Relationship between sleep duration and childhood obesity: Systematic review including the potential underlying mechanisms

Accepted Manuscript Relationship between sleep duration and childhood obesity: systematic review including the potential underlying mechanisms Regina Felső, Szimonetta Lohner, Katalin Hollódy, Éva Erhardt, Dénes Molnár PII:

S0939-4753(17)30163-1

DOI:

10.1016/j.numecd.2017.07.008

Reference:

NUMECD 1759

To appear in:

Nutrition, Metabolism and Cardiovascular Diseases

Received Date: 9 March 2017 Revised Date:

12 July 2017

Accepted Date: 13 July 2017

Please cite this article as: Felső R, Lohner S, Hollódy K, Erhardt É, Molnár D, Relationship between sleep duration and childhood obesity: systematic review including the potential underlying mechanisms, Nutrition, Metabolism and Cardiovascular Diseases (2017), doi: 10.1016/j.numecd.2017.07.008. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT Relationship between sleep duration and childhood obesity: systematic review including the potential underlying mechanisms Regina Felső a, Szimonetta Lohner b, Katalin Hollódy a, Éva Erhardt a, Dénes Molnár a University of Pécs, Department of Paediatric, Pécs, Hungary

b

University of Pécs, Cochrane Hungary

SC

M AN U

Corresponding author: Dénes Molnár, MD., PhD, DSc. University of Pécs, Department of Paediatrics, József Attila Street 7., H7623, Pécs, Hungary Telephone: +36 72 535 944 E-mail address: [email protected]

RI PT

a

Abstract:

TE D

Aim: The prevalence of obesity is continually increasing worldwide. Determining risk factors for obesity may facilitate effective preventive programs. The present review focuses on sleep duration as a potential risk factor for childhood obesity. The aim is to summarize the evidence on the association of sleep duration and obesity and to discuss the underlying potential physiological and/or pathophysiological mechanisms.

AC C

EP

Methods: The Ovid MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for papers using text words with appropriate truncation and relevant indexing terms. All studies objectively measuring sleep duration and investigating the association between sleep duration and obesity or factors (lifestyle and hormonal) possibly associated with obesity were included, without making restrictions based on study design or language. Data from eligible studies were extracted in tabular form and summarized narratively. Results: After removing duplicates, 3540 articles were obtained. Finally, 33 studies (including 3 randomized controlled trials and 30 observational studies) were included in the review. Conclusion: Sleep duration seems to influence weight gain in children, however, the underlying explanatory mechanisms are still uncertain. In our review only the link between short sleep duration and the development of insulin resistance, sedentarism and unhealthy dietary patterns could be verified, while the role of other mediators, such as physical activity, screen time, change in ghrelin and leptin levels, remained uncertain. There are 1

ACCEPTED MANUSCRIPT numerous evidence gaps. To answer the remaining questions, there is a need for studies meeting high methodological standards and including a large number of children.

AC C

EP

TE D

M AN U

SC

RI PT

Keywords: childhood obesity, sleep duration, ghrelin, leptin, insulin, physical activity, diet, screen time

2

ACCEPTED MANUSCRIPT

Introduction

RI PT

Childhood obesity is one of the most alarming nutritional problems and threatens a huge burden for both individuals and societies. Although the prevalence of childhood obesity may be plateauing in some contexts, according to the report of the Commission on Ending Childhood Obesity the global “prevalence of overweight among children aged under five years has risen between 1990 and 2014, from 4.8 per cent to 6.1 per cent with numbers of affected children rising from 31 million to 41 million during that time”.[1] The prevention of childhood obesity is thus an outstanding public health challenge.

M AN U

SC

Several preventive strategies focus on the role of nutrition, dietary patterns, physical activity and different environmental factors. Sleep duration has also recently been recognized as a possible risk factor. Locard et al. were among the first researchers to describe a significant relationship between obesity and short sleep duration in a case controlled study of five year old children.[2]. Since then the role of sleep duration in childhood overweight or obesity risk has received considerable scientific attention.

TE D

Sleep deprivation may influence the development of obesity through several possible biological pathways including increased energy intake (unhealthy dietary patterns)[3–5] and/or decreased energy expenditure (decreased physical activity, increased screen time)[6–8]. Other potential mediators are hormonal (leptin, insulin, ghrelin)[9–11] changes evoked by sleep deficiency. Reviews suggesting hypothetical pathways by which sleep deprivation may predispose to obesity included the above mentioned mediators and emphasize that these mechanisms are poorly understood .[12–14]

AC C

EP

So far, nine systematic reviews[12,13,15–21] (including three meta-analyses) have been published concerning the impact of sleep on overweight and obesity. Five of the reviews focused exclusively on paediatric populations and demonstrated a clear association between short sleep duration and increased risk of childhood obesity.[12,15–17,20] However, all of these reviews included both subjective and objective measures of sleep time. Subjective measures (questionnaire and sleep diary) have a high risk of bias and therefore, summaries based on such measures should be interpreted cautiously. The main goal of the present review is to investigate the association between objectively measured sleep duration and childhood obesity. A further aim is to summarize the state of evidence regarding possible mechanisms and pathways by which sleep duration may influence energy balance. Methods Criteria for considering studies for this review 3

ACCEPTED MANUSCRIPT

Search methods for identification of studies

RI PT

Studies were included investigating sleep duration as a risk factor for childhood adiposity in healthy children aged 0-19 years. We also included the studies which examined the possible factors (dietary habits, physical activity or sedentarism, screen time, hormonal effects [insulin, or HOMA, leptin, ghrelin]) that may be related to sleep duration and obesity. Studies investigating a disease population, an adult population or a minority group (e.g. migrant population) or those investigating exclusively obese population were excluded. Only studies measuring sleep duration objectively (e.g. using actigraph, actiwatch, polysomnograph) were included, while studies using self-reported tools (e.g. questionnaires, diaries) were excluded. No restrictions were made according to study design.

Data collection and analysis

M AN U

SC

The Ovid MEDLINE, Scopus and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for papers published from inception until March 2016, using text words with appropriate truncation and relevant indexing terms (MeSH). The search was in the form [terms for obesity] AND [terms for sleep] AND [terms for children or adolescence]. The results were limited to studies conducted in humans. We included all articles investigating the association between sleep duration and childhood obesity. No language limitation was applied.

AC C

Results

EP

TE D

The titles and abstracts of studies identified by the search were screened by a single reviewer and clearly irrelevant studies were excluded. Then the full text reports of all potentially relevant studies were obtained and assessed for eligibility. Standardised data extraction forms were used for data extraction and management; for each included study the following data were extracted: source, country, study design, subject, age group, boy/girls rate, classification of obesity, sleep measurement tool, sleep reference, main findings.

2048 publications were found in Scopus database, 1549 in Ovid and 264 in the Cochrane database. After removing duplicates, 3540 articles were obtained to screen. Figure 1 shows the flow of information through the different phases of our systematic review by describing the number of records identified, included and excluded at different review stages. Following the abstract screening 850 full text articles were assessed for eligibility. Finally, 33 studies objectively measuring sleep duration were included into the review. The majority of the studies were conducted in America followed by Europe and Asia and there was also one multicentre study including data from five different continents. From the 33 studies 3 had randomized controlled design and 30 studies were observational investigations. The 30 observational studies comprised of 3 cohort studies and 25 cross4

ACCEPTED MANUSCRIPT sectional studies. There was one publication describing both, a cross-sectional and a cohort study; a further publication included repeated cross-sectional analyses. Sleep duration and obesity

RI PT

The characteristics and findings of the 23 studies are summarized in Table 1. The objective method used for measuring sleep duration in the included studies was wrist worn accelerometer in 9 and waist worn accelerometer in 14 studies. A negative relationship between sleep time and different measures of adiposity (i.e. short sleep duration was associated with increased risk of obesity and vice versa) was consequently described in childhood and adolescence in 17 studies, while there were only 6 studies which could not find any association between sleep time and adiposity.

AC C

EP

TE D

M AN U

SC

There was only one large multicentre study (Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, United Kingdom, United States) investigating 6025 9-11 years old children where sleep duration negatively associated with the risk of obesity (OR= 0,79). [22] Two longitudinal investigations measuring sleep duration objectively were found. Carter et al. found that after adjustment for multiple confounders, each additional hour of sleep at ages 3-5 was associated with a reduction in BMI of 0.48 and a reduced risk of being overweight at the age 7.[23] Martinez et al. investigating 229, 8-10 years old children demonstrated that those sleeping longer at baseline had significantly (p=0.002, in adjusted model) lower weight gain during two years follow up.[24] In an experimental study Hart et al. investigated the acute effect of changes in children’s sleep duration on weight as secondary outcome in a randomized crossover design. Measured weights were 0.22 kg lower during the increased than during the decreased sleep period (p<0.001)[25] There was only one investigation where both children with shortest (< 10 h) and longest (>= 12 h) sleep duration had higher BMI (p<0.001) than children with intermediate sleep duration. [26] Eleven studies used exclusively BMI or BMI z-score as their outcome measure. In 4 investigations body fat per cent, waist to height ratio or abdominal adiposity measured by DEXA were the outcome parameters. In the remaining 8 studies beyond BMI or BMI z-score other measures of adiposity were also used (Table 1.). Sleep duration and dietary habits 6 out of 33 relevant studies investigated the association between objectively measured sleep duration and dietary habits. Table 2 shows the main findings and description of these studies. There were two randomized crossover, one prospective cohort and three crosssectional studies detected. Beebe et al. demonstrated in an experiment that 5 days long sleep restriction (6.5 hours) resulted in the consumption of higher glycaemic index foods, higher glycaemic load and in a trend toward greater consumption of total calories.[27] In another experiment Hart et al. investigated the effect of continuous sleep reduction (1.5 hours/night for one week) on food 5

ACCEPTED MANUSCRIPT

SC

RI PT

intake. Sleep restriction caused significant increase of caloric intake.[25] Hjorth et al. investigated the association between objectively measured sleep duration and diet quantity and quality in a 200 days follow-up study including 441, 8-11-year-old children. Baseline sleep duration did not predict changes in dietary intake (energy density of diet, added sugar, sugar sweetened beverage), however, 1 hour per day shorter sleep duration increased the intake of added sugar and sugar-sweetened beverages.[28] Chaput et. al. reported relationship between sleep duration and eating patterns. They found that shorter sleep duration was associated with unhealthy eating patterns. [29] The main findings of the crosssectional studies were the following: (1) decreased sleep duration was associated with more external eating (eating in response to the sight or smell of food).[30] (2) short sleepers consumed higher energy density foods, more added sugar and sugar sweetened beverages compered to long sleepers[31].

Sleep duration and physical activity

M AN U

On the whole, all investigations demonstrated an association between short sleep duration and less favourable diet quality in childhood.

6 studies investigated the relationship between physical activity (PA) and objectively measured sleep duration (5 cross-sectional and one repeated cross-sectional). The main findings and characteristics of these studies are shown in Table 2.

AC C

EP

TE D

Two cross-sectional studies could not demonstrate relationship between sleep duration and PA.[32,33] Three studies found negative association between sleep time and sedentary time.[32,29,34] Herrington et al. showed an inverse correlation between sleep duration and the number of moderate to vigorous activity bouts, but not with time spent in moderate to vigorous activity.[35] Williams et al. measured sleep time and PA objectively and repeatedly in 216, 205 and 167 children at the age of 3, 5 and 7 years, respectively. According to the results the time spent asleep at night wasn’t related to the time spent in MVPA but appeared to be related to time spent in sedentary or light activities.[36] In an observational multinational cross-sectional study including 5777 children Chaput et. al. [29] demonstrated that short sleep was associated with higher MVPA and also with increased sedentary time. Sleep duration and screen time During the review process we found only two paper which investigated the relationship between objectively measured sleep duration and screen time (Table 2). Kjeldsen et al. investigated 8-11-year-old children in a cross-sectional study and reported a significant negative association between sleep duration and screen time. However, the main goal of this study was to evaluate the effect of short sleep duration on dietary risk factors.[31] The multinational, cross-sectional investigation of Chaput et. al. could not find significant relationship between sleep time and screen time. [29] 6

ACCEPTED MANUSCRIPT Sleep duration and insulin resistance/sensitivity

SC

The effect of sleep duration on leptin and ghrelin levels

RI PT

Studies investigating the link between sleep duration (measured by actigraph and polysomnography) and insulin levels, insulin sensitivity and/or insulin resistance are shown in Table 3. In summary, we identified one RCT and one prospective cohort and one crosssectional study describing the association between sleep duration and HOMA-index (two with negative, and one with “U-shape” association). The studies also demonstrated positive association with insulin sensitivity (Matshuda index) and insulin secretion sensitivity index 2 and negative association with fasting insulin level.

M AN U

Only two studies investigated the association between sleep duration and leptin level (Table 3). In a randomized control trial (RCT) investigating 8-11 years old children Hart et al demonstrated that an experimental increase in children’s average nightly sleep decreased serum fasting leptin levels as compared to those decreasing sleep duration (during the experimental investigation the average nightly sleep time was decreased or increased by 1,5 hours/ night for a week).[25] On the contrary, Kjeldsen et al demonstrated a positive association between sleep duration and fasting leptin level; however, this became insignificant following adjustment for confounders. [31]

AC C

EP

TE D

The same two studies investigated the association between sleep duration and fasting ghrelin level in children (Table 3). Hart et al. could not demonstrate any effect of change in sleep time on fasting ghrelin levels in a randomized controlled study investigating 8-11 years old children.[25] In a cross-sectional study Kjeldsen et al. demonstrated a positive association between fasting ghrelin level and sleep duration when adjusting for age, sex and pubertal status. However, this association disappeared after adjustments for further confounders (age, sex, pubertal status, height, weight, screen time, moderate-to-vigorous physical activity and parental education and ethnicity).[31] Discussion

Over the last century there has been a secular decline of 0.75 min per year in children’s sleep duration.[37] Even the recommended sleep duration has become shorter during the last decades.[38] During the same period of time, a dramatic increase in the prevalence of obesity has been observed in both children and adults. However, the causative relationship between these two factors is still uncertain.

The evidence summarized in this review shows a strong relationship between obesity and short sleep duration in children. We found 17 studies out of 23 which demonstrated a 7

ACCEPTED MANUSCRIPT

RI PT

negative relationship between objectively measured sleep time and different measures of adiposity in children and adolescences. Out of these 17 studies only two were prospective cohorts, while the others had a cross-sectional design. The only randomized controlled experiment found that children weighed less at the end of the increased as compared to the decreased sleep period with a mean difference in weight of 0.22 kg (P < 0.001). The limitations of the latter study were its small sample size, short observation period (one week) and relatively large difference between the decreased and increased sleep conditions (2 hours 21 min).[25] The results of the present review are in line with previous reviews that have relied heavily on self-reported sleep and concluded that there is a need for randomized controlled trials and intervention studies that examine the changes in different outcome measures against various amounts of objectively measured sleep. [14,15]

M AN U

SC

The association of objectively measured sleep duration and dietary habits was analysed in only few studies with different study designs and a large variety of food intake outcomes. The reviewed studies unequivocally demonstrated an association between short sleep duration and less favourable diet quality in childhood. Two experimental studies found association between sleep restriction and higher daily calorie intake, and the consumption of higher glycemic index foods. Our findings harmonize with the conclusion of the review by Lundahl and Nelson (“In summary, sleep problems, including short sleep duration and variable sleep schedules, are associated with – and – even cause – increased food intake in both adults and children”). [39]

AC C

EP

TE D

Hypothetically, children with shortened sleep duration may be less active because of increased tiredness. However, this hypothesis could not be confirmed based on the available evidence. The results of cross-sectional studies on MVPA and sleep duration are controversial. If anything, they suggest a link between sedentary activity and sleep duration i.e. short sleepers are more sedentary. This is indirectly supported by results showing that short sleepers spend more time in front of a screen [31] and by other studies using nonobjective tools for sleep duration measurements. [40,41]

Insufficient sleep duration may also have a negative effect on glucose homeostasis. The findings were unequivocal in this context, i.e. curtailed sleep increased fasting insulin concentration and insulin resistance (HOMA index), decreased insulin sensitivity and betacell function (Matsuda index, insulin secretion-sensitivity index-2). Since the above effects were confirmed in experimental conditions and by a longitudinal, prospective study, a causal relationship is very probable.[42,43] However, it should be considered that in only one of the above mentioned studies was the association of sleep duration and insulin level/insulin resistance adjusted for BMI or other measures of adiposity.

8

ACCEPTED MANUSCRIPT

RI PT

Leptin and ghrelin are hormones responsible for the physiological drives of satiation and appetite; ghrelin plays a role in stimulating hunger while leptin is responsible for the modulation of satiety. In the present review only two studies were detected investigating the association of ghrelin and leptin levels with sleep duration with inconsistent results. Adult studies showed that experimental reduction of sleep duration downregulates the satiety hormone, leptin and upregulates the appetite-stimulating hormone, ghrelin and increases hunger and appetite.[44,45] The only RCT we identified in our review, however, described the opposite effect in school age children. [25] This topic clearly needs further, good quality studies in children.

M AN U

SC

In Figure 2 we summarize the mechanisms that potentially explain the association between reduced sleep duration and obesity observed in several adult studies. In our systematic review focusing on the paediatric population and studies measuring sleep time objectively, the development of insulin resistance, unhealthy dietary patterns and sedentarism as links between sleep restriction and excess weight gain could be confirmed. The question whether primary hyperinsulinemia induces weight gain and leads to obesity is controversial.[46] However, several studies demonstrated that insulin-resistant individuals are particularly susceptible to weight gain associated with high levels of dietary fat intake.[47,48] Presently there are numerous evidence gaps related to the role of decreased sleep time in weight gain and risk of overweight and obesity.

TE D

The strength of our systematic review is that it summarizes all types of primary studies which investigate the association of objectively measured sleep duration with obesity and obesity-related factors. We are therefore able to present a comprehensive overview of the available scientific evidence on this relationship.

AC C

EP

However, our review might be limited by the following factors. Firstly, both the title and abstract screening and full text screening were conducted by only one reviewer, who might have accidentally excluded relevant studies. Secondly, since we focused only on objectively measured sleep time, we were able to identify only a limited number of studies with limited numbers of participants. In third place, detailed assessment of study quality was not a primary aim of our review. The heterogeneity (wide age range, different socio-economic status and cultural background) of the populations and of the outcome measures investigated by the reviewed studies made comparisons and interpretations difficult. Conclusion

Sleep duration seems to influence weight gain in children; however, the underlying mechanisms playing a role in sleep deprivation leading to increased weight gain are still uncertain. According to our review the role of insulin resistance, sedentarism and unhealthy dietary patterns predisposing children with short sleep to excess weight gain seems very likely, while the role of other presumed mediators, such as physical activity, screen time, 9

ACCEPTED MANUSCRIPT ghrelin and leptin levels is still uncertain. There are numerous evidence gaps and further studies conducted according to high methodological standards and in a large number of children are needed to answer the remaining questions.

Acknowledgement

RI PT

This work was supported by the Medical Faculty and Endocrine Studies, Centre of Excellence, University of Pécs.

SC

We would like to express our gratitude to Garrath Williams (Department of Politics, Philosophy and Religion, Lancaster University, Lancaster, UK.) for improving the English language of the manuscript.

AC C

EP

TE D

M AN U

The paper is dedicated to the 650th anniversary of the foundation of the University of Pecs/Hungary

10

ACCEPTED MANUSCRIPT References Obesity C on EC. Report of the Commission on Ending Childhood Obesity. Geneva: World Health Organization. 2016.

[2]

Locard E, Mamelle N, Billette A, Miginiac M, Munoz F, Rey S. Risk factors of obesity in a five year old population. Parental versus environmental factors. Int J Obes Relat Metab Disord 1992;16:721–9.

[3]

Bel S, Michels N, De Vriendt T, Patterson E, Cuenca-García M, Diethelm K, et al. Association between self-reported sleep duration and dietary quality in European adolescents. Br J Nutr 2013;110:949–59. doi:10.1017/S0007114512006046.

[4]

Hunsberger M, Mehlig K, Börnhorst C, Hebestreit A, Moreno L, Veidebaum T, et al. Dietary carbohydrate and nocturnal sleep duration in relation to children’s BMI: Findings from the idefics study in eight european countries. Nutrients 2015;7:10223– 36. doi:10.3390/nu7125529.

[5]

Golley RK, Maher CA, Matricciani L, Olds TS. Sleep duration or bedtime? Exploring the association between sleep timing behaviour, diet and BMI in children and adolescents. Int J Obes 2013;37:546–51. doi:http://dx.doi.org/10.1038/ijo.2012.212.

[6]

Hense S, Barba G, Pohlabeln H, De Henauw S, Marild S, Molnar D, et al. Factors that Influence Weekday Sleep Duration in European Children. Sleep 2011;34:633–9. doi:10.1093/sleep/34.5.633.

[7]

Garaulet M, Ortega FB, Ruiz JR, Rey-López JP, Béghin L, Manios Y, et al. Short sleep duration is associated with increased obesity markers in European adolescents: effect of physical activity and dietary habits. The HELENA study. Int J Obes (Lond) 2011;35:1308–17. doi:10.1038/ijo.2011.149.

[8]

de Jong E, Stocks T, Visscher TLS, HiraSing RA, Seidell JC, Renders CM. Association between sleep duration and overweight: the importance of parenting. Int J Obes 2012;36:1278–84. doi:10.1038/ijo.2012.119.

[9]

Jiang F, Zhu S, Yan C, Jin X, Bandla H, Shen X. Sleep and obesity in preschool children. J Pediatr 2009;154:814–8. doi:http://dx.doi.org/10.1016/j.jpeds.2008.12.043.

SC

M AN U

TE D

EP

AC C

[10]

RI PT

[1]

Hitze B, Bosy-Westphal A, Bielfeldt F, Settler U, Plachta-Danielzik S, Pfeuffer M, et al. Determinants and impact of sleep duration in children and adolescents: data of the Kiel Obesity Prevention Study. Eur J Clin Nutr 2009;63:739–46. doi:http://dx.doi.org/10.1038/ejcn.2008.41.

[11]

Boeke CE, Storfer-Isser A, Redline S, Taveras EM. Childhood sleep duration and quality in relation to leptin concentration in two cohort studies. Sleep 2014;37:613–20. doi:10.5665/sleep.3510.

[12]

Chen X, Beydoun M a, Wang Y. Is sleep duration associated with childhood obesity? A systematic review and meta-analysis. Obesity (Silver Spring) 2008;16:265–74. doi:10.1038/oby.2007.63. 11

ACCEPTED MANUSCRIPT Patel SR, Hu FB. Short sleep duration and weight gain: a systematic review. Obesity (Silver Spring) 2008;16:643–53. doi:10.1038/oby.2007.118.

[14]

Taheri S. The link between short sleep duration and obesity: we should recommend more sleep to prevent obesity. Arch Dis Child 2006;91:881–4. doi:10.1136/adc.2005.093013.

[15]

Chaput J, Gray CE, Poitras VJ, Carson V, Gruber R, Olds T, et al. Systematic review of the relationships between sleep duration and health indicators in school-aged children and youth 1. Appl Physiol Nutr Metab 2016;41:S266–82. doi:10.1139/apnm2015-0627.

[16]

Cappuccio FP, Taggart FM, Kandala N-B, Currie A, Peile E, Stranges S, et al. MetaAnalysis of Short Sleep Duration and Obesity in Children and Adults. Sleep 2008;31:619–26. doi:10.1093/sleep/31.5.619.

[17]

Fatima Y, Doi SAR, Mamun AA. Longitudinal impact of sleep on overweight and obesity in children and adolescents: A systematic review and bias-adjusted metaanalysis. Obes Rev 2015;16:137–49. doi:10.1111/obr.12245.

[18]

Magee L, Hale L. Longitudinal associations between sleep duration and subsequent weight gain: A systematic review. Sleep Med Rev 2012;16:231–41. doi:10.1016/j.smrv.2011.05.005.

[19]

Nielsen LS, Danielsen K V, Sørensen TIA. Short sleep duration as a possible cause of obesity: critical analysis of the epidemiological evidence. Obes Rev 2011;12:78–92. doi:10.1111/j.1467-789X.2010.00724.x.

[20]

Liu J, Zhang A, Li L. Sleep duration and overweight/obesity in children: Review and implications for pediatric nursing. J Spec Pediatr Nurs 2012;17:193–204. doi:10.1111/j.1744-6155.2012.00332.x.

[21]

Guidolin M, Gradisar M. Is shortened sleep duration a risk factor for overweight and obesity during adolescence? A review of the empirical literature. Sleep Med 2012;13:779–86. doi:10.1016/j.sleep.2012.03.016.

[22]

Katzmarzyk PT, Barreira T V, Broyles ST, Champagne CM, Chaput JP, Fogelholm M, et al. Relationship between lifestyle behaviors and obesity in children ages 9-11: Results from a 12-country study. Obesity 2015;23:1696–702. doi:http://dx.doi.org/10.1002/oby.21152.

[24]

SC

M AN U

TE D

EP

AC C

[23]

RI PT

[13]

Carter PJ, Taylor BJ, Williams SM, Taylor RW. Longitudinal analysis of sleep in relation to BMI and body fat in children: The FLAME study. BMJ 2011;342. doi:10.1136/bmj.d2712. Martinez SM, Tschann JM, Greenspan LC, Deardorff J, Penilla C, Flores E, et al. Is it time for bed? Short sleep duration increases risk of obesity in Mexican American children. Sleep Med 2014;15:1484–9. doi:http://dx.doi.org/10.1016/j.sleep.2014.09.009. 12

ACCEPTED MANUSCRIPT Hart CN, Carskadon M a, Considine R V, Fava JL, Lawton J, Raynor H a, et al. Changes in children’s sleep duration on food intake, weight, and leptin. Pediatrics 2013;132:e1473-80. doi:10.1542/peds.2013-1274.

[26]

Chaput JP, Lambert M, Gray-Donald K, McGrath JJ, Tremblay MS, O’Loughlin J, et al. Short sleep duration is independently associated with overweight and obesity in Canadian children. Can J Diabetes 2011;35:143–4. doi:10.1016/S14992671(11)52027-1.

[27]

Beebe DW, Simon S, Summer S, Hemmer S, Strotman D, Dolan LM. Dietary intake following experimentally restricted sleep in adolescents. Sleep 2013;36:827–34. doi:10.5665/sleep.2704.

[28]

Hjorth MF, Quist JS, Andersen R, Michaelsen KF, Tetens I, Astrup A, et al. Change in sleep duration and proposed dietary risk factors for obesity in Danish school children. Pediatr Obes 2014;9:e156–9. doi:10.1111/ijpo.264.

[29]

Chaput J-P, Katzmarzyk PT, LeBlanc AG, Tremblay MS, Barreira T V, Broyles ST, et al. Associations between sleep patterns and lifestyle behaviors in children: an international comparison. Int J Obes Suppl 2015;5:S59–65. doi:10.1038/ijosup.2015.21.

[30]

Burt J, Dube L, Thibault L, Gruber R. Sleep and eating in childhood: a potential behavioral mechanism underlying the relationship between poor sleep and obesity. Sleep Med 2014;15:71–5. doi:http://dx.doi.org/10.1016/j.sleep.2013.07.015.

[31]

Kjeldsen JS, Hjorth MF, Andersen R, Michaelsen KF, Tetens I, Astrup a, et al. Short sleep duration and large variability in sleep duration are independently associated with dietary risk factors for obesity in Danish school children. Int J Obes (Lond) 2014;38:32–9. doi:10.1038/ijo.2013.147.

[32]

Nixon GM, Thompson JMD, Han DY, Becroft DM, Clark PM, Robinson E, et al. Short Sleep Duration in Middle Childhood: Risk Factors and Consequences. Sleep 2008;31:71–8. doi:10.1093/sleep/31.1.71.

[33]

Ekstedt M, Nyberg G, Ingre M, Ekblom O, Marcus C. Sleep, physical activity and BMI in six to ten-year-old children measured by accelerometry: a cross-sectional study. Int J Behav Nutr Phys Act 2013;10:82. doi:http://dx.doi.org/10.1186/1479-5868-10-82.

SC

M AN U

TE D

EP

AC C

[34]

RI PT

[25]

Gomes TN, dos Santos FK, Santos D, Pereira S, Chaves R, Katzmarzyk PT, et al. Correlates of sedentary time in children: a multilevel modelling approach. BMC Public Health 2014;14:890. doi:http://dx.doi.org/10.1186/1471-2458-14-890.

[35]

Harrington SA. Relationships of objectively measured physical activity and sleep with BMI and academic outcomes in 8-year-old children. Appl Nurs Res 2013;26:63–70. doi:http://dx.doi.org/10.1016/j.apnr.2013.02.001.

[36]

Williams SM, Farmer VL, Taylor BJ, Taylor RW. Do more active children sleep more? A repeated cross-sectional analysis using accelerometry 2014;9:e93117. doi:http://dx.doi.org/10.1371/journal.pone.0093117. 13

Matricciani L, Olds T, Petkov J. In search of lost sleep: Secular trends in the sleep time of school-aged children and adolescents. Sleep Med Rev 2012;16:203–11. doi:10.1016/j.smrv.2011.03.005.

[38]

Matricciani LA, Olds TS, Blunden S, Rigney G, Williams MT. Never enough sleep: a brief history of sleep recommendations for children. Pediatrics 2012;129:548–56. doi:10.1542/peds.2011-2039.

[39]

Lundahl A, Nelson TD. Sleep and food intake: A multisystem review of mechanisms in children and adults. J Health Psychol 2015;20:794–805. doi:10.1177/1359105315573427.

[40]

Busto-Zapico R, Amigo-Vázquez I, Peña-Suárez E, Fernández-Rodríguez C. Relationships between sleeping habits, sedentary leisure activities and childhood overweight and obesity. Psychol Heal Med 2014;19:667–72. doi:10.1080/13548506.2013.878805.

[41]

Ortega FB, Ruiz JR, Labayen I, Kwak L, Harro J, Oja L, et al. Sleep duration and activity levels in Estonian and Swedish children and adolescents. Eur J Appl Physiol 2011;111:2615–23. doi:http://dx.doi.org/10.1007/s00421-011-1883-6.

[42]

Hjorth MF, Chaput J-P, Damsgaard CT, Dalskov S-M, Andersen R, Astrup A, et al. Low physical activity level and short sleep duration are associated with an increased cardio-metabolic risk profile: a longitudinal study in 8-11 year old Danish children. PLoS One 2014;9:e104677. doi:10.1371/journal.pone.0104677.

[43]

Klingenberg L, Chaput JP, Holmbäck U, Visby T, Jennum P, Nikolic M, et al. Acute sleep restriction reduces insulin sensitivity in adolescent boys. Sleep 2013;36:1085–90. doi:10.5665/sleep.2816.

[44]

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. doi:10.1038/nrendo.2009.23.

[45]

Van Cauter E, Knutson KL. Sleep and the epidemic of obesity in children and adults. Eur J Endocrinol 2008;159:59–66. doi:10.1530/EJE-08-0298.

[46]

[47]

[48]

EP

TE D

M AN U

SC

RI PT

[37]

AC C

ACCEPTED MANUSCRIPT

Templeman NM, Skovsø S, Page MM, Lim GE, Johnson JD. A causal role for hyperinsulinemia in obesity. J Endocrinol 2017;3:JOE-16-0449. doi:10.1530/JOE-160449. Morrison J a, Glueck CJ, Wang P. Preteen insulin levels interact with caloric intake to predict increases in obesity at ages 18 to 19 years: a 10-year prospective study of black and white girls. Metabolism 2010;59:718–27. doi:10.1016/j.metabol.2009.09.016. Mosca CL, Marshall J a, Grunwald GK, Cornier M a, Baxter J. Insulin resistance as a modifier of the relationship between dietary fat intake and weight gain. Int J Obes Relat Metab Disord 2004;28:803–12. doi:10.1038/sj.ijo.0802621. 14

ACCEPTED MANUSCRIPT Bagley EJ, El-Sheikh M. Familial risk moderates the association between sleep and zBMI in children. J Pediatr Psychol 2013;38:775–84. doi:http://dx.doi.org/10.1093/jpepsy/jst031.

[50]

Chaput JP, Leduc G, Boyer C, Belanger P, LeBlanc AG, Borghese MM, et al. Objectively measured physical activity, sedentary time and sleep duration: independent and combined associations with adiposity in canadian children. Nutr Diabetes 2014;4:e117. doi:http://dx.doi.org/10.1038/nutd.2014.14.

[51]

Gomes TN, Katzmarzyk PT, dos Santos FK, Souza M, Pereira S, Maia JA. Overweight and obesity in Portuguese children: prevalence and correlates. Int J Environ Res Public Heal [Electronic Resour 2014;11:11398–417. doi:http://dx.doi.org/10.3390/ijerph111111398.

[52]

Gupta NK, Mueller WH, Chan W, Meininger JC. Is obesity associated with poor sleep quality in adolescents? Am J Hum Biol 2002;14:762–8. doi:10.1002/ajhb.10093.

[53]

He F, Bixler EO, Berg A, Imamura Kawasawa Y, Vgontzas AN, Fernandez-Mendoza J, et al. Habitual sleep variability, not sleep duration, is associated with caloric intake in adolescents. Sleep Med 2015;16:856–61. doi:http://dx.doi.org/10.1016/j.sleep.2015.03.004.

[54]

Hjorth MF, Sjodin A, Dalskov SM, Damsgaard CT, Michaelsen KF, Biltoft-Jensen A, et al. Sleep duration modifies effects of free ad libitum school meals on adiposity and blood pressure. Appl Physiol Nutr Metab 2016;41:33–40. doi:http://dx.doi.org/10.1139/apnm-2015-0319.

[55]

Javaheri S, Storfer-Isser A, Rosen CL, Redline S. Association of short and long sleep durations with insulin sensitivity in adolescents. J Pediatr 2011;158:617–23. doi:http://dx.doi.org/10.1016/j.jpeds.2010.09.080.

[56]

Klingenberg L, Christensen LB, Hjorth MF, Zangenberg S, Chaput JP, Sjodin A, et al. No relation between sleep duration and adiposity indicators in 9-36 months old children: the SKOT cohort. Pediatr Obes 2012;8:e14-8. doi:http://dx.doi.org/10.1111/j.20476310.2012.00109.x.

[57]

Martinez SM, Greenspan LC, Butte NF, Gregorich SE, De Groat CL, Deardorff J, et al. Mother-reported sleep, accelerometer-estimated sleep and weight status in Mexican American children: sleep duration is associated with increased adiposity and risk for overweight/obese status. J Sleep Res 2014;23:326–34. doi:http://dx.doi.org/10.1111/jsr.12114.

AC C

EP

TE D

M AN U

SC

RI PT

[49]

[58]

Michels N, Verbeiren A, Ahrens W, De Henauw S, Sioen I. Children’s sleep quality: Relation with sleep duration and adiposity. Public Health 2014;128:488–90. doi:10.1016/j.puhe.2014.02.003.

[59]

Spruyt K, Molfese DL, Gozal D. Sleep duration, sleep regularity, body weight, and metabolic homeostasis in school-aged children. Pediatrics 2011;127:e345-52. doi:10.1542/peds.2010-0497. 15

ACCEPTED MANUSCRIPT Tikotzky L, De Marcas G, Har-Toov J, Dollberg S, Bar-Haim Y, Sadeh A. Sleep and physical growth in infants during the first 6 months. J Sleep Res 2010;19:103–10. doi:http://dx.doi.org/10.1111/j.1365-2869.2009.00772.x.

[61]

Valrie CR, Bond K, Lutes LD, Carraway M, Collier DN. Relationship of sleep quality, baseline weight status, and weight-loss responsiveness in obese adolescents in an immersion treatment program. Sleep Med 2015;16:432–4. doi:http://dx.doi.org/10.1016/j.sleep.2014.11.007.

[62]

Wilkie HJ, Standage M, Gillison FB, Cumming SP, Katzmarzyk PT. Multiple lifestyle behaviours and overweight and obesity among children aged 9-11 years: results from the UK site of the International Study of Childhood Obesity, Lifestyle and the Environment. BMJ Open 2016;6:e010677. doi:http://dx.doi.org/10.1136/bmjopen2015-010677.

[63]

Wong WW, Ortiz CL, Lathan D, Moore LA, Konzelmann KL, Adolph AL, et al. Sleep duration of underserved minority children in a cross-sectional study. BMC Public Health 2013;13:648. doi:http://dx.doi.org/10.1186/1471-2458-13-648.

[64]

Zhu Y, Li AM, Au CT, Kong APS, Zhang J, Wong CK, et al. Association between sleep architecture and glucose tolerance in children and adolescents. J Diabetes 2015;7:10– 5. doi:10.1111/1753-0407.12138.

AC C

EP

TE D

M AN U

SC

RI PT

[60]

16

ACCEPTED MANUSCRIPT Figure Legends: Figure 1: Flow diagram of study selection Figure 2: Potential mechanisms by which sleep deprivation may predispose to obesity

AC C

EP

TE D

M AN U

SC

RI PT

↑ - short sleep duration leads to the increase of the affected factors; ↓ - short sleep duration leads to the decrease of the affected factors; (?) sufficient evidence is not available

17

ACCEPTED MANUSCRIPT

Country

Study design

Subjects (n)

Age range/mean

Sleep reference

Sleep parameter

Outcome variables

Association

Bagley 2013 [49]

USA

crosssectional

228

9–12 y

N/A

sleep duration (min/night)

zBMI (CDC)

neg

Chaput 2011 [26]

Canada

crosssectional

550

8-10 y

>10 h; <12 h

sleep duration (h/day)

zBMI (CDC)

U-shape

Chaput 2014 [50]

Canada

crosssectional

507

9-11 y

>10 hours

sleep duration (min/day)

body fat%, waist-to-height ratio

none

1231

6-10 y

N/A

sleep duration (min/day)

zBMI (IOTF)

neg

686

9-11 y

>10 h

sleep time (h/night)

BMI (WHO)

none

361

11-16 y

N/A

sleep duration (min/day)

Body fat %

neg

305

16,7 y

N/A

habitual sleep duration

abdominal adiposity

none

sleep duration (h/day)

weigh, BMI, zBMI (IOTF), Fat mass, Android fat mass, FMI,

neg

sleep duration (h/day)

BMI percentile (CDC), Waist circumference

none

sleep duration (min/night)

zBMI (WHO)

neg

USA

Denmark

crosssectional

530

8-11 y

Javaheri 2011 [55]

USA

crosssectional

471

8-19 y

Katzmarzyk 2015 [22]

Multicentre crossstudy a sectional

6025

9-11 y

M AN U

USA

>9 h

>6,5 h

AC C

Hjorth 2016 [54]

Portugal

crosssectional crosssectional crosssectional crosssectional

TE D

He 2015 [53]

Sweden

EP

Ekstedt 2013 [33] Gomes 2014 [51] Gupta 2002 [52]

SC

Source

RI PT

Table 1. Association between sleep duration and adiposity in children and adolescence

N/A

18

ACCEPTED MANUSCRIPT

Valrie 2015 [61] Wilkie 2016 [62] Wong 2013 [63]

Belgium New Zealand USA

Israel

USA UK USA

Carter 2011 [23]

New Zealand

Martinez

USA

crosssectional crosssectional crosssectional crosssectional crosssectional and prospective cohort prospective

zBMI (WHO)

neg

none

neg

311

3y

>12 h

sleep duration (min/night)

zBMI (WHO), Sum of skinfolds (mm), body fat (%), fat mass (kg)

303

8-10 y

>10 h

sleep duration (h/day)

zBMI (CDC)

523

6-12 y

N/A

sleep duration (h/day)

591

7y

>9 h

Waist circumference, body fat (%), BMI Risk of overweight/obese (IOTF), body fat (%)

308

4-10 y

N/A

RI PT

crosssectional crosssectional crosssectional crosssectional

sleep duration (min/night)

SC

USA

8-11 y

M AN U

Tikotzky 2010 [60]

Denmark

crosssectional

676

sleep duration (h/day) sleep duration (h/day)

weight above weight expected for length, weight to length ratio waist circumference, zBMI (CDC) Risk of overweight/obese (WHO)

neg none

0,5 y

N/A

25

12-16 y

N/A

sleep duration (min/night)

374

9-11 y

age 9: ≥10 h; age 10: ≥9.75 h; age 11: ≥9.5 h

sleep duration (min/night)

483

9-12 y

N/A

sleep duration (h/day)

zBMI (reference N/A)

neg

244

229

sleep duration (min/night)

zBMI (CDC)

neg

96

TE D

Martinez 2014 [57] Michels 2014 [58] Nixon 2008 [32] Spruyt 2011 [59]

crosssectional

EP

Klingenberg 2012 [56]

Denmark

AC C

Kjeldsen 2014 [31]

‘short sleep’ duration: 7.47–8.56 h ‘long sleep’ duration: (9.32–10.50 h per night)

neg

neg neg

3-7 y

N/A

sleep duration (h/night)

BMI

neg

8-10 y

>10 h

sleep duration (h/day)

zBMI (CDC)

neg 19

ACCEPTED MANUSCRIPT

2014 [24]

cohort

Hart 2013 [25]

randomized controlled trial

USA

37

8-11 y

N/A

sleep duration (min /night)

body weight

neg

AC C

EP

TE D

M AN U

SC

RI PT

y, years; N/A, no answer; min, minutes; BMI, body mass index; zBMI, body mass index z-score; neg, negative; CDC, Centres for Disease Control; IOTF, International Obesity Task Force; h, hours; WHO, World Health Organization; DEXA, Dual-energy X-ray absorptiometry; FMI, fat mass index a Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, United Kingdom, United States

20

ACCEPTED MANUSCRIPT

Table 2. Association between sleep duration and lifestyle factors Source

Country

Study design

Subjects (n)

Age group

Sleep reference

Sleep parameter

Outcome variable

Association

Hjorth 2014 [28]

prospective cohort

>7 hours

sleep restriction (<7h/day; no. of day)

glycemic index, glycemic load

neg

37

8-11 y

N/A

sleep duration (min/night)

consumption of calories (kcal/day)

neg

sleep duration (h/day)

Added sugar (E %), sugar sweetened beverage (E %)

neg

sleep duration (h/day)

energy density of diet

none

‘short sleep’ duration: 7.47–8.56 h ‘long sleep’ duration: (9.32–10.50 h per night)

sleep duration (min/night)

energy density, added sugar (E %), sugar sweetened beverage (E %)

neg

NSF

sleep duration (h/night)

“unhealthy diet pattern”, “healthy diet pattern”

neg

sleep duration (min/night)

level of external (eating in response to the sight or smell of food), emotional eating (food intake in response to emotional distress)

neg

441

Denmark

Chaput et al. 2015[29]

Burt 2014 [30]

Multicentre study a

Canada

8-11 y crosssectional

676

crosssectional

5777

crosssectional

9-11 y

EP

Kjeldsen 2014 [31]

N/A

SC

USA

14-16 y

M AN U

Hart 2013 [25]

41

TE D

USA

randomize controlled trial randomize controlled trial

56

AC C

Beebe 2013 [27]

RI PT

Association between sleep duration and dietary habits

5-12 y

N/A

21

ACCEPTED MANUSCRIPT

restrained eating (food intake is initially reduced to lose or maintain body weight, but followed by increased consumption and binge eating)

pos

sleep duration (h/night)

MVPA (min/day), sedentary activity (h/day)

neg

sleep duration (min/night)

MVPA (min/day)

none

sleep duration (h/day)

sedentary activity (min/day

neg

sleep duration (h/night)

number of MVPA bouts/day

neg

sleep duration (h/day)

sedentary activity (min/day)

neg

sleep duration (h/day)

moderate activity (min/day), vigorous activity (min/day)

sleep duration (min/night)

MVPA (min/day)

RI PT

later bedtime

cross-sectional

5777

9-11 y

NSF

Ekstedt 2013 [33]

Sweden

cross-sectional

1231

6-10 y

N/A

Gomes 2014 [34]

Portugal

cross-sectional

686

9-10 y

N/A

Harrington 2013 [35]

USA

cross-sectional

55

8y

N/A

cross-sectional

Williams 2014 [36]

New Zealand

repeated crosssectional

591

216; 205; 167

7y

>9 h

EP

New Zealand

AC C

Nixon 2008 [32]

3, 5, 7 y

M AN U

Multicentre study a

TE D

Chaput et al. 2015[29]

SC

Association between sleep duration and physical activity

N/A

none

neg

Association between sleep duration and screen time

22

ACCEPTED MANUSCRIPT

crosssectional

5777

676

9-11 y

NSF

sleep duration (h/night)

8-11 y

‘short sleep’ duration: 7.47–8.56 h ‘long sleep’ duration: (9.32–10.50 h per night)

sleep duration (min/night)

RI PT

Denmark

crosssectional

Screen time score

none

screen time (min/day)

neg

SC

Kjeldsen 2014 [31]

Multicentre study a

M AN U

Chaput et al. 2015[29]

AC C

EP

TE D

y, years; N/A, no answer; neg, negative; E%, Energy %; NSF, National Sleep Fundation; pos, positive; MVPA, moderate to vigorous physical activity; min, minute; h, hour a Australia, Brazil, Canada, China, Colombia, Finland, India, Kenya, Portugal, South Africa, the United Kingdom and the United States

23

ACCEPTED MANUSCRIPT

Table 3.Association between sleep duration and hormone level (Insulin/insulin sensitivity, leptin, ghrelin) Source

Country

Study design

Subject (n)

Age group

Sleep measurement

Sleep reference

Sleep parameters

Outcome variable

Association

sleep duration (min/night)

HOMA

neg

sleep duration (h/day)

HOMA

neg

sleep duration (h/day)

Matsuda Index

pos

sleep duration (h/day)

fasting insulin

neg

sleep duration (h/day)

HOMA

“u-shape”

sleep duration (min/day)

Matsuda index

pos

sleep duration (min/day)

2-h glucose

neg

sleep duration (min/day)

insulin secretionsensitivity index 2

pos

sleep duration (min/night)

leptin

neg

sleep duration (min/night)

ghrelin

none

Zhu 2015 [64]

USA

China

crosssectional

crosssectional

21

471

118

8-11 y

15-19 y

16-19 y

13.1 ± 3.3

Hart 2013 [25]

USA

randomized controlled trial

37

polysomnogra phy

accelerometer

polysomnogra phy

AC C

Association between sleep duration and leptin, ghrelin level

accelerometer

N/A

8 h/night

SC

randomized crossover

473

M AN U

Javaheri 2011 [55]

Denmark

prospective cohort

TE D

Klingenberg 2013 [43]

Denmark

N/A

N/A

EP

Hjorth 2014 [42]

8-11 y

RI PT

Association between sleep duration and insulin level/ insulin sensitivity

accelerometer

N/A

24

ACCEPTED MANUSCRIPT

leptin, ghrelin

pos*

AC C

EP

TE D

M AN U

SC

RI PT

short sleep’ duration: 7.47– Kjeldsen 2014 cross8.56 h Denmark 676 8-11 y accelerometer sleep duration (h/night) [31] sectional ‘long sleep’ duration: (9.32– 10.50 h per night) y, years; N/A, no answer; min, minutes; HOMA, homeostasis model of insulin; neg, negative; h, hour; pos, positive Matsuda index refers to insulin sensitivity; Inslulin secretion-sensitivity index 2 is a measure of β-cell function * The significance of the association disappeared after adjustment for confounders.

25

ACCEPTED MANUSCRIPT Scopus n=2048

Ovid n=1549

Cochrane n=264

RI PT

3861 article identified

321 duplicates removed

M AN U

SC

3540 studies screened

2690 abstracts did not meet inclusion criteria

TE D

850 studies assessed for full- text eligibility

AC C

EP

817 articles did not meet inclusion criteria

23 sleep duration and obesity

6 sleep duration and diet

6 sleep duration and physical activity

33 studies included after full text screening

2 sleep duration and screen time

4 sleep duration and insulin level/insuli n sensitivity

2 sleep duration and leptin level

2 sleep duration and ghrelin level

ACCEPTED MANUSCRIPT

Unhealthy dietary patterns Biological factors

Energy intake ↑

RI PT

total calories intake ↑ emotional eating ↑(?) glycemic load, glycemic index ↑ sugar sweetened beverage intake ↑(?)

M AN U

SC

Leptin ↓(?) Ghrelin ↑(?) Insulin/insulin resistance↑

Obesity

AC C

EP

TE D

Short sleep duration

Screen time ↑(?)

Behavioural factors

Physical activity ↓(?)

Sedentarism ↑

Energy expenditure ↓

ACCEPTED MANUSCRIPT

RI PT SC M AN U TE D

•

EP

•

Sleep duration seems to influence weight gain in children. The underlying mechanisms playing a role in sleep deprivation leading to increased weight gain are still uncertain The role of insulin resistance predisposing children with less sleep to weight gain could be confirmed.

AC C

•