Sleep duration: Waking up to a major metabolic risk factor
The effect of sleep duration on glucose regulation and cardiometabolic risk is becoming an increasingly high-profile issue. medwireNews takes a look at the latest evidence, which shows the gravity of the problem but also offers some solutions.
Sleep, or the lack of it, has become a big issue in our 24-hour society. The melatonin-suppressing effects of blue-light-emitting phone and tablet screens, and the resulting impact on sleep time, have been a focus of recent attention, but even the existence of electric light per se results in people getting less sleep, as shown in a 2015 study of Amazon rubber tappers with or without electric lighting in their homes .
Add to that the effects of long working hours eating into people’s leisure time and rotating shift-working patterns disrupting circadian rhythms and you have a major societal issue, accused of contributing to a range of health ills including obesity and diabetes, depression, cardiovascular disease, and poor cognitive performance. Data from the American Time Use Survey for 2003–2016, involving 181,335 people, revealed that in 2003 approximately 16% regularly slept for 6 hours or less on workdays, with a further 16% sleeping for 6–7 hours, and these rates declined only slightly over time . The scale of the problem prompted the American Academy of Sleep Medicine and Sleep Research Society to release a joint consensus statement in 2015, recommending that for optimal health adults should aim to have at least 7 hours of sleep per night on a regular basis .
Consequences: The long and the short of it
The link between sleep duration and risk for type 2 diabetes is firmly established, with the authors of a 2015 meta-analysis able to draw on data from 482,502 people with follow-up ranging from 2.5 to 16 years . Most research shows a U-shaped association, with both excessively short and overly long sleep durations increasing diabetes risk. In the meta-analysis, each 1 hour reduction in habitual sleep duration below 7 hours was associated with an additional 68 cases of diabetes per 100,000 individuals per year. Conversely, each 1 hour increase above 7 hours’ duration resulted in an additional 106 cases.
Likewise, the link between sleep duration and cardiovascular health is sufficiently strong to have prompted a 2016 scientific statement from the American Heart Association, containing a detailed evidence summary and a call for health organizations to include evidence-based sleep recommendations in their guidelines . However, a recent study suggests that the effect of sleep duration on cardiovascular outcomes could be indirect, no more than an inevitable consequence of the increased diabetes risk .
More than a lifestyle marker
Direct effects of insufficient sleep…
So what links sleep duration to diabetes risk? It is possible that short sleep duration is a marker for a generally chaotic and unhealthy lifestyle; however, research in sleep laboratories has built up a convincing argument for the existence of direct causative pathways from sleep duration to cardiometabolic risk.
One pathway is through increased adiposity. Several, although not all, studies have found increased energy expenditure among sleep-restricted people, but this is offset by changes in appetite-regulating hormones. For example, two studies from the same research group that assessed 24-hour leptin profiles and closely controlled participants’ calorie intake and activity levels recorded around a 20% reduction in leptin levels associated with sleep restriction [7, 8]. The second of these also reported a simultaneous increase in hunger and appetite. Increased appetite, especially for unhealthy foods, and consequently increased calorie intake, has been noted in a number of other studies, although the results of one suggested that this varies between individuals .
Given the above, it is not surprising that researchers have found that even short-term sleep restriction (2–5 nights) results in weight gain. Equally problematic is that sleep restriction may hamper people’s efforts to lose weight – or, more precisely, it results in them losing fat-free mass, rather than fat .
Another pathway to diabetes is the direct dysregulation of glucose metabolism. This was demonstrated as early as 1999 in a paper published in The Lancet, in which the rate of glucose clearance was reduced by nearly 40% in young men subjected to sleep restriction, and the acute insulin response to glucose was reduced by 30% . Many other studies published since have shown similar findings, using a variety of methodologies, and a small number have reported comparable effects in people subjected to sleep fragmentation – for example, insulin sensitivity decreased by 25% in 11 healthy people after 2 nights of fragmented sleep .
Worth noting is that people who work rotating shifts may experience a double whammy of adverse metabolic effects. Disruption of circadian rhythms can reduce the amount people are able to sleep when given the opportunity, even in those well used to rotating shift-work , but it also disrupts glucose metabolism independently of total sleep time [13, 14], with consequences for workers’ diabetes risk .
What is encouraging, however, is a small amount of research suggesting that these changes are reversible if people catch up on missed sleep. Most positive in terms of easy applicability was the significant improvements in insulin sensitivity observed in chronically under-slept people who increased the amount they slept at the weekends .
…and of excessive sleep
The vast majority of mechanistic studies have focused on short sleep duration, but the adverse effects of excessive sleep also appear consistently in epidemiologic studies, including two that examined changes in sleep duration over time, rather than being based purely on a baseline measure, and accounted for chronic illness [17, 18]. In both studies, adjustment for BMI attenuated the effects of short sleep duration on diabetes risk more than it did the effects of long sleep, implying different underlying causes.
Proposed mechanisms for the effects of long sleep duration include a general reduction in physical activity, due to extended time in bed or to feeling lethargic after excessive sleep, and increased sleep fragmentation during extended sleep. One randomized study showed increased sleepiness and depression and elevated levels of an inflammatory cytokine when time in bed was increased by 3 hours per night above the median at baseline . However, glucose dysregulation may still play a role, as shown in a study of adolescents in which both short and long sleep reduced insulin sensitivity, with the latter effect being independent of adiposity .
A complicating factor for diabetes patients
Given its effects on glucose metabolism, sleep duration is logically also an issue for people with pre-existing diabetes, whether type 1 or type 2. Indeed, the 2017 edition of the ADA Standards of Care for the first time singled out sleep duration as something clinicians should take into account when helping patients to manage their blood glucose .
Findings in patients with type 2 diabetes largely replicate those obtained in healthy people. In a meta-analysis, both short and long duration of sleep were associated with significantly higher glycated hemoglobin (HbA1c) levels, compared with the reference category, which was most commonly 6–8 hours .
Things become more complicated, however, when obstructive sleep apnea enters the picture, causing sleep deprivation despite people sleeping for the recommended number of hours. The condition is relatively common in patients with type 2 diabetes, thanks partly to the shared association with obesity, although a recent study indicates a bidirectional link with diabetes per se .
For a more in-depth look at sleep apnea and diabetes, read the linked article by Medicine Matters editorial board member John Wilding.
The situation for type 1 diabetes is, unsurprisingly, more complex. Studies have found evidence of diabetes-related sleep disturbances in patients with type 1 diabetes, including a high rate of probable sleep apnea, even in a generally non-obese population , and fear of hypoglycemia can cause both patients and caregivers to wake in the night to conduct blood glucose tests. And sleep disturbances, including both short and long sleep duration, have been linked to less effective self-management of diabetes [reviewed in 25].
In a 2016 meta-analysis, six studies in adults found no association between sleep duration and HbA1c, whereas four found short duration to be linked to higher HbA1c levels. In children and adolescents there were no associations, but these studies were fairly small. However, the same direct ill effects of short sleep on glucose regulation observed in healthy adults have also been reported in patients with type 1 diabetes  and two more recent studies assessing larger populations of children and adolescents (191 and 515 participants) found that short sleep duration (in one study) and poor sleep quality (in both studies) were linked to poor glycemic control [27, 28]. Of particular concern, children with poor sleep quality were at increased risk for severe hypoglycemia and diabetic ketoacidosis, underscoring the importance of taking patients’ sleep patterns into account.
A helping hand from technology
Recent advances in glucose monitoring technology may offer some assistance, by allowing patients and caregivers an easier means of checking blood glucose during the night, and sounding an alarm if patients are entering hypoglycemia, although that itself can be a frequent cause of disrupted sleep . The artificial pancreas could help to alleviate these problems by monitoring blood glucose and automatically adjusting insulin, in theory removing any need to wake in the night. Indeed, in one study, six of 15 adolescent patients felt that using an artificial pancreas had improved their sleep. However, alarms remained an issue, and for some caregivers the closed-loop system left them frustratingly disempowered as they were required to leave insulin adjustments to the algorithm . And of course cost is a limiting factor for all these new technologies.
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