Sleep and diabetes
For healthy existence, humans need to spend one-third of their time sleeping. Any qualitative or quantitative disturbances in sleep would result in increased prevalence of obesity, metabolic disorders, diabetes, cardiovascular events, and hypertension. Shorter and longer duration of sleep has been adversely related to insulin resistance, though the link between sleep deprivation and diabetes is more or less understood, however, little is known about how oversleeping increases risk of diabetes. Obstructive sleep apnea is another common sleep disorder, which is characterized by chronic intermittent hypoxia and increased sympathetic activity, thus leading to the higher prevalence of diabetes. Sleep therapy may serve as a low-cost method for fighting against the epidemics of diabetes.
Keywords: sleep, sleep duration, obstructive sleep apnea, diabetes
Sleep disorder is either qualitative or quantitative alterations in sleep behavior. Thus some people may sleep more, while others less, some may have difficulty in getting asleep or may get woken up by breathing difficulties while asleep. Lack of enough sleep and obstructive sleep apnea are two most common sleep disorders. It is recommended that adults must sleep 7-8 hours a day. However, sleep duration during last 40 years has decreased by 2-hours due to workload, lifestyle, social activities, and technology (1).CDC data indicates that almost 35% of adults in the US are not sleeping enough, with not much gender and ethnicity difference. Thus, lack of sleep increases the risk of obesity, diabetes, hypertension, heart attack, coronary heart disease, stroke, asthma, COPD, cancer, arthritis, depression, and chronic kidney disease (2). At the same time, the obstructive sleep disorder is estimated to affect 14-49% of the adult population (3), while moderate to severe form of sleep apnea is present in around 10% of the adults above 30 years of age, and prevalence increases sharply with age. Obstructive sleep apnea is more common among the men than in women (4). Prevalence of diabetes is equally common in the US. Latest statistics indicate that more than 100 million US adults have either diabetes or prediabetes, among them 30 million, that is close to 10% of the adult population, has been diagnosed with diabetes (5,6). Thus diabetes is one of the most prevalent diseases in the USalong with various sleep disorders. Sleep disturbances are inherently linked to the increase of various non-communicable diseases, including diabetes.
Sleep and diabetes
Relations ship between sleep disturbance and diabetes is dual sided. Chronic sleep disturbances would elevate the risk of developing insulin resistance, while diabetes would worsen the quality of sleep. Both the qualitative and quantitative disturbances in sleep significantly increase the risk of developing diabetes. When taking into consideration quantitative aspect, it should be understood that both the short duration and long duration of sleep are associated with higher prevalence of diabetes, though the underlying mechanism and causes in both the conditions may differ (7,8).
Sleep duration and risk of diabetes
It is evident from various studies that both the extended hours of sleep and shorter length are related to higher risk of diabetes. Yagi et al. analyzed data from Massachusetts Male Aging Study. In the study, they included the men who were found to be borderline diabetic between the year 1987-1989, and they followed them till 2004. Men were divided into groups according to the duration of sleep, those who slept less than 5 hours, 6-hours, 7-hours, 8-hours, and more than 8 hours. They calculated the relative risk of developing diabetes. The study demonstrated that those who slept for 6 or less than 5 hours were twice at higher risk of developing diabetes, while those who slept more than 8 hours were thrice at risk of developing diabetes in comparison to those who slept for 7 hours a day. Further, the risk did not change, when investigators considered the presence of other factors like smoking, age, education, waist circumference, hypertension. Interestingly study did show the relation between sleep deprivation or oversleeping and testosterone levels in men, thus suggesting the role of hormones (9).
In another study, Mallon et al. studied the relationship between sleep complaints and duration of sleep with diabetes in a 12-year follow-up study of the middle-aged Swedish population. They randomly sampled 2663 individuals aged between 5 to 65 years. They gave them questions about sleep complaints, sleep duration, and other factors like depression, sociodemographic characteristics, and other comorbidities. The study demonstrated that men who slept less were at 2.8 times greater risk of developing diabetes, those who had difficulty falling asleep has almost 5 times higher risk of diabetes, and those with difficulty in maintaining sleep had 4.8 times greater risk. Amazingly study also revealed that sleep duration and quality was not much associated with the development of new diabetes in women(10).
Hence it seems both the longer duration and shorter durations are linked to higher prevalence of diabetes. It is especially true for men, while women display the lower relationship between sleep duration and development of diabetes. It has been confirmed in several reviews and meta-analysis (11).
Relationship between diabetes and sleep quality: sleep apnea
Sleep apnea needs separate treatment for its link with diabetes, due to increasingly high prevalence in various demographic groups, especially in men. In Wisconsin Sleep Cohort full polysomnography was used to characterize sleep apnea in 1387 individuals, while diabetes was diagnosed either based on physician’s diagnosis or fasting glucose above 126 mg/dl. The study demonstrated the increase in prevalence related to the severity of sleep apnea. Thus the prevalence of diabetes was almost 15% in those with an apnea-hypopnea index of 15 or above, for comparison, the prevalence of diabetes was less than 3% in those with an apnea-hypopnea index of 5 or below. Thus clearly demonstrating not the only links between diabetes and sleep apnea, but also confirming the relationship between diabetes and severity of sleep apnea. When the risk of developing diabetes in 4 years was adjusted taking age and sex into consideration, it was found that moderate to severe apnea increased the risk by 1.62 times(12).
Another common form of sleep disturbance is lack of sleep hygiene and shift in circadian rhythm due to various reasons like shift work, or sleep restriction due to other causes. It has been demonstrated that those who stay awake during the night are at higher risk of developing diabetes when compared to day workers. Misalignment of circadian rhythm has been shown to promote insulin resistance (13).
Prevalence of sleep disorders in diabetes
It is well demonstrated that those with sleep disorders are at higher risk of developing diabetes. However, the picture would be incomplete without considering the prevalence of sleep disorders in those with diabetes. Foster et al. studied the prevalence of sleep apnea in the obese population living with type 2 diabetes. They performed the polysomnography in 306 participants. Sleep apnea was diagnosed in 86% of individuals, thus confirming the relationship between sleep disorders and diabetes, another way. In the study, 30.5% of the participants had moderate sleep apnea with an apnea-hypopnea index between 15-30, and 22.6% were diagnosed with severe sleep apnea with an apnea-hypopnea index of above 30. They also noted that severity of sleep apnea in people with diabetes was related to waist circumference. This study confirmed the much higher prevalence of sleep apnea in those with obesity and diabetes; the study also demonstrated that sleep apnea tends to be more severe when coexisting with diabetes and obesity(14).
Type 1 diabetes is comparatively uncommon, with around 5-6% of those diagnosed with diabetes have type 1 diabetes (15). Type 1 diabetes is very different from type 2, as it is a disease that is usually diagnosed at a young age, most of those diagnosed are lean, and dietary habits or lifestyle has far muted role in disease development. However, studies do confirm the sleep disturbances in those with type 1 diabetes, although the underlying mechanism seems to be entirely different. In type 1 diabetes there is a clear link between neuropathy and sleep disturbances, thus sleep apnea may be either obstructive or central to type 1 diabetes(16).
Mechanism of development of diabetes in sleep disorder
Sleep disorder leads to insulin resistance and beta-cell dysfunction through various pathways. Hypoxia, sleep fragmentations, and activation of the sympathetic nervous system are some of the pathways playing a role in the development of diabetes in those with sleep disorders.
Sleep fragmentation results in elevated sympathetic activity, and a higher level of inflammation. Sleep fragmentation may also contribute to the development of obesity. It is also possible that sleep fragmentation may lead to adipose tissue inflammation that is NADPH oxidase 2 mediated (17).
When a person is asleep, the parasympathetic nervous system is predominant, resulting in a slowdown of heart rate, blood pressure, respiration rate, gut movement, other bodily functions, body temperature and basal metabolism. However, if sleep is disturbed too often, this predominance of the parasympathetic nervous system does not occur, and sympathetic tone is elevated. It results in a higher load on the circulatory system, a higher rate of basal metabolism, a higher level of stress hormones, and finally higher hazard of developing insulin resistance or diabetes (18).
Hypoxia is another important mechanism behind the development of insulin resistance. Hypoxia in sleep apnea differs in a way that it is intermittent. Thus there are periods of low oxygen perfusion followed by compensatory high oxygen perfusion. It disturbs the normal metabolism, resulting in the elevated formation of reactive oxygen, which is damaging to various cells. Another proposed pathway of insulin resistance in intermittent hypoxia is through inflammation of adipose tissues. In mouse models, it has been demonstrated that intermittent hypoxia leads to downregulation of insulin receptors, lower uptake of glucose by adipocytes, and higher levels of pro-inflammatory markers (19).
In fact, chronic intermittent hypoxia has been proposed as the single most crucial factor in the development of insulin resistance in those with sleep apnea. It seems that intermittent hypoxia may directly cause beta cells dysfunction, it may lead to changes in liver enzymes and liver functioning thus affecting the glucose homeostasis. Chronic intermittent hypoxia may also be related to changes in skeletal muscles and glucose uptake by them (20).
Although the relationship between long sleep duration and a higher risk of diabetes is well established, however, no plausible explanation has been found. It seems that insulin resistance is probably caused by sleep disturbances and altered sleep quality in prolonged duration of sleep, though it remains the subject of further investigations (7).
Better sleep hygiene may decrease prevalence of diabetes
If sleep disruption, qualitative or quantitative, may lead to obesity, insulin resistance and development of diabetes, then it is entirely possible that simple, low-cost method of sleep correction may help to prevent diabetes in an avast number of cases. Although there has been limited research in this direction, some of the research seems to support the idea of the positive effect of adequate sleep on insulin sensitivity.
Thus in one of the interventions obese volunteers were asked to increase their sleep duration by just one hour, they were intermittently monitored for sleep quality and fasting glucose. The study was continued for 40 days. At the end of the research, insulin sensitivity and fasting glucose were improved just through sleep prescription, thus demonstrating the value of this low-tech and low-cost approach to diabetes preventions (21).
There has been a number of studies regarding the beneficial effect of treating chronic intermittent hypoxia in those diagnosed with obstructive sleep apnea. One of the most effective treatment approaches is the use of continuous positive airway pressure (CPAP). In the meta-analysis of various random clinical trials, CPAP has been demonstrated to provide significant benefit in reducing insulin resistance and thus decreasing the risk of developing diabetes.
Conversely, it should be understood that good glycemic control in diabetes would result in better sleep quality, decrease in REM sleep latency, and thus serving to improve the quality of life and reducing the risk of other adverse effects of sleep deprivation(22).
In conclusion, it can be said that qualitative and quantitative sleep disorder would increase the risk of insulin resistance and diabetes. Sleep disorder would also increase the risk of complications related to diabetes. The relationship between sleep and diabetes is bi-directional, meaning that well-managed diabetes would result in better sleep quality too. There are certain limitations of what we know about the relationship between sleep and diabetes. Firstly, the underlying mechanism is not wholly understood. Secondly, most of the studies looking at the link between the conditions have focused on type 2 diabetes. Thus there is little information about the role of sleep disorders in type 1 diabetes. Finally, it may be wise to say that importance of sleep prescription and sleep hygiene has not been fully realized in diabetes prevention.
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