By 2025, the World Health Organization (WHO) estimates there will be 300 million people living with type 2 diabetes mellitus (T2DM), a metabolic condition caused by impaired glucose tolerance leading to insulin resistance. Traditionally, risks for T2DM have included genetic predispositions and lifestyle factors such as diet and physical activity levels. In the last decade an increasing amount of research is exploring the impact of sleep dysregulation on metabolic health.
SLEEP: A METABOLIC REGULATOR
Sleep is a biological process essential for health and is mediated by circadian rhythms, ultradian rhythms (sleep architecture) and homeostatic processes (sleep pressure). Sleep serves a multitude of functions including cardiovascular regulation, immune enhancement, recuperation and restoration of both brain and body, memory consolidation and nervous system and metabolic regulation.
THE CHANGING SLEEP ENVIRONMENT
The invention of the electric light bulb in the late 19th century has created a seismic shift in how our days and nights are structured. The availability of inexpensive, bright artificial illumination has extended the work day, changed our recreational activities and increased the portion of the population who do shift work. Our ability to control the light in our environment has seen a 1.5-2 hour per night decrease in the average person’s sleep over the last 50 years.
A number of studies have shown short sleep duration of less than 5-6 hours increases the risk of diabetes from anywhere between 48-57%.[2,5-7] It’s not just about sleep duration; circadian dysregulation (commonly experienced by shift workers) increases the risk of T2DM by 40%. In addition, difficulty with going to sleep and frequent night awakenings are associated with an even greater risk.
HOW SLEEP DYSREGULATION CONTRIBUTES TO METABOLIC DYSREGULATION
ALTERATIONS TO GLUCOSE METABOLISM AND INSULIN SENSITIVITY
Sleep curtailment has shown reductions in the circulating concentration of the hormone glucagon, suggesting an inhibitory effect on pancreatic function and a reduced capacity to access hepatic stores of glycogen for energy.(9) In addition to alterations in pancreatic function, adipocytes and skeletal muscle also become less sensitive to insulin.[1,7]
Slow-wave sleep may be particularly important. Studies in healthy adults showed that disrupting slow-wave sleep decreases glucose tolerance and insulin sensitivity, possibly related to stimulation of the hypothalamic pituitary adrenal (HPA) axis. There are implications for people who use pharmaceutical hypnotics such as benzodiazepines and Z-drugs as these tend to suppress slow-wave sleep.
Alterations to sleep impact the hormones and neurotransmitters controlling the HPA axis and stress response. Short sleep duration increases catecholamine production and cortisol, which increases the release of glycogen and inhibits insulin. These also negatively influence sleep duration and efficiency, due to sympathetic nervous stimulation and inhibitory effects on melatonin.
APPETITE AND FOOD INTAKE
Lack of sleep alters neuroendocrine appetite regulation mechanisms and reduces the ability to exert inhibitory control over food. These are mediated primarily by decreases in the satiety hormone leptin and increases in the appetite stimulant grehlin. This appetite dysregulation results in an increased consumption of calories.
Adolescents who had a reduction in sleep from 8.9 hours to 6.3 hours increased their average energy intake by 680kcal – the equivalent of one additional meal. This additional energy was made up of foods with a high glycaemic index (GI). Meal portions were larger and snacking increased.
In evolutionary terms, these adaptive appetite mechanisms would have encouraged food foraging to meet additional energy requirements from loss of sleep. However, in a modern world where high calorie food is available without the energy required to forage or hunt, this can easily lead to an energy surplus and resultant weight gain.
DECREASED PHYSICAL ACTIVITY AND ENERGY EXPENDITURE
Physical activity has been shown to improve insulin sensitivity by increasing glucose uptake in skeletal muscle during exercise and increasing insulin sensitivity post exercise. Daily physical activity is therefore an essential part of metabolic control.
Sleep of less than 5.5 hours per night reduced physical activity by 31%. This reduced desire for physical activity is likely to be hormonally modulated, as reduced sleep alters levels of thyroid stimulating hormone.
Chronic low-grade inflammation is a well recognised contributing factor to T2DM. Lack of sleep increases the production of pro-inflammatory cytokines, such as tumour necrosis factor-alpha (TNF-alpha) and interleukin-6, and 24 hour secretion of cortisol is also elevated.
Circadian dysregulation also alters the neuroendocrine pathways influencing insulin resistance. This has been well studied in shift workers who, even in the absence of sleep restriction, still experience signs of insulin resistance possibly due to consumption of food outside the circadian eating window. However, voluntary circadian misalignment is also frequently observed in the non-shift-working population, due to change in working habits and lifestyle where there is decreased exposure to daylight and increased exposure to artificial light at night.
Artificial light in the evening has a known suppressing effect on melatonin. Dim room lighting and short-wave length light (found in electronic devices) can reduce melatonin production by 88%. In addition to its sleep promoting effects, melatonin has a inhibitory effect on insulin secretion (with melatonin receptors present on pancreatic beta cells).
PRESENCE OF OBSTRUCTIVE SLEEP APNOEA
Obstructive sleep apnoea (OSA) impacts glucose and insulin in multiple ways. The intermittent hypoxia increases sympathetic nervous stimulation, inflammatory markers such as C-reactive protein (CRP) and alters leptin sensitivity. Continuous positive airway pressure (CPAP) is considered a front line treatment for OSA and has been shown to improve markers of insulin resistance.
The impact of sleep and circadian dysregulation on our metabolic health are complex and multifaceted. Supporting healthy sleep habits are vital to reducing the burden of diabetes.
- Evaluate sleep habits of patients with increasing blood glucose and signs of insulin resistance.
- Encourage sleep hygiene practices, with a particular focus on exposure to light at night and limiting electronic device use.
- Consider screening for OSA, especially in non-obese patients who have signs of insulin resistance.
- Encourage healthy circadian rhythms with daily exposure to sunlight, and regular sleep and wake times.
- In shift-workers, ensure regular daily physical activity to help improve insulin sensitivity.
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