The global pandemic of metabolic disease is worsening. The metabolic theory of obesity proposes that hormonal changes, especially hyperinsulinaemia, precede metabolic disease development. Although quality sleep is recognised as a key factor for good health, less is known about disrupted sleep as a risk factor for hyperinsulinaemia.
To explore the relationship between sleep, especially sleep architecture and the nasal cycle, on insulin secretion in obstructive sleep apnoea (OSA) with comorbid metabolic disease. This review includes a discussion of the potential role of Rest-Activity-Cycler positive airway pressure (RACer-PAP), a novel non-pharmacological OSA treatment strategy.
A narrative review of all the relevant papers known to the authors was conducted. This review also included results from a polysomnographic sleep clinic pilot study (
Metabolic disease is strongly associated with disturbed sleep. Sleep architecture influences cerebral hormonal secretion, lateral shifts in the autonomic nervous system and nasal airflow dominance. Disturbed sleep shortens short-wave sleep periods, decreasing insulin sensitivity and glucose tolerance. Improvements to metabolic function during n-CPAP treatment are inconsistent. If RACer-PAP demonstrates superior effects on sleep architecture and autonomic function, it may offer advantages in OSA patients with comorbid metabolic disease.
Improving sleep architecture by maintaining the nasal cycle proposes a novel non-pharmacological treatment paradigm for treating OSA with comorbid metabolic disease. Research is required to demonstrate if RACer-PAP therapy influences whole night sleep architecture, sympathovagal balance and markers of metabolic disease.
The pandemic of metabolic disease, especially type 2 diabetes, cardiovascular disease, cancers, morbid obesity and dementias, is a global public health crisis carrying a significant economic burden. Despite some advances in the treatment of these conditions, preventative measures to date have made little impact on the increasing prevalence.
Obesity is considered to be the main aetiological driver of metabolic disease. Volitional control (eat less and move more) is usually promoted as the best way to manage obesity. However, there are a number of reasons why this approach is unlikely to succeed at a population level, especially neurological control and hormonal influences. The metabolic theory of obesity
Sleep is being increasingly recognised as being a key factor in determining health. Sleep loss is considered a significant risk factor for impaired insulin homeostasis.
The literature was reviewed under the broad headings of non-communicable disease, insulin and metabolic disease, type 2 diabetes, sleep staging and architecture, and the effect of sleep deprivation, targeting full-test English language studies. There was no date criterion. Articles were selected on the basis of providing a descriptive context associating metabolic disease with sleep quality. The final selection of articles was based on the authors’ judgement of relevance, completeness and compatibility with epidemiological, pathological and clinical criteria.
A review of how pressurised breathing treatment affects the nasal airflow of OSA sufferers as this cohort commonly exhibit markers of metabolic disease is included. A new form of breathing therapy is introduced that could positively influence sleep architecture and sleep quality, and the findings from a pilot sleep study comparing sleep efficiency between these two treatments are presented. This new therapy, delivered by the Rest-Activity-Cycler positive airway pressure (RACer-PAP) system, is a new variant of OSA pressurised breathing treatment that regulates and cycles inter-nasal airflow apportionment throughout the night.
Insulin is one of the central hormones of glucose homeostasis. Population studies demonstrate that elevations are an early marker of metabolic disease.
While it is likely that the management of hyperinsulinaemia will be multifactorial, some of the influencing factors are under the control of the autonomic nervous system (ANS).
It is recognised that maintaining healthy metabolic homeostasis requires exquisitely precise adjustments between the sympathetic and parasympathetic arms of the ANS. For example, insulin secretion is stimulated by vagal activation and inhibited by sympathetic adrenal activation. This process can be disturbed by numerous factors, including excessive sympathetic stimulation, such as stress. Sympathovagal, or autonomic, imbalance is associated with metabolic disease, although the direction of causality remains unclear.
Insulin and glucagon are secreted from the beta cells of the pancreas in order to maintain blood glucose levels within a narrow therapeutic range. Insulin both decreases hepatic gluconeogenesis and increases cellular uptake of glucose in order to lower excessive blood glucose levels. It is generally believed that there is a basal secretion of insulin to maintain homeostasis, with additional insulin being secreted as a bolus to manage hyperglycaemia. Recent research suggests that insulin secretion occurs in a rhythmic and pulsatile manner with an ultradian periodicity ranging from 80 to 180 min.
Over the last half century, changes in developed society and lifestyle have resulted in both adults and adolescents experiencing a 1.5–2 h reduction in sleep duration, as demonstrated by more than 30% of Americans who reported less than 6 h of sleep per night.
Although the relationship between sleep quality and good health is recognised, it remains difficult to quantify ‘quality sleep’. The Pittsburgh Sleep Quality Index differentiates ‘poor’ sleep from ‘good’ sleep using subjective sleep quality, sleep disturbances and daytime dysfunction, amongst other measures.
Adult hypnogram demonstrating the different sleep stages. The four stages of NREM sleep typically precede a period of REM sleep.
In a normal sleep cycle, people move between the lighter NREM stages of sleep (Stages 1 and 1) into the deeper stages (Stage 3 and 4), followed by a period of REM.
During sleep, a healthy young adult experiences alternation in REM and NREM sleep staging approximately every 90–110 min throughout the duration of sleep,
If sleep is disturbed, a person may not return to his or her previous sleep stage. Instead, he or she commences a new sleep cycle. This means that people with disturbed sleep typically spend less time in SWS and have increased hypothalamic-pituitary-adrenal (HPA) axis activation and subsequent cortisol secretion, and hence increased insulin resistance and potentially other metabolic disturbances.
A common cause of disrupted sleep is OSA. This condition manifests as repeated episodes of upper airway closure leading to repeated dips in blood oxygen tissue saturation causing recurring CNS arousals that disrupt normal sleep architecture.
There are conflicting reports regarding the prevalence of OSA in the general population. The 1993 Wisconsin Sleep Cohort study reported the prevalence of OSA as 4% in men and 2% in women (ages 30–60 years).
People suffering from OSA are predisposed to experiencing reductions in SWS
Less is known about how OSA affects normal neuromodulatory functioning including sleep staging. However, NREM and REM sleep staging has been shown to be closely linked with the ultradian rhythms of alternating cerebral hemispheric activity
Obstructive sleep apnoea is currently managed by lifestyle measures (e.g. encouraging the patients to lose weight, avoid alcohol and not sleeping on their back or stomach) and by medical devices depending on the severity of the disease. People with moderate to severe OSA may be prescribed continuous positive airway pressure (CPAP) therapy. This device delivers a continuous supply of compressed air via a mask that covers the nose alone or both nose and mouth. CPAP therapy decreases daytime sleepiness but only causes slight to modest improvements in metabolic outcomes.
A significant challenge to managing OSA is the lack of adherence to CPAP therapy. Although CPAP is routinely prescribed for use during all sleep periods, full adherence to CPAP is accepted to be at least 4 h per night on 70% of nights.
The nasal cycle is a normal ultradian physiological phenomenon that manifests in all mammals,
Despite there being a strong correlation between the duration of sleep and adherence to n-CPAP therapy,
Unilateral nostril breathing (UNB) is a yogic breathing technique where the user occludes one nostril and breathes exclusively through the other. This has been shown to selectively activate either the sympathetic or parasympathetic branch of the ANS depending on the side of the occluded nostril.
Previous work has shown that in the awake state, blood glucose levels significantly increase during right UNB and lower during left UNB.
The RACer-PAP system is a new instrument for treating OSA that utilises pressurised air selectively through one nostril and then the other to reinstate the normal rhythm of the nasal cycle that is abolished by n-CPAP therapy.
A polysomnographic sleep clinic pilot study has recently been conducted with three n-CPAP-compliant OSA sufferers who received breathing treatment pressures ranging from 8 cm H2O to 14 cm H2O. This study compared treatment efficacy during full overnight use of RACer-PAP and n-CPAP systems. With each individual acting as his or her own control, AHI was equivalent between nights for all patients. Arousal index (AI) was within night-to-night variation for all three participants between nights. Two participants experienced a 27.6% improvement in sleep efficiency, while one showed no change. Despite the limitation of this initial pilot study (
Given the disappointing results from the SAVE study on cardiometabolic outcomes,
Metabolic disease is strongly associated with disordered sleep architecture. RACer-PAP breathing therapy potentially offers a new form of non-pharmaceutical treatment for OSA-related metabolic disease. Further research is required to demonstrate if RACer-PAP therapy influences whole night sleep architecture and has effect on markers of metabolic disease.
The authors would like to thank KiwiNet, the Health Innovation Hub and Auckland University of Technology (AUT) for providing them financial support.
D.E.W. and J.B. declare that they are listed as co-inventors in a patent application of a new pressurised breathing technology. C.A.P.C., A.N. and A.C. declare that they have no financial or personal relationship(s) that may have inappropriately influenced them in writing this article.
C.A.P.C. and D.W. (AUT) were the project coleaders and were responsible for the concept and design, writing of the article, data retrieval and interpretation. A.N., A.C. and J.B. (University of Otago) were the reviewers and were responsible for data retrieval and interpretation