Metabolic dysfunction in obstructive sleep apnea: A critical examination of underlying mechanisms

Abstract

It has recently become clear that obstructive sleep apnea (OSA) is an independent risk factor for the development of metabolic syndrome, a disorder of defective energy storage and use. Several mechanisms have been proposed to explain this finding, drawing upon the characteristics that define OSA. In particular, intermittent hypoxia, sleep fragmentation, elevated sympathetic tone, and oxidative stress – all consequences of OSA – have been implicated in the progression of poor metabolic outcomes in OSA. In this review we examine the evidence to support each of these disease manifestations of OSA as a unique risk for metabolic dysfunction. Tissue hypoxia and sleep fragmentation are each directly connected to insulin resistance and hypertension, and each of these also may increase sympathetic tone, resulting in defective glucose homeostasis, excessive lipolysis, and elevated blood pressure. Oxidative stress further worsens insulin resistance and in turn, metabolic dysfunction also increases oxidative stress. However, despite many studies linking each of these individual components of OSA to the development of metabolic syndrome, there are very few reports that actually provide a coherent narrative about the mechanism underlying metabolic dysfunction in OSA.

Inflammation in sleep apnea: An update

“…It should be emphasized that IH does not fully recapitulate all the effects of OSA (for example, changes in intrathoracic pressure, hypercapnia, or sleep loss). Furthermore, the hypoxia induced by such models may not reflect the actual burden of hypoxia present in human OSA[14] – a problem that has been recently recognized and addressed in some animal models of IH[104]. Nevertheless, the data generated from these IH studies may be useful in understanding effects of tissue hypoxia per se on metabolism.…”

“…The constellation of sleep fragmentation, intermittent hypoxia, hypercapnia, and ineffectual breathing efforts are believed to account for the majority of physiological derangements in OSA[14]. The prototypical symptom of OSA is excessive daytime sleepiness.…”

Sleep Apnea Research in Animals. Past, Present, and Future

“…IH is but one of several potentially injurious aspects of OSA that also include upper airway obstruction with intrathoracic pressure swings, and SF (30). In addition, most of the currently employed models of IH resemble very severe OSA, and the findings should be applied to clinical OSA with caution.…”

“…However, due to the labor-intensive nature of this approach, most experiments using IH forego sleep/ awake detection systems in favor of high throughput. IH has since become the most widely used OSA model, as it is believed to be one of the more noxious stimuli of OSA (30), and because IH can be easily adjusted to induce OSA of varying severity. An example of one such IH system is shown in Figure 3.…”

Morning Diastolic Blood Pressure May Be Independently Associated With Severity of Obstructive Sleep Apnea in Non-Hypertensive Patients: A Cross-Sectional Study

“…5 Both OSA and HT are comorbidities of obesity and are related to metabolic syndrome. 6,7 In some patients, HT may be solely secondary to OSA. It is presumed that the arterial blood pressure (BP) is elevated by intermittent hypoxemia during the night, which activates the sympathetic system via peripheral and central chemoreceptors.…”