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Cited by 134Sleep and related disordersSleep and Wakefulness ResearchCircadian rhythm and melatonin

Sleep architecture and glucose and insulin homeostasis in obese adolescents

Open access
Koren, Dorit, Levitt Katz, Lorraine E., Brar, Preneet C., Gallagher, Paul R., Berkowitz, Robert I., Brooks, Lee J.·2011·Diabetes Care
DOI 10.2337/dc11-1093PMC PMC3198280
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Abstract

OBJECTIVE: Sleep deprivation is associated with increased risk of adult type 2 diabetes mellitus (T2DM). It is uncertain whether sleep deprivation and/or altered sleep architecture affects glycemic regulation or insulin sensitivity or secretion. We hypothesized that in obese adolescents, sleep disturbances would associate with altered glucose and insulin homeostasis. RESEARCH DESIGN AND METHODS: This cross-sectional observational study of 62 obese adolescents took place at the Clinical and Translational Research Center and Sleep Laboratory in a tertiary care children’s hospital. Subjects underwent oral glucose tolerance test (OGTT), anthropometric measurements, overnight polysomnography, and frequently sampled intravenous glucose tolerance test (FSIGT). Hemoglobin A1c (HbA1c) and serial insulin and glucose levels were obtained, indices of insulin sensitivity and secretion were calculated, and sleep architecture was assessed. Correlation and regression analyses were performed to assess the association of total sleep and sleep stages with measures of insulin and glucose homeostasis, adjusted for confounding variables. RESULTS: We found significant U-shaped (quadratic) associations between sleep duration and both HbA1c and serial glucose levels on OGTT and positive associations between slow-wave sleep (N3) duration and insulin secretory measures, independent of degree of obesity, pubertal stage, sex, and obstructive sleep apnea measures. CONCLUSIONS: Insufficient and excessive sleep was associated with short-term and long-term hyperglycemia in our obese adolescents. Decreased N3 was associated with decreased insulin secretion. These effects may be related, with reduced insulin secretory capacity leading to hyperglycemia. We speculate that optimizing sleep may stave off the development of T2DM in obese adolescents.

AI snapshot

Written from the paper’s full text.

TL;DR

In 62 obese adolescents, total sleep duration showed U-shaped associations with short- and long-term glycemia, and slow-wave sleep (N3) was positively associated with insulin secretory measures. The authors conclude that insufficient or excessive sleep and reduced N3 may contribute to hyperglycemia and impaired insulin secretion in this population.

Key findings

  • Sleep duration had significant U-shaped (quadratic) relationships with fasting glucose, 1-h and 2-h OGTT glucose, and HbA1c; optimal glucose homeostasis appeared at 420–510 min (7–8.5 h) of sleep, with regression adjusted R² values of 0.201 (P = 0.002) for fasting glucose, 0.442 (P < 0.0005) for 2-h glucose, and 0.200 (P = 0.002) for HbA1c.
  • N3 duration and %TST in N3 correlated positively with insulin secretory measures, including 1-h insulin, 2-h insulin, IGI, and AIRg; N3 remained the strongest predictor of insulin secretion in stepwise regression (adjusted R² = 0.161, P = 0.002 for IGI; adjusted R² = 0.383, P < 0.0005 for AIRg).
  • Curve estimation showed a cubic relationship between N3 and AIRg (r² = 0.286; P = 0.001), with inflection points at approximately 65 and 98 min of N3.
  • OSA measures did not associate significantly with glucose homeostasis or insulin secretion; N2 sleep showed marginal negative associations with insulin sensitivity measures, and AHI had a marginal negative correlation with SI (r = −0.338; P = 0.025).

Methods

  • Cross-sectional observational study of 62 obese pubertal adolescents (BMI >95th percentile; mean age 14.4 ± 2.1 years; mean BMI 36.76 ± 6.82 kg/m²) recruited from an obesity clinic.
  • Participants underwent anthropometrics, Tanner staging, OGTT with serial glucose and insulin, HbA1c, overnight polysomnography, and FSIGT; sleep architecture and OSA measures were scored by a single sleep board-certified investigator blinded to metabolic status.
  • Analyses included Pearson/Spearman correlations, hierarchical linear regression, polynomial regressions for curvilinear relationships, and ANCOVA, with an adjusted significance threshold of P < 0.017 for the three underlying hypotheses.

Limitations

  • The paper states that a night in the sleep laboratory may not reflect sleep at home; however, only 32% of families reported worse sleep in the laboratory, and those subjects had no significant demographic, anthropometric, or glucose/insulin differences, with only lower absolute REM duration among sleep parameters.
  • Evident from the text: the cross-sectional design cannot establish causality, and the findings are from a single-center sample of obese adolescents, limiting generalizability to other populations.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.2337/dc11-1093

Cites

25 of 25 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 17 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Sex did not contribute significantly to any glucose model.

    “Sex did not contribute significantly to any glucose model.”
    Quote in the paperNot a substantial claim
  • Findingown data

    On regression analysis, total sleep time was the most significant predictor of glucose homeostasis measures.

    “On regression analysis, TST was the most significant predictor of glucose homeostasis measures.”
    Quote in the paperSubstantial claim
  • Findingown data

    N3 sleep, both total duration and %TST in N3, correlated significantly or marginally with several insulin secretory measures in bivariate analysis.

    “N3 sleep, both total duration and the percentage of total sleep time in N3 (%TST in N3), correlated significantly or with marginal significance (P value between 0.017 and 0.05) with several insulin secretory measures (Table 4) in bivariate analysis.”
    Quote in the paperSubstantial claim
  • Findingown data

    On regression analysis, no strong associations were seen between sleep architecture or OSA and OGTT-derived insulin sensitivity measures.

    “However, on regression analysis, no strong associations were seen between sleep architecture or OSA and OGTT-derived insulin sensitivity measures.”
    Quote in the paperSubstantial claim
  • Findingown data

    We found a marginal relationship between N2 duration and HOMA-IR (overall R2=0.088; P=0.040).

    “We found a marginal relationship between N2 duration and HOMA-IR (overall R2 = 0.088; P = 0.040)”
    Quote in the paperNot a substantial claim
  • May combine two claims. 18
  • Classified as probably not a substantial claim. 11

  • May combine two claims.

    Findingown data

    BMI z score contributed significantly to the AIRg final model but not to the IGI model, and pubertal stage contributed significantly to the final IGI model but not the AIRg model.

    “BMI z score contributed significantly to the AIRg final model but not to the IGI model, and pubertal stage contributed significantly to the final IGI model but not the AIRg model.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    There was no association between pubertal stage and any of the insulin secretory measures examined, or between sex and insulin secretory measures.

    “there was no association between pubertal stage and any of the insulin secretory measures examined, or between sex and insulin secretory measures.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Although the relationship between %TST in N2 and SI was stronger, BMI z score was the strongest predictor in that model (overall model R2=0.400; P<0.0005).

    “although the relationship between %TST in N2 and SI was stronger, BMI z score (i.e., degree of obesity) was the strongest predictor in that model (overall model R2 = 0.400; P < 0.0005).”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Individual sleep stages, pubertal stage, and sex were not significant predictors of any glucose homeostasis measure.

    “Individual sleep stages, pubertal stage, and sex were not significant predictors of any glucose homeostasis measure”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Insulin-like growth factor-1 levels in our subjects did not correlate significantly with either sleep duration or any individual sleep stage.

    “insulin-like growth factor-1 levels in our subjects did not correlate significantly with either sleep duration or any individual sleep stage”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Pubertal stage and sex did not associate significantly with any insulin sensitivity measure.

    “Pubertal stage and sex did not associate significantly with any insulin sensitivity measure.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    BMI z score was a significant contributor, and Tanner stage a marginal contributor, to the overall 2-h glucose model only, not to the overall fasting glucose or HbA1c models.

    “BMI z score was a significant contributor, and Tanner stage was a marginal contributor, to the overall 2-h glucose model only (not to the overall fasting glucose or HbA1c models).”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    Only 32% of families indicated worse sleep in the laboratory; these subjects had no significant demographic, anthropometric, or glucose/insulin parameter differences compared with the remaining subjects, and of the sleep parameters, the only difference seen was a lower absolute REM duration in the 'poorer sleep' group.

    “Only 32% indicated worse sleep in the laboratory; these subjects had no significant demographic, anthropometric, or glucose/insulin parameter differences compared with the remaining subjects, and of the sleep parameters, the only difference seen was a lower absolute REM duration in the “poorer sleep” group.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    A marginally significant negative association was seen between pubertal stage and both N3 duration (r=-0.282; P=0.028) and %TST in N3 (r=-0.252; P=0.050).

    “A marginally significant negative association was seen between pubertal stage and both N3 duration (r = −0.282; P = 0.028) and %TST in N3 (r = −0.252; P = 0.050)”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    We found a positive association between N2 sleep and insulin sensitivity, with varying contribution from degree of obesity.

    “Finally, we found a positive association between N2 sleep and insulin sensitivity, with varying contribution from degree of obesity.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Adjusted R2 and P values for overall regression models were 0.201 (P=0.002) for fasting glucose, 0.442 (P<0.0005) for 2-h glucose, and 0.200 (P=0.002) for HbA1c.

    “adjusted R2 and P values were as follows: 0.201 (P = 0.002) for fasting glucose, 0.442 (P < 0.0005) for 2-h glucose, and 0.200 (P = 0.002) for HbA1c.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Findingown data

    Other sleep stages, TST, OSA measures, and sex were not significant predictors of insulin secretory measures in the final regression model.

    “Other sleep stages, TST, OSA measures, and sex were not significant predictors of insulin secretory measures in the final regression model.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Findingcitation

    Our subjects' mean TST of 7.1 h was similar to the mean 7.2-h sleep duration reported in the 2006 National Sleep Foundation adolescent poll.

    “Our subjects’ mean TST of 7.1 h was similar to the mean 7.2-h sleep duration reported in the 2006 National Sleep Foundation adolescent poll (2).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [2] Carskadon, Contemporary sleep patterns of adolescents in the USA: results of the 2006 National Sleep Foundation Sleep in America Poll. Presented at the Annual Meeting of the European Sleep Research Society, Innsbruck, Switzerland, 14 September 2006

      Not checked in the free run.

  • May combine two claims.

    Findingown data

    Adjusted R2 and P values for the overall models were 0.161 (P=0.002) for IGI and 0.383 (P<0.0005) for AIRg.

    “Adjusted R2 and P values for the overall models were 0.161 (P = 0.002) for IGI and 0.383 (P < 0.0005) for AIRg.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Findingown data

    In obese adolescents, U-shaped relationships between total sleep duration and measures of both short- and long-term glycemia, and positive or cubic associations between N3 and insulin secretory measures, persisted after adjusting for potential confounders such as degree of obesity, OSA, sex, and pubertal stage.

    “Specifically, we found U-shaped relationships between total sleep duration and measures of both short- and long-term glycemia, and positive or cubic associations between N3 and insulin secretory measures, even after adjusting for potential confounders such as degree of obesity, OSA, sex, and pubertal stage.”
    • Also stated in: § RESULTS · plain
      “We found significant U-shaped (quadratic) associations between sleep duration and both HbA1c and serial glucose levels on OGTT and positive associations between slow-wave sleep (N3) duration and insulin secretory measures, independent of degree of obesity, pubertal stage, sex, and obstructive sleep apnea measures.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationnone given

    A night in the sleep laboratory does not necessarily reflect sleep at home, a possible limitation of the study.

    “A night in the sleep laboratory does not necessarily reflect sleep at home, a possible limitation of our study.”
    Quote in the paperNot a substantial claim

  • May combine two claims.

    Interpretationnone given

    This is the first report of an association between N3 sleep and changes in β-cell function and of a U-shaped association between sleep duration and glucose levels in a pediatric population.

    “To our knowledge, this is the first report of an association between N3 sleep and changes in β-cell function and of a U-shaped association between sleep duration and glucose levels in a pediatric population.”
    Quote in the paperSubstantial claim

  • May combine two claims.

    Interpretationown data

    An absolute N3 duration of 1 h may be needed to achieve a stable amount of insulin secretion, and increasing N3 might greatly improve insulin secretion.

    “suggested that an absolute N3 duration of 1 h may be needed to achieve a stable amount of insulin secretion, and that increasing N3 might greatly improve insulin secretion.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    In adult studies, plasma glucose rises in N3 sleep.

    “In adult studies, cerebral glucose utilization declines (7) and plasma glucose rises (8) in N3 sleep.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [8] Boyle, 1994, Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans, J Clin Invest source

      Not checked in the free run.

  • May combine two claims.

    Interpretationcitation

    The results may help explain the association between N3 lack and T2DM, as a loss in first-phase insulin secretion is both an early marker of T2DM and part of its pathogenesis.

    “Our results may help explain the aforementioned association between N3 lack and T2DM, as a loss in first-phase insulin secretion is both an early marker of T2DM and part of its pathogenesis (20).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [20] Weyer, 1999, The natural history of insulin secretory dysfunction and insulin resistance in the pathogenesis of type 2 diabetes mellitus, J Clin Invest source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Assumptions of linearity were tested by examining plots of standardized residuals as a function of standardized predicted values.

    “Assumptions of linearity were tested by examining plots of the standardized residuals as a function of standardized predicted values.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    One pediatric study found a negative association between REM sleep duration and obesity.

    “One pediatric study found a negative association between REM sleep duration and obesity (9)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [9] Liu, 2008, Rapid eye movement sleep in relation to overweight in children and adolescents, Arch Gen Psychiatry source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductnone given

    Sleep studies were reviewed by a single sleep Board-certified investigator who had no knowledge of subjects' metabolic status.

    “Studies were reviewed by a single sleep Board-certified investigator (L.J.B.), who had no knowledge of subjects’ metabolic status.”
    Quote in the paperNot a substantial claim

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    An adjusted P value of <0.017 (0.05/3) was used for statistical significance because three underlying hypotheses were tested.

    “As we tested three underlying hypotheses relating to the relationship between sleep architecture and insulin secretion and sensitivity and overall glycemia, we used an adjusted P value of <0.017 (0.05/3) for statistical significance.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    IGI is a measure of insulin secretion that has been validated in children against the hyperglycemic clamp.

    “Insulinogenic index (IGI) is a measure of insulin secretion that has been validated in children against the hyperglycemic clamp (16)”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [16] Sinha, 2002, Prevalence of impaired glucose tolerance among children and adolescents with marked obesity, N Engl J Med source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Sleep architecture and respiratory disturbances were scored using standard pediatric criteria.

    “Sleep architecture (N1, N2, N3, and REM sleep stages) and respiratory disturbances (including the apnea-hypopnea index [AHI], arousal index, and lowest oxyhemoglobin saturation [lowest SaO2]) were scored using standard pediatric criteria (17).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    The protocol was approved by the Institutional Review Board; informed consent and assent were obtained.

    “The protocol was approved by The Children’s Hospital of Philadelphia Institutional Review Board; informed consent was obtained from the parents or guardians, and assent was obtained from the participants.”
    Quote in the paperNot a substantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    OSA has been associated with T2DM risk in adults.

    “OSA has been associated with T2DM risk in adults (10) and with IR in children (11,12).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [10] Tasali, 2008, Obstructive sleep apnea and type 2 diabetes: interacting epidemics, Chest source

      Not checked in the free run.

28 of 28

  • The paper relies on this without support.

    There is little pediatric data on sleep architecture and glucose and insulin homeostasis.

    “but there is little pediatric data on sleep architecture and glucose and insulin homeostasis.”
1 of 1

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • One prior study identified a U-shaped relationship, with short and long sleep duration both predicting impaired glucose tolerance in children, similar to adults.

    “One prior study identified a U-shaped relationship, with short and long sleep duration both predicting impaired glucose tolerance, similar to adults (192).”

    From Sleep: important considerations for the prevention of cardiovascular disease (2016) · cites this paper as [192]

  • Shorter sleep duration and worse sleep efficiency were associated with impaired glucose tolerance in a recent study.

    “A recent study showed that shorter sleep duration, as well as worse sleep efficiency, was associated with impaired glucose tolerance (190).”

    From Sleep: important considerations for the prevention of cardiovascular disease (2016) · cites this paper as [190]

  • Short sleep duration is linked to impaired glucose metabolism in children and adolescents.

    “Additionally, there is robust evidence linking short sleep duration to impaired glucose metabolism.”

    From Sleep: important considerations for the prevention of cardiovascular disease (2016) · cites this paper as [190]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

  • Non-Hispanic percentage does not match the participant count

    Minor

    Of 62 participants, 54 represent 87.1%, not 82.3%.

    Reported 82.3 · recomputed 87.096774

  • Hispanic percentage does not match the participant count

    Minor

    The study reports 62 participants, so 8 Hispanic participants represent 12.9%, not 17.7%.

    Reported 17.7 · recomputed 12.903226

2 of 2

Cites

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Related

Authors
Koren, D., Levitt Katz, L. E., Brar, P. C., Gallagher, P. R., Berkowitz, R. I., & Brooks, L. J.
Affiliations
  • Children's Hospital of Philadelphia (US)
  • Division of Pediatric Endocrinology and Diabetes, The Children’s Hospital of Philadelphia, and Department of Pediatrics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania
  • NYU Langone Health (US)
  • University of Pennsylvania (US)
Corresponding author
Koren, Dorit
ORCID
Venue
Diabetes Care
Publisher
American Diabetes Association
Published
2011-10-15
Volume
34
Issue
11
Pages
2442-2447
ISSN
  • 0149-5992 (ISSN-L)
  • 1935-5548
DOI
10.2337/dc11-1093
PMC
PMC3198280
OpenAlex
W2100716242
Semantic Scholar
28a9ae54fb39712e574eae500dd6c855c8376c77
Cited by
134
References
25
Citations by year
2026: 3 · 2025: 3 · 2024: 11 · 2023: 7 · 2022: 10 · 2021: 9 · 2020: 7 · 2019: 6 · 2018: 17 · 2017: 9 · 2016: 18 · 2015: 10 · 2014: 9 · 2013: 11 · 2012: 4
FWCI
9.88
Type
journal article
Language
en
Open access
Licence
Locations
  • Diabetes Care (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
Funders
  • National Institute of Diabetes and Digestive and Kidney Diseases (T32DK063688)
  • National Center for Research Resources (UL1-RR-24134, UL1RR024134)
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
  • Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Keywords
sleep architecture, sleep duration, sleep deprivation, sleep disorders, glucose homeostasis, insulin homeostasis, insulin secretion, insulin sensitivity, hyperglycemia, type 2 diabetes risk, obesity, adolescents, slow-wave sleep, HbA1c, polysomnography
MeSH terms
Insulin Secretion, Adolescent, Blood Glucose, Child, Cross-Sectional Studies, Diabetes Mellitus, Female, Glucose Tolerance Test, Glycated Hemoglobin, Homeostasis, Hospitals, Pediatric, Humans, Hyperglycemia, Insulin, Male, Obesity, Sensitivity and Specificity, Sleep, Sleep Wake Disorders, Philadelphia, Body Mass Index, Polysomnography

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