Metabolic Risk Factors for Vascular Disease in Obstructive Sleep Apnea

McArdle, Nigel; Hillman, David R.; Beilin, Lawrie J.; Watts, Gerald F.

doi:10.1164/rccm.200602-270oc

Cited by 214 publications

(164 citation statements)

References 27 publications

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“…Contrary to such an expectation, we found significant increases in SC fat and WC and very small increases in TBF, while TBM remained almost constant over the 8 months of ventilation. It is currently unclear if such changes impact upon the metabolic burden of OSAS patients, since several alterations associated with this disease are independent of fat tissues (12,39). Apparently, the effects of CPAP on BC in OSAS are distinct from the effects of GH in GHD, where TBF is usually decreased, in addition to an increase in IGF1 and LBM.…”

Section: Discussionmentioning

confidence: 99%

“…The physiologic release of GH in healthy humans is stimulated by GHRH as a function of sleep depth (9). Thus, continuous positive airway pressure (CPAP) therapy may lead to a restoration of the GH axis activity to a more physiological pattern, and consecutively affect BC (6,(10)(11)(12). Adipose tissue has been associated with most of the metabolic burden associated with OSAS (7,13,14), and short-term CPAP reduces V fat (15).…”

Section: Introductionmentioning

confidence: 99%

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Effects of long-term continuous positive airway pressure on body composition and IGF1

Münzer

Hegglin

Stannek

et al. 2010

European Journal of Endocrinology

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Objective: To investigate the long-term effects of nasal continuous positive airway pressure (CPAP) ventilation in patients with obstructive sleep apnea syndrome (OSAS) on body composition (BC) and IGF1. Design: Observational study. Subjects: Seventy-eight (11 females and 67 males) OSAS patients who were compliant with CPAP (age 51G1.1 years) participated in the study. We assessed body mass index (BMI), total body mass (TBM), total body fat (TBF; kg) and lean body mass (LBM; kg), abdominal subcutaneous (SC) and visceral (V) fat (cm 2 ), and waist circumference (WC; cm) by magnetic resonance imaging, and IGF1 (ng/ml) before and after 7.8G1.3 months of CPAP use of an average of 5.9G1.2 h. Results: Women had a higher BMI, WC; TBM, TBF, and more SC fat. Men had a higher LBM and more V fat. CPAP increased WC (C2.8G9.6 cm, PZ0.02) and LBM (2.2G0.5 kg, PZ0.006), but not IGF1. In men, CPAP increased BMI (0.5G0.2 kg/m 2 , PZ0.02), WC (1.7G6.9 cm, PZ0.002), TBM (1.7G0.4 kg, PZ0.0001), LBM (1.5G0.4 kg, PZ0.0003), SC fat (12.9G5.1 cm 2 , PZ0.02), and IGF1 (13.6G4.2 ng/ml, PZ0.002). Compliance with CPAP increased LBM in men aged !60 years, but not in those aged O60 years, and IGF1 increased in men aged 40-60 years only. Conclusions: Long-term CPAP increased LBM in both sexes and IGF1 in men, while fat mass remained unchanged, suggesting a sexually dimorphic response of IGF1 to CPAP. The role of the GH axis activity and age to this response is unclear. The metabolic consequences of changes in LBM are still to be determined. Future studies on the effects of CPAP on BC should include LBM as an outcome.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Effects of long-term continuous positive airway pressure on body composition and IGF1

Münzer

Hegglin

Stannek

et al. 2010

European Journal of Endocrinology

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“…Lastly, a more recent study, 27 reported that leptin was significantly higher in 21 OSA patients, compared to 21 healthy subjects matched for age and BMI, but this was not retained in multiple regression analysis which accounted for BMI. Three previous studies have investigated the relation between OSA and ghrelin.…”

Section: Neuropeptides and Impaired Glucose Tolerancementioning

confidence: 94%

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Patterson¹,

Twigg²,

Vazir³

et al. 2011

Journal of Clinical Sleep Medicine

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Study Objectives: Understanding the etiologic mechanisms underlying impaired glucose tolerance in obstructive sleep apnea (OSA) would assist development of therapies against this comorbidity. We hypothesized that in patients with OSA impaired glucose tolerance (IGT) would be associated with elevated levels of hormones associated with appetite regulation (leptin, ghrelin, neuropeptide Y [NPY] and peptide tyrosine-tyrosine [PYY]). Method: We studied 68 OSA patients (mean AHI 22 events/h) and 37 age and weight matched healthy controls recruited by advertisement. All participants received a standardized evening meal, attended polysomnography and an oral glucose tolerance test (OGTT) on waking. Hormones were measured in blood taken before sleep (22:30) and at the start of the OGTT. Results: Impaired glucose tolerance was present in 54% of patients and 32% of controls (p = 0.05). The only differences between groups was that leptin was signifi cantly higher at 22:30 in OSA patients compared to controls (9.6 ng/L vs 7.9 ng/L, p = 0.05). OSA patients had marginally elevated plasma NPY levels at 22:30 (56.6 [52, 67] S C I E N T I F I C I N v E S T I G A T I O N SU ntreated obstructive sleep apnea (OSA) is associated with insulin resistance, 1,2 and some studies suggest that treatment with CPAP improves glucose control, 3,4 although this was not found in a randomized controlled trial of diabetics with sleep apnea. 5 The observation that established type 2 diabetics cannot improve glucose control when their OSA is treated with CPAP, emphasizes the importance of understanding the pathophysiology of insulin resistance associated with OSA.One mechanism linking OSA with impaired glucose tolerance could be sympathetic nerve activity which is a recognized phenomenon in OSA 6 ; indeed it has previously been hypothesized that this process is responsible for the elevated leptin levels seen in newly diagnosed OSA patients. 7 Consistent with this sibutramine, a serotonin and noradrenaline reuptake inhibitor, was able to improve insulin resistance in OSA independent of visceral fat. 8 Moreover two studies raise the hypothesis that hormones involved in appetite regulation could contribute to impaired glucose tolerance. Broglio et al. 9 demonstrated that ghrelin administered to healthy subjects simultaneously with glucose, resulted in a transient decrease of insulin concentration that was coupled with signifi cant increase in glucose levels. In addition it has been reported that IR is associated with increased plasma leptin concentration independent of the body fat. 10 Consistent with this hypothesis, previous studies have reported that OSA is independently associated with neuroendocrine dysregulation; in fact OSA has been reported to be bRIEF SUMMARY Current knowledge/Study Rationale: Impaired glucose tolerance is a common and important co-morbidity of obstructive sleep apnea yet its pathogenesis, beyond the shared etiology of obesity is unknown. Here we tested the hypothesis that OSA might induce increases of appetite regulating h...

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“…Obesity and sleep apnea are often associated with dysregulation of glucose and lipid metabolism (121)(122)(123)(124)(125), although the precise mechanisms for these associations are not well understood. In recent years, investigators have examined metabolic responses to excess caloric intake and have identified specific signaling factors responsible for disturbances in metabolic and upper airway control.…”

Section: Putative Adipokine Modulators Of Upper Airway Functionmentioning

confidence: 99%

Obesity and Obstructive Sleep Apnea: Pathogenic Mechanisms and Therapeutic Approaches

Schwartz

Patil²,

Laffan

et al. 2008

Proceedings of the American Thoracic Society

574

395

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Obstructive sleep apnea is a common disorder whose prevalence is linked to an epidemic of obesity in Western society. Sleep apnea is due to recurrent episodes of upper airway obstruction during sleep that are caused by elevations in upper airway collapsibility during sleep. Collapsibility can be increased by underlying anatomic alterations and/or disturbances in upper airway neuromuscular control, both of which play key roles in the pathogenesis of obstructive sleep apnea. Obesity and particularly central adiposity are potent risk factors for sleep apnea. They can increase pharyngeal collapsibility through mechanical effects on pharyngeal soft tissues and lung volume, and through central nervous system-acting signaling proteins (adipokines) that may affect airway neuromuscular control. Specific molecular signaling pathways encode differences in the distribution and metabolic activity of adipose tissue. These differences can produce alterations in the mechanical and neural control of upper airway collapsibility, which determine sleep apnea susceptibility. Although weight loss reduces upper airway collapsibility during sleep, it is not known whether its effects are mediated primarily by improvement in upper airway mechanical properties or neuromuscular control. A variety of behavioral, pharmacologic, and surgical approaches to weight loss may be of benefit to patients with sleep apnea, through distinct effects on the mass and activity of regional adipose stores. Examining responses to specific weight loss strategies will provide critical insight into mechanisms linking obesity and sleep apnea, and will help to elucidate the humoral and molecular predictors of weight loss responses.

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Metabolic Risk Factors for Vascular Disease in Obstructive Sleep Apnea

Abstract: In a sleep clinic population, men with OSA and no identifiable cardiovascular disease have increased insulin resistance and other metabolic changes that act to increase the risk of vascular disease, compared with age- and body mass index-matched attendees without OSA.

Cited by 214 publications

References 27 publications

Effects of long-term continuous positive airway pressure on body composition and IGF1

Effects of long-term continuous positive airway pressure on body composition and IGF1

Lack of Association Between Impaired Glucose Tolerance and Appetite Regulating Hormones in Patients with Obstructive Sleep Apnea

Obesity and Obstructive Sleep Apnea: Pathogenic Mechanisms and Therapeutic Approaches

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