The Journal of Pediatrics
Volume 150, Issue 4 , Pages 331-332, April 2007

The Systemic Effects of Short Sleep Period

  • Joseph Crisalli, MD
    • ,
  • Raouf S. Amin, MD

      Affiliations

    • Corresponding Author InformationReprint requests: Dr. Raouf S. Amin, Pulmonary Medicine, OSB- 5, MLC 7029, Children’s Hospital Medical Center, Cincinnati, OH.

Cincinnati Children’s Hospital Medical Center, Cincinnati, OH

Article Outline

Abbreviations: CRP, C-reactive protein, HOMA-IR, Homeostasis Model Assessment of Insulin Resistance, SDB, Sleep-disordered breathing

 

The prevalence of obesity in children continues to increase at an alarming rate. In 2004, 17% of children in the United States were obese, an increase of more than 20% in 6 years.1 Parallel to this trend in obesity, the prevalence of impaired glucose tolerance and type 2 diabetes mellitus in children has increased dramatically. One study found that more than 20% of obese children referred to a weight management program had impaired glucose tolerance, and 4% of the obese adolescents had type 2 diabetes mellitus.2 There is substantial evidence linking obesity to an increased risk of insulin resistance.3 Insulin resistance is predictive of the development of type 2 diabetes mellitus4 and is central to the development of the metabolic syndrome.5 Thus, prevention of obesity and insulin resistance in children is of great public health importance.

See related article, p 364

A key to effective prevention strategies is identifying risk factors for disease. Along these lines, attention has been directed toward gaining more insight into the possible role of sleep disorders in the development of obesity, insulin resistance, and other risk factors for cardiovascular disease in children.

In the current issue of The Journal, Flint et al6 report on an investigation into the relationships among nocturnal sleep duration, sleep-disordered breathing (SDB), and markers of insulin resistance in a cohort of 40 obese children evaluated for sleep-related complaints. Children receiving less than 6 hours of sleep on overnight polysomnography demonstrated increased insulin resistance as measured by the Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) compared with those receiving more than 6 hours of sleep. There was no difference in mean body mass index between the 2 groups. Similarly, children with SDB had significantly higher HOMA-IR values than those without SDB, indicating a greater degree of insulin resistance. In multiple linear regression analysis, increasing age and decreasing percentage of rapid eye movement sleep were associated with a higher index of HOMA-IR. The severity of SDB, as measured by the apnea-hypopnea index, was not predictive of HOMA-IR. Notably, increased—not decreased—sleep duration was associated with a greater degree of insulin resistance in the regression model.

A strong association has been demonstrated between short sleep period and obesity in children. In a large cross-sectional study of 6- to 7-year-old Japanese children, Sekine et al7 found a dose-response relationship between short sleep period and obesity. After adjusting for physical activity and television watching, children receiving less than 8 hours of sleep per night were almost 3 times as likely to be obese than children receiving 10 or more hours of sleep per night.7 Multiple studies of pediatric cohorts have replicated these findings.8, 9

The relationships among sleep period, glucose metabolism, and insulin resistance have been studied primarily in adults. In an experimental study of healthy adult subjects, Spiegel et al10 found that restriction to 4 hours of sleep for 6 consecutive nights was associated with impaired glucose tolerance. Normalization of the sleep period resulted in resolution of glucose intolerance. Gonzalez-Ortiz et al11 reported decreased insulin sensitivity after 24 hours of sleep deprivation in healthy subjects. Numerous observational studies in adults have also demonstrated an increased prevalence of type 2 diabetes mellitus in subjects with habitually short sleep periods.12, 13, 14, 15 However, in 2 of these studies, the association was no longer significant after adjusting for potential confounders, including obesity.14, 15 The association between obesity and both short sleep period and insulin resistance raises the question of whether the observed relationship between short sleep period and insulin resistance is at least partially mediated through the development of obesity.

The possibility that sleep loss may play a role in the development of obesity and insulin resistance has biologic plausibility. Studies have demonstrated that short sleep period is associated with decreased serum leptin and increased ghrelin levels, which promote increased appetite.16, 17 Furthermore, sleep loss has been associated with increased levels of the counterregulatory hormone cortisol10, 18 and with activation of the sympathetic nervous system,10 creating a milieu favoring insulin resistance. In addition, the up-regulation of proinflammatory mediators, such as tumor necrosis factor, interleukin-6, and C-reactive protein (CRP), in association with sleep loss19, 20 represents an alternative pathway linking sleep disorders to insulin resistance. Increasing levels of CRP have been demonstrated to predict the development of type 2 diabetes mellitus.21 Therefore, it is plausible that habitual sleep loss may lead to a chronic inflammatory state predisposing to the development of insulin resistance.

The study of Flint el al6 is an important first step in investigating the relationship between short sleep period and insulin resistance in children. This study has several limitations, however. The cross-sectional design prevents assessment of the direction of causation in the relationships among short sleep period, SDB, and insulin resistance. Moreover, in multiple linear regression analysis, increased—not decreased—sleep duration predicted a greater degree of insulin resistance. Therefore, the finding of increased insulin resistance in children with short sleep period may be due to confounding factors. Alternatively, the relationship between sleep period and insulin resistance may be nonlinear in nature. Several studies in adults have demonstrated increased insulin resistance with both long and short sleep periods relative to 7 or 8 hours of sleep per night.12, 14, 15

Prospective studies are needed to characterize the complex interactions among sleep disorders, obesity, and insulin resistance. The study of such a complex model requires sophisticated statistical approaches to determine the relative contributions of SBD and sleep loss to the risk of developing insulin resistance. In future investigations of the relationships among sleep period, SDB, and insulin resistance, incorporating measures of statistical mediation22 will prove essential in determining direct causation versus effects mediated through intermediate processes such as obesity.

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PII: S0022-3476(07)00020-0

doi:10.1016/j.jpeds.2007.01.009

Refers to article:

  • Association between Inadequate Sleep and Insulin Resistance in Obese Children

    Janna Flint, Sanjeev V. Kothare, Mamoon Zihlif, Elizabeth Suarez, Ruth Adams, Agustin Legido, Francesco De Luca
    The Journal of Pediatrics April 2007 (Vol. 150, Issue 4, Pages 364-369)

The Journal of Pediatrics
Volume 150, Issue 4 , Pages 331-332, April 2007

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