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Review

Association between sleep disorders, obesity, and exercise: a review

, , &
Pages 27-35 | Published online: 01 Mar 2013

Abstract

Decreased sleep duration and quality is associated with an increase in body weight and adiposity. Insomnia, obstructive sleep apnea, and restless legs syndrome are three of the most prevalent types of sleep disorder that lead to an increased risk for numerous chronic health conditions. Various studies have examined the impact of these sleep disorders on obesity, and are an important link in understanding the relationship between sleep disorders and chronic disease. Physical activity and exercise are important prognostic tools in obesity and chronic disease, and numerous studies have explored the relationship between obesity, sleep disorders, and exercise. As such, this review will examine the relationship between sleep disorders and obesity. In addition, how sleep disorders may impact the exercise response and how exercise may impact patient outcomes with regard to sleep disorders will also be reviewed.

Introduction

The International Classification of Sleep Disorders currently lists more than 80 distinct sleep disorders (SD) divided into eight categories, including insomnia, sleep disordered breathing (SDB), and sleep-related movement disorders.Citation1 SD occur in a large proportion of the adult population, with 10%–13% of adults estimated to suffer from chronic insomnia and an additional 25%–35% having occasional insomnia.Citation2 Obstructive sleep apnea (OSA), the most prevalent form of SDB, has been estimated to occur in approximately 2%–4% of adults.Citation3 It is further estimated, however, that a large proportion of individuals (93% of women and 82% of men) with clinically significant OSA remain undiagnosed, suggesting a much larger overall prevalence rate.Citation4 Restless legs syndrome (RLS) is a prevalent form of sleep-related movement disorder with prevalence estimates ranging between 4% and 29%.Citation5 These disorders all result in decreased sleep duration and quality, which has been associated with increases in body weight and adiposity.Citation6,Citation7 In OSA alone, it has recently been estimated that in those with a body mass index (BMI) of 25–28 kg/m2 (overweight classification), prevalence rates increase to 20% and 7% for mild and moderate to severe OSA, respectively.Citation8

The relationship between SD and obesity is likely an important mediating factor in the emerging research linking SD and other chronic disease, including cardiovascular disease (CVD) and diabetes mellitus, across all age groups.Citation9Citation12 Understanding this link may increase the chances for the development of effective treatment interventions for both SD and obesity. A well-known treatment intervention for obesity is regular physical activity/exercise, which has recently begun to be investigated in relation to SD as well. Recent evidence, which will be reviewed within this manuscript, has suggested that the presence of a SD may impact the response to physical activity/exercise, be it acutely or chronically. This may have implications as to the effectiveness of physical activity/exercise as an intervention, but it may also aid in serving as a prognostic tool for the identification of those at increased risk for SD or other chronic conditions. Thus, this review will examine (1) the relationship between obesity and sleep disorders (ie, insomnia, OSA, and RLS); (2) the pathophysiological mechanisms linking these SD to obesity; and (3) the potential impact of these SD on physical activity and exercise, a primary intervention in addressing increased adiposity and obesity. Further, this review will focus on, but not be limited to, the previous 10 years (January 2002 to December 2012).

Insomnia

Diagnostic criteria for insomnia consists of symptoms relating to sleep disturbance, including difficulty initiating sleep, difficulty maintaining sleep, awakening too early, or sleep that is poor in quality in the presence of adequate opportunity and appropriate circumstances for sleep.Citation13 Diagnosis of insomnia, unlike many other SD, is based on self-reported, and therefore subjective, sleep behaviors and sleep diaries completed by patients.Citation14

The predominant theory regarding the pathophysiology of primary insomnia centers around a state of hyperarousal, manifested in hyperactivity of corticotropin-releasing factor (CRF).Citation2,Citation14,Citation15 Initial insomnia may occur as a result of some psychosocial stressor or other precipitating factor that increases arousal of the hypothalamic–pituitary–adrenal axis.Citation14 A study of young patients with insomnia, compared to age- and BMI-matched healthy controls, revealed higher 24-hour mean secretions of adrenocorticotropic hormone and cortisol.Citation16 Levels were markedly higher in patients with insomnia in the afternoon, evening, and early night measurements. Interestingly, the increase in 24-hour secretion did not appear to come from increased magnitude of pulsatile releases, but rather from increased concentrations during the “valley” periods of the 24-hour pulsatile profile and from an increased number of adrenocorticotropic hormone and cortisol pulsatile releases. Additionally, hyperactivity of the regions of the brain responsible for wake promotion was supported by studies that utilized positron emission tomography scans to map glucose metabolism during wakefulness and non-REM sleep, and that this increase in glucose metabolism was associated with the number of times persons with primary insomnia awoke during the night.Citation17,Citation18

Insomnia and obesity

Previous studies have indicated that persons with obesity are significantly more likely to report insomnia or difficulty with sleep.Citation19 Additionally, over an average 7.5-year follow-up, persons with obesity were significantly more likely to develop chronic insomnia, although this effect was partially negated when controlling for sociodemographic and behavioral factors.Citation20 Finally, in persons with obesity, complaints of chronic emotional stress or sleep disturbance have been reported to be predictors for short sleep duration, rather than voluntary sleep curtailment as previously thought.Citation21 Vgontzas et al further showed that in persons with obesity and without sleep disturbances or emotional stress, sleep duration was similar to non-obese control subjects.Citation21 This may indicate the importance of detection and treatment of sleep disturbances as a potential therapeutic intervention for obesity.Citation21

Insomnia, or its underlying pathophysiology, may play a role in predisposing one to overconsumption of energy, thus leading to weight gain. In a study of over 1000 volunteers from the Wisconsin Sleep Cohort Study, Taheri et al found that shorter sleep durations (5 hours per night versus 8 hours per night) were associated with 15.5% lower leptin levels and 14.9% higher ghrelin levels, independent of BMI, which may indicate that chronically shortened sleep duration could increase appetite, leading to overconsumption.Citation22 Additionally, Dallman et al have proposed that chronic elevation of glucocorticoids, such as cortisol, similar to the proposed mechanism for insomnia, may play a role in increasing a person’s desire to consume high fat and high sugar foods, as well as their propensity to store fat in the abdominal region.Citation23 They proposed that the chronically elevated levels of glucocorticoid hormones increase CRF activity in the central nucleus of the amygdala, increase stimulus salience, and increase abdominal obesity, which then serves as a means of increasing the metabolic inhibitory feedback on the catecholamines in the brain and CRF expression. This would indicate that the same pathway associated with hyperactivity in insomnia may promote the overconsumption of high fat and high sugar foods, as well as the deposition of abdominal fat stores, in an attempt to calm the hyperactivity occurring in the brain.Citation23

Insomnia and physical activity and exercise

Experimental evidence has suggested that exercise may be associated with better sleep quality.Citation24Citation27 Although not specific to those diagnosed with insomnia, these studies have suggested that, in those with sleep difficulties, exercise may be effective at improving sleep outcomes, although this remains unclear. Cross-sectional data has shown that physical inactivity has consistently arisen as a factor that increases one’s likelihood for reporting symptoms of insomnia or poor sleep, even after controlling for other factors believed to affect insomnia risk.Citation28Citation31 Further, it has recently been reported that maximal aerobic capacity was lower in those diagnosed with insomnia compared to those without insomnia, independent of other factors like age and sex.Citation32

In regards to exercise training with insomnia, an acute bout of moderate-intensity aerobic exercise approximately 3 hours before bedtime has been shown to reduce sleep onset latency, total wake time, and pre-sleep anxiety, while increasing total sleep time and sleep efficiency in those diagnosed with insomnia.Citation33 High-intensity aerobic exercise and moderate-intensity resistance training did not confer the same benefits. In older adults, a 16-week moderate intensity aerobic training program, with sleep hygiene education, was shown to improve self-reported sleep quality, mood, and quality of life versus sleep hygiene education alone.Citation34 The effects in this study were reported to be comparable to other reported cognitive behavioral interventions.Citation35,Citation36

Obstructive sleep apnea

The pathophysiologic mechanisms of OSA are complex and compelling. Population based studies demonstrate a strong relationship between OSA and obesity – over 70% of individuals with OSA are considered clinically obese based on BMI statusCitation37 – in addition to chronic diseases including hypertension, type 2 diabetes mellitus, CVD, and stroke.Citation12,Citation38 The link between OSA and obesity has been clearly documented with weight change impacting the Apnea-Hypopnea Index (AHI), a measure of OSA severity. In another analysis from the Wisconsin Sleep Cohort Study, which used a sample of 700 subjects, a 10% weight gain predicted a 32% increase in AHI score; conversely a 10% weight loss predicted a 26% decrease in AHI score over a 4-year period.Citation39 The strong relationship between OSA and obesity was replicated in the Sleep Heart Health Study and the Cleveland Family Study.Citation40,Citation41 Considerable research has demonstrated the reduction of OSA and related symptoms, including excessive daytime sleepiness, with weight loss, induced by diet and/or physical activity behavior change, medication, or through bariatric surgery.Citation42Citation44

OSA and obesity

Knowledge of the underlying connection with OSA and obesity is evolving and involves a two-way relationship affecting both the contribution of obesity to OSA and the implications of OSA contributing to obesity. Obesity contributes to the development and severity of OSA through influences on the upper airway involving both respiratory neuromuscular control, and adipokine production. Independently, obesity appears to affect control of the upper airway through several mechanisms, including alterations in upper airway structure and function, reductions in resting load volume, and negative effects on respiratory drive and load compensation.Citation45 Additionally, neuromuscular control of the upper airway is negatively impacted by alterations in several key cytokines related to obesity, including leptin, tumor necrosis factor-alpha, and interleukin-6.Citation46 Independently, leptin can inhibit respiratory drive and OSA has been correlated with increased leptin levels.Citation47 Insulin resistance is also associated with OSA severity, independent of body weight, and may be linked with sleep deprivation or sympathetic activation.Citation8 Location of fat deposition, specifically in the neck and viscera, can also contribute to OSA susceptibility.Citation42

The role of OSA contributing to obesity is less direct than the impact of obesity on the pathophysiology of OSA. Nonetheless, it is important to consider the contribution of OSA to obesity, thus potentially exacerbating obesity’s impact on OSA. As described by Ong et al,Citation45 OSA impacts energy expenditure and caloric intake and thus overall body weight in a variety of ways, including: (1) changes in energy expenditure during times of sleep and wakefulness; (2) increased preference for energy dense food and increased caloric intake; (3) alteration in hormonal regulation specific to appetite and satiety; and (4) changes in sleep duration, which may decrease physical activity that is attributable to lethargy and daytime sleepiness.

Several studies have shown an increased preference for calorie dense foods, specifically fats and carbohydrates, in patients with OSA, independent from obesity.Citation45,Citation48,Citation49 This preference may be tied to sleep fragmentation but has not been clearly elucidated.Citation46 Leptin and ghrelin are the key hormones related to appetite control. Increased leptin, to a state of leptin resistance, has been noted in obesity and as mentioned previously, increased leptin is associated with OSA status.Citation47

Obesity is a strong risk factor influencing OSA development, maintenance, and severity. Continued understanding of the mechanisms underpinning this relationship are critical to help determine appropriate treatment options. Weight reduction through various means continues to be viewed as a viable option to ameliorate OSA and related symptoms and thus potentially favorably impact associated chronic diseases. Additional research is warranted to determine the overall efficacy of weight reduction treatment modalities with long-term success.

OSA and physical activity and exercise

A physically active lifestyle can provide important health benefits for individuals with OSA. Importantly, regular exercise is associated with reductions in blood pressureCitation51Citation54 and in the prevention of CVDCitation41,Citation55,Citation56 – two of the most serious comorbidities associated with OSA.Citation57 Unfortunately, the salient clinical features of OSA suggest that patients are often disinclined or unable to initiate or maintain a regular exercise program. The sleep fragmentation of OSA frequently leads to excessive daytime sleepiness and lack of physical vigor. Furthermore, obesity is present in over 70% of patients,Citation58 and is implicated in both the development and progression of OSA.Citation41 Although weight loss has been shown to decrease the severity of OSA, recent evidence suggests a bidirectional relationship between OSA and obesity, such that OSA also may promote weight gain and obesity.Citation59,Citation60 These findings present unique challenges for patients, and may partly explain why patients with OSA have difficulty losing weight.

The means by which effective and permanent weight loss is achieved is of growing importance to physicians treating patients with OSA. When used effectively, continuous positive airway pressure (CPAP) therapy is beneficial and has been shown to improve several adverse outcomes of OSA. Unfortunately, adherence levels are often suboptimal, particularly for patients with mild to moderate OSACitation61 and poor adherence often precludes important health benefits that otherwise may be associated with treatment. Furthermore, weight loss is not a consistent finding among obese OSA patients effectively treated with CPAPCitation62 and preliminary evidence suggests that physical activity levels are not improved with CPAP, despite reductions in daytime drowsiness.Citation63 In this regard, encouraging patients to become more physically active may help break the cycle of weight gain and progression of OSA.

Exercise cardiopulmonary response characteristics in OSA

The majority of research to date on exercise in OSA has utilized graded exercise testing to help characterize the nature of cardiopulmonary stress attendant to this disorder, as well as to better understand functional abnormalities associated with OSA. These studies have demonstrated several distinct exercise response characteristics in OSA, including chronotropic incompetence,Citation64Citation67 exaggerated blood pressure,Citation65,Citation66,Citation68 and delayed heart rate recovery.Citation69Citation71 Some studies also report that VO2 peak is reduced in OSA.Citation64,Citation72Citation76 However, this is not a consistent finding, as others have reported no differences in exercise capacity between untreated patients with OSA and matched counterparts without OSA.Citation65,Citation69Citation71,Citation77,Citation78 Several mediating factors may partly explain why some studies have found that OSA is associated with a reduced functional capacity, including OSA disease severity,Citation77 impaired muscle metabolism,Citation76,Citation79 reduced habitual daily physical activity secondary to daytime sleepiness,Citation68,Citation71,Citation73,Citation74,Citation77 and cardiac dysfunction.Citation78,Citation80 Clearly, additional randomized controlled studies are needed to better understand the hemodynamic and pulmonary response characteristics in OSA. However, these studies lend preliminary support to the notion that OSA is associated with unique physiological response patterns during exercise, which may partially explain self-reports by patients that sustained exercise is unusually fatiguing.

Exercise training in OSA

Increasing interest has been generated in recent years concerning the potential benefits of exercise as an adjunct to primary treatment with CPAP. Since regular aerobic exercise is associated with body weight maintenance and, at higher volumes, weight loss,Citation81 recommendations for increased physical activity frequently accompany primary treatment with CPAPCitation82 and may be a viable means to increase daily energy expenditure and reduce secondary risk factors in OSA. In this regard, combining both exercise and weight loss with CPAP may provide the most effective treatment for many patients with OSA.

Few studies have examined the effects of exercise training on measures of OSA disease severity or other key clinical outcome measures in patients with OSA. Furthermore, a review of the published literature reveals that many of the previous studies that evaluated the efficacy of exercise training in OSA are limited by relatively small sample sizesCitation83Citation87 that oftentimes lacked control groups.Citation85Citation87 Moreover, several notable methodological differences exist between the majority of exercise training studies in OSA that complicate meaningful comparisons, including OSA sample population, disease severity, exercise testing protocols (exercise modes and test end points), and exercise training dose. Despite these limitations, preliminary evidence is encouraging and suggests that exercise training may be associated with reductions in OSA disease severity,Citation86Citation89 improved exercise capacity,Citation69,Citation83,Citation84,Citation86 as well as improvements in daytime sleepiness, quality of life, and mood state.Citation84,Citation86,Citation90 Although it seems likely that weight loss secondary to exercise training is the most likely mechanism for improvement in OSA disease severity, exercise alone has been shown to improve OSA severity even without significant weight loss.Citation83,Citation87Citation89

Despite the lack of evidence to support specific exercise recommendations in OSA, it is reassuring that regular physical activity appears to be associated with higher vitality, increased physical vigor, and reduced fatigue in patients with OSA.Citation91 Epidemiological research also suggests a modest association between higher volumes of exercise and reduced severity of OSA that is independent of body habitus.Citation92 Furthermore, data from the Sleep Heart Health Study demonstrate that vigorous exercise performed for at least 3 hours each week is associated with decreased odds of developing OSA.Citation93

Additional research is needed on the potential benefits of exercise in treating OSA. However, the results from these studies are encouraging and suggest that a physically active lifestyle may have long-term potential to forestall or even reverse the symptoms associated with OSA, and possibly prevent the development of OSA altogether. Furthermore, that the majority of these changes appear soon after initiation of CPAP therapy suggests that there is good potential to increase aerobic physical activity shortly after therapy has begun.

Restless legs syndrome

RLS is a disorder characterized by the irresistible urge to move the legs in response to a “creeping or crawly” sensation in the legs.Citation94 The sensation in the legs can be as severe as pain and is temporarily relieved by movement.Citation94 The impact of RLS on the individual can be profound and debilitating. RLS is associated with reductions in quality of life – reductions that are comparable to Parkinson’s disease and other chronic diseases.Citation95 RLS can negatively impact daily activities, where prolonged activities like sitting at a desk or riding in a vehicle can be difficult to impossible.Citation96 RLS is associated with delayed sleep onset, difficulty maintaining sleep, decreased total sleep time, and reduced or no slow-wave sleep.Citation97 Individuals with RLS are at increased risk for psychological disorders like panic disorder, generalized anxiety disorder, and depression.Citation98 In addition, RLS has demonstrated a positive relationship to increased CVD incidence, independent of confounding factors like age, sex, BMI, other sleep disorders, and lifestyle factors.Citation5

The pathophysiological mechanisms of RLS are not well understood. The primary causes of RLS are believed to be dopaminergic and iron metabolism dysfunction,Citation94,Citation99Citation104 although this may only be a partial explanation.Citation105 Iron deficiency is not common in all RLS sufferers, and iron supplementation and dopaminergic agents have shown variable success in RLS treatment.Citation5

RLS and obesity

Several studies across different countries have examined the relationship between RLS and obesity, most being cross-sectional in nature. As a result, assessing the causal nature between the two is difficult. A majority of studies, however, do show a small yet significant relationship between RLS and obesity.Citation106Citation113 This relationship has been demonstrated through a significantly greater BMI in those with RLS versus those without,Citation107,Citation113 an increased prevalence of RLS in obese versus nonobese individuals,Citation109,Citation110,Citation112 or an increased prevalence of obesity in RLS versus non-RLS.Citation106,Citation111 These studies all adjusted for common confounding variables such as age, sex, and lifestyle factors (caffeine or alcohol consumption, smoking, physical activity).

The strength of the relationship between RLS and obesity, however, is open to interpretation. For instance, Schlesinger et alCitation113 reported mean ± standard deviation BMI values of 27.3 ± 0.3 and 26.5 ± 0.3 for RLS and non-RLS, respectively (P = 0.003). Elwood et alCitation107 reported similar mean values in their study (27.5 vs 26.6 for RLS vs non-RLS, P < 0.001). While statistically significant, the mean differences reported are small. In contrast, reported prevalence data may suggest a stronger relationship. Mustafa et alCitation112 reported that the prevalence of RLS was significantly higher in obese subjects (23%) versus nonobese subjects (16.4%). When comparing men with RLS versus those without, Mallon et alCitation106 reported an obesity prevalence (BMI ≥ 30 kg/m2) of 7.2% and 4.3%, respectively (P = 0.05). In women, the prevalence of obesity was 9.4% and 5.2% in RLS and non-RLS, respectively (P = 0.01).

RLS and physical activity and exercise

To date, very few studies have examined the impact of RLS on physical activity or exercise. One epidemiological study in over 1800 subjects reported that a lack of exercise (<3 hours per month vs ≥3 hours per month) was associated with an increased risk of RLS (odds ratio = 3.32).Citation114 A recent study by Daniele et alCitation115 examined the physical activity habits of RLS patients and found that while RLS severity did not differ across physical activity levels assessed by questionnaire, more active RLS patients reported greater quality of life variables, suggesting the potential value of physical activity in RLS patients.

Exercise training in RLS

Only two recent studies were identified that have examined the impact of exercise training on RLS. Esteves et alCitation116 trained eleven RLS subjects at their anaerobic ventilatory threshold for 72 sessions (approximately 6 months) and found that subjective symptoms of RLS were significantly improved after training. One randomized controlled trial has been conducted in RLS patients.Citation117 In this study, 41 subjects were randomized to either an exercise or non-exercise group. The exercise group performed aerobic and lower extremity resistance training 3 days per week for 12 weeks. Similar to the previous study, RLS symptoms were significantly improved following the training period (total severity score 20.6 vs 12.1 for baseline and 12 weeks, respectively) whereas the control group did not change (22.5 vs 21.5). These findings suggest that physical activity and/or exercise may have a significant positive impact on the quality of life of RLS sufferers, and may aid in improving the obesity status of those with RLS.

Summary and future directions

Sleep disturbances and sleep deprivation, whether caused by insomnia, SDB, or a sleep-related movement disorder, does appear to have a relationship with development of or exacerbation of body adiposity or vice versa. The nature of the published research, predominantly cross-sectional and observational in nature, makes it difficult to ascertain clearly whether it is the SD contributing to obesity, or obesity contributing to the SD. More research, with large sample sizes and controlled for confounding factors are needed. It is most likely a combination of both, each contributing to a downward spiral of worsening sleep habits and body adiposity. In all three cases discussed within this review (insomnia, OSA, RLS) however, evidence does exist suggesting that the presence of a SD may increase the risk for obesity.

There does, however, appear to be a positive influence of exercise in SD. In all three cases, quality of life and/or severity outcomes appear to be positively impacted by regular exercise. Adopting a physically active lifestyle may be a key intervention for the treatment of SD and obesity, and may be a long-term solution to improved quality of life and decreased risk for the chronic conditions associated with these SD. Further research is needed with long-term randomized controlled trials to best elucidate this relationship.

Disclosure

The authors report no conflict of interest in this work.

References

  • International Classification of Sleep DisordersDiagnostic and Coding Manual2nd edWestchester, ILAmerican Academy of Sleep Medicine2005
  • RothTRoehrsTPiesRInsomnia: pathophysiology and implications for treatmentSleep Med Rev200711717917175184
  • YoungTPaltaMDempseyJSkatrudJWeberSBadrSThe occurrence of sleep-disordered breathing among middle-aged adultsN Engl J Med1993328123012358464434
  • YoungTEvansLFinnLPaltaMEstimation of the clinically diagnosed proportion of sleep apnea syndrome in middle-aged men and womenSleep1997207057069406321
  • InnesKESelfeTKAgarwalPPrevalence of restless legs syndrome in North American and Western European populations: a systematic reviewSleep Med20111262363421752711
  • Lopez-GarciaEFaubelRLeon-MunozLZuluagaMCBanegasJRRodriguez-ArtalejoFSleep duration, general and abdominal obesity, and weight change among the older adult population of SpainAm J Clin Nutr20088731031618258619
  • PatelSRBlackwellTRedlineSThe association between sleep duration and obesity in older adultsInt J Obes (Lond)2008321825183418936766
  • CaplesSMGamiASSomersVKObstructive sleep apneaAnn Intern Med200514218719715684207
  • CarotenutoMSantoroNGrandoneAThe insulin gene variable number of tandemrepeats (INS VNTR) genotype and sleep disordered breathing in childhood obesityJ Endocrinol Invest20093275275519574727
  • CarotenutoMBruniOSantoroNDel GiudiceEMPerroneLPascottoAWaist circumference predicts the occurrence of sleep-disordered breathing in obese children and adolescents: a questionnaire-based studySleep Med2006735736116713341
  • PunjabiNMShaharERedlineSGottliebDJGivelberRResnickHESleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health StudyAm J Epidemiol200416052153015353412
  • SomersVKWhiteDPAminRSleep apnea and cardiovascular disease: an American Heart Association/American College Of Cardiology Foundation Scientific Statement from the American Heart Association Council for High Blood Pressure Research Professional Education Committee, Council on Clinical Cardiology, Stroke Council, and Council On Cardiovascular Nursing. In collaboration with the National Heart, Lung, and Blood Institute National Center on Sleep Disorders Research (National Institutes of Health)Circulation20081181080111118725495
  • EdingerJDBonnetMHBootzinRRDerivation of research diagnostic criteria for insomnia: report of an American Academy of Sleep Medicine Work GroupSleep2004271567159615683149
  • RiemannDKloepferCBergerMFunctional and structural brain alterations in insomnia: implications for pathophysiologyEur J Neurosci2009291754176019473230
  • RothTInsomnia: definition, prevalence, etiology, and consequencesJ Clin Sleep Med20073S7S1017824495
  • VgontzasANBixlerEOLinH-MChronic insomnia is associated with nyctohemeral activation of the hypothalamic-pituitary-adrenal axis: clinical implicationsJ Clin Endocrinol Metab2001863787379411502812
  • NofzingerEANissenCGermainARegional cerebral metabolic correlates of WASO during NREM sleep in insomniaJ Clin Sleep Med2006231632217561544
  • NofzingerEABuysseDJGermainAPriceJCMiewaldJMKupferDJFunctional neuroimaging evidence for hyperarousal in insomniaAm J Psychiatry20041612126212815514418
  • PearsonNJJohnsonLLNahinRLInsomnia, trouble sleeping, and complementary and alternative medicine: Analysis of the 2002 national health interview survey dataArch Intern Med20061661775178216983058
  • SingareddyRVgontzasANFernandez-MendozaJRisk factors for incident chronic insomnia: a general population prospective studySleep Med20121334635322425576
  • VgontzasANLinHMPapaliagaMShort sleep duration and obesity: the role of emotional stress and sleep disturbancesInt J Obes (Lond)20083280180918253159
  • TaheriSLinLAustinDYoungTMignotEShort sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass indexPLoS Med20041e6215602591
  • DallmanMFPecoraroNAkanaSFChronic stress and obesity: a new view of “comfort food”Proc Natl Acad Sci U S A2003100116961170112975524
  • KingACOmanRFBrassingtonGSBliwiseDLHaskellWLModerate-intensity exercise and self-rated quality of sleep in older adults. A randomized controlled trialJAMA199727732378980207
  • KlineCESuiXHallMHDose-response effects of exercise training on the subjective sleep quality of postmenopausal women: exploratory analyses of a randomised controlled trialBMJ Open20122e001044
  • BrandSGerberMBeckJHatzingerMPuhseUHolsboer-TrachslerEHigh exercise levels are related to favorable sleep patterns and psychological functioning in adolescents: a comparison of athletes and controlsJ Adolesc Health20104613314120113919
  • GrandnerMAPatelNPPerlisMLObesity, diabetes, and exercise associated with sleep-related complaints in the American populationZ Gesundh Wiss20111946347422791935
  • ChasensERYangKInsomnia and physical activity in adults with prediabetesClin Nurs Res20122129430821788447
  • PaparrigopoulosTTzavaraCTheleritisCPsarrosCSoldatosCTountasYInsomnia and its correlates in a representative sample of the Greek populationBMC Public Health20101053120815870
  • FoleyDAncoli-IsraelSBritzPWalshJSleep disturbances and chronic disease in older adults: results of the 2003 National Sleep Foundation Sleep in America SurveyJ Psychosom Res20045649750215172205
  • MorganKDaytime activity and risk factors for late-life insomniaJ Sleep Res20031223123812941062
  • StrandLBLaugsandLEWisloffUNesBMVattenLJanszkyIInsomnia symptoms and cardiorespiratory fitness in healthy individuals: the Nord-Trondelag Health Study (HUNT)Sleep20133699C108C23288976
  • PassosGSPoyaresDSantanaMGGarbuioSATufikSMelloMTEffect of acute physical exercise on patients with chronic primary insomniaJ Clin Sleep Med2010627027520572421
  • ReidKJBaronKGLuBNaylorEWolfeLZeePCAerobic exercise improves self-reported sleep and quality of life in older adults with insomniaSleep Med20101193494020813580
  • SinghNAClementsKMFiataroneMAA randomized controlled trial of the effect of exercise on sleepSleep1997202951019143068
  • KingACPruittLAWooSEffects of moderate-intensity exercise on polysomnographic and subjective sleep quality in older adults with mild to moderate sleep complaintsJ Gerontol A Biol Sci Med Sci2008639997100418840807
  • MalhotraAWhiteDPObstructive sleep apnoeaLancet200236023724512133673
  • KatoMAdachiTKoshinoYSomersVKObstructive sleep apnea and cardiovascular diseaseCirc J2009731363137019564701
  • PeppardPEYoungTPaltaMDempseyJSkatrudJLongitudinal study of moderate weight change and sleep-disordered breathingJAMA20002843015302111122588
  • TishlerPVLarkinEKSchluchterMDRedlineSIncidence of sleep-disordered breathing in an urban adult population: the relative importance of risk factors in the development of sleep-disordered breathingJAMA20032892230223712734134
  • YoungTShaharENietoFJPredictors of sleep-disordered breathing in community-dwelling adults: the Sleep Heart Health StudyArch Intern Med200216289390011966340
  • TuomilehtoHSeppaJUusitupaMObesity and obstructive sleep apnea – Clinical significance of weight lossSleep Med Rev2012
  • JohanssonKNeoviusMLagerrosYTEffect of a very low energy diet on moderate and severe obstructive sleep apnoea in obese men: a randomised controlled trialBMJ2009339b460919959590
  • FosterGDBorradaileKESandersMHA randomized study on the effect of weight loss on obstructive sleep apnea among obese patients with type 2 diabetes: the Sleep AHEAD studyArch Intern Med20091691619162619786682
  • OngCWO’DriscollDMTrubyHNaughtonMTHamiltonGSThe reciprocal interaction between obesity and obstructive sleep apnoeaSleep Med Rev Epub July 17, 2012
  • CalvinADAlbuquerqueFNLopez-JimenezFSomersVKObstructive sleep apnea, inflammation, and the metabolic syndromeMetab Syndr Relat Disord2009727127819344228
  • EnrioriPJEvansAESinnayahPCowleyMALeptin resistance and obesityObesity200614 Suppl 5254S258S17021377
  • GrunsteinRRStenlofKHednerJSjostromLImpact of obstructive sleep apnea and sleepiness on metabolic and cardiovascular risk factors in the Swedish Obese Subjects (SOS) StudyInt J Obes Relat Metab Disord19951964104187550526
  • BeebeDWMillerNKirkSDanielsSRAminRThe association between obstructive sleep apnea and dietary choices among obese individuals during middle to late childhoodSleep Med201112879779921871836
  • SpiegelKTasaliEPenevPVan CauterEBrief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetiteAnn Intern Med200414184685015583226
  • WijnenHBoothroydCYoungMWClaridge-ChangAMolecular genetics of timing in intrinsic circadian rhythm sleep disordersAnn Med20023438639312452482
  • QuanSFGriswoldMEIberCShort-term variability of respiration and sleep during unattended nonlaboratory polysomnography–the Sleep Heart Health Study. [corrected]Sleep20022584384912489889
  • PedrazzoliMLingLYoungTBFinnLTufikSMignotEEffect of the prion 129 polymorphism on nocturnal sleep and insomnia complaints: a population-based studyJ Sleep Res20021135735812464104
  • MalhotraAAyasNTEpsteinLJThe art and science of continuous positive airway pressure therapy in obstructive sleep apneaCurr Opin Pulm Med2000649049511100958
  • HlaKMSkatrudJBFinnLPaltaMYoungTThe effect of correction of sleep-disordered breathing on BP in untreated hypertensionChest20021221125113212377832
  • AtamerADelaneyMYoungLRAn expert system for fault management assistance on a space sleep experimentArch Ital Biol200214030331312228983
  • HackneyJEWeaverTEPackAIHealth literacy and sleep disorders: a reviewSleep Med Rev20081214315118222098
  • VgontzasANTanTLBixlerEOMartinLFShubertDKalesASleep apnea and sleep disruption in obese patientsArch Intern Med1994154170517118042887
  • BrownMAGoodwinJLSilvaGEThe impact of sleep-disordered breathing on body mass index (BMI): the Sleep Heart Health Study (SHHS)Southwest J Pulm Crit Care2011315916822288025
  • PillarGShehadehNAbdominal fat and sleep apnea: the chicken or the egg?Diabetes Care200831 Suppl 2S303S30918227501
  • ShahNRouxFMohseninVImproving health-related quality of life in patients with obstructive sleep apnea: what are the available options?Treat Respir Med2006523524416808543
  • RedeniusRMurphyCO’NeillEAl-HamwiMZallekSNDoes CPAP lead to change in BMI?J Clin Sleep Med2008420520918595431
  • WestSDKohlerMNicollDJStradlingJRThe effect of continuous positive airway pressure treatment on physical activity in patients with obstructive sleep apnoea: a randomised controlled trialSleep Med2009101056105819427263
  • VanheckeTEFranklinBAZalesinKCCardiorespiratory fitness and obstructive sleep apnea syndrome in morbidly obese patientsChest200813453954518779193
  • KalethASChittendenTWHawkinsBJUnique cardiopulmonary exercise test responses in overweight middle-aged adults with obstructive sleep apneaSleep Med2007816016817275399
  • GroteLHednerJPeterJHThe heart rate response to exercise is blunted in patients with sleep-related breathing disorderCardiology2004102939915103179
  • AguillardRNRiedelBWLichsteinKLGrieveFGJohnsonCTNoeSLDaytime functioning in obstructive sleep apnea patients: exercise tolerance, subjective fatigue, and sleepinessApp Psychophysiol Biofeedback199823207217
  • TryfonSStanopoulosIDascalopoulouEArgyropoulouPBourosDMavrofridisESleep apnea syndrome and diastolic blood pressure elevation during exerciseRespiration20047149950415467328
  • KlineCECrowleyEPEwingGBBlunted heart rate recovery is improved following exercise training in overweight adults with obstructive sleep apneaInt J Cardiol Epub May 7, 2012
  • MaederMTMunzerTRickliHAssociation between heart rate recovery and severity of obstructive sleep apnea syndromeSleep Med2008975376117980656
  • HargensTAGuillSGZedalisDGreggJMNickols-RichardsonSMHerbertWGAttenuated heart rate recovery following exercise testing in overweight young men with untreated obstructive sleep apneaSleep20083110411018220083
  • NanasSSakellariouDKapsimalakouSHeart rate recovery and oxygen kinetics after exercise in obstructive sleep apnea syndromeClin Cardiol201033465120063292
  • UcokKAycicekASezerMAerobic and anaerobic exercise capacities in obstructive sleep apnea and associations with subcutaneous fat distributionsLung2009187293619023624
  • LinCCHsiehWYChouCSLiawSFCardiopulmonary exercise testing in obstructive sleep apnea syndromeRespir Physiol Neurobiol2006150273416448931
  • GuillermoLQGalTJMairEADoes obstructive sleep apnea affect aerobic fitness?Ann Otol Rhinol Laryngol200611571572017076091
  • VanuxemDBadierMGuillotCDelpierreSJahjahFVanuxemPImpairment of muscle energy metabolism in patients with sleep apnoea syndromeRespir Med1997915515579415356
  • Alonso-FernandezAGarcia-RioFAriasMAObstructive sleep apnoea-hypoapnoea syndrome reversibly depresses cardiac response to exerciseEur Heart J20062720721516267074
  • OzturkLMMetinGCuhadarogluCUtkusavasATutluogluBCardiopulmonary responses to exercise in moderate-to-severe obstructive sleep apneaTuberk Toraks200553101915765282
  • BonanniEPasqualiLMancaMLLactate production and catecholamine profile during aerobic exercise in normotensive OSAS patientsSleep Med2004513714515033133
  • TremelFPepinJLVealeDHigh prevalence and persistence of sleep apnoea in patients referred for acute left ventricular failure and medically treated over 2 monthsEur Heart J1999201201120910448029
  • DonnellyJEBlairSNJakicicJMAmerican College of Sports Medicine Position Stand. Appropriate physical activity intervention strategies for weight loss and prevention of weight regain for adultsMedicine and Science in Sports and Exercise200941245947119127177
  • EpsteinLJKristoDStrolloPJJrClinical guideline for the evaluation, management and long-term care of obstructive sleep apnea in adultsJ Clin Sleep Med2009526327619960649
  • SengulYSOzalevliSOzturaIItilOBaklanBThe effect of exercise on obstructive sleep apnea: a randomized and controlled trialSleep Breath201115495619898884
  • UenoLMDragerLFRodriguesACEffects of exercise training in patients with chronic heart failure and sleep apneaSleep20093263764719480231
  • BarnesMGoldsworthyURCaryBAHillCJA diet and exercise program to improve clinical outcomes in patients with obstructive sleep apnea – a feasibility studyJ Clin Sleep Med2009540941519961023
  • NormanJFVon EssenSGFuchsRHMcElligottMExercise training effect on obstructive sleep apnea syndromeSleep Res20003121129
  • GiebelhausVStrohlKPLormesWLehmannMNetzerNPhysical exercise as an adjunct therapy in sleep apnea-an open trialSleep Breath2000417317611894204
  • KlineCECrowleyEPEwingGBThe effect of exercise training on obstructive sleep apnea and sleep quality: a randomized controlled trialSleep2011341631164022131599
  • NetzerNLormesWGiebelhausVPhysical training of patients with sleep apneaPneumologie199751Suppl 3779782 German9340640
  • Ackel-D’EliaCda SilvaACSilvaRSEffects of exercise training associated with continuous positive airway pressure treatment in patients with obstructive sleep apnea syndromeSleep Breath20121672373521805226
  • HongSDimsdaleJEPhysical activity and perception of energy and fatigue in obstructive sleep apneaMed Sci Sports Exerc2003351088109212840627
  • PeppardPEYoungTExercise and sleep-disordered breathing: an association independent of body habitusSleep20042748048415164902
  • QuanSFO’ConnorGTQuanJSAssociation of physical activity with sleep-disordered breathingSleep Breath20071114915717221274
  • ConnorJRBoyerPJMenziesSLNeuropathological examination suggests impaired brain iron acquisition in restless legs syndromeNeurology20036130430912913188
  • ReeseJPStiasny-KolsterKOertelWHDodelRCHealth-related quality of life and economic burden in patients with restless legs syndromeExpert Rev Pharmacoecon Outcomes Res2007750352120528395
  • KruegerBRRestless legs syndrome and periodic movements of sleepMayo Clin Proc19906599910062198400
  • StiasnyKWetterTCTrenkwalderCOertelWHRestless legs syndrome and its treatment by dopamine agonistsParkinsonism Relat Disord20007212511008192
  • WinkelmannJPragerMLiebR“Anxietas tibiarum”. Depression and anxiety disorders in patients with restless legs syndromeJ Neurol2005252677115654556
  • KriegerJSchroederCIron, brain and restless legs syndromeSleep Med Rev2001527728612530992
  • EkbomKUlfbergJRestless legs syndromeJ Intern Med200926641943119817966
  • AllenRDopamine and iron in the pathophysiology of restless legs syndrome (RLS)Sleep Med2004538539115222997
  • TrenkwalderCHoglBWinkelmannJRecent advances in the diagnosis, genetics and treatment of restless legs syndromeJ Neurol200925653955319444530
  • TrenkwalderCPaulusWRestless legs syndrome: pathophysiology, clinical presentation and managementNat Rev Neurol2010633734620531433
  • AllenRPBarkerPBWehrlFSongHKEarleyCJMRI measurement of brain iron in patients with restless legs syndromeNeurology20015626326511160969
  • TrottiLMBhadrirajuSRyeDBAn update on the pathophysiology and genetics of restless legs syndromeCurr Neurol Neurosci Rep2008828128718590611
  • MallonLBromanJEHettaJRestless legs symptoms with sleepiness in relation to mortality: 20-year follow-up study of a middle-aged Swedish populationPsychiatry Clin Neurosci20086245746318778444
  • ElwoodPHackMPickeringJHughesJGallacherJSleep disturbance, stroke, and heart disease events: evidence from the Caerphilly cohortJ Epidemiol Community Health200660697316361457
  • GaoXSchwarzschildMAWangHAscherioAObesity and restless legs syndrome in men and womenNeurology2009721255126119349606
  • OhayonMMRothTPrevalence of restless legs syndrome and periodic limb movement disorder in the general populationJ Psychosom Res20025354755412127170
  • AlattarMHarringtonJJMitchellCMSloanePSleep problems in primary care: a North Carolina Family Practice Research Network (NC-FP-RN) studyJ Am Board Fam Med20072036537417615417
  • MollerCWetterTCKosterJStiasny-KolsterKDifferential diagnosis of unpleasant sensations in the legs: prevalence of restless legs syndrome in a primary care populationSleep Med20101116116620022805
  • MustafaMErokwuNEboseIStrohlKSleep problems and the risk for sleep disorders in an outpatient veteran populationSleep Breath20059576315875229
  • SchlesingerIErikhIAvizoharOSprecherEYarnitskyDCardiovascular risk factors in restless legs syndromeMov Disord2009241587159219526583
  • PhillipsBYoungTFinnLAsherKHeningWAPurvisCEpidemiology of restless legs symptoms in adultsArch Intern Med20001602137214110904456
  • DanieleTMde BruinVMACEFde OliveiraDSPompeuCMde BruinPFThe relationship between physical activity, restless legs syndrome, and health-related quality of life in type 2 diabetesEndocrine Epub December 1, 2012
  • EstevesAMMelloMTBenedito-SilvaAATufikSImpact of aerobic physical exerise on Restless Legs SyndromeSleep Sci201144548
  • AukermanMMAukermanDBayardMTudiverFThorpLBaileyBExercise and restless legs syndrome: a randomized controlled trialJ Am Board Fam Med20061948749316951298