The DOI matches its Crossref record; 36 of the 36 references it cites were found in a registry or an index; none of the 22 sources its claims cite is checked for support yet.
Sleep restriction increases free fatty acids in healthy men
Open accessAbstract
Aims/hypothesisSleep loss is associated with insulin resistance and an increased risk for type 2 diabetes, yet underlying mechanisms are not understood. Elevation of circulating non-esterified (i.e. free) fatty acid (NEFA) concentrations can lead to insulin resistance and plays a central role in the development of metabolic diseases. Circulating NEFA in healthy individuals shows a marked diurnal variation with maximum levels occurring at night, yet the impact of sleep loss on NEFA levels across the 24 h cycle remains unknown. We hypothesised that sleep restriction would alter hormones that are known to stimulate lipolysis and lead to an increase in NEFA levels.MethodsWe studied 19 healthy young men under controlled laboratory conditions with four consecutive nights of 8.5 h in bed (normal sleep) and 4.5 h in bed (sleep restriction) in randomised order. The 24 h blood profiles of NEFA, growth hormone (GH), noradrenaline (norepinephrine), cortisol, glucose and insulin were simultaneously assessed. Insulin sensitivity was estimated by a frequently sampled intravenous glucose tolerance test.ResultsSleep restriction relative to normal sleep resulted in increased NEFA levels during the nocturnal and early-morning hours. The elevation in NEFA was related to prolonged nocturnal GH secretion and higher early-morning noradrenaline levels. Insulin sensitivity was decreased after sleep restriction and the reduction in insulin sensitivity was correlated with the increase in nocturnal NEFA levels.Conclusions/interpretationSleep restriction in healthy men results in increased nocturnal and early-morning NEFA levels, which may partly contribute to insulin resistance and the elevated diabetes risk associated with sleep loss.
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TL;DR
In 19 healthy young men, four nights of sleep restriction (4.5 h in bed) increased nocturnal and early-morning non-esterified fatty acid (NEFA) levels and reduced insulin sensitivity compared with normal sleep (8.5 h in bed). The NEFA rise was linked to prolonged nocturnal growth hormone secretion and higher early-morning noradrenaline.
Key findings
- Sleep restriction increased mean NEFA levels by approximately 15–30% during nocturnal and early-morning hours and prolonged the duration of the nocturnal NEFA increase by approximately 50 min.
- Nocturnal GH secretion became biphasic in 14 of 19 participants and was prolonged by approximately 50 min; the increase in GH secretion duration correlated with prolonged NEFA rise (r = 0.81, p < 0.0001).
- Early-morning noradrenaline increased by approximately 30% and correlated with the early-morning NEFA increase (r = 0.55, p = 0.015); evening/early-night cortisol was 23% higher but did not correlate with NEFA changes.
- Insulin sensitivity by IVGTT decreased by 23% after sleep restriction (p = 0.004), and the decrease correlated with increased mean nocturnal NEFA (r = 0.52, p = 0.05) and nocturnal NEFA AUC (r = −0.53, p = 0.05); disposition index was lower (p = 0.042).
Methods
- Randomised, controlled laboratory crossover study of 19 healthy young lean men aged 18–30 years, comparing four consecutive nights of 8.5 h in bed (normal sleep) versus 4.5 h in bed (sleep restriction), spaced at least 4 weeks apart.
- 24 h blood profiles were collected at 15–30 min intervals for NEFA, GH, noradrenaline, cortisol, glucose and insulin; diet and energy intake were identical across conditions, and insulin sensitivity was estimated by frequently sampled IVGTT.
- Analyses used mixed-model ANOVA with participants as random factor and sleep condition as fixed factor, Pearson correlations, and Benjamini–Hochberg correction for NEFA time-point comparisons; data reported as mean ± SEM.
Limitations
- The paper states that it cannot exclude altered circadian timing as a contributor, provides no information on long-term effects of sleep restriction or recovery sleep, and notes that correlations do not demonstrate direct causality.
- The paper notes the NEFA increase was modest (approximately 15–30%) and that future mechanistic studies, such as pharmacological NEFA suppression, are needed to test causality.
- Evident from the text: the sample was small (n = 19) and restricted to healthy young lean men, limiting generalisability; technical difficulties invalidated IVGTT estimates in six normal-sleep and two sleep-restriction sessions, with five of the six normal-sleep invalid tests repeated.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The total amount of nocturnal GH secreted did not differ between sleep conditions (Table 2).”
§ Sleep restriction increases free fatty acids in healthy men > Results
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In the paper
“cortisol levels were 23% higher in the evening hours as well as during the early night with extended wakefulness (Table 2).”
§ Sleep restriction increases free fatty acids in healthy men > Results
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The alterations in cortisol secretory patterns did not correlate with any changes in NEFA (p > 0.05 for all variables).”
§ Sleep restriction increases free fatty acids in healthy men > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, the early-morning increase in noradrenaline was positively correlated with the early-morning increase in NEFA levels (r = 0.55, p = 0.015).”
§ Sleep restriction increases free fatty acids in healthy men > Results
Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Insulin sensitivity estimated by the IVGTT was reduced by 23% during sleep restriction as compared with normal sleep (p = 0.004, Fig. 5a).”
§ Sleep restriction increases free fatty acids in healthy men > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, daytime NEFA levels were similar between sleep conditions”
§ Sleep restriction increases free fatty acids in healthy men > Discussion
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In the paper
“The 24 h profile of NEFA displayed a marked circadian variation under both sleep conditions (Fig. 2a).”
§ Sleep restriction increases free fatty acids in healthy men > Results
Strength:boosted· not yet calibratedn = 19Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The acute insulin response to glucose did not differ between sleep conditions (p = 0.22).”
§ Sleep restriction increases free fatty acids in healthy men > Results
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In the paper
“When sleep was restricted, the duration of the nocturnal NEFA increase was prolonged by approximately 50 min (Table 2).”
§ Sleep restriction increases free fatty acids in healthy men > Results
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In the paper
“During normal sleep, a single nocturnal GH pulse was observed in all but four of the 19 participants (Fig. 2b).”
§ Sleep restriction increases free fatty acids in healthy men > Results
Strength:plain· not yet calibratedn = 19Tests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passes
- Probably not a substantial claim. 10
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In the paper
“The normal post-awakening cortisol peak occurred approximately 2 h earlier when sleep was restricted (Fig. 2d)”
§ Sleep restriction increases free fatty acids in healthy men > Results
Strength:plain· not yet calibratedCausal:direct· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
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In the paper
“Overnight (21:30–09:00 hours) mean fasting insulin levels were higher after sleep restriction as compared with normal sleep (51.0 ± 5.1 vs 46.7 ± 5.1 pmol/l; p = 0.036) despite similar glucose levels (5.08 ± 0.07 vs 5.05 ± 0.07 mmol/l; p = 0.410)”
§ Sleep restriction increases free fatty acids in healthy men > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“When sleep was restricted, the AUC for glucose response to breakfast tended to be higher (p = 0.061) and the AUC for insulin response was significantly increased (p = 0.045)”
§ Sleep restriction increases free fatty acids in healthy men > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“The decrease in insulin sensitivity was correlated with the increase in mean nocturnal NEFA levels (r = 0.52; p = 0.05; Fig. 5b) and the AUC for nocturnal NEFA levels (r = −0.53, p = 0.05).”
§ Sleep restriction increases free fatty acids in healthy men > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
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In the paper
“In contrast, during sleep restriction 14 of the 19 participants showed a biphasic nocturnal GH release, resulting in GH secretion being prolonged by approximately 50 min.”
§ Sleep restriction increases free fatty acids in healthy men > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
None of the sources cited for this claim have been checked yet.
In the paper
“Acute elevation in circulating NEFA levels in healthy individuals has been linked to insulin resistance in multiple investigations [10–13].”
- Also stated in: § Discussion · boosted
“acute elevation in circulating NEFA concentrations has been shown to induce insulin resistance in healthy participants in multiple previous studies [10–13].”
§ Sleep restriction increases free fatty acids in healthy men > Introduction
What the sources say
- Not checked yetcites [10] Boden G, Lebed B, Schatz M, Homko C, Lemieux S (2001) Effects of acute changes of plasma free fatty acids on intramyocellular fat content and insulin resistance in healthy participants. Diabetes 50:1612–1617 source
- Not checked yetcites [11] Roden M, Price TB, Perseghin G et al (1996) Mechanism of free fatty acid-induced insulin resistance in humans. J Clin Invest 97:2859–2865 source
- Not checked yetcites [12] Chavez AO, Kamath S, Jani R et al (2010) Effect of short-term free fatty acids elevation on mitochondrial function in skeletal muscle of healthy individuals. J Clin Endocrinol Metab 95:422–429 source
- Not checked yetcites [13] Yoshino J, Almeda-Valdes P, Patterson BW et al (2014) Diurnal variation in insulin sensitivity of glucose metabolism is associated with diurnal variations in whole-body and cellular fatty acid metabolism in metabolically normal women. J Clin Endocrinol Metab 99:E1666–E1670 source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
- Also stated in: § Discussion · boosted
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In the paper
“likely due to the stimulating effects of morning awakening.”
§ Sleep restriction increases free fatty acids in healthy men > Discussion
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In the paper
“Sleep was recorded by polysomnography (Nihon Kohden, Irvine, CA, USA) during each night in each sleep condition.”
§ Sleep restriction increases free fatty acids in healthy men > Methods > Experimental protocol
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In the paper
“Diet was strictly controlled (2 day cycle menu of three isoenergetic meals per day) and energy intake was identical under both sleep conditions.”
§ Sleep restriction increases free fatty acids in healthy men > Methods > Experimental protocol
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In the paper
“For each 24 h profile, all samples obtained from the same individual were measured in the same assay.”
§ Sleep restriction increases free fatty acids in healthy men > Methods > Hormonal measurements
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In the paper
“On average, participants slept for 7.8 ± 0.1 h during normal sleep vs 4.3 ± 0.0 h during sleep restriction (Table 1).”
§ Sleep restriction increases free fatty acids in healthy men > Results
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In the paper
“after controlling for multiple comparisons with a Benjamini and Hochberg procedure”
§ Sleep restriction increases free fatty acids in healthy men > Methods > Statistical analyses
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In the paper
“In six IVGTTs during the normal sleep condition and two IVGTTs during the sleep restriction condition, technical difficulties invalidated the estimation of insulin sensitivity and secretion. Five of the six invalid IVGTTs during the normal sleep condition were repeated on a separate day”
§ Sleep restriction increases free fatty acids in healthy men > Methods > Experimental protocol
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In the paper
“Compliance with this schedule was verified by sleep diaries and continuous wrist activity monitoring (Actiwatch; Philips-Respironics, Bend, OR, USA).”
§ Sleep restriction increases free fatty acids in healthy men > Methods > Experimental protocol
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In the paper
“Participants were studied at the University of Chicago Clinical Resource Center under two experimental conditions in randomised order spaced at least 4 weeks apart”
§ Sleep restriction increases free fatty acids in healthy men > Methods > Experimental protocol
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In the paper
“Average body mass index (23.4 ± 0.4 vs 23.3 ± 0.4 kg/m2; p = 0.12) and percentage body fat (19.3 ± 1.1% vs 19.2 ± 1.0%; p = 0.86) did not differ between sleep conditions.”
§ Sleep restriction increases free fatty acids in healthy men > Results
Strength:plain· not yet calibratedn = 19Tests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
The paper relies on this without support.
Growth hormone, noradrenaline and cortisol increase the rate of lipolysis and thereby raise circulating NEFA concentrations.
“In addition, these hormones are known to increase the rate of lipolysis, resulting in elevated circulating NEFA concentrations.”
The paper relies on this without support.
This study is the first to examine how sleep loss affects 24-hour NEFA profiles.
“To our knowledge, this is the first study to examine the impact of sleep loss on 24 h NEFA profiles.”
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?
The source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“When appraised collectively, these studies show that sleep restriction increases afternoon cortisol: Table 2.”
From Sleep, testosterone and cortisol balance, and ageing men (2022) · cites this paper as [78]
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Opposite correlation signs for mean nocturnal NEFA and its AUC
MinorThe paper reports a positive correlation between the insulin-sensitivity decrease and mean nocturnal NEFA, but a negative correlation with nocturnal NEFA AUC. For the same nocturnal interval, the mean and AUC represent the same concentration profile and should not give opposite directions for this relationship.
“The decrease in insulin sensitivity was correlated with the increase in mean nocturnal NEFA levels (r = 0.52; p = 0.05; Fig. 5b)”
“and the AUC for nocturnal NEFA levels (r = −0.53, p = 0.05).”
Citations
Cites
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Mechanism of free fatty acid-induced insulin resistance in humans.
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“Experimental sleep restriction in healthy young adults has been associated with alterations in nocturnal GH secretion [15], increased night-time noradrenaline concentrations [5] and elevated evening cortisol levels [4, 16, 17].”
Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men
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“We previously reported the effects of sleep restriction on total body insulin sensitivity and insulin signalling in adipocytes from six men who were included in this report [6].”
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“We observed the maximum NEFA levels occurring at night, as reported in earlier studies [20–23].”
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“Disruption of circadian rhythms has also been associated with adverse effects on metabolism [29, 35].”
Kashyap, S. R., Belfort, R., Berria, R., Suraamornkul, S., Pratipranawatr, T., Finlayson, J., Barrentine, A., Bajaj, M., Mandarino, L., DeFronzo, R., et al. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00541.2003 · Cited by 103 · cited 1×
“Although the increase in NEFA levels during sleep restriction was modest (an increase of approximately 15–30% during nocturnal and early-morning hours) in our healthy participants, these findings are consistent with the notion that even a very small sustained increase in NEFA concentrations can alter insulin sensitivi…”
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“Consistent with earlier reports [4, 28], we found an increase in evening cortisol levels during sleep restriction.”
Self-citationSleep-stage-specific regulation of plasma catecholamine concentration
Rasch, B., Dodt, C., Mölle, M., & Jan Born, A. (2007) · Psychoneuroendocrinology · doi:10.1016/j.psyneuen.2007.06.007 · Cited by 70 · cited 1×
“We also found that noradrenaline levels were elevated during the early-night and early-morning hours when participants had to remain awake during the sleep restriction condition, consistent with the known inhibitory effect of sleep on noradrenaline [26].”
Quantitative Methods for the Analysis of Circadian and Episodic Hormone Fluctuations
Cauter, E. V. (1981) · Springer eBooks · doi:10.1007/978-94-009-8282-6_1 · Cited by 70 · cited 1×
“Significant GH secretory pulses were identified as previously described [19].”
Clore, J. N., Nestler, J. E., & Blackard, W. G. (1989) · Diabetes · doi:10.2337/diab.38.3.285 · Cited by 62
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Chavez, A. O., Kamath, S., Jani, R., Sharma, L. K., Monroy, A., Abdul-Ghani, M. A., Centonze, V. E., Sathyanarayana, P., Coletta, D. K., Jenkinson, C. P., et al. (2010) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2009-1387 · Cited by 52 · cited 2×
“Acute elevation in circulating NEFA levels in healthy individuals has been linked to insulin resistance in multiple investigations [10–13].”
Wehrens, S. M. T., Hampton, S. M., Finn, R. E., & Skene, D. J. (2010) · Journal of Endocrinology · doi:10.1677/joe-10-0077 · Cited by 47 · cited 2×
“Thus far, two studies have explored the effects of sleep deprivation on NEFA concentrations, but measurements were taken only in the morning over a limited number of time points [24, 25].”
Nedeltcheva, A. V., Imperial, J., & Penev, P. D. (2012) · Obesity · doi:10.1038/oby.2012.97 · Cited by 38 · cited 3×
“Thus far, two studies have explored the effects of sleep deprivation on NEFA concentrations, but measurements were taken only in the morning over a limited number of time points [24, 25].”
Nocturnal regulation of free fatty acids in healthy young and elderly men
Rosenthal, M. J., & Woodside, W. F. (1988) · Metabolism · doi:10.1016/0026-0495(88)90083-2 · Cited by 35 · cited 1×
“We observed the maximum NEFA levels occurring at night, as reported in earlier studies [20–23].”
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Sorted by citations
Panel, C. C., Watson, N. F., Badr, M. S., Belenky, G., Bliwise, D. L., Buxton, O. M., Buysse, D., Dinges, D. F., Gangwisch, J., Grandner, M. A., et al. (2015) · Sleep · doi:10.5665/sleep.4886 · Cited by 906
Self-citationCircadian Rhythm and Sleep Disruption: Causes, Metabolic Consequences, and Countermeasures
Potter, G. D., Skene, D. J., Arendt, J., Cade, J. E., Grant, P. J., & Hardie, L. J. (2016) · Endocrine Reviews · doi:10.1210/er.2016-1083 · Cited by 781
The gut microbiome and metabolic syndrome
Dabke, K., Hendrick, G., & Devkota, S. (2019) · Journal of Clinical Investigation · doi:10.1172/jci129194 · Cited by 684
“Interference with this cycle has been shown to promote obesity (40, 41), and affect insulin sensitivity (42) and lipid metabolism (43).”
BackgroundSleep influences on obesity, insulin resistance, and risk of type 2 diabetes
Reutrakul, S., & Van Cauter, E. (2018) · Metabolism · doi:10.1016/j.metabol.2018.02.010 · Cited by 584
Watson, N. F., Badr, M. S., Belenky, G., Bliwise, D. L., Buxton, O. M., Buysse, D., Dinges, D. F., Gangwisch, J., Grandner, M. A., Kushida, C., et al. (2015) · Journal of Clinical Sleep Medicine · doi:10.5664/jcsm.4950 · Cited by 568
Self-citation
Metadata
- Authors
- Broussard, J. L., Chapotot, F., Abraham, V., Day, A., Delebecque, F., Whitmore, H. R., & Tasali, E.
- Affiliations
- Cedars-Sinai Medical Center (US)
- University of Chicago (US)
- University of Wisconsin–Madison (US)
- Corresponding author
- Broussard, Josiane L.
- Venue
- Diabetologia
- Published
- 2015-02-22
- Volume
- 58
- Issue
- 4
- Pages
- 791-798
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC4358810
- OpenAlex
- W2009304756
- Semantic Scholar
- 68b543b0674afaf084769a174abe95ec8d63f249
- Cited by
- 156
- References
- 36
- Citations by year
- 2026: 9 · 2025: 17 · 2024: 12 · 2023: 7 · 2022: 19 · 2021: 15 · 2020: 8 · 2019: 14 · 2018: 22 · 2017: 15 · 2016: 9 · 2015: 9
- FWCI
- 27.61
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Diabetologia (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- U.S. Department of Defense (W81XWH)
- University of Chicago (UL1 TR000430)
- Georgia Clinical and Translational Science Alliance (UL1 TR000430)
- National Institutes of Health (UL1TR000430, W81XWH, P60 DK20595, TR000430)
- National Institute on Aging (P01-AG11412., P01AG011412)
- National Heart, Lung, and Blood Institute (R01HL086459, R01HL075079, T32HL007909)
- National Institute of Diabetes and Digestive and Kidney Diseases (P60DK20595, P60DK020595, P30DK020595)
- National Center for Research Resources (P41RR013642)
- National Center for Advancing Translational Sciences (CTSA-UL1 TR000430)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (P50HD057796)
- Topics
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- sleep restriction, free fatty acids, insulin resistance, type 2 diabetes risk, growth hormone, norepinephrine, cortisol, lipolysis, insulin sensitivity, circadian rhythm
- MeSH terms
- Adolescent, Adult, Blood Glucose, Circadian Rhythm, Fatty Acids, Nonesterified, Humans, Hydrocortisone, Insulin, Insulin Resistance, Male, Norepinephrine, Random Allocation, Sleep, Sleep Deprivation, Time Factors, Biomarkers, Up-Regulation, Human Growth Hormone, Young Adult, Healthy Volunteers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
A language model drew the claims from the paper on 2026-10-09, under version 3 of the claim definition (model deepseek-v4.1-flash, prompt extract-v3).
A second model labelled each claim on 2026-10-09 (model jev-1.13-20260917, definition revision gold-guideline-v0.2).
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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