Chronic Insufficient Sleep Has a Limited Impact on Circadian Rhythmicity of Subjective Hunger and Awakening Fasted Metabolic Hormones

Andrew W McHill, Joseph T Hull, Ciaran J McMullan, Elizabeth B Klerman, Andrew W McHill, Joseph T Hull, Ciaran J McMullan, Elizabeth B Klerman

Abstract

Weight gain and obesity have reached epidemic proportions in modern society. Insufficient sleep-which is also prevalent in modern society-and eating at inappropriate circadian times have been identified as risk factors for weight gain, yet the impact of chronic insufficient sleep on the circadian timing of subjective hunger and physiologic metabolic outcomes are not well understood. We investigated how chronic insufficient sleep impacts the circadian timing of subjective hunger and fasting metabolic hormones in a 32-day in-laboratory randomized single-blind control study, with healthy younger participants (range, 20-34 years) randomized to either Control (1:2 sleep:wake ratio, 6.67 h sleep:13.33 h wake, n = 7, equivalent to 8 h of sleep per 24 h) or chronic sleep restriction (CSR, 1:3.3 sleep:wake ratio, 4.67 h sleep:15.33 h wake, n = 8, equivalent to 5.6 h of sleep per 24 h) conditions. Participants lived on a "20 h day" designed to distribute all behaviors and food intake equally across all phases of the circadian cycle over every six consecutive 20 h protocol days. During each 20 h day, participants were provided a nutritionist-designed, isocaloric diet consisting of 45-50% carbohydrate, 30-35% fat, and 15-20% protein adjusted for sex, weight, and age. Subjective non-numeric ratings of hunger were recorded before and after meals and fasting blood samples were taken within 5 min of awakening. Subjective levels of hunger and fasting concentrations of leptin, ghrelin, insulin, glucose, adiponectin, and cortisol all demonstrated circadian patterns; there were no differences, however, between CSR and Control conditions in subjective hunger ratings or any fasting hormone concentrations. These findings suggest that chronic insufficient sleep may have a limited role in altering the robust circadian profile of subjective hunger and fasted metabolic hormones.

Clinical trial registration: The study was registered as clinical trial #NCT01581125.

Keywords: appetite; circadian rhythms; endocrinology; fasting hormones; forced desynchrony; hunger; sleep loss; sleep restriction.

Figures

Figure 1
Figure 1
Raster plot of the Control (n = 7, 1:2 sleep:wake ratio, equivalent to 8 h sleep opportunity per 24 h day) and chronic sleep restriction (n = 8, 1:3.3 sleep:wake ratio, equivalent to 5.6 per 24 h day) forced desynchrony protocols. Clock hour is plotted on the horizontal axis and day of study on the vertical axis. Solid black bars represent sleep opportunities, yellow circles represent fasted blood draws, and the red dashed line represents the daily marker of a participant’s circadian period. Days are double plotted such that each consecutive study day is plotted next to and below the previous day.
Figure 2
Figure 2
Influence of circadian phase and sleep restriction on (A,B) subjective hunger, (C,D) leptin, and (E,F) ghrelin. The Control (n = 7, 1:2 sleep:wake ratio, equivalent to 8 h sleep opportunity per 24 h day) condition is denoted by open circles and the chronic sleep restriction (CSR, n = 8, 1:3.3 sleep:wake ratio, equivalent to 5.6 h sleep opportunity per 24 h day) condition by closed circles. Data are represented as raw scores (left) and z-scores (right) and double plotted across circadian phase and relative clock hour for an individual with a habitual sleep time of 2300–0700 hours. Error bars represent SEM.
Figure 3
Figure 3
Influence of circadian phase and sleep restriction on fasted (A,B) insulin and (C,D) glucose concentrations. The Control (n = 7, 1:2 sleep:wake ratio, equivalent to 8 h sleep opportunity per 24 h day) condition is denoted by open circles and the chronic sleep restriction (CSR, n = 7, 1:3.3 sleep:wake ratio, equivalent to 5.6 h sleep opportunity per 24 h day) condition by closed circles. Data are represented as raw scores (left) and z-scores (right) and double plotted across circadian phase and relative clock hour for an individual with a habitual sleep time of 2300–0700 hours. Error bars represent SEM.
Figure 4
Figure 4
Influence of circadian phase and sleep restriction on fasted (A,B) adiponectin and (C,D) cortisol concentrations. The Control (n = 7, 1:2 sleep:wake ratio, equivalent to 8 h sleep opportunity per 24 h day) condition is denoted by open circles and the chronic sleep restriction (CSR, n = 8, 1:3.3 sleep:wake ratio, equivalent to 5.6 h sleep opportunity per 24 h day) condition by closed circles. Data are represented as raw scores (left) and z-scores (right) and double plotted across circadian phase and relative clock hour for an individual with a habitual sleep time of 2300–0700 hours. Error bars represent SEM.

References

    1. Ogden CL, Carroll MD, Kit BK, Flegal KM. Prevalence of obesity among adults: United States, 2011–2012. NCHS Data Brief (2013) 131:1–8.
    1. Finucane MM, Stevens GA, Cowan MJ, Danaei G, Lin JK, Paciorek CJ, et al. National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9.1 million participants. Lancet (2011) 377:557–67.10.1016/S0140-6736(10)62037-5
    1. de Onis M, Blossner M, Borghi E. Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr (2010) 92:1257–64.10.3945/ajcn.2010.29786
    1. Executive Summary. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults – the evidence report. National Institutes of Health. Obes Res (1998) 6(Suppl 2):51s–209s.
    1. Finkelstein EA, Trogdon JG, Cohen JW, Dietz W. Annual medical spending attributable to obesity: payer-and service-specific estimates. Health Aff (Millwood) (2009) 28:w822–31.10.1377/hlthaff.28.5.w822
    1. Nedeltcheva AV, Scheer FA. Metabolic effects of sleep disruption, links to obesity and diabetes. Curr Opin Endocrinol Diabetes Obes (2014) 21:293–8.10.1097/MED.0000000000000082
    1. Faraut B, Boudjeltia KZ, Vanhamme L, Kerkhofs M. Immune, inflammatory and cardiovascular consequences of sleep restriction and recovery. Sleep Med Rev (2012) 16:137–49.10.1016/j.smrv.2011.05.001
    1. Cohen DA, Wang W, Wyatt JK, Kronauer RE, Dijk DJ, Czeisler CA, et al. Uncovering residual effects of chronic sleep loss on human performance. Sci Transl Med (2010) 2:14ra3.10.1126/scitranslmed.3000458
    1. Schoenborn CA, Adams PE. Health behaviors of adults: United States, 2005–2007. Vital Health Stat 10 (2010) (245):1–132.
    1. Taheri S, Lin L, Austin D, Young T, Mignot E. Short sleep duration is associated with reduced leptin, elevated ghrelin, and increased body mass index. PLoS Med (2004) 1:e62.10.1371/journal.pmed.0010062
    1. Patel SR, Hu FB. Short sleep duration and weight gain: a systematic review. Obesity (2008) 16:643–53.10.1038/oby.2007.118
    1. Garaulet M, Ortega FB, Ruiz JR, Rey-Lopez JP, Beghin 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) 35:1308–17.10.1038/ijo.2011.149
    1. Knutson KL, Van Cauter E. Associations between sleep loss and increased risk of obesity and diabetes. Ann N Y Acad Sci (2008) 1129:287–304.10.1196/annals.1417.033
    1. Brondel L, Romer MA, Nougues PM, Touyarou P, Davenne D. Acute partial sleep deprivation increases food intake in healthy men. Am J Clin Nutr (2010) 91(6):1550–9.10.3945/ajcn.2009.28523
    1. Markwald RR, Melanson EL, Smith MR, Higgins J, Perreault L, Eckel RH, et al. Impact of insufficient sleep on total daily energy expenditure, food intake, and weight gain. Proc Natl Acad Sci U S A (2013) 110:5695–700.10.1073/pnas.1216951110
    1. Nedeltcheva AV, Kilkus JM, Imperial J, Kasza K, Schoeller DA, Penev PD. Sleep curtailment is accompanied by increased intake of calories from snacks. Am J Clin Nutr (2009) 89:126–33.10.3945/ajcn.2008.26574
    1. Spaeth AM, Dinges DF, Goel N. Effects of experimental sleep restriction on weight gain, caloric intake, and meal timing in healthy adults. Sleep (2013) 36:981–90.10.5665/sleep.2792
    1. Spiegel K, Leproult R, L’Hermite-Baleriaux M, Copinschi G, Penev PD, Van Cauter E. Leptin levels are dependent on sleep duration: relationships with sympathovagal balance, carbohydrate regulation, cortisol, and thyrotropin. J Clin Endocrinol Metab (2004) 89:5762–71.10.1210/jc.2004-1003
    1. Spiegel K, Tasali E, Penev P, Van Cauter E. Brief communication: sleep curtailment in healthy young men is associated with decreased leptin levels, elevated ghrelin levels, and increased hunger and appetite. Ann Intern Med (2004) 141:846–50.10.7326/0003-4819-141-11-200412070-00008
    1. Chaput JP, Després JP, Bouchard C, Tremblay A. Short sleep duration is associated with reduced leptin levels and increased adiposity: results from the Quebec family study. Obesity (2007) 15:253–61.10.1038/oby.2007.512
    1. Schmid SM, Hallschmid M, Jauch-Chara K, Born J, Schultes B. A single night of sleep deprivation increases ghrelin levels and feelings of hunger in normal-weight healthy men. J Sleep Res (2008) 17:331–4.10.1111/j.1365-2869.2008.00662.x
    1. Broussard JL, Kilkus JM, Delebecque F, Abraham V, Day A, Whitmore HR, et al. Elevated ghrelin predicts food intake during experimental sleep restriction. Obesity (2016) 24:132–8.10.1002/oby.21321
    1. St-Onge MP, O’Keeffe M, Roberts AL, RoyChoudhury A, Laferrere B. Short sleep duration, glucose dysregulation and hormonal regulation of appetite in men and women. Sleep (2012) 35(11):1503–10.10.5665/sleep.2198
    1. Chaput JP, St-Onge MP. Increased food intake by insufficient sleep in humans: are we jumping the gun on the hormonal explanation? Front Endocrinol (2014) 5:116.10.3389/fendo.2014.00116
    1. Hill JO, Wyatt HR, Reed GW, Peters JC. Obesity and the environment: where do we go from here? Science (2003) 299:853–5.10.1126/science.1079857
    1. Antunes LC, Levandovski R, Dantas G, Caumo W, Hidalgo MP. Obesity and shift work: chronobiological aspects. Nutr Res Rev (2010) 23:155–68.10.1017/S0954422410000016
    1. Karlsson B, Knutsson A, Lindahl B. Is there an association between shift work and having a metabolic syndrome? Results from a population based study of 27,485 people. Occup Environ Med (2001) 58:747–52.10.1136/oem.58.11.747
    1. Shea SA. Obesity and pharmacologic control of the body clock. N Engl J Med (2012) 367:175–8.10.1056/NEJMcibr1204644
    1. Guo Y, Liu Y, Huang X, Rong Y, He M, Wang Y, et al. The effects of shift work on sleeping quality, hypertension and diabetes in retired workers. PLoS One (2013) 8:e71107.10.1371/journal.pone.0071107
    1. McHill AW, Phillips AJ, Czeisler CA, Keating L, Yee K, Barger LK, et al. Later circadian timing of food intake is associated with increased body fat. Am J Clin Nutr (2017) 106:1213–9.10.3945/ajcn.117.161588
    1. Buxton OM, Cain SW, O’Connor SP, Porter JH, Duffy JF, Wang W, et al. Adverse metabolic consequences in humans of prolonged sleep restriction combined with circadian disruption. Sci Transl Med (2012) 4:129ra43.10.1126/scitranslmed.3003200
    1. McHill A, Melanson E, Higgins J, Connick E, Moehlman T, Stothard E, et al. Impact of circadian misalignment on energy metabolism during simulated shiftwork. Proc Natl Acad Sci U S A (2014) 111:17302–7.10.1073/pnas.1412021111
    1. Morris CJ, Garcia JI, Myers S, Yang JN, Trienekens N, Scheer FA. The human circadian system has a dominating role in causing the morning/evening difference in diet-induced thermogenesis. Obesity (2015) 23:2053–8.10.1002/oby.21189
    1. Scheer FA, Morris CJ, Shea SA. The internal circadian clock increases hunger and appetite in the evening independent of food intake and other behaviors. Obesity (2013) 21:421–3.10.1002/oby.20351
    1. Sinha MK, Ohannesian JP, Heiman ML, Kriauciunas A, Stephens TW, Magosin S, et al. Nocturnal rise of leptin in lean, obese, and non-insulin-dependent diabetes mellitus subjects. J Clin Invest (1996) 97:1344.10.1172/JCI118551
    1. Bodosi B, Gardi J, Hajdu I, Szentirmai E, Obal F, Jr, Krueger JM. Rhythms of ghrelin, leptin, and sleep in rats: effects of the normal diurnal cycle, restricted feeding, and sleep deprivation. Am J Physiol Regul Integr Comp Physiol (2004) 287:R1071–9.10.1152/ajpregu.00294.2004
    1. Dzaja A, Dalal MA, Himmerich H, Uhr M, Pollmacher T, Schuld A. Sleep enhances nocturnal plasma ghrelin levels in healthy subjects. Am J Physiol Endocrinol Metab (2004) 286:E963–7.10.1152/ajpendo.00527.2003
    1. Espelund U, Hansen TK, Hojlund K, Beck-Nielsen H, Clausen JT, Hansen BS, et al. Fasting unmasks a strong inverse association between ghrelin and cortisol in serum: studies in obese and normal-weight subjects. J Clin Endocrinol Metab (2005) 90:741–6.10.1210/jc.2004-0604
    1. Schoeller DA, Cella LK, Sinha MK, Caro JF. Entrainment of the diurnal rhythm of plasma leptin to meal timing. J Clin Invest (1997) 100(7):1882–7.10.1172/JCI119717
    1. Simon C, Gronfier C, Schlienger JL, Brandenberger G. Circadian and ultradian variations of leptin in normal man under continuous enteral nutrition: relationship to sleep and body temperature. J Clin Endocrinol Metab (1998) 83:1893–9.10.1210/jcem.83.6.4864
    1. Duffy JF, Dijk DJ. Getting through to circadian oscillators: why use constant routines? J Biol Rhythms (2002) 17(1):4–13.10.1177/074873002129002294
    1. Morgan L, Arendt J, Owens D, Folkard S, Hampton S, Deacon S, et al. Effects of the endogenous clock and sleep time on melatonin, insulin, glucose and lipid metabolism. J Endocrinol (1998) 157:443–51.10.1677/joe.0.1570443
    1. Shea SA, Hilton MF, Orlova C, Ayers RT, Mantzoros CS. Independent circadian and sleep/wake regulation of adipokines and glucose in humans. J Clin Endocrinol Metab (2005) 90:2537–44.10.1210/jc.2004-2232
    1. Harris JA, Benedict FG. A biometric study of human basal metabolism. Proc Natl Acad Sci U S A (1918) 4:370–3.10.1073/pnas.4.12.370
    1. Czeisler CA, Duffy JF, Shanahan TL, Brown EN, Mitchell JF, Rimmer DW, et al. Stability, precision, and near-24-hour period of the human circadian pacemaker. Science (1999) 284:2177–81.10.1126/science.284.5423.2177
    1. Carnell S, Grillot C, Ungredda T, Ellis S, Mehta N, Holst J, et al. Morning and afternoon appetite and gut hormone responses to meal and stress challenges in obese individuals with and without binge eating disorder. Int J Obes (Lond) (2018) 42(4):841–9.10.1038/ijo.2017.307
    1. Scheer FA, Hilton MF, Mantzoros CS, Shea SA. Adverse metabolic and cardiovascular consequences of circadian misalignment. Proc Natl Acad Sci U S A (2009) 106:4453–8.10.1073/pnas.0808180106
    1. Spiegel K, Knutson K, Leproult R, Tasali E, Van Cauter E. Sleep loss: a novel risk factor for insulin resistance and type 2 diabetes. J Appl Physiol (2005) 99:2008–19.10.1152/japplphysiol.00660.2005
    1. Buxton OM, Pavlova M, Reid EW, Wang W, Simonson DC, Adler GK. Sleep restriction for 1 week reduces insulin sensitivity in healthy men. Diabetes (2010) 59:2126–33.10.2337/db09-0699
    1. Broussard JL, Ehrmann DA, Van Cauter E, Tasali E, Brady MJ. Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study. Ann Intern Med (2012) 157:549–57.10.7326/0003-4819-157-8-201210160-00005
    1. Tasali E, Leproult R, Ehrmann DA, Van Cauter E. Slow-wave sleep and the risk of type 2 diabetes in humans. Proc Natl Acad Sci U S A (2008) 105:1044–9.10.1073/pnas.0706446105
    1. Shaw ND, McHill AW, Schiavon M, Kangarloo T, Mankowski PW, Cobelli C, et al. Effect of slow-wave sleep disruption on metabolic parameters in adolescents. Sleep (2016) 39:1591–9.10.5665/sleep.6028
    1. Leproult R, Holmbäck U, Van Cauter E. Circadian misalignment augments markers of insulin resistance and inflammation, independently of sleep loss. Diabetes (2014) 63:1860–9.10.2337/db13-1546
    1. Morris CJ, Yang JN, Garcia JI, Myers S, Bozzi I, Wang W, et al. Endogenous circadian system and circadian misalignment impact glucose tolerance via separate mechanisms in humans. Proc Natl Acad Sci U S A (2015) 112:E2225–34.10.1073/pnas.1418955112
    1. Eckel RH, Depner CM, Perreault L, Markwald RR, Smith MR, McHill AW, et al. Morning circadian misalignment during short sleep duration impacts insulin sensitivity. Curr Biol (2015) 25:3004–10.10.1016/j.cub.2015.10.011
    1. Rubio-Sastre P, Scheer FA, Gomez-Abellan P, Madrid JA, Garaulet M. Acute melatonin administration in humans impairs glucose tolerance in both the morning and evening. Sleep (2014) 37:1715–9.10.5665/sleep.4088
    1. Cagnacci A, Arangino S, Renzi A, Paoletti AM, Melis GB, Cagnacci P, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (2001) 54:339–46.10.1046/j.1365-2265.2001.01232.x
    1. Tuomi T, Nagorny CL, Singh P, Bennet H, Yu Q, Alenkvist I, et al. Increased melatonin signaling is a risk factor for type 2 diabetes. Cell Metab (2016) 23:1067–77.10.1016/j.cmet.2016.04.009
    1. Lane JM, Chang AM, Bjonnes AC, Aeschbach D, Anderson C, Cade BE, et al. Impact of common diabetes risk variant in MTNR1B on sleep, circadian and melatonin physiology. Diabetes (2016) 65:1741–51.10.2337/db15-0999
    1. Robertson MD, Russell-Jones D, Umpleby AM, Dijk DJ. Effects of three weeks of mild sleep restriction implemented in the home environment on multiple metabolic and endocrine markers in healthy young men. Metabolism (2013) 62:204–11.10.1016/j.metabol.2012.07.016
    1. Simpson NS, Banks S, Arroyo S, Dinges DF. Effects of sleep restriction on adiponectin levels in healthy men and women. Physiol Behav (2010) 101:693–8.10.1016/j.physbeh.2010.08.006
    1. Leproult R, Copinschi G, Buxton O, Van Cauter E. Sleep loss results in an elevation of cortisol levels the next evening. Sleep (1997) 20:865–70.
    1. Broussard JL, Chapotot F, Abraham V, Day A, Delebecque F, Whitmore HR, et al. Sleep restriction increases free fatty acids in healthy men. Diabetologia (2015) 58:791–8.10.1007/s00125-015-3500-4
    1. Schmid SM, Hallschmid M, Jauch-Chara K, Bandorf N, Born J, Schultes B. Sleep loss alters basal metabolic hormone secretion and modulates the dynamic counterregulatory response to hypoglycemia. J Clin Endocrinol Metab (2007) 92:3044–51.10.1210/jc.2006-2788
    1. Donga E, van Dijk M, van Dijk JG, Biermasz NR, Lammers GJ, van Kralingen KW, et al. A single night of partial sleep deprivation induces insulin resistance in multiple metabolic pathways in healthy subjects. J Clin Endocrinol Metab (2010) 95:2963–8.10.1210/jc.2009-2430
    1. Pejovic S, Basta M, Vgontzas AN, Kritikou I, Shaffer ML, Tsaoussoglou M, et al. Effects of recovery sleep after one work week of mild sleep restriction on interleukin-6 and cortisol secretion and daytime sleepiness and performance. Am J Physiol Endocrinol Metab (2013) 305:E890–6.10.1152/ajpendo.00301.2013

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