are interrelated by several factors, correcting one or the other appears to be beneficial to improving both conditions.
Mary L. Marzec, RPSGT, is an associate in sleep research, University of Michigan General Clinical Research Center, Ann Arbor.
1. Flegal KM, Carroll MD, Ogden CL, Johnson CL. Prevalence and trends in obesity among US adults, 1999-2000. JAMA. 2002;288(14):1723-7.
2. Kyzer S, Charuzi I. Obstructive sleep apnea in the obese. World J Surg. 1998;22(9):998-1001.
3. Fogel RB, Malhotra A, Dalagiorgou G, et al. Anatomic and physiologic predictors of apnea severity in morbidly obese subjects. Sleep. 2003;26(2):150-5.
4. Gomez de Terreros FJ, Caballero P, Santiago A, Soleto MJ, Martin-Duce A, Alvarez-Sala R. The upper airway and obstructive sleep apnea in morbidly obese women. Sleep. 2004;27:352.
5. Dixon JB, Schachter LM, OBrien PE. Predicting sleep apnea and excessive day sleepiness in the severely obese: indicators for polysomnography. Chest. 2003;123(4):1134-41.
6. Jubber AS. Respiratory complications of obesity. Int J Clin Pract. 2004;58(6):573-80.
7. Rodenstein D, Dooms G, Thomas Y, et al. Pharyngeal shape and dimensions in healthy subjects, snorers, and patients with obstructive sleep apnea. Thorax. 1990;45(10):722-7.
8. Schafer H, Pauleit D, Sudhop T, Gouni-Berthold I, Ewig S, Berthold HK. Body fat distribution, serum leptin, and cardiovascular risk factors in men with obstructive sleep apnea. Chest. 2002;122(3):829-39.
9. Kessler R, Chaouat A, Schinkewitch P, et al. The obesity-hypoventilation syndrome revisited. Chest. 2001;120(2):369-76.
10. Berger K, Ayappa I, Chatramontri B, et al. Obesity hypoventilation syndrome as a spectrum of respiratory disturbances during sleep. Chest. 2001;120(4):1231-8.
11. ODonnell C, Tankersley C, Polotsky V, Schwartz A, Smith P. Leptin, obesity and respiratory function. Respir Physiol. 2000;119(2-3):173-80.
12. Considine R, Sinha M, Heiman M, et al. Immunoreactive-leptin concentrations in normal-weight and obese humans. N Engl J Med. 1996;334(5):292-5.
13. Philips B, Kato M, Narkiewicz K, Choe I, Somers V. Increases in leptin levels, sympathetic drive and weight gain in obstructive sleep apnea. Am J Physiol Heart Circ Physiol. 2000;279(1):H234-7.
14. Sanner B, Kollhossser P, Buechner N, Zidek W, Tepel M. Influence of treatment on leptin levels in patients with obstructive sleep apnoea. Eur Respir J. 2004;23(4):601-604.
15. Yun AJ, Lee PY, Bazar KA. Autonomic dysregulation as a basis for cardiovascular, endocrine, and inflammatory disturbances associated with obstructive sleep apnea and other chronic conditions of chronic hypoxia, hypercapnia, and acidosis. Med Hypotheses. 2004;62(6):852-6.
16. Elmasry A, Lindberg E, Berne C, et al. Sleep-disordered breathing and glucose metabolism in hypertensive men: a population-based study. J Intern Med. 2001;249(2):153-61.
17. Nagai Y, Nakatsumi Y, Abe T, Nomura G. Is the severity of obstructive sleep apnoea associated with the degree of insulin resistance? Diabet Med. 2003;20(1):80-2.
18. Tiihonen M, Partinen M, Narvanen S. The severity of obstructive sleep apnoea is associated with insulin resistance. J Sleep Res. 1993;2(1):56-61.
19. Smurra M, Philip P, Taillard J, Guilleminault C, Bioulac B, Gin H. CPAP treatment does not affect glucose-insulin metabolism in sleep apneic patients. Sleep Med. 2001;2(3):207-13.
20. Babu AR, Herdegen J, Fogelfeld L, Shott S, Mazzone T. Type 2 diabetes, glycemic control, and continuous positive airway pressure in obstructive sleep apnea. Arch Intern Med. 2005;165(4):447-52.
21. Peppard PE, Young T, Palta M, Dempsey J, Skatrud J. Longitudinal study of moderate weight change and sleep-disordered breathing. JAMA. 2000;284(23):3015-21.
22. Buchwald H, Avidor Y, Braunwald E, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292:1724-37.
23. Chin K, Shimizu K, Nakamura T, et al. Changes in intra-abdominal visceral fat and serum leptin levels in patients with obstructive sleep apnea syndrome following nasal continuous positive airway pressure therapy. Circulation. 1999;100(7):706-2.