Obstructive sleep apnoea and metabolic syndrome: a vicious circle of health issues

Metabolic syndrome and obstructive sleep apnoea have a bidirectional relationship – especially in the obese

At the time unconnected with metabolic syndrome, the first case of sleep apnoea I ever saw was in a 35-year-old morbidly obese lady from Portugal who had recently moved to London. This was more than 25 years ago when I was working at King’s College Hospital, but I still have her clinical details very clearly in mind. She presented with a recurrent severe headache, not related to head trauma but associated with lethargy and a tendency to sleep during the day.

Given her weight issues and slightly raised blood pressure, I performed a head CT scan to exclude a possible minor stroke. This was clear, but, given the severity of the headache, I admitted her for 24-hour observation. However, the patient was admitted to the wrong bed, one in the high dependency unit.

As things turned out, this was very fortunate.

On my morning round, the attending nurse reported that they had to summon the on-call medical team several times during the night. This was because the monitor observation showed intermittent severe drops in the patient’s oxygen level. This suggested a breathing problem rather than a head or neurological issue. The nurse also reported that her blood pressure kept fluctuating, reaching worryingly high levels at times. The patient was snoring badly during the night, disturbing all the other patients.

Fortunately, I saw a senior respiratory physician enter the unit, and I asked for their medical opinion. To my amazement, they expressed great interest in the patient, muttering about the possibility of sleep apnoea.

Snoring was a major factor in her split with her boyfriend

I went back to the patient to take more history, and she admitted that she had moved to the UK after splitting with her boyfriend in Portugal. She said that her snoring was a major part of the problem, and she was desperate for a treatment that could resolve her headache and get rid of her snoring.

The patient underwent a sleep study, and the diagnosis of sleep apnoea was confirmed. She was offered overnight home Continuous Positive Airway Pressure (CPAP, a mask) but was very keen to resolve the whole problem. With my holistic medical hat on, I advised her to lose weight.

This is because I believed her condition to be related to metabolic syndrome.

The metabolic syndrome constitutes a cluster of risk factors that include general or mid-body obesity, high blood pressure, high blood sugar, and abnormal blood fat, characterised by high triglycerides and low HDL (the good guy). Obstructive sleep apnoea (OSA) is characterised by recurrent episodes of partial or complete obstruction of the upper airway, resulting in intermittent hypoxia (low oxygen levels), frequent waking, unrefreshing sleep, and loud snoring. This represents a growing epidemic, affecting 60% of the general population due to our progressive increase in body mass index (BMI) over the last few decades.

Multiple studies have identified OSA as a risk factor for the development of obesity, diabetes, and cardiovascular diseases. Moreover, emerging evidence indicates that metabolic disorders like these can exacerbate OSA, creating a bidirectional relationship between OSA and metabolic syndrome.

In this review, we will explore this bidirectional relationship, including discussion of hormones insulin and leptin, and blood sugar control, as well as the obstructive component of OSA.

Apnoea has been documented since 4000 BC. Charles Dickens wrote in The Pickwick Papers about Joe the fat boy, who was always asleep, and his snoring was given the term Pickwickian syndrome. The term “sleep apnoea” was introduced in the 1960s to indicate partial or complete closure of the airways of obese people during sleep.

Why do you snore?

People who are overweight are much more likely to snore. Snoring gets worse with age. Men are three times more likely to snore than women, but after menopause, women tend to catch men up. Alcohol makes snoring worse because alcohol relaxes the muscles of the throat, and this causes the airway to collapse; the same happens will sleeping pills. Smoking makes snoring worse.

Snoring may run in families who share a common throat shape. If you have a blocked nose, this may cause snoring. Often lying on your side reduces snoring because, when you are lying on your back, your tongue tends to fall backward and block the airway. Large tonsils and adenoids can cause severe snoring and sleep apnoea in children, which may require urgent treatment.

Sleep apnoea is when you stop breathing for more than 10 seconds during sleep. The sleep apnoea which occurs in snorers is called obstructive sleep apnoea because of partial blockage of the airways while you are sleeping. Sufferers can be seen to be struggling for air and tend to wake with a loud grunt to breathe again. Sometimes they hear their own snoring, and if a snorer is waking himself up at night, it is often because of sleep apnoea.

OSA sufferers wake up many times during the night and consequently complain of excessive daytime sleepiness, morning headaches; they fall asleep at work or during a conversation or whilst driving, are irritable with a short temper, have mood swings, anxiety, or depression, and loss of libido.

Present in up to 66% of obese adolescents

OSA occurs in 2%-3% of healthy children, but between 13% and 66% among obese adolescents. Children with OSA are reported to have over 6 times more risk of developing metabolic syndrome. The principal predictor is hypoxemia (low oxygen level.) Screening of obese children for OSA is therefore important since their outcomes are modifiable by lifestyle changes.

Neck circumference is a better predictor of OSA than general obesity. Patients with OSA have approximately 67% more total neck fat compared with the normal person. This causes a smaller upper airway and a greater chance of the upper airway narrowing during sleep.

During evaluation in the sleep laboratory, an individual with OSA experiences periods of breathing reduction (hypopnea) or cessation (apnoea), coincident with respiratory effort.

The severity of an individual’s apnoea and hypopnea is defined by the apnoea-hypopnea index (AHI). An individual with mild OSA experiences 5–15 AHI per hour, moderate 15-30 AHI per hour, and severe >30. These events reduce blood oxygen saturation, and over the course of the night, present as intermittent hypoxia. It is estimated that an individual with severe OSA may reach blood oxygen saturation levels as low as 76%.

Continuous Positive Airflow Pressure

CPAP is the most widely used treatment for OSA. CPAP actively keeps the airway open and can improve the AHI by an average of 13 events/hour. Despite great improvement in AHI from CPAP, compliance is low. Only 39–50% of users will use CPAP for the recommended minimum of at least 4 hours a night, 5 days a week.

Metabolic syndrome contributes to OSA in other ways.

Obese people show an impairment in glycaemic control, which has been associated with nocturnal hypoxemia (low oxygen.) OSA has been shown to exhibit peaks in circulating blood glucose levels following blood oxygen desaturation. Taken together, these studies demonstrate that OSA, and nocturnal hypoxemia (low oxygen), likely leads to elevated blood glucose levels, suggesting that the association between OSA and improper glucose control may lead to type 2 diabetes. Individuals with nocturnal hypoglycaemia (low blood sugar) are at increased risk of OSA.

Leptin, the anti-obesity hormone, is another root cause of OSA, as leptin increases with fat mass. However, too much leptin can lead to leptin resistance, wherein the anti-obesity property is lost. It is possible that elevated leptin observed in obesity may be contributing to OSA.

OSA results in frequent low oxygen levels, which activate the sympathetic system (stress response), resulting in high inflammation and oxidative stress.

Apnoea and blood pressure

Management of apnoea will result in blood pressure control. This is important because sleep apnoea increases the risk of congestive heart failure, heart attack, and stroke. OSA causes cardiac arrhythmia that can result in extreme bradycardia (slow heart rate) or ventricular asystole (loss of the heartbeat) for more than 10 seconds.

Nasal CPAP will abolish ventricular asystole. Some studies have shown that CPAP restored normal cardiac rhythm in eight patients out of 10 with OSA-induced asystole. Adequate treatment reduces insulin resistance and prevents diabetic complications.

OSA prevalence among patients with type 2 diabetes seems to exceed that in the general population for the same age range and BMI. OSA might increase the risk of developing type 2 diabetes through a deterioration in insulin sensitivity.

An eminently modifiable risk factor

Obesity is the most important modifiable risk factor associated with OSA. A weight gain of 10% is associated with a 32% increase in disease severity (AHI), whilst a 10% weight loss results in a 26% severity reduction.

Visceral or central adipose tissue is thought to be the source of many of the metabolic abnormalities that contribute to the increased cardiovascular risk associated with obesity. Although CPAP is considered the gold standard treatment for severe OSA, it variably ameliorates OSA-related symptoms and hypertension, and it is unclear whether it impacts insulin sensitivity.

Intensive lifestyle interventions, employing a caloric restriction and/or physical activity, are effective in reducing obesity and the severity of OSA. Lower intensity interventions, combined with CPAP therapy, also work but to a significantly lesser degree.

Solutions: diet and exercise

Let’s compare the Mediterranean and the Prudent diets, the latter complying with healthy eating recommendations, being typically high in vegetables, legumes, fruit, fish and shellfish, poultry, and low-fat dairy products.

Waist circumference and waist-to-hip ratio are reduced more by the Mediterranean diet than the Prudent diet. Mediterranean diet supplemented with extra-virgin olive oil reduces the incidence of major cardiovascular events among people at high cardiovascular risk. A recent systematic review revealed that the Mediterranean diet had a greater effect on glycaemic control, as well as greater weight loss in the management of type 2 diabetes.

On to exercise. The American College of Sports Medicine currently recommends at least 250 minutes per week of moderate-intensity cardiorespiratory exercise for significant weight loss, in addition to two strength training sessions. The typical characteristics of the OSA patient, being sleepy and lacking energy, may compromise their ability to comply with these high volumes of exercise. Therefore, tailored exercise programmes with a progressive workload are recommended.

So, once again, my friends, the solution to yet another health problem related to metabolic syndrome lies in the right diet and activity. Sleep apnoea, like so many other severe health issues, will respond better to these relatively straightforward lifestyle changes than more complex medical, mechanical (CPAP in this case) or chemical interventions.

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References

Metabolic syndrome and sleep apnoea

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2464309/

Correlation between metabolic syndrome and sleep apnoea

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5951892/

Sleep apnoea and metabolic dysfunction

https://err.ersjournals.com/content/22/129/353

The bidirectional relationship between obstructive sleep apnoea and metabolic syndrome

https://www.frontiersin.org/articles/10.3389/fendo.2018.00440/full

Dietary patterns and the heart

https://assets.heartfoundation.org.nz/documents/shop/submissions/dietary-patterns-evidence-paper.pdf

Snoring and sleep apnoea