Cardiometabolic changes after continuous positive airway pressure for obstructive sleep apnoea: A randomised sham-controlled study

Endocrine and Cardiometabolic Research Group, NHMRC Centre for Integrated Research and Understanding of Sleep (CIRUS), Woolcock Institute of Medical Research, University of Sydney, Glebe, Australia.
Thorax (Impact Factor: 8.29). 05/2012; 67(12). DOI: 10.1136/thoraxjnl-2011-201420
Source: PubMed

ABSTRACT RATIONALE AND OBJECTIVES: Impaired insulin sensitivity (ISx), increased visceral abdominal fat (VAF) and liver fat are all central components of the metabolic syndrome and characteristics of men with obstructive sleep apnoea (OSA). The reversibility of these observed changes with continuous positive airway pressure (CPAP) treatment in men with OSA has not been systematically studied in a randomised sham-controlled fashion. METHODS: 65 men without diabetes who were CPAP naïve and had moderate to severe OSA (age=49±12 years, apnoea hypopnoea index (AHI)=39.9±17.7 events/h, body mass index=31.3±5.2 kg/m(2)) were randomised to receive either real (n=34) or sham (n=31) CPAP for 12 weeks. At 12 weeks, all subjects received real CPAP for an additional 12 weeks. MEASUREMENTS AND MAIN RESULTS: Main outcomes were the change at week 12 from baseline in VAF, ISx and liver fat. Other metabolic outcomes were changes in the disposition index, total fat, and blood leptin and adiponectin concentrations. The AHI was lower on CPAP compared with sham by 33 events/h (95% CI-43.9 to -22.2, p<0.0001) after 12 weeks. There were no between-group differences at 12 weeks in VAF (-13.0 cm(3), -42.4 to 16.2, p=0.37), ISx (-0.13 (min(-1))(μU/ml))(-1), -0.40 to 0.14, p=0.33), liver fat (-0.5 cm(3), -3.8 to 2.7, p=0.74) or any other cardiometabolic parameter. At 24 weeks, ISx (3.2×10(4) (min(-1))(μU/ml))(-1), 0.9×10(4) to 6.0×10(4), p=0.009), but not VAF (-1.4 cm(3), -19.2 to 16.4, p=0.87) or liver fat (-0.2 Hounsfield units, -2.4 to 2.0, p=0.83) were improved compared with baseline in the whole study group. CONCLUSION: Reducing visceral adiposity in men with OSA cannot be achieved with CPAP alone and is likely to require weight-loss interventions. Longer-term effects of CPAP on other cardiometabolic markers such as ISx require further investigation to fully examine time dependencies. TRIAL REGISTRATION NUMBER: ACTRN12608000301369.

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    • "In one of these, West and colleagues [45] reported no improvement in HbA1c and insulin sensitivity in 42 men with type 2 diabetes and with baseline 4% oxygen-desaturation index (ODI) >10 epiepisodes/h , which however as a single variable without any other respiratory and other outcome measures does not prove the presence of moderate or severe OSA. In the other one, Hoyos and colleagues [46] conducted a 12-week CPAP vs. sham CPAP trial in 65 non-diabetes men (17 had an impaired glucose tolerance) with OSA (mean apnoea-hypopnea index AHI 39.9 episodes/h), and found no change in insulin sensitivity. Despite the benefits of the randomized sham CPAP controlled studies, it is worth mentioning that even the sham CPAP at a pressure sufficient to wash out carbon dioxide may prevent upper airway narrowing and thus can be an effective therapy in some patients. "
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    ABSTRACT: An increasing body of evidence suggests that obstructive sleep apnoea (OSA) is independently associated with an increased risk of cardiovascular disease, glucose intolerance, and deteriorations in glycaemic control. Despite the knowledge of a multifactorial pathogenesis of long-term diabetes complications, there is a paucity of information on impact of comorbidities associated with chronic intermittent hypoxemia on development and progression of chronic diabetes complications. This review explores the clinical and scientific overlap of OSA and type 2 diabetes mellitus (T2DM) and its possible impact on the development and progression of diabetes macrovascular and microvascular complications. Multiple prospective observational cohort studies have demonstrated that OSA significantly increases the risk of cardiovascular disease independent of potential confounding risk factors. The current evidence further suggests that OSA with concurrent T2DM is associated with an increased risk of oxidative stress-induced damage of vulnerable endothelial and mesangial cells and peripheral nerves. Further studies are needed to validate the impact of OSA treatment on diabetes micro- and macrovascular complications. Since it is presently still unknown whether OSA treatment may provide a diabetes-modifying intervention that could delay or halt the progression of chronic diabetes complications, the emphasis is on early diagnosis and satisfactory treatment of both OSA and T2DM.
    Diabetes Research and Clinical Practice 05/2014; 104(2). DOI:10.1016/j.diabres.2014.01.007 · 2.54 Impact Factor
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    • "For instance, Sharma et al. [9], who demonstrated that CPAP therapy was able to partially reverse metabolic disorders in apneic patients, showed that, meanwhile, CPAP treatment was associated with body weight loss and reduction in visceral adiposity. Such a positive effect on body weight and abdominal fat under CPAP treatment was not found by Hoyos et al. [10] and insulin sensitivity did not improved, accordingly. Thus, whereas association between obstructive sleep apnea and metabolic abnormalities has been clearly documented, the respective contribution of obstructive sleep apnea and excess visceral fat to the cardiometabolic risk is not clearly established. "
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    ABSTRACT: Beyond obesity, sleep apnea syndrome is frequently associated with excess abdominal adiposity that could contribute to the deteriorated cardiometabolic risk profile of apneic patients. The present study addressed the respective contribution of the severity of sleep apnea syndrome and excess abdominal adiposity to the cardiometabolic risk profile of 38 non obese men with polysomnography-diagnosed sleep apnea syndrome (apnea-hypopnea index >15 events/hour). These otherwise healthy men performed a 75g-oral glucose tolerance test (OGTT) with plasma lipid/inflammatory and redox profiles. Twenty-one apneic men with high-waist circumference (>94 cm) were compared to 17 apneic men with low-waist circumference. Apneic men with high-waist circumference had higher AUC glucose and AUC insulin than apneic men with low-waist circumference. Accordingly, apneic men with high-waist circumference had higher hepatic insulin resistance as reflected by higher HOMA-resistance index, and lower global insulin sensitivity as reflected by lower insulin sensitivity index of Matsuda (derived from OGTT). The sleep structure and the apnea-hypopnea index were not different between the two groups. However, apneic men with high-waist circumference presented with lower mean nocturnal oxyhemoglobin (SpO2). In the 38 men, waist circumference and mean nocturnal SpO2 were inversely correlated (r = -0.43, p = 0.011) and were both associated with plasma glucose/insulin homeostasis indices: the higher the waist circumference, the lower the mean nocturnal SpO2, the lower the insulin-sensitivity. Finally, in multivariable regression model, mean nocturnal SpO2 and not waist circumference was associated with insulin-resistance. Thus, excess abdominal adiposity in non obese apneic men was associated with a deteriorated insulin-sensitivity that could be driven by a more severe nocturnal hypoxemia.
    PLoS ONE 08/2013; 8(8):e71000. DOI:10.1371/journal.pone.0071000 · 3.23 Impact Factor
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    • "To our knowledge, there have been only four liver imaging studies in patients with OSA, three of which utilized computer tomography (CT) to assess the degree of hepatic steatosis (Tatsumi and Saibara, 2005; Shpirer et al., 2010; Hoyos et al., 2012) and one study used MRI/MRS. Tatsumi and Saibara (2005) measured the amount of visceral and liver fat in patients with OSA (AHI > 5/h) compared to non-OSA subjects and found that the presence of OSA was associated with increased visceral adiposity, but not with the degree of hepatic steatosis (Table 1). "
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    ABSTRACT: Obstructive sleep apnea (OSA) is recurrent obstruction of the upper airway during sleep leading to intermittent hypoxia (IH). OSA has been associated with all components of the metabolic syndrome as well as with non-alcoholic fatty liver disease (NAFLD). NAFLD is a common condition ranging in severity from uncomplicated hepatic steatosis to steatohep-atitis (NASH), liver fibrosis, and cirrhosis. The gold standard for the diagnosis and staging of NAFLD is liver biopsy. Obesity and insulin resistance lead to liver steatosis, but the causes of the progression to NASH are not known. Emerging evidence suggests that OSA may play a role in the progression of hepatic steatosis and the development of NASH. Several cross-sectional studies showed that the severity of IH in patients with OSA predicted the severity of NAFLD on liver biopsy. However, neither prospective nor interventional studies with continuous positive airway pressure treatment have been performed. Studies in a mouse model showed that IH causes triglyceride accumulation in the liver and liver injury as well as hepatic inflammation. The mouse model provided insight in the pathogenesis of liver injury showing that (1) IH accelerates the progression of hepatic steatosis by inducing adipose tissue lipolysis and increasing free fatty acids (FFA) flux into the liver; (2) IH up-regulates lipid biosynthetic pathways in the liver; (3) IH induces oxidative stress in the liver; (4) IH up-regulates hypoxia inducible factor 1 alpha and possibly HIF-2 alpha, which may increase hepatic steatosis and induce liver inflammation and fibrosis. However, the role of FFA and different transcription factors in the pathogenesis of IH-induced NAFLD is yet to be established. Thus, multiple lines of evidence suggest that IH of OSA may contribute to the progression of NAFLD but definitive clinical studies and experiments in the mouse model have yet to be done.
    Frontiers in Neurology 10/2012; 3. DOI:10.3389/fneur.2012.00149
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