Rebuttal from Alexandros N. Vgontzas, Jordan Gaines, Silke Ryan and Walter T. McNicholas

From reading the opposing view by Phillips et al. (2016), it is clear that both of our arguments acknowledge the strong link between obstructive sleep apnoea (OSA) and the metabolic syndrome, highlighting the important role of obesity in this relationship. We could not agree more with the statement in the last paragraph that ‘it is without dispute that obesity is a primary cause of OSA’. Many points made in both of our arguments, in fact, suggest common unifying views in untangling the complex relationship between OSA and the metabolic syndrome. We and others have demonstrated independent associations of OSA with inflammation and insulin resistance which, at face value, suggest a causative role of OSA. Substantial evidence suggests, however, that OSA functions to exacerbate, but not necessarily cause, health conditions – which were already present or beginning to develop – resulting from obesity. The key question is, which comes first? Consistent empirical observations from many sleep clinicians and well-controlled studies over the last 40 years have demonstrated that obesity precedes the development of OSA in adults and children (Lugaresi 1975; Peppard et al. 2000; Bixler et al. 2016). Importantly, obesity – in particular, central (abdominal) obesity – is the fundamental pillar of the metabolic syndrome. In fact, according to the IDF consensus worldwide definition, a large waist circumference (> 94 cm men, > 80 cm women) must be present in order to receive the diagnosis (International Diabetes Federation 2006). In both obese and even non-obese adults with OSA, visceral fat is most strongly associated with OSA (Kritikou et al. 2013). Taken together, the statement that ‘obesity is a primary cause of OSA’ fundamentally suggests that the metabolic syndrome precedes the development of OSA. Furthermore, the review of CPAP studies in Phillips et al.’s argument suggests that, in general, CPAP is only modestly and partially effective in reversing the components of the metabolic syndrome. Importantly, in the study by Chirinos et al. (2014) cited by the authors, CPAP did not reduce CRP, insulin sensitivity, or triglycerides unless combined with weight loss. This adds to the argument that modifiable factors that address the root cause of OSA, such as weight loss, may be the best approach – particularly in those with mild-to-moderate OSA who comprise the large majority of patients, and whose compliance tends to be lowest. In sum, while we agree that OSA exacerbates the metabolic syndrome, the overwhelming evidence demonstrates that obesity, particularly central obesity, and the metabolic syndrome precede the development of OSA. Taken together, both proposals suggest the presence of a vicious cycle of weight gain, upper airway narrowing, OSA, hypoxia, worsening metabolic profile, further weight gain, and so forth in OSA pathology (Vgontzas et al. 2005).