Year : 2021 | Volume
: 10 | Issue : 17 | Page : 1--6
Diabetes and sleep
RS Reng, GA Onwuegbuzie
Department of Medicine, University of Abuja Teaching Hospital, Abuja, Nigeria
Dr. G A Onwuegbuzie
Department of Medicine, University of Abuja Teaching Hospital, Abuja
Sleep has often been thought of as a “restorative” process for the mind and the body; however, it has been shown that it also directly affects many metabolic and hormonal processes. Sleep which is a key factor in physiological restitution also modulates the metabolic, endocrine, and cardiovascular systems and thus has medical implications which include decreased glucose tolerance and insulin sensitivity. Reduction in the time available for sleep is a hallmark of modern society which has developed during the past few decades with increase in the time available for work and leisure, often viewed as harmless and efficient. In normal, healthy individuals, glucose tolerance varies across the day, with total sleep loss or even a 2-h reduction of sleep/night for 1 week there is increased levels of proinflammatory cytokines and low grade inflammation, a condition known to predispose to insulin resistance and diabetes. Sleep deprivation is associated with disturbances in the secretion of the counter regulatory hormones such as growth hormone and cortisol. Elevated evening cortisol levels can lead to morning insulin resistance, while the sympathetic nervous system inhibits insulin release while the parasympathetic system stimulates it, thus leading to elevated glucose levels. Adults are sleeping less and less in our society. Yet sleep is no longer thought of as strictly a restorative process for the body. The importance of sleep for metabolic function and specifically glucose homeostasis is now widely accepted, as many studies have shown a correlation between sleep deprivation or poor sleep quality and an increased risk of diabetes.
|How to cite this article:|
Reng R S, Onwuegbuzie G A. Diabetes and sleep.N Niger J Clin Res 2021;10:1-6
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Reng R S, Onwuegbuzie G A. Diabetes and sleep. N Niger J Clin Res [serial online] 2021 [cited 2023 Feb 8 ];10:1-6
Available from: https://www.mdcan-uath.org/text.asp?2021/10/17/1/314599
Sleep is a complex behavioral state that occupies one-third of the human life span. Although viewed as a passive condition, sleep is a highly active and dynamic process. Until recently, it was believed that sleep was important primarily for restoring brain functions. However, there is increasing evidence that sleep also modulates the metabolic, endocrine, and cardiovascular systems, thus, key factor in physiological restitution, with far-reaching medical implications.
Therefore, although the primary function of sleep may be cerebral restoration, sleep deprivation also has consequences for peripheral function, that, if maintained chronically, could have an impact on carbohydrate metabolism and endocrine function, including decreased glucose tolerance and insulin sensitivity.
Sleep is a state of mental and physical inactivity from which the subject can be roused. It is a normal variation though a state of altered consciousness. Sleep is a physiological state occurring in alternation with wakefulness, and its duration and quality are equally important for the quality of life. Our sleeping patterns have a direct influence on our waking behavior and our daytime activities influence our sleep. Sleep plays a not only fundamental role in the recovery process of fatigue but other functions can be dependent of it as well.
In human, sleep is basically made up of five stages, rapid-eye-movement (REM) sleep and stages 1, 2, 3, and 4 of non-REM (NREM) sleep. The most “restorative” part of sleep is the deeper stages of NREM sleep, i.e., stages 3 and 4, also known as slow-wave sleep (SWS).
Sleep has often been thought of as a “restorative” process for the mind and the body; however, it has been shown that it also directly affects many metabolic and hormonal processes. The initiation of the restorative part of sleep is associated with transient metabolic, hormonal, and neurophysiologic changes, which includes decreased brain glucose utilization, stimulation of growth hormone (GH) release, inhibition of corticotropic activity, decreased sympathetic nervous activity, and increased vagal tone all of which play a role in glucose homeostasis. As a result, in the first part of the night, when SWS predominates, glucose metabolism is slower. These effects are reversed in the second part of the night, when REM sleep, stage 1, and awakening are more likely.
Reduction in the time available for sleep is a hallmark of modern society, with increase in the time available for work and leisure, often viewed as harmless and efficient. In our modern 24-h-a-day society, people work during the night and sleep during the day or work during both night and day for economic gains, a schedule that generally results in substantial sleep loss. On the average adults sleep seven to 9 h per night. The decline of SWS amount can start at the age of 40 years. After the age of 60 years, NREM stages 1, and 2 and REM episodes constitute the majority of sleep content and waking episodes are frequent throughout the night, even if they are not lasting too long. The change in easiness to fall asleep and the increased frequency of nocturnal awakenings are clear indicators of the aging process affecting sleep structure. This therefore raises a pertinent question of whether age-related changes in sleep quality contribute to the development of these metabolic alterations. These effects are similar to those seen in normal aging and therefore, it would not be unreasonable to raise the hypothesis that sleep deprivation increases the severity of age-related chronic disorders such as type 2 diabetes. Sleep loss can occur as a result of poor sleep hygiene or due to the presence of a disease process that is associated with reduced total sleep time.
In the Nurses' Health Study including 69,852 US female nurses aged 40–65 years, it was found that 1957 women were diagnosed with type 2 diabetes during a 10-year follow-up period.
In another population-based Swedish study, 2668 men aged 30–69 years were followed up from 1984 to 1994. In that study, 5.4% of the snorers developed diabetes in comparison with only 2.4% of the nonsnorers.
Habitual snoring and sleep apnea, both parts of a spectrum of sleep-related breathing disorders, are associated with abnormal fasting glucose and insulin resistance., However, there is an emerging body of literature showing that sleep itself, independent of snoring and sleep apnea, is important in glucose and insulin regulation.,
Diabetes and obesity are not fully explained by changes in traditional lifestyle factors such as diet and physical activity alone. Reduction in sleep time and behavior that seems to have developed during the past few decades has become highly prevalent.
Mechanisms of Action Linking Sleep and Risk of Diabetes
Glucose regulation and sleep loss
The human body regulates blood levels of glucose within a narrow range. Glucose tolerance refers to the ability to maintain euglycemia by disposing of exogenous glucose through insulin-mediated and noninsulin-mediated mechanisms. Normal glucose tolerance depends on the ability of the pancreatic beta cells to produce insulin and also the balance between glucose production by the liver and glucose utilization by insulin-dependent tissues, such as muscle and fat, and noninsulin-dependent tissues, such as the brain. Thus, glucose tolerance is critically dependent on the ability of pancreatic beta cells to release insulin both acutely (i.e., acute insulin response to glucose or beta cell responsiveness) and in a sustained fashion and on the ability of insulin to inhibit glucose production by the liver and promote glucose utilization by peripheral tissues (i.e., insulin sensitivity). As insulin sensitivity declines, insulin secretion increases to maintain normal glucose levels. Reduced insulin sensitivity, or insulin resistance, occurs when higher amounts of insulin are needed to reduce blood glucose levels following the administration of the same amount of exogenous glucose. Diabetes becomes manifest when the pancreatic beta cells fail to compensate for the decreased insulin sensitivity. Glucose tolerance varies in a circadian rhythm, including during the different stages of sleep. Blood levels of glucose are tightly regulated within in a narrow range to avoid hypoglycemia and hyperglycemia as both conditions have adverse life-threatening consequences.
In normal healthy individuals, glucose tolerance varies across the day such that plasma glucose responses to exogenous glucose are markedly higher in the evening than in the morning, and glucose tolerance is at its minimum in the middle of the night. The reduced glucose tolerance in the evening is at least partly due to a reduction in insulin sensitivity concomitant with a reduction in the insulin secretory response to elevate glucose levels. The further decrease in glucose tolerance during the night is dependent on the occurrence of sleep. Overall glucose utilization is greatest during wake and lowest during NREM (Stages 2, 3, and 4) sleep with intermediate levels during REM sleep.
In the first half of the night, glucose metabolism is slower, partly because of the predominance of SWS that is associated with a marked reduction in cerebral glucose uptake,, and may be also because of a reduction in peripheral glucose utilization. These effects are reversed during the second half of the night, when light NREM sleep and REM sleep are dominant and awakenings are more likely to occur. These major modulatory effects of sleep on glucose regulation can also be observed when the sleep period occurs during the daytime.
The acute reduction in insulin release could be due to increased sympathetic nervous activity at the level of the pancreatic beta-cell.
Disturbances in the secretory profiles of the counter-regulatory hormones, GH and cortisol, may also contribute to the alterations in glucose regulation observed during sleep loss. Indeed, 6 days of sleep restriction were associated with an extended duration of elevated night time GH concentrations and with an increase in evening cortisol levels.
Acute total sleep loss or even a 2-h reduction of sleep/night for 1 week is associated with increased levels of proinflammatory cytokines and low-grade inflammation, a condition known to predispose to insulin resistance and diabetes.,
Appetite regulation and sleep loss
Appetite is regulated by the interaction between metabolic and hormonal signals and neural mechanisms. Among these peripheral signals are leptin, an appetite-inhibiting hormone, and ghrelin, an appetite stimulating hormone. Leptin is primarily secreted by adipose tissue and appears to promote satiety. Ghrelin is a peptide released primarily from the stomach. In rodents, ghrelin generates a positive energy balance and increased adiposity through increased food intake and reduced fat oxidation. Studies in humans also indicate that ghrelin increases appetite and food intake. Plasma ghrelin levels are rapidly suppressed by food intake and then rebound after 1.5–2 h, paralleling the resurgence in hunger. Thus, leptin and ghrelin exert opposing effects on appetite. Under normal conditions, the 24-h profile of human plasma leptin levels shows a marked nocturnal rise, which is partly dependent on meal intake. The 24-h profile of ghrelin levels also shows a nocturnal rise, which may partly reflect the postdinner rebound. However, ghrelin levels spontaneously decrease in the second half of the sleep period, despite the maintenance of the fasting condition.
The identification in the lateral hypothalamus and perifornical area of a population of neurons that express two excitatory neuropeptides (orexin A and orexin B, also referred to as hypocretin A and hypocretin B) derived from the same precursor (pre-pro-orexin) that have potent wake promoting effects and stimulate food intake, has provided a molecular basis for the interactions between feeding and sleeping., Orexinergic activity is in turn influenced by both central and peripheral signals, with glucose and leptin exerting inhibitory effects while ghrelin promotes further activation. not needed to fulfill a caloric need) related to emotional and psychosocial factors in humans. Consistent with this hypothesis, epidemiological data show an association between short sleep duration and irregular eating habits, snacking between meals, excessive food seasoning, and reduced consumption of vegetables., Sleep loss could also affect energy expenditure through its impact on the levels of leptin and ghrelin. Indeed, in rodent models, there is good evidence to indicate that leptin and ghrelin have opposite effects on energy expenditure. Leptin appears to increase energy expenditure, possibly through increased thermogenesis in brown adipose tissue, while central ghrelin administration has been reported to decrease locomotor activity in rats. Since several human studies have demonstrated reduced levels of leptin after sleep loss,,, it is possible that the reduction in leptin is associated with a reduction in energy expenditure.
Impact of sleep loss
The major ways by which sleep affects the release of hormones are the autonomic nervous system and hypothalamic-pituitary axis. The sympathetic nervous system activity is generally decreased during deep sleep and that of the parasympathetic nervous system increased, hence sleep loss deprivation will result in an elevation of sympathovagal balance, with higher sympathetic but lower parasympathetic tone. Sleep influences the release of hormones by the pituitary that controls the secretion of other hormones from the peripheral endocrine glands. During sleep, these hypothalamic factors may be activated-as in the case of GH-releasing hormone-or inhibited, as is the case for corticotropin-releasing hormone.
Metabolic effect and sleep loss
Recent work also indicates that sleep loss may adversely affect glucose tolerance and involve an increased risk of type 2 diabetes. In young, healthy controls who were studied after 6 days of sleep restriction (4 h in bed) and after full sleep recovery, the levels of blood glucose after breakfast were higher in the state of sleep debt despite normal or even slightly elevated insulin responses. Indeed, the rate of disappearance of glucose post injection – a quantitative measure of glucose tolerance – was nearly 40% slower in the sleep-debt condition than after recovery, and the acute insulin response to glucose was reduced by 30%. Thus, <1 week of sleep restriction can result in a prediabetic state in young, healthy controls.
Sleep deprivation is associated with disturbances in the secretion of the counter regulatory hormones such as GH and cortisol. Young, healthy volunteers who were allowed to sleep only 4 h per night for 6 nights showed a change in their patterns of GH release, from a normal single pulse to a biphasic pattern. They were exposed to a higher overall amount of GH in the sleep-deprived condition, which could contribute to higher glucose levels. Furthermore, evening cortisol levels were significantly higher in young, healthy men who were allowed to sleep only 4 h per night for 6 nights, as well as in young, healthy women who were allowed to sleep only 3 h for 1 night. A cross-sectional analysis that included 2,751 men and women also demonstrated that short sleep duration and sleep disturbances are independently associated with more cortisol secretion in the evening. Elevated evening cortisol levels can lead to morning insulin resistance.
Patients who have been sleep-deprived have been shown to have higher sympathetic nervous system activity, lower parasympathetic activity, or both., The sympathetic nervous system inhibits insulin release while the parasympathetic system stimulates it, so these changes both increase glucose levels. Sympathetic hyperactivity can alter glucose homeostasis and induce insulin resistance by increasing glycogen breakdown and gluconeogenesis. Moreover, over activity of the sympathetic nervous system results in insulin resistance. Obesity is a well-established risk factor for type 2 diabetes mellitus, and studies have shown that sleep loss may increase the risk of becoming overweight or obese,, which would ultimately increase the risk of type 2 diabetes. A primary mechanism linking sleep deprivation and weight gain is likely to be hyperactivity of the orexin system. Orexigenic neurons play a central role in wakefulness and also promote feeding, thus the orexin system is overactive during sleep deprivation,,, and this could be in part mediated by the increase in sympathetic activity. Increased sympathetic activity also affects the levels of peripheral appetite hormones, inhibiting leptin release, and stimulating ghrelin release. Lower leptin levels and higher ghrelin levels act in concert to further activate orexin neurons,, resulting in increased food intake. Sleeping and feeding are intricately related. Sleep loss is associated with an up regulation of appetite, more time to eat and a decrease in energy expenditure that is excessive in relation to the caloric demands of extended wakefulness. The regulation of leptin, a hormone released by the fat cells that signals satiety to the brain and thus suppresses appetite, is markedly dependent on sleep duration. A study had shown that after bedtime restriction to 4 h per night, the plasma concentration of leptin was markedly decreased, particularly during the night time.
In another study, sleep restriction was associated with reductions in leptin (the appetite suppressant) and elevations in ghrelin (the appetite stimulant) and increased hunger and appetite, especially an appetite for foods with high-carbohydrate contents. Sleep loss and its associated sleepiness and fatigue may result in reduced energy expenditure, partly due to less exercise but also due to less nonexercise activity thermogenesis. This have been shown to increase the risk of obesity and sleep-disordered breathing (SDB), a reported independent risk factor for insulin resistance., Snoring, which is a common symptom of SDB, has also been shown to predict the onset of diabetes in both men and women.,
Studies have shown that chronic shallow non-REM sleep, decreased insulin sensitivity, and thus elevated diabetes risk are typical of aging.,,, Indeed, obesity is a major risk factor for sleep-disordered breathing (SDB), an increasingly common condition characterized by repetitive respiratory disturbances and sleep fragmentation by microarousals resulting in low amounts of SWS and delta power. Even in the absence of SDB, obese individuals have reduced sleep quality with low amounts of SWS., Thus, low SWS may increase the severity of insulin resistance in obesity. A study findings demonstrated that chronic insomnia associated with objectively measured short sleep duration is a clinically significant risk factor for type 2 diabetes. This increased risk is independent of co-morbid conditions frequently associated with insomnia or diabetes, such as age, race, obesity, alcohol consumption, smoking, SDB, periodic limb movements, or depression.
Lack of sleep exerts deleterious effects on a variety of systems with detectable changes in metabolic,, endocrine,, and immune pathways. Short-term, acute, laboratory, and cross-sectional observational studies indicate that disturbed or reduced sleep is associated with glucose intolerance, insulin resistance, reduced acute insulin response to glucose, and a reduction in the disposition index, thus predisposing individuals to type 2 diabetes.
In the past decade, there has been growing evidence that too little sleep can affect hormones and metabolism in ways that promote diabetes. Experts also believe that chronic sleep deprivation may lead to elevated levels of the stress hormone, cortisol. Elevated cortisol may in turn promote insulin resistance, in which the body cannot use the hormone insulin properly to help move glucose into cells for energy. Further, research shows that sleep loss reduces levels of the hormone leptin, an appetite suppressant, while boosting levels of ghrelin, an appetite stimulant. That's a poor combination that may prompt sleep-deprived people to eat more.
In view of these important changes in glucose metabolism during sleep, it is not surprising that getting less sleep or poorer sleep on a regular basis could affect overall glucose homeostasis, which has been collaborated by several studies. Short sleep duration, sleep disturbances, and unsynchronized circadian sleep rhythms are associated with metabolic disorders, markedly, obesity and type 2 diabetes, prompting suggestions that sleep needs to be addressed in a much more structured way than it is currently done in clinical routine. Adults are sleeping less and less in our society. Yet sleep is no longer thought of as strictly a restorative process for the body. The importance of sleep for metabolic function and specifically glucose homeostasis is now widely accepted, as many studies have shown a correlation between sleep deprivation or poor sleep quality and an increased risk of diabetes.
At the same time, people are sleeping less, and sleep disorders are on the rise. The sleep curtailment of our times probably is partly self-imposed, as the pace and the opportunities of modern society place more demands on time for work and leisure activities and leave less time for sleep. Taken together, the current evidence suggests that strategies to improve sleep duration and quality should be considered as a potential intervention to prevent or delay the development of type 2 diabetes in at-risk populations. Adequate sleep and good sleep hygiene should be included among the goals of a healthy lifestyle, especially for patients with diabetes. We urge clinicians to recommend at least 7 h of uninterrupted sleep per night as part of a healthy lifestyle.
Sleep which is a highly active and dynamic process was thought of as been mainly restorative has been shown to modulate the metabolic, endocrine, and cardiovascular systems. With industrialization reduction in the available time for sleep remains the hallmark of modern society and thus has medical implication like decrease in glucose tolerance and insulin sensitivity.
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|1||Trenell MI, Marshall NS, Rogers NL. Sleep and metabolic control: Waking to a problem? Clin Exp Pharmacol Physiol 2007;34:1-9.|
|2||Van Cauter E, Polonsky KS, Scheen AJ. Roles of circadian rhythmicity and sleep in human glucose regulation. Endocr Rev 1997;18:716-38.|
|3||Cappuccio FP, Miller MA, Lockley SW. Sleep, Health and Society: From Aetiology to Public Health. Cary, NC: Oxford University Press; 2010. p. 111-40.|
|4||Spiegel K, Leproult R, Van Cauter E. Impact of sleep debt on metabolic and endocrine function. Lancet 1999;354:1435-9.|
|5||Mokdad AH, Ford ES, Bowman BA, Dietz WH, Vinicor F, Bales VS, et al. Prevalence of obesity, diabetes, and obesity-related health risk factors, J Am Med Assoc 2003;289:76-9.|
|6||Brandle M, Zhou H, Smith BR, Marriott D, Burke R, Tabaei BP, et al. The direct medical cost of type 2 diabetes. Diabetes Care 2003;26:2300-4.|
|7||Young T, Peppard PE, Taheri S. Excessive weight and sleep disordered breathing. J Appl Physiol 2005;99:1592-9.|
|8||Morisson F, Décary A, Petit D, Lavigne G, Malo J, Montplaisir J. Daytime sleepiness and EEG spectral analysis in apneic patients before and after treatment with continuous positive airway pressure. Chest 2001;119:45-52.|
|9||Resta O, Foschino Barbaro MP, Bonfitto P, Giliberti T, Depalo A, Pannacciulli N, et al. Low sleep quality and daytime sleepiness in obese patients without obstructive sleep apnoea syndrome. J Intern Med 2003;253:536-43.|
|10||Vgontzas AN, Tan TL, Bixler EO, Martin LF, Shubert D, Kales A. Sleep apnea and sleep disruption in obese patients. Arch Intern Med 1994;154:1705-11.|
|11||Scheen AJ, Byrne MM, Plat L, Leproult R, Van Cauter E. Relationships between sleep quality and glucose regulation in normal humans. Am J Physiol 1996;271:E261-70.|
|12||Nofzinger EA, Buysse DJ, Miewald JM, Meltzer CC, Price JC, Sembrat RC, et al. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking. Brain 2002;125:1105-15.|
|13||Maquet P. Functional neuroimaging of normal human sleep by positron emission tomography. J Sleep Res 2000;9:207-31.|
|14||Van Cauter E, Blackman JD, Roland D, Spire JP, Refetoff S, Polonsky KS. Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep. J Clin Invest 1991;88:934-42.|
|15||Spiegel K, Leproult R, Colecchia EF, L'Hermite-Balériaux M, Nie Z, Copinschi G, et al. Adaptation of the 24-h growth hormone profile to a state of sleep debt. Am J Physiol Regul Integr Comp Physiol 2000;279:R874-83.|
|16||Vgontzas AN, Papanicolaou DA, Bixler EO, Lotsikas A, Zachman K, Kales A, et al. Circadian interleukin-6 secretion and quantity and depth of sleep. J Clin Endocrinol Metab 1999;84:2603-7.|
|17||Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med 2004;1:e62.|
|18||Gale SM, Castracane VD, Mantzoros CS. Energy homeostasis, obesity and eating disorders: Recent advances in endocrinology. J Nutr 2004;134:295-8.|
|19||van der Lely AJ, Tschöp M, Heiman ML, Ghigo E. Biological, physiological, pathophysiological, and pharmacological aspects of ghrelin. Endocr Rev 2004;25:426-57.|
|20||Schoeller DA, Cella LK, Sinha MK, Caro JF. Entrainment of the diurnal rhythm of plasma leptin to meal timing. J Clin Invest 1997;100:1882-7.|
|21||Dzaja A, Dalal MA, Himmerich H, Uhr M, Pollmächer T, Schuld A. Sleep enhances nocturnal plasma ghrelin levels in healthy subjects. Am J Physiol Endocrinol Metab 2004;286:E963-7.|
|22||Taheri S, Zeitzer JM, Mignot E. The role of hypocretins (orexins) in sleep regulation and narcolepsy. Annu Rev Neurosci 2002;25:283-313.|
|23||Sakurai T. Roles of orexin/hypocretin in regulation of sleep/wakefulness and energy homeostasis. Sleep Med Rev 2005;9:231-41.|
|24||Imaki M, Hatanaka Y, Ogawa Y, Yoshida Y, Tanada S. An epidemiological study on relationship between the hours of sleep and life style factors in Japanese factory workers. J Physiol Anthropol Appl Human Sci 2002;21:115-20.|
|25||Ohida T, Kamal AM, Uchiyama M, Kim K, Takemura S, Sone T, et al. The influence of lifestyle and health status factors on sleep loss among the Japanese general population. Sleep 2001;24:333-8.|
|26||Scarpace PJ, Matheny M, Pollock BH, Tümer N. Leptin increases uncoupling protein expression and energy expenditure. Am J Physiol 1997;273:E226-30.|
|27||Tang-Christensen M, Vrang N, Ortmann S, Bidlingmaier M, Horvath TL, Tschöp M. Central administration of ghrelin and agouti-related protein (83-132) increases food intake and decreases spontaneous locomotor activity in rats. Endocrinology 2004;145:4645-52.|
|28||Spiegel K, Leproult R, L'hermite-Balériaux M, Copinschi G, Penev PD, Van Cauter E. Leptin levels are dependent on sleep duration: Relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab 2004;89:5762-71.|
|29||Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: Sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med 2004;141:846-50.|
|30||Omisade A, Buxton OM, Rusak B. Impact of acute sleep restriction on cortisol and leptin levels in young women. Physiol Behav 2010;99:651-6.|
|31||Kumari M, Badrick E, Ferrie J, Perski A, Marmot M, Chandola T. Self-reported sleep duration and sleep disturbance are independently associated with cortisol secretion in the Whitehall II study. J Clin Endocrinol Metab 2009;94:4801-9.|
|32||Teff KL. Visceral nerves: Vagal and sympathetic innervation. JPEN J Parenter Enteral Nutr 2008;32:569-71.|
|33||Esler M, Rumantir M, Wiesner G, Kaye D, Hastings J, Lambert G. Sympathetic nervous system and insulin resistance: From obesity to diabetes. Am J Hypertens 2001;14:304S-309S.|
|34||Pannain S, Van Cauter E. Sleep loss, obesity and diabetes: Prevalence, association and emerging evidence for causation. Obesity Metab 2008;4:28-41.|
|35||Cappuccio FP, Miller MA, Lockley SW, Cappuccio F, Miller MA. The epidemiology of sleep and cardiovascular risk and disease. In: Cappuccio FP, Miller MA, Lockley SW, editors. Sleep, Health and Society: From Aetiology to Public Health. Cary, NC: Oxford University Press; 2010. p. 111-40.|
|36||Wu MF, John J, Maidment N, Lam HA, Siegel JM. Hypocretin release in normal and narcoleptic dogs after food and sleep deprivation, eating, and movement. Am J Physiol Regul Integr Comp Physiol 2002;283:R1079-86.|
|37||Estabrooke IV, McCarthy MT, Ko E, Chou TC, Chemelli RM, Yanagisawa M, et al. Fos expression in orexin neurons varies with behavioral state. J Neurosci 2001;21:1656-62.|
|38||Zeitzer JM, Buckmaster CL, Lyons DM, Mignot E. Increasing length of wakefulness and modulation of hypocretin-1 in the wake-consolidated squirrel monkey. Am J Physiol Regul Integr Comp Physiol 2007;293:R1736-42.|
|39||Rayner DV, Trayhurn P. Regulation of leptin production: Sympathetic nervous system interactions. J Mol Med (Berl) 2001;79:8-20.|
|40||Samson WK, Taylor MM, Ferguson AV. Non-sleep effects of hypocretin/orexin. Sleep Med Rev 2005;9:243-52.|
|41||Willie JT, Chemelli RM, Sinton CM, Yanagisawa M. To eat or to sleep? Orexin in the regulation of feeding and wakefulness. Annu Rev Neurosci 2001;24:429-58.|
|42||Ip MS, Lam B, Ng MM, Lam WK, Tsang KW, Lam KS. Obstructive sleep apnea is independently associated with insulin resistance. Am J Respir Crit Care Med 2002;165:670-6.|
|43||Punjabi NM, Shahar E, Redline S, Gottlieb DJ, Givelber R, Resnick HE. Sleep Heart Health Study Investigators. Sleep-disordered breathing, glucose intolerance, and insulin resistance: The Sleep Heart Health Study. Am J Epidemiol 2004;160:521-30.|
|44||Al-Delaimy WK, Manson JE, Willett WC, Stampfer MJ, Hu FB. Snoring as a risk factor for type II diabetes mellitus: A prospective study. Am J Epidemiol 2002;155:387-93.|
|45||Van Cauter E, Leproult R, Plat L. Age-related changes in slow wave sleep and REM sleep and relationship with growth hormone and cortisol levels in healthy men. JAMA 2000;284:861-8.|
|46||Carrier J, Land S, Buysse DJ, Kupfer DJ, Monk TH. The effects of age and gender on sleep EEG power spectral density in the middle years of life (ages 20-60 years old). Psychophysiology 2001;38:232-42.|
|47||Vgontzas AN, Liao D, Pejovic S, Calhoun S, Karataraki M, Bixler EO. Insomnia with objective short sleep duration is associated with type 2 diabetes: A population-based study. Diabetes Care 2009;32:1980-5.|
|48||Knutson KL, Spiegel K, Penev P, Van Cauter E. The metabolic consequences of sleep deprivation. Sleep Med Rev 2007;11:163-78.|
|49||Spiegel K, Tasali E, Leproult R, Van Cauter E. Effects of poor and short sleep on glucose metabolism and obesity risk. Nat Rev Endocrinol 2009;5:253-61.|
|50||Miller MA, Cappuccio FP. Inflammation, sleep, obesity and cardiovascular disease. Curr Vasc Pharmacol 2007;5:93-102.|