Li Chiu Kong Family Sleep Assessment Unit, Department of Psychiatry, Faculty of Medicine, The Chinese University of Hong Kong. The Second School of Clinical Medicine, Zhujiang Hospital, Southern Medical University.

Correspondence: Jihui Zhang, MD, PhD, Center for Sleep and Circadian Medicine, The Affiliated Brain Hospital of Guangzhou Medical University, Guangzhou, Guangdong, China.

Email: jihui. zhang cuhk. hk ; Sizhi Ai, MD, PhD, Department of Cardiology, Life Science Center, The First Affiliated Hospital of Xinxiang Medical University, Weihui, China. Sizhi Ai.

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Purchasing options for books and journals across Oxford Academic. Short-term Access To purchase short-term access, please sign in to your personal account above. Additional support for the epidemiological evidence has been provided by experimental studies demonstrating that healthy human volunteers exposed to a rather severe paradigm of total sleep deprivation lasting from one to five days develop insulin resistance [ 73 , 74 ] and β-cell dysfunction [ 75 ].

As a consequence of insulin resistance combined with defects in insulin secretion, fasting and postprandial glucose levels were increased following sleep deprivation [ 75 - 79 ]. Despite the heterogeneity of study designs, partially sleep-deprived subjects also exhibited impairments in numerous parameters of glucose tolerance and insulin sensitivity [ 80 - 87 ].

Interestingly, the metabolic profile observed after sleep restriction shared several similarities with T2DM, including decreased muscle glucose uptake, increased liver glucose output and pancreatic β-cell dysfunction [ 80 , 83 , 84 , 88 ].

Despite the clear association between short sleep and metabolic impairments, the underlying endocrine and molecular mechanisms remain only partially elucidated.

Among the suggested mechanisms, the causal role of the hypothalamo-pituitary-adrenal HPA axis and sympathetic activation are supported by the largest body of literature. Circulating cortisol, assessed either by 24 h profiles or by single measurements of evening cortisol levels, were elevated together with markers of sympathetic activation [ 81 ] and circulating catecholamines [ 86 ] after total or partial sleep deprivation [ 79 - 81 , 83 , 89 , 90 ] as well as in short sleepers [ 91 ].

In contrast, some studies reported impairments in glucose homeostasis in sleep restricted individuals along with unchanged cortisol and catecholamine levels [ 82 - 84 , 88 ].

The complexity of associated endocrine mechanisms can be further demonstrated by observations of elevated levels of pro-inflammatory cytokines, lower circulating testosterone, decreased thyroid stimulating hormone levels, impaired pulsatility of growth hormone secretion [ 81 , 92 , 93 ] and changes in adipokines secreted from adipose tissue [ 94 - 96 ] in short sleepers [ 97 - ] as well as after sleep deprivation [ - ] also reviewed in [ ].

Prospective and cross-sectional studies have also identified short sleep duration as an independent risk factor for weight gain and abdominal fat accumulation as reviewed in [ , ].

It is therefore reasonable to suggest that insufficient sleep stimulates food intake [ ] and contributes to the development of obesity and metabolic syndrome. Furthermore, short sleep duration decreased the amount of fat overweight subjects lost during caloric restriction [ ].

Within the complex network of factors regulating food intake [ ], increased drive to eat in subjects exposed to sleep deprivation [ 81 , , , - ] or in patients with short sleep duration [ 39 , ] has been linked to decreased leptin limits food intake, secreted from adipose tissue and elevated ghrelin increases food intake, secreted mainly from the stomach plasma levels.

However, opposite or conflicting results have also been published [ 79 , 85 , 90 , , , , , ] pointing to the role of other factors, e. decreased levels of anorexigenic peptide YY PYY [ ].

In summary, it is safe to conclude that development of obesity, due to neuroendocrine changes, induced by inadequate sleep represents an additional independent risk factor for the development of metabolic abnormalities.

Non-traditional work schedules including shift and night work together with travel across time zones represent typical examples of circadian disruption. Furthermore, cells of peripheral organs involved in metabolic control including the liver, adipose tissue and muscle express a functional network of pacemaker genes and exhibit circadian cycling in expression of these genes, similar to the autonomous circadian rhythmicity observed in the SCN.

As a result, expression of hundreds of tissue-specific genes undergo circadian variation in peripheral tissues [ - ]. At the transcriptional level, entrainment of metabolic function in peripheral tissues could be mediated by glucocorticoids. Plasma levels of cortisol or corticosterone in mice exhibit a rigid circadian variability persisting even under conditions of experimental forced desynchronization [ 22 ].

Glucocorticoid synthesis and release is controlled by a peripheral clock-oscillator [ ] entrained to the SCN via direct sympathetic innervation of the adrenals [ - ].

The resulting circadian oscillations in plasma glucocorticoid levels induce oscillations in gene expression in target tissues e. the liver by binding to the promoter region of the Per gene, which represents a key component of the peripheral pacemaker network in the liver, adipose tissue and skeletal muscle [ - ].

The unique feature of peripheral oscillators is that they can be entrained by external cues. For example, nutrition has been identified as a potent zeitgeber for peripheral pacemakers even when clock genes were deleted or the SCN damaged [ , ].

Similarly, physical activity and exercise have been shown to entrain peripheral oscillators especially in skeletal muscle [ ]. Together with the transcriptional regulation of genes participating in peripheral pacemaker activity, metabolism in peripheral tissues can be synchronized with SCN via endocrine mechanisms.

For example, metabolic responses to oscillations in plasma levels of melatonin a hormone released from the pineal gland under direct SCN control were documented in fat [ ], muscle [ - ], the liver [ , ] and the pancreas [ ].

Studies revealed that melatonin or melatonin receptor agonist administration improved glucose homeostasis through various mechanisms including enhanced glucose uptake, increased glucose-induced insulin secretion, improved insulin sensitivity or decreased liver gluconeogenesis in various animal models [ , , , , - ].

Melatonin or melatonin receptor agonists also increased glycogen synthesis in hepatocytes [ ], limited fat accumulation in adipocytes [ ] and even decreased adiposity in humans [ ] and rats [ ]. Additionally, growth hormone [ ], thyroid stimulating hormone [ ] and direct sympathetic innervation of peripheral tissues [ ] also exhibits strong circadian rhythmicity and contributes to entrainment of peripheral pacemakers to the SCN and the metabolic needs of the whole organism.

Complete re-setting of the central biological pacemaker to a night shift work is extremely rare in humans, especially under rotating shift schedules [ - ]. Incomplete adaptation to irregular sleep pattern results in a significant misalignment between biological pacemakers and the living environment.

Metabolically active tissues obtain environmental cues e. Alignment of central and peripheral pacemakers is important for survival and overall needs of the organism [ ], while dyssynchrony results in serious consequences including increased cardiovascular mortality and morbidity [ - ] and higher risk of cancer reviewed in [ , ].

Shift work and circadian misalignment profoundly impair metabolic function and glucose homeostasis. Cross sectional and retrospective studies have found a higher prevalence of T2DM [ - ], glucose intolerance [ ], insulin resistance [ , ] and metabolic syndrome in shift workers [ - ].

Furthermore, a meta-analysis of observational studies confirmed higher risk of T2DM in shift workers, particularly men, in all shift-working schedules except evening and mixed shifts [ ]. Shift workers also gained more weight over time [ , ]. Causal effect of shift work in the development of metabolic abnormalities has been corroborated in several prospective studies conducted in men and women who engaged in shift work.

The studies found a higher risk of developing metabolic syndrome [ - ] and T2DM [ , - ], although some of these findings lost significance after being adjusted for changes in body weight. All of the above effects seem to resonate in patients who have already developed diabetes and seem to be especially affected by the negative consequences of shift work.

Elevated HBA1C levels were reported in diabetics engaged in shift work and insufficient diabetes control was linked to the duration of shift work employment and the number of hours worked per shift [ , , , , ]. Studies using mice with whole-body or organ-selective mutations in pacemaker genes have demonstrated the crucial role of central and peripheral pacemakers in the regulation of glucose levels, glucose tolerance, insulin sensitivity, insulin secretion and food intake [ - ].

For example, liver-specific loss of the Bmal gene induces hypoglycemia and altered expression of genes involved in glucose metabolism [ ], while the β-cell-specific Bmal gene deletion results in hyperglycemia and impaired glucose-induced insulin secretion [ ] caused by excessive production of reactive oxygen species [ ].

Similarly, mice fed under conditions of central and peripheral pacemaker misalignment gained more weight and developed insulin resistance [ ]. Additionally, healthy human volunteers subjected to circadian misalignment exhibited decreased insulin sensitivity, impaired compensatory insulin secretion and increased CRP C-reactive protein despite preserved total sleep time [ ].

These regulations were also observed in shift work subjects, where plasma glucose and insulin responses to a test meal were significantly higher when identical food was administered during the night as opposed to during the day [ ].

In parallel, insulin resistance and hyperinsulinemia were observed in shift work individuals [ , ]. Prolonging the natural hour day to 28 hours or more for several consecutive days provides an experimental tool to investigate the metabolic impact of circadian misalignment and shift work independently of the possible influence of circadian oscillations in metabolic and endocrine pathways.

Using such an experimental paradigm of forced dyssynchrony in human volunteers resulted in elevated glucose and insulin levels along with impaired glucose tolerance and pancreatic β-cell dysfunction [ 22 , 84 ].

Additionally, circadian disruption accelerated diabetes development in diabetes-prone rats due to apoptosis of insulin secreting β-cells [ ]. Furthermore, increased secretion of pro-inflammatory cytokines by macrophages has been reported after circadian disruption in mice [ , ], suggesting a putative mechanism for the overall pro-inflammatory activation typical of T2DM [ ].

Its prevalence is actually increasing along with the prevalence of obesity, which represents the most important risk factor for OSA [ ].

OSA is about twice as common in men than in women [ , ]. OSA is characterized by repeated obstructions of the upper airways during sleep, causing intermittent oxygen desaturations and arousals during sleep.

OSA is widely recognized as an independent risk factor for cardiovascular diseases [ - ]. Moreover, a growing body of evidence suggests that OSA is also associated with a number of metabolic alterations such as dyslipidemia, insulin resistance, glucose intolerance and T2DM.

This has been reviewed extensively in the last few years [ - ]. More importantly, the severity of nocturnal hypoxia in non-obese OSA patients was associated with insulin resistance [ ], suggesting that the OSA-related hypoxia-reoxygenation sequences play a major role in this metabolic dysfunction.

In large longitudinal studies, such as the Wisconsin cohort or the Busselton Health Study, the authors were able to demonstrate that OSA was associated with a higher prevalence of T2DM over 2 to 11 year follow-up periods [ - ].

Finally, based on the hypothesis that OSA can cause insulin resistance and diabetes, several studies have investigated whether OSA treatment by CPAP could reverse these deleterious effects. Uncontrolled studies examining the effect of CPAP on glucose tolerance and insulin sensitivity in OSA patients with or without diabetes have yielded mixed results, leading to no clear conclusion [ ].

Of the nine randomized controlled trials that have examined the effect of CPAP compared with sham- CPAP on glucose metabolism, only four studies demonstrated beneficial effects for therapeutic CPAP [ ].

However, it should be emphasized that overall compliance with CPAP therapy has been demonstrated to be rather limited [ ] and could influence outcomes of published studies. Non-Alcoholic Fatty Liver Disease NAFLD , a prevalent liver disease in which fat excessively deposits in the liver, has been recently associated with OSA [ ].

NAFLD is related to insulin resistance and is included among the clinical conditions associated with metabolic syndrome. Interestingly, it was suggested that OSA-induced intermittent hypoxia was associated with hepatic fibrosis and inflammation in both obese or non-obese patients [ - ].

Minville et al. further suggested that the severity of nocturnal hypoxia was independently associated with steatosis, and that pre-existing obesity exacerbated this effect [ ]. These results were confirmed in pediatric OSA patients [ ].

Numerous studies have investigated the link between intermittent hypoxia, as a component of OSA, and insulin resistance.

In several rodent models, chronic exposure to IH induced impaired glucose tolerance GTT [ - ], increased HOMA index [ - ] and impaired glucose clearance [ ]. Moreover, acute IH exposure of healthy human volunteers resulted in a decrease in insulin sensitivity and glucose effectiveness the ability of glucose itself to stimulate glucose uptake and suppress hepatic glucose production [ ].

Overall, CIH appears to be responsible for carbohydrate dysregulation, nonetheless, the mechanisms involved remain unclear. In the following sections, we will review the consequences of IH on insulin target tissues, namely the liver, skeletal muscle, the pancreas and adipose tissue summarized in Figure 2 , with special emphasis on the molecular mechanisms involved, such as impaired lipid metabolism, inflammation, oxidative stress and sympathetic nervous system activation.

Mechanisms linking intermittent hypoxia to impaired glucose metabolism. Intermittent hypoxia acts on pancreatic insulin production and secretion as well as on insulin target organs such as adipose tissue, liver and skeletal muscle.

These combined effects induce impaired glucose tolerance, insulin resistance and dyslipidemia. HIF-1α hypoxia inducible factor 1-alpha , NF-κB nuclear factor-κB , GLUT4 glucose transporter type 4.

Structural damage. Studies have demonstrated that CIH can induce liver damage and increase serum levels and activity of key liver enzymes such as serum aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase in both mice and humans [ , - ].

Several weeks of IH exposure resulted in liver steatosis, necrosis, inflammation with neutrophil accumulation and collagen deposits [ , , ]. While triglyceride content is increased by CIH in lean and obese mice [ , ], hepatic cholesterol content appears to be depleted after 12 weeks of IH but was, by contrast, increased after 6 months in another study [ , ].

Exposure to IH led to increases in key lipid biosynthesis enzymes in the liver SREBP-1, SCD-1 or HDL receptor [ , ], at least partly mediated by HIF-1 transcription factor [ ]. Glucose production is upregulated by IH, as supported by the observation of higher glycogen content [ , ], increased gene expression and protein levels of key gluconeogenic enzymes [ ] and increased glucose output from isolated hepatocytes [ ].

Oxidative stress and inflammation. Nitric oxide metabolites as well as liver iNOS levels have been shown to be increased by CIH along with reduced activity of liver antioxidant enzymes and DNA damage and apoptosis [ , ].

Moreover, IH resulted in increased lipid peroxidation and up-regulated p47phox expression and phosphorylation [ ]. Pro-inflammatory cytokines, TNFα and Macrophage Inflammatory Protein 2 MIP2 expression were unaffected by IH in lean mice but were increased in obese mice exposed to 4 weeks of IH [ ].

However, longer periods of IH enhanced liver pro-inflammatory cytokines, such as IL-1β, IL-6 and MIP2 in lean mice, together with activation of the pro-inflammatory transcription factor NFkB [ ]. Also, both HIF-1α and NFkB transcription factors have been shown to be up-regulated in the liver after 5 weeks of IH [ ].

Overall, experimental evidence suggests that IH promotes liver injury and increases hepatocyte glucose output through several mechanisms. It should be noted that structural and functional lesions observed in IH-exposed livers resemble those of non-alcoholic fatty liver disease NAFLD , a prevalent liver disease associated with OSA [ , ].

Therefore, apnea-related intermittent hypoxia appears to play a major role in OSA-related liver injury. However, probably because of the lack of consensus about the time-course of insulin resistance development, very few studies have focused on skeletal muscle metabolism in response to IH.

It was suggested that IH-induced modifications of muscle metabolism were characterized by a decrease in creatine phosphate, citrate, alpha-ketoglutarate and glutamate content and by alterations in the anaerobic glycolytic pathway [ ].

More recently, Liyori et al. observed a decrease in glucose metabolism in the soleus, a mostly oxidative muscle, using a mice model of CIH [ ]. Finally, an alteration of the cytosolic-to-membrane translocation of GLUT4 that could provide an explanation for the development of IR in mice exposed to CIH [ ].

Insight into the effects of IH on pancreatic function is of great importance for understanding mechanisms leading to impaired glucose homeostasis.

Although many hypotheses have been proposed, only a few have been confirmed [ ]. In severely obese adults, OSA was independently associated with an increase in basal pancreatic beta-cell function although glucose metabolism remained normal [ ].

On the other hand, pancreatic insulin secretion was not affected in healthy volunteers exposed to IH, although insulin sensitivity and glucose effectiveness were diminished [ ]. In mice exposed to CIH, beta-cell death as well as proliferation were observed [ , ].

Due to down-regulation of the enzyme prohormone convertase 1 converting proinsulin to insulin , insulin content was decreased in islets from CIH-treated mice [ ]. Finally, studies in mice models using antioxidant strategies suggested that ROS are involved in IH-induced pancreatic damages [ , ].

Adipose tissue is generally recognized as a key player in insulin resistance. Free fatty acids FFA released by lipolysis of adipose tissue are able to induce insulin resistance through their effects on muscle, liver and adipose tissue itself see [ ] for review.

Results from several studies showed that IH can cause dyslipidemia through an increased FFA release [ - ] than can be normalized by oxygen supplementation in humans [ ] and is accompanied with morphological and functional remodeling of the adipose tissue in mice [ ].

Moreover, IH-induced dyslipidemia can also be related to decreased lipoprotein clearance due to the inhibition of lipoprotein lipase LPL mediated by HIF-1 and Angiopoietin-Like 4 Angptl4 [ , , ]. Finally, Iintermittent hypoxia down-regulates adiponectin in 3 T3-L1 adipocytes [ ], which is a potent insulin-sensitizing hormone and increases adipose tissue production of resistin that can contribute to the development of insulin resistance through pro-inflammatory processes involving TNFα and IL-6 production [ ].

Healthy adults display lower sympathetic nervous system SNS activity during sleep than during wake-time. In contrast, OSA patients exhibit high level of sympathetic nervous system activity during both wake-time and sleep, accompanied by higher levels of circulating catecholamines [ , ]. Both human and animal models of IH reproduce this phenotype.

Indeed, IH exposure has been shown to increase sympathetic nervous system activity in healthy humans [ ] and in rodents [ , ]. Oxidative stress, increased HIF-1α signaling and decreased HIF-2 signaling as well as endothelin-1 have been proposed as key mechanisms in IH-induced SNS activation [ ].

Increased sympathetic tone strongly impacts lipid and glucose metabolism, through circulating factors as well as neural innervation of the liver, pancreas, skeletal muscle and white adipose tissue [ - ], depicted in Figure 2. Adrenal epinephrine released during sympathetic activation triggers glucose production and impairs insulin secretion, thereby promoting insulin resistance [ ].

Consistently, sympathetic nervous system inhibition by carotid body denervation abolished insulin resistance in a rat model of diet induced obesity [ ] and abolished IH-induced fasting hyperglycemia and HOMA-IR elevation [ ].

Moreover, epinephrine, and to a lesser degree norepinephrine, have been largely studied and acknowledged as crucial mediators of adipose tissue lipolysis [ , ] acting through several β-adrenoceptor subtypes [ , ]. It is therefore tempting to postulate that IH-induced lipolysis and insulin resistance might be mediated through sympathetic nervous system activation.

Finally, sympathetic innervations could be involved in hepatic glucose release [ ] and in muscle insulin resistance [ ]. In human volunteers, a 5 hour IH exposure induces a decrease in insulin sensitivity along with an increase in sympathetic nervous system activity but to date no causal link has been demonstrated [ ].

Even though using α-blockers or inhibiting epinephrine release by adrenal medullectomy improved glucose tolerance [ , ] and phentolamine treatment additionally prevented impairments in insulin secretion induced in mice by IH [ ], the impact of IH on insulin sensitivity seems to be independent of autonomic activity as neither medullectomy, phentolamine treatment or administration of SNS blocking agent hexamethonium improved IH-induced insulin resistance in mice [ , , ].

More studies are therefore needed to clarify the involvement of SNS activation in IH-induced metabolic dysregulation. Apneic episodes, a cornerstone of OSA, are associated with bouts of increased brain activity arousals leading to repetitive partial or full awakenings and thus, sleep fragmentation [ ].

Taking into consideration the multiple detrimental metabolic consequences of intermittent hypoxic exposure, the obvious question with important clinical and therapeutic implications has been asked: does sleep fragmentation per se, without concomitant hypoxemia contribute to the development of metabolic impairments observed in OSA?

Sleep fragmentation represents a situation where total sleep duration is preserved, but continuous sleep and its architecture is interrupted by internal e.

arousals in OSA or external e. auditory stimuli in experiments factors. Experimental studies using sleep fragmentation paradigm showed, that disruption of sleep by auditory and mechanical stimuli for two to three nights decreased insulin sensitivity [ - ], which was not compensated by increased insulin secretion [ ], suggesting that such exposures compromise fundaments of glucose homeostasis and induce impairments typical for pathogenesis of T2DM.

Epidemiological studies support the experimental evidence. Importantly, it was observed that sleep fragmentation exerts a negative impact in subjects with clinically manifested diabetes, as suggested by a community-based study investigating middle-age adults assessing sleep using wrist actigraphy which demonstrated that sleep fragmentation was associated with higher fasting glucose and insulin levels as well as with reduced insulin sensitivity in patients with T2DM, but not in non-diabetics [ 56 ].

Additionally, sleep of patients with T2DM is characterized by higher sleep fragmentation scores detected by wrist actigraphy [ ]. Mechanisms linking sleep fragmentation to altered metabolic control probably include elevated night and morning cortisol levels [ , ] as well as sympathetic activation [ ].

Additionally, sleep fragmentation is independently associated with increased adiposity [ ] and less weight reduction during weight loss program [ ]. Experiments performed in rodent models of acute and prolonged 2 weeks sleep fragmentation confirmed increased adiposity, insulin resistance, hyperglycemia and impaired insulin secretion [ - ].

Additionally, animal demonstrated increased markers of inflammation and oxidative stress in adipose tissue, in parallel to elevated corticosteroid levels [ , ]. Sleep fragmentation in mice also induced changes in visceral adipose tissue transcriptome with modifications in signaling and metabolic pathways including glucose metabolism [ ] and adipocyte differentiation [ ], however it is not known, whether these changes happen also in humans.

Besides endocrine effects, sleep fragmentation seems to also have epigenetic effects demonstrated by insulin resistance and increased body weight of offspring of pregnant dams exposed to sleep fragmentation [ ].

Sleep fragmentation is typically accompanied by a reduction in slow-wave sleep duration, which represents another mechanism for impaired glucose metabolism. It has been proposed that slow-wave sleep is particularly important for metabolic homeostasis as selective suppression of slow-wave sleep SWS , without perturbation of total sleep time, resulted in glucose intolerance, insulin resistance and impaired β-cell function [ ].

Selective SWS suppression but not REM sleep suppression also elevated morning glucose and insulin levels and impaired post-prandial glucose homeostasis in healthy men [ ]. Furthermore, sleep fragmentation impaired satiety perception, impaired insulin and glucagon-like peptide 1 response to meals [ ] and reduced fat oxidation [ ], making subjects prone to adipose tissue accumulation, especially under conditions of reduced satiety perception [ ].

The importance of SWS in glucose homeostasis is further supported by cross-sectional studies documenting that SWS duration is strongly predicting glucose-induced insulin secretion in obese individuals [ 43 ] as well as by studies reporting shorter SWS in T2DM compared to nondiabetic subjects [ 58 ].

Importantly, duration of SWS was negatively associated with HbA1c levels also in T1DM patients [ ], suggesting a global position of SWS in the regulation of glucose metabolism, independently of obesity or pathogenesis of T2DM.

In contrast, REM sleep duration seems to be more related to energy homeostasis, as reduction in REM sleep is associated with obesity in children and adults [ - ], which could be at least partly explained by increased metabolic rate during REM sleep, which is lost with REM time reduction [ ].

In this review, we summarized the current knowledge of molecular and endocrine mechanisms underlying independent and possibly causal associations between short sleep, circadian rhythm disruption as observed with shift working and OSA with glucose intolerance, insulin resistance, impaired insulin secretion and ultimately T2DM.

Based on the literature, it can be concluded that hypothalamic-pituitary-adrenal axis activation with increased circulating cortisol levels, misalignment between central and peripheral pacemakers, enhanced lipolysis and modified adipokine release in adipose tissue and intermittent hypoxia-induced sympathetic nervous system activation, generation of reactive oxygen species and the induction of a whole-body pro-inflammatory state are the most likely mediators.

Several of these mechanisms represent potential drug targets, however future research is warranted to determine, whether targeting the above mentioned molecular regulations would provide metabolic benefit in patients with inappropriate sleep.

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Do differences in sleep architecture exist between persons with type 2 diabetes and nondiabetic controls?

J Diabetes Sci Technol. Nakanishi-Minami T, Kishida K, Funahashi T, Shimomura I. Sleep-wake cycle irregularities in type 2 diabetics. Diabetol Metab Syndr. Ayas NT, White DP, Al-Delaimy WK, Manson JE, Stampfer MJ, Speizer FE, et al.

A prospective study of self-reported sleep duration and incident diabetes in women. Nilsson PM, Roost M, Engstrom G, Hedblad B, Berglund G. Incidence of diabetes in middle-aged men is related to sleep disturbances. Bjorkelund C, Bondyr-Carlsson D, Lapidus L, Lissner L, Mansson J, Skoog I, et al.

Sleep disturbances in midlife unrelated to year diabetes incidence: the prospective population study of women in Gothenburg. Mallon L, Broman JE, Hetta J. High incidence of diabetes in men with sleep complaints or short sleep duration: a year follow-up study of a middle-aged population.

Yaggi HK, Araujo AB, McKinlay JB. Sleep duration as a risk factor for the development of type 2 diabetes. Gangwisch JE, Heymsfield SB, Boden-Albala B, Buijs RM, Kreier F, Pickering TG, et al. Sleep duration as a risk factor for diabetes incidence in a large U. Beihl DA, Liese AD, Haffner SM.

Sleep duration as a risk factor for incident type 2 diabetes in a multiethnic cohort. Ann Epidemiol. Hayashino Y, Fukuhara S, Suzukamo Y, Okamura T, Tanaka T, Ueshima H.

Relation between sleep quality and quantity, quality of life, and risk of developing diabetes in healthy workers in Japan: the High-risk and Population Strategy for Occupational Health Promotion HIPOP-OHP Study.

BMC Public Health. Kawakami N, Takatsuka N, Shimizu H. Sleep disturbance and onset of type 2 diabetes. Meisinger C, Heier M, Loewel H. Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population.

Kita T, Yoshioka E, Satoh H, Saijo Y, Kawaharada M, Okada E, et al. Short sleep duration and poor sleep quality increase the risk of diabetes in Japanese workers with no family history of diabetes. von RA, Weikert C, Fietze I, Boeing H.

Association of sleep duration with chronic diseases in the European Prospective Investigation into Cancer and Nutrition EPIC -Potsdam study. Holliday EG, Magee CA, Kritharides L, Banks E, Attia J.

Short sleep duration is associated with risk of future diabetes but not cardiovascular disease: a prospective study and meta-analysis.

Gonzalez-Ortiz M, Martinez-Abundis E, Balcazar-Munoz BR, Pascoe-Gonzalez S. Accessed November 17, Real-World Data Reveal Inconsistency in Sleep Duration. Evidence Linking Sleep to Improved Lower Back Pain Outcomes Is Weak, More Studies Needed. A systematic review of randomized controlled trials and prospective cohort studies concludes that sleep could be a prognostic component of lower back pain, but better evidence is needed.

Meta-Analysis Investigates Individual Components of CBT for Insomnia. A meta-analysis explored the individual components of cognitive behavioral therapy for insomnia CBT-I and suggested that cognitive restructuring, stimulus control and sleep restrictions provide the more benefits to patients.

Insomnia in Patients Undergoing Dialysis Not Impacted by CBT nor Pharmacotherapy. Insomnia in patients undergoing hemodialysis was not found to be significantly affected by cognitive behavioral therapy for insomnia CBT-I or pharmacotherapy. Circadian Rhythm, Sleep May Influence Risk of Anorexia Nervosa, Study Finds.

A genetic association study evaluated the relationship between anorexia nervosa and various sleep traits, indicating potential avenues for future research on the link between circadian rhythms and eating disorders.

Top 5 Most-Read Sleep Content of The top 5 most-read articles on sleep published on AJMC. com this year include content focusing on narcolepsy management, approval of medication to treat insomnia, and the association of metabolic syndrome with sleep duration.

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