Metabolic syndrome is a cluster of biochemical and physiological abnormalities that occur together, increasing the risk of type 2 diabetes mellitus, stroke and cardiovascular disease (Swarup et. al., 2019). There is growing interest surrounding metabolic syndrome due to the current obesity crisis; it is estimated that as much as 1/3 of the US has metabolic syndrome, both diagnosed and undiagnosed (Saklayen et. al., 2018). Sleep is often overlooked but there is emerging evidence that sleep has a key role as a modulator of metabolic homeostasis (Koren et. al., 2016). Due to modern society’s busy lifestyles, sleep deprivation has become increasingly more commonplace and research supports that it increases the chances of obesity, diabetes and hypertension (Nagai et. al., 2010). This essay explores the relationship between sleep deprivation and the metabolic syndrome, with obstructive sleep apnoea and the consequences of night shift-work as examples of sleep dysfunction.
To be diagnosed with metabolic syndrome patients must have at least three of the following symptoms; elevated waist circumference, high triglyceride levels, low HDL cholesterol, hypertension and high fasting glucose levels (Amihăesei IC et. al., 2014). There is an increasing spotlight on metabolic syndrome due to the global increase in obesity levels, which is an important component of metabolic syndrome. This obesity epidemic has put a strain on our health services; between 2014 and 2015 it was estimated that the NHS spent £6.1 billion on obesity related health issues alone (Gov.uk, 2017). Although there are many other factors responsible for this surge in the occurrence of obesity and metabolic syndrome – such as the marketing of junk food, bigger portions and a more sedentary lifestyle – sleep deprivation is thought to have played a key role.
Other underlying risk factors of metabolic syndrome include ageing, non-alcoholic fatty liver disease and hormonal imbalance such as PCOS.
It is estimated that most adults require approximately 8 hours of sleep per day (NHS, 2019). However, sleep deprivation is increasingly becoming a bigger problem for society, with 30% of adults reporting to sleep less than 6 hours per night, according to a study conducted by Sharma et. al. Sleep deprivation can be chronic or acute and may range extensively in severity (Medic et. al., 2017). As well as causing fatigue and having a negative impact on mental wellbeing, there is growing evidence to support that sleep deprivation may be a risk factor for metabolic syndrome (Koren et. al., 2016). Conversely, greater than 10 hours of sleep per day was also found to be associated with symptoms relating to metabolic syndrome (Kim et. al., 2018).
Sleep has been found to be essential in maintaining metabolic homeostasis. There are three main pathways that could mediate an adverse effect of sleep loss on the risks associated with metabolic syndrome; changes in hormonal secretion, sympathetic stimulation or inflammation (Sharma et. al., 2010). The focus of this essay is on hormonal changes following sleep deprivation and its association with dysfunction in the HPA axis, leading to neuroendocrine dysregulation.
The Influence of Sleep Deprivation on the Endocrine System
When there is a disruption or lack of sleep, this can cause a dysregulation of the hormones that are involved in managing metabolism (Sharma et. al., 2010).
The pituitary gland releases adrenocorticotropic hormone (ACTH) which acts on the adrenal gland to release cortisol. Cortisol has glucocorticoid effects; it is involved in increasing blood glucose levels and regulating metabolism. This system is illustrated by figure 1. The concentration of cortisol varies throughout the day, with its highest concentrations occurring in the morning and rapidly decreases in the evening before bed. However, a study carried out by Cauter et. al. showed that this decrease in cortisol levels in the evening was 6-fold slower in subjects who had been sleep deprived for 6 days prior. It is therefore thought that the higher levels of cortisol in sleep deprived patients is likely to promote the development of insulin resistance, due to cortisol raising blood glucose levels. Insulin resistance is a risk factor for diabetes and metabolic syndrome, and may help to explain why sleep deprived subjects are more susceptible to obesity.
Other hormones affected by sleep deprivation include growth hormone (GH). Figure 2 shows that the hypothalamus releases gonadotropin releasing hormone (GNRH), which stimulates the pituitary gland to produce GH. GH enhances triglyceride breakdown and oxidation of adipocytes. It plays a critical role in regulating metabolism and also increases insulin secretion and glucose uptake. Studies have found that there are lower levels of GH in sleep deprived patients (Leproult et. al., 2009). GH deficiency is characterised by increased insulin resistance. This is a risk factor for type 2 diabetes, a condition closely associated with metabolic syndrome.
It has also been found that the hormones leptin and ghrelin have a relationship with sleep deprivation and metabolism. Leptin is a hormone that inhibits hunger, whereas ghrelin is a hormone that stimulates appetite. Reduced leptin and increased ghrelin appear to correspond with increases in hunger when subjects have been deprived of sleep (Cauter et. al., 2015).
Sleep Apnoea and Metabolism
Sleep consists of two different stages – NREM AND REM – that occur alternately in 90-minute cycles throughout the night. Metabolism is at its slowest rate during NREM and highest during REM (Sharma et. al., 2010). Obstructive sleep apnoea (OSA) is an example of a common condition that disturbs sleep architecture. During sleep, when the throat and tongue muscles are more relaxed, this soft tissue can cause the airway to become blocked and leads to breathing stopping and starting (Spicuzza et. al., 2015). Syndrome Z is the term used to describe the co-occurrence of OSA and metabolic syndrome (Castaneda et. al., 2018).
There is accumulating evidence to support the importance of effectively diagnosing and treating obstructive sleep apnoea as more is discovered about its long-term effects (Montesi et. al., 2012). OSA causes intermittent hypoxemia due to airway collapse. The subsequent nocturnal desaturation followed by reoxygenation can cause inflammation which damages the blood vessels and leads to hypertension (Dewan et. al., 2015).
Treatment for OSA may include using a CPAP machine which gently pumps oxygen into a mask that the patient wears over their mouth while they sleep. This can improve the patient’s breathing by stopping airways from becoming too constricted, improving quality of sleep and reducing the risk of problems linked to OSA (Spicuzza et. al., 2015).
Night Shift Work and Metabolism
Getting an insufficient amount of sleep is becoming increasingly more typical due to modern lifestyles. For example, night shift work has become highly prevalent in industrialised society and is associated with lack of sleep because of interference with the circadian rhythm (Åkerstedt et. al., 2010). Night-shift work affect mental health and has negative social implications, but there is also growing evidence to support that night-shift work increases the risk of developing metabolic syndrome (Pietroiusti et. al., 2009).
It was found that obesity, high triglycerides and low concentration of HDL cholesterol seem to occur together more frequently in night shift workers than in day workers (Nikpour et. al., 2019). These are all symptoms of metabolic syndrome. There could be many reasons behind these findings, for example the impact of sleep-wake cycles, eating and exercise habits, hormone secretion and blood pressure levels (Brum et. al., 2015).
Disturbance in metabolism of night-shift workers was found to be primarily caused by peripheral oscillators. They detect changes in light and synchronise the body’s organs and tissues. Following a night-shift, 24hr rhythms in metabolites related to the digestive system – which include peripheral oscillators in the gut, pancreas and liver – shifted by 12hrs whereas the biological clock only moved by two. This is likely to have a significant impact on metabolism (James et. al., 2017).
Research strongly indicates that there is a relationship between sleep deprivation and the metabolic syndrome. This is likely due to the fact that sleep deprivation leads to dysregulation of the neuroendocrine system, increased nocturnal sympathetic activity and activation of inflammatory pathways (for example in OSA). Sleep architecture can be disrupted by OSA, which can cause sleep deprivation. OSA increases the chances of hypertension due to damage of the blood vessels caused by hypoxemia as a result of narrowing airways during sleep. Night shift workers have a disrupted circadian rhythm and this strongly associated with increased risk of obesity due to the effects of peripheral oscillators in the digestive organs.
Current methods to treat metabolic syndrome include lifestyle advice and medication to tackle the various symptoms. Weight loss is recommended to prevent OSA and night shift workers are advised to change their schedules where possible to reduce the risk of developing metabolic syndrome. Overall, sleep plays a remarkable role in regulating metabolism and more research should be done on the effects on sleep deprivation to better understand it and potentially minimise the risk of developing metabolic syndrome.