CLINICAL REVIEW
The metabolic consequences of sleep deprivation

https://doi.org/10.1016/j.smrv.2007.01.002Get rights and content

Summary

The prevalence of diabetes and obesity is increasing at an alarming rate worldwide, and the causes of this pandemic are not fully understood. Chronic sleep curtailment is a behavior that has developed over the past 2–3 decades. Laboratory and epidemiological studies suggest that sleep loss may play a role in the increased prevalence of diabetes and/or obesity. Current data suggest the relationship between sleep restriction, weight gain and diabetes risk may involve at least three pathways: (1) alterations in glucose metabolism; (2) upregulation of appetite; and (3) decreased energy expenditure. The present article reviews the current evidence in support of these three mechanisms that might link short sleep and increased obesity and diabetes risk.

Introduction

The prevalence of obesity and type 2 diabetes is increasing worldwide but particularly in the US.1 Obesity and diabetes are both associated with increased age-adjusted mortality risk as well as a substantial economic burden.2 The causes of this pandemic are not fully explained by changes in traditional lifestyle factors such as diet and physical activity. One behavior that seems to have developed during the past few decades and has become highly prevalent, particularly amongst Americans, is sleep curtailment. In 1960, a survey study conducted by the American Cancer Society found modal sleep duration to be 8.0–8.9 h,3 while in 1995 the modal category of the survey conducted by the National Sleep Foundation poll had dropped to 7 h.4 Recent analyses of national data indicate that a greater percentage of adult Americans report sleeping 6 h or less in 2004 than in 1985.5 Today, more than 30% of adult men and women between the ages of 30 and 64 years report sleeping less than 6 h/night.5 The decrease in average sleep duration in the US has occurred over the same time period as the increase in the prevalence of obesity and diabetes.

The present review examines the existing evidence for a link between short sleep and increased risk of obesity and diabetes and explores putative causal mechanisms. By “short sleep”, we mean sleep durations under 7 h/night. There is substantial evidence in support of an association between long sleep (>8 h) and increased morbidity and mortality,6, 7, 8 but the mechanisms linking long sleep and poor health are likely to be distinct from those mediating the adverse effects of short sleep.

Figure 1 provides a schematic representation of the three major pathways that could mediate an adverse effect of sleep loss on the risk of obesity and diabetes. Obesity is in itself a major risk factor for type 2 diabetes but recent data indicate that short sleep may impair glucose metabolism and increase the risk of diabetes independently of changes in body mass index (BMI). Sleep restriction may affect energy balance and result in weight gain because of an upregulation of appetite, more time to eat and a decrease in energy expenditure. Significant weight gain may in turn result in insulin resistance, a condition that increases the risk of developing diabetes and may promote further adiposity. This cascade of negative events is likely to be accelerated in many overweight and obese individuals by sleep-disordered breathing (SDB), a reported independent risk factor for insulin resistance.9, 10 The present article will only focus on sleep loss resulting from behavioral sleep restriction rather than from the presence of a sleep disorder.

We will first review the experimental and epidemiologic evidence for an association between short sleep, alterations in glucose metabolism and increased diabetes risk. As a cautionary note, translating the effects of experimental sleep restriction in the laboratory to the real world is not straightforward. Furthermore, laboratory studies of sleep restriction cannot be conducted for periods of time extending beyond 1–2 weeks. Epidemiologic studies that involve population-based samples often do not provide evidence for causal direction. In many such studies, the effects of sleep loss cannot be distinguished from effects of sleep disturbances. A presentation of the evidence linking short sleep, upregulation of appetite and increased BMI will follow. Finally, we will address the possibility that individuals exposed to insufficient sleep and the resulting sleepiness and fatigue may also have lower levels of energy expenditure than well-rested adults, particularly in an environment that promotes physical inactivity.

Section snippets

Normal physiology

Blood levels of glucose are tightly regulated within a narrow range to avoid hypoglycemia and hyperglycemia as both conditions have adverse life threatening consequences. Glucose tolerance refers to the ability to metabolize exogenous glucose and return to baseline normoglycemia. In clinical settings, glucose tolerance is assessed by the oral glucose tolerance test, which consists of ingesting a glucose solution and measuring glucose levels at frequent intervals during the next 2 h. Glucose

Normal conditions

Appetite is regulated by the interaction between metabolic and hormonal signals and neural mechanisms. The arcuate nucleus of the hypothalamus has two opposing sets of neuronal circuitry, appetite simulating and appetite-inhibiting, and several peripheral hormonal signals have been identified that affect these neuronal regions.42 Among these peripheral signals are leptin, an appetite-inhibiting hormone, and ghrelin, an appetite stimulating hormone. Leptin is primarily secreted by adipose tissue

Sleep loss and energy expenditure

Energy expenditure plays an important role in the control of body weight and adiposity. The total amount of daily energy expenditure (TEE) is divided into three components: (a) resting metabolic rate under basal conditions (RMR), which is measured as the energy expenditure of an individual resting in bed in the morning after sleep in the fasting state; RMR represents approximately 60% of TEE in people with sedentary occupations; (b) thermic effect of meals (TEM), which is the energy expenditure

Conclusion

The research reviewed here suggests that chronic partial sleep loss may increase the risk of obesity and diabetes via multiple pathways, including an adverse effect on parameters of glucose regulation, including insulin resistance and a dysregulation of the neuroendocrine control of appetite leading to excessive food intake and decreased energy expenditure. Epidemiological studies have generally supported the laboratory findings. As the causes of the dramatic increase in the prevalence of

Acknowledgements

Research was supported by the following grants: P01 AG-11412, R01 HL-075079, RO1 HL-72694, University of Chicago Diabetes Research and Training Grant (NIH P60 DK-20595), and from The University of Chicago General Clinical Research Center (NIH MO1-RR-00055).

References (100)

  • K.L. Knutson

    Sex differences in the association between sleep and body mass index in adolescents

    J Pediatr

    (2005)
  • R. Rising et al.

    Determinants of total daily energy expenditure: variability in physical activity

    Am J Clin Nutr

    (1994)
  • M.S. Westerterp-Plantenga et al.

    Effects of weekly administration of pegylated recombinant human OB protein on appetite profile and energy metabolism in obese men

    Am J Clin Nutr

    (2001)
  • C.J. Hukshorn et al.

    Pegylated human recombinant leptin (PEG-OB) causes additional weight loss in severely energy-restricted, overweight men

    Am J Clin Nutr

    (2003)
  • A. Mokdad et al.

    The continuing epidemics of obesity and diabetes in the United States

    JAMA

    (2001)
  • L. Ettaro et al.

    Cost-of-illness studies in diabetes mellitus

    Pharmacoeconomics

    (2004)
  • D. Kripke et al.

    Short and long sleep and sleeping pills. Is increased mortality associated?

    Arch Gen Psychiatry

    (1979)
  • Gallup Organization, editors. Gallup organization. Sleep in America,...
  • QuickStats: Percentage of adults who reported an average of ⩽6 h of sleep per 24-hour period, by sex and age group—United States, 1985 and 2004

    Morb Mortal Wkly Rep

    (2005)
  • D.F. Kripke et al.

    Mortality associated with sleep duration and insomnia

    Arch Gen Psychiatry

    (2002)
  • N.T. Ayas et al.

    A prospective study of self-reported sleep duration and incident diabetes in women

    Diabetes Care

    (2003)
  • N.T. Ayas et al.

    A prospective study of sleep duration and coronary heart disease in women

    Arch Intern Med

    (2003)
  • M.S. Ip et al.

    Obstructive sleep apnea is independently associated with insulin resistance

    Am J Respir Crit Care Med

    (2002)
  • N.M. Punjabi et al.

    Sleep-disordered breathing, glucose intolerance, and insulin resistance: the Sleep Heart Health Study

    Am J Epidemiol

    (2004)
  • E. Van Cauter et al.

    Roles of circadian rhythmicity and sleep in human glucose regulation

    Endocr Rev

    (1997)
  • A.J. Scheen et al.

    Relationships between sleep quality and glucose regulation in normal humans

    Am J Physiol

    (1996)
  • E.A. Nofzinger et al.

    Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking

    Brain

    (2002)
  • P. Maquet

    Functional neuroimaging of normal human sleep by positron emission tomography

    J Sleep Res

    (2000)
  • E. Van Cauter et al.

    Modulation of glucose regulation and insulin secretion by circadian rhythmicity and sleep

    J Clin Invest

    (1991)
  • K. Spiegel et al.

    Metabolic and Endocrine Changes

  • K. Spiegel et al.

    Adaptation of the 24-h growth hormone profile to a state of sleep debt

    Am J Physiol

    (2000)
  • J.S. Allan et al.

    Persistence of the circadian thyrotropin rhythm under constant conditions and after light-induced shifts of circadian phase

    J Clin Endocrinol Metab

    (1994)
  • E. Van Cauter et al.

    Demonstration of rapid light-induced advances and delays of the human circadian clock using hormonal phase markers

    Am J Physiol

    (1994)
  • R.N. Bergman

    Minimal model: perspective from 2005

    Horm Res

    (2005)
  • N.D. Palmer et al.

    Genetic mapping of disposition index and acute insulin response loci on chromosome 11q. The Insulin Resistance Atherosclerosis Study (IRAS) Family Study

    Diabetes

    (2006)
  • R.N. Bergman et al.

    Accurate assessment of beta-cell function: the hyperbolic correction

    Diabetes

    (2002)
  • A.H. Xiang et al.

    Effect of pioglitazone on pancreatic beta-cell function and diabetes risk in Hispanic women with prior gestational diabetes

    Diabetes

    (2006)
  • G. Garcia et al.

    Glucose metabolism in older adults: a study including subjects more than 80 years of age

    J Am Geriatr Soc

    (1997)
  • K. Spiegel et al.

    Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes

    J Appl Physiol

    (2005)
  • K. Spiegel et al.

    Leptin levels are dependent on sleep duration: Relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin

    J Clin Endocrinol Metab

    (2004)
  • T. VanHelder et al.

    Effects of sleep deprivation and exercise on glucose tolerance

    Aviat Space Environ Med

    (1993)
  • M. Thomas et al.

    Neural basis of alertness and cognitive performance impairments during sleepiness. I. Effects of 24 h of sleep deprivation on waking human regional brain activity

    J Sleep Res

    (2000)
  • A.N. Vgontzas et al.

    Circadian interleukin-6 secretion and quantity and depth of sleep

    J Clin Endocrinol Metab

    (1999)
  • A.N. Vgontzas et al.

    Adverse effects of modest sleep restriction on sleepiness, performance, and inflammatory cytokines

    J Clin Endocrin Metabol

    (2004)
  • K.L. Knutson et al.

    Role of sleep duration and quality in the risk and severity of type 2 diabetes mellitus

    Arch Intern Med

    (2006)
  • N. Kawakami et al.

    Sleep disturbance and onset of type 2 diabetes

    Diabetes Care

    (2004)
  • P.M. Nilsson et al.

    Incidence of diabetes in middle-aged men is related to sleep disturbances

    Diabetes Care

    (2004)
  • L. Mallon et al.

    High incidence of diabetes in men with sleep complaints or short sleep duration: a 12-year follow-up study of a middle-aged population

    Diabetes Care

    (2005)
  • C. Bjorkelund et al.

    Sleep disturbances in midlife unrelated to 32-year diabetes incidence: the prospective population study of women in Gothenburg

    Diabetes Care

    (2005)
  • C. Meisinger et al.

    Sleep disturbance as a predictor of type 2 diabetes mellitus in men and women from the general population

    Diabetologia

    (2005)
  • Cited by (998)

    • Blood pressure monitoring with piezoelectric bed sensor systems

      2024, Biomedical Signal Processing and Control
    View all citing articles on Scopus
    *

    The most important references are denoted by an asterisk.

    View full text