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Published in final edited form as: Sleep Health. 2023 Nov 23;10(1 Suppl):S96–S102. doi: 10.1016/j.sleh.2023.10.010

Influence of circadian phase and extended wakefulness on glucose levels during forced desynchrony

Josiane L Broussard 1,2, Brent C Knud-Hansen 1,2, Scott Grady 3,4,5, Oliver A Knauer 1, Joseph M Ronda 3,4, Daniel Aeschbach 3,4,6, Charles A Czeisler 3,4, Kenneth P Wright Jr 1,3,4
PMCID: PMC11031343  NIHMSID: NIHMS1947417  PMID: 37996284

Abstract

Objectives.

Circadian misalignment and sleep deprivation often occur in tandem, and both negatively impact glucose homeostasis and metabolic health. The present study employed a forced desynchrony protocol to examine the influence of extended wakefulness and circadian misalignment on hourly glucose levels.

Methods.

Nine healthy adults (4F/5M; 26±4 years) completed a 31-day in-laboratory protocol. After three 24h baseline days with 8h scheduled sleep opportunities, participants were scheduled to 14 consecutive 42.85h sleep-wake cycles, with 28.57h extended wakefulness and 14.28h sleep opportunities each cycle. Blood was sampled hourly across the forced desynchrony and over 600 plasma samples per participant were analyzed for glucose levels.

Results.

Both hours into the 42.85h forced desynchrony day and circadian phase modulated glucose levels (p<0.0001). Glucose peaked after each meal during scheduled wakefulness and decreased during scheduled sleep/fasting. Glucose levels were, on average, lowest during the biological daytime and rose throughout the biological night, peaking in the biological morning. When analyzed separately for scheduled sleep versus wakefulness, the peak timing of the circadian rhythm in glucose was later during sleep (p<0.05). Glucose area under the curve levels increased rapidly from the beginning of the forced desynchrony protocol and were highest on the second forced desynchrony day (p<0.01), returning towards forced desynchrony day 1 levels thereafter.

Conclusions.

These findings have important implications for understanding factors contributing to altered glucose metabolism during sleep loss and circadian misalignment, and for potential physiological adaptation of metabolism in healthy adults, who are increasingly exposed to such conditions in our society.

Keywords: Circadian misalignment, sleep deprivation, glucose metabolism, forced desynchrony

Introduction

Type 2 diabetes is a major health problem that increases risk of other medical issues including cardiovascular, kidney, cancer, mood, sleep, and neurodegenerative diseases, as well as diabetic neuropathy and eye disorders (1). Traditional risk factors for Type 2 diabetes include overweight and obesity, a family history of Type 2 diabetes, physical inactivity, and being 45 years or older; yet the incidence of Type 2 diabetes has been increasing in children and young adults (2).

Sleep insufficiency and circadian disruption are increasingly recognized as important factors that impair glycemic control, contribute to metabolic dysregulation, and increase the risk of metabolic diseases (3–10). Sleep and circadian disturbances may thus represent important and modifiable factors that contribute to the ongoing Type 2 diabetes epidemic (3–5).

Plasma glucose levels fluctuate over the course of the day in humans, resulting from a tightly controlled balance between glucose appearance—either from hepatic glucose production in the post-absorptive state or delivery of glucose from the gut following a meal—and glucose clearance, predominantly by insulin sensitive tissues (11). Glucose tolerance, which refers to the body’s ability to clear glucose from the blood and depends on the ability of insulin to promote glucose disappearance from circulation and inhibit endogenous glucose production (12), has a well-documented day-night rhythm in humans. For example, findings from a number of studies in which oral glucose tests were conducted at multiple time points across the day show higher blood glucose area under the curve in the afternoon and/or evening, compared to the morning (13–15). In support of this day-night variation in oral glucose tolerance, similar findings are observed when glucose is administered via an intravenous glucose tolerance test (15, 16), when continuously administered intravenously (17, 18), or as enteral nutrition (19, 20). Related, this daily variation in glucose levels has been shown in response to identical or similar mixed meals that in most cases were rich carbohydrates, with higher elevation in plasma glucose in the evening as compared of the morning in healthy adults (21–24).

Behavioral cycles of eating/fasting and wakefulness/sleep impact glucose metabolism across the day. The typical day-night pattern of these behaviors, therefore, interact with any endogenous circadian rhythms, making it impossible to assess the circadian rhythm of glucose. Thus, circadian protocols (25, 26) such as the constant routine and forced desynchrony have been used to elucidate the underlying circadian rather than the day-night rhythm of circulating glucose. The constant routine eliminates, makes constant or equally distributes across the circadian cycle factors that influence circadian variables (25, 27). Using the constant routine protocol, a circadian rhythm can be observed in plasma glucose levels with a peak during the biological night (i.e., when endogenous melatonin levels are high) (28–31) or biological morning (32) and lower levels during the biological day (i.e., when endogenous melatonin levels are low). Forced desynchrony protocols schedule participants wakefulness-sleep, activity-rest, eating-fasting and light-dark times to non-24h cycles, with imposed periods, T-cycles, to which the circadian rhythm cannot entrain (26). Thus, wakefulness-sleep/activity-rest/eating-fasting and light-dark times are distributed across a range of circadian phases. Under forced desynchrony conditions, a circadian rhythm in plasma glucose is also apparent with a peak during the biological night (33, 34). Given the circadian variation in glucose levels, it is not surprising that disruption of the circadian system adversely impacts glucose metabolism. For example, glucose homeostasis is impaired during extended wakefulness (insufficient sleep and/or sleep deprivation) and circadian misalignment (e.g., shift work models) (3–7).

In addition to determining circadian contribution to human physiology, the forced desynchrony protocol also allows for the determination of wakefulness-sleep/eating-fasting/activity-rest patterns on physiological outcomes in humans. We therefore used a controlled 31-day inpatient forced desynchrony protocol with a 42.85-hour T-cycle to examine the influence of extended wakefulness (28.57h) and of food intake and subsequent sleep and fasting each forced desynchrony day, distributed across a range of circadian phases on glucose levels.

Methods

Participants

Nine healthy young adults (4F/5M; 26±4 years old [range 19-30y], BMI: 24.6±1.6 kg/m2 [range 22–27.2 kg/m2]; mean±SD) completed the study. Participants were from the control group in a randomized double-blind placebo-controlled study for which core temperature circadian period and levels, performance, sleepiness, alertness, and attentive ratings, slow eye movements, and sleep efficiency data have been published as part of a larger wakefulness promoting therapeutic investigation (35). Participants were deemed healthy based on questionnaires, medical, psychiatric, and sleep history, physical, and psychological examinations, 12-lead electrocardiogram, blood (complete blood cell count and comprehensive metabolic panel) and urine chemistries, as well as toxicology screen for drug use at screening and at laboratory admission. Exclusionary criteria included any current medical or sleep disorder, or personal or immediate family history of psychopathology. Written informed consent was obtained and procedures and data analyses were approved by local IRBs.

Procedures

Participants maintained habitual self-selected ~8h nighttime sleep schedules at home for three weeks prior to the inpatient portion of the study, verified by sleep logs and time stamped call-ins to a voice recorder and at least one-week of wrist actigraphy (Actiwatch-L, Minimitter Respironics, Inc). Following outpatient monitoring, participants were admitted to the Intensive Physiological Monitoring Unit in the General Clinical Research Center of the Brigham and Women’s Hospital. Participants were tested individually in an environment free of time cues (i.e., no knowledge of the time of day, day of the week/month, or how long they have been awake or asleep; no access to the internet, or personal electronic devices). During free time participants were permitted to read, watch movies, and/or engage in personal work, and board games/hobbies. Ambient light, room temperature, wakefulness-sleep opportunities, activity, and energy intake were strictly controlled. Exercise and napping were proscribed.

After three consecutive baseline days with 8h scheduled nighttime sleep opportunities at the participants’ habitual times, participants were scheduled to a forced desynchrony protocol composed of 14 consecutive 42.85h wakefulness-sleep/food intake-fasting/activity-rest/light-dark T-cycles (‘14 forced desynchrony days’) with 28.57h extended wakefulness and 14.28h sleep opportunities (maintaining a 2:1 wakefulness-sleep schedule), occurring over twenty-five 24h days (Figure 1). Participants were required to remain awake during scheduled wakefulness episodes and to remain lying down in bed trying to sleep during scheduled sleep episodes. Wakefulness and sleep opportunities were verified by continuous EEG recordings and monitoring by research technicians. Artificial lighting was provided by ceiling-mounted fluorescent lamps [Phillips (Eindhoven, The Netherlands) T8 and T80; 4,100 K color temperature] and clear polycarbonate lenses were used to filtered 99.9% of light in the UV range. Ambient light intensity was measured with an IL-1400 photometer (International Light, Newburyport, MA). Participants were studied in darkness during scheduled sleep opportunities and light levels were <15 lux maximum in the room at a height of ~183 cm and < 5 lux at a height of 76 cm with the sensor aimed toward the light fixtures during scheduled wakefulness. Light levels in the angle of gaze during scheduled wakefulness were < 3 lux. Dim light during scheduled wakefulness was used to minimize any acute effects of brighter light on physiology (e.g., elevated body temperature) and to minimize phase shifting of the circadian rhythm (26).

Figure 1. Double plot of the study protocol.

Figure 1

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Day on left axis indicates consecutive study days on a 24h basis whereas numbers within black bars show the 14 consecutive forced desynchrony scheduled sleep episodes on the 42.85h forced day. Baseline days 1–3 and recovery days 30–31 were 24h days with 16h of scheduled wakefulness and 8h of scheduled rest/sleep. Participants were studied in a forced desynchrony protocol on days 4–29 (left axis) consisting of fourteen 42.85h days with of 28.57h of scheduled wakefulness and 14.28h of scheduled sleep.

During the 28.57h episodes of wakefulness on each forced desynchrony day, 6 meals (2 breakfasts, 2 lunches, 2 dinners) and 1 snack were provided. Fluid and isocaloric caloric intake (BMR x 1.3) were determined based on a 28.57 scheduled wake episode and a 42.85h forced desynchrony day. The 42.85h daylength is outside the range of entrainment of the human circadian pacemaker (35, 36), and under the dim light conditions studied, the central circadian pacemaker oscillates near its endogenous 24h intrinsic period (26, 37, 38).

Core body temperature was measured every minute with a rectal thermistor (Yellow Springs Instruments, Yellow Springs, OH, USA), which was removed for daily showers and bowel movements. The intrinsic circadian period of the core body temperature rhythm was estimated for each participant using non-orthogonal spectral analysis (NOSA), which is a harmonic regression model with correlated noise (26, 35–38). Every sixth minute of the temperature data was entered into NOSA, and these data were fitted with an evoked component of the scheduled sleep-wakefulness cycle (T=42.85 h) and its harmonics, and a circadian component with a period of ~24 h and its harmonics. Serial correlated noise in the model was used to account for perturbations of the body temperature time series that persist (e.g., higher core temperatures due to showers; see (26)). Missing data were intermittent, which is tolerated by NOSA (26).

Hourly blood samples were obtained via a forearm indwelling venous catheter with heparinized saline drip. The 12-foot extension tubing was passed through the research suite porthole during scheduled sleep episodes so that blood sampling could occur without staff entering the participant’s room during scheduled sleep episodes. Participants were provided with ferrous gluconate tablets (324 mg) to be taken at the first breakfast, second lunch and second dinner during forced desynchrony to support red blood cell production during continuous blood sampling. Participant’s hemoglobin levels were tested ~daily to ensure appropriate levels. Blood samples were rapidly centrifuged at 4°C, separated, and the plasma was stored at ~70°C until analyzed for glucose with a YSI 2900 autoanalyzer (Yellow Springs Instrument Co.). Plasma samples had undergone one prior freeze thaw cycle prior to analysis of glucose levels.

Statistical analysis

Based on each individual’s circadian period and trajectory of the phase of the core body temperature rhythm, plasma glucose levels were assigned a 15-degree (1 circadian hour) bin with zero degrees corresponding to the fitted minimum of the endogenous circadian temperature rhythm. Data were also assigned a 1h, hours into the 42.85h forced desynchrony day bin and identified as sampled either during scheduled ‘wakefulness’ or ‘sleep’. Endogenous circadian amplitude and peak phase of the wakefulness and sleep glucose rhythms were determined using NOSA (37, 38) on individual participant data. Further, trapezoidal area under the curve (AUC) was calculated for each of the fourteen 42.85h forced desynchrony days.

Influence of circadian phase and hours into 42.85h forced desynchrony day were analyzed with Mixed-Model ANOVA with hours into 42.85h forced desynchrony day, wakefulness or sleep, and circadian phase bin as fixed factors. Influence of circadian bin, amplitude, and peak phase were also examined for the glucose rhythm during scheduled wakefulness versus sleep with Mixed-Model ANOVA circadian phase bin or ‘state’ as a fixed factor. Influence of forced desynchrony day AUC was analyzed with Mixed-Model ANOVA with participant as a random factor and 42.85h forced desynchrony day as a fixed factor.

Results

Hours into the forced desynchrony day and glucose levels

Hourly glucose levels averaged with respect to the imposed 42.85h T cycle (and thus independent of circadian time) are displayed in Figure 2a and demonstrate a significant main effect of the imposed sleep-wake cycle (Figure 2a; p<0.0001). Glucose peaked after each meal during scheduled wakefulness, with the largest peak occurring after the first meal of the day. Glucose levels decreased during scheduled sleep/fasting.

Figure 2. Impact of extended wakefulness and circadian misalignment on glucose profiles as derived from the forced desynchrony protocol.

Figure 2.

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Glucose was averaged across the fourteen 42.85h forced desynchrony days and profiles are expressed as a function of hours into the 42.85h forced day (A) and 15° circadian phase bins (B). Glucose levels as a function of circadian phase (C) were further divided into values during scheduled wakefulness (red line) and sleep (black line). Blue box represents an approximation of the biological night when endogenous melatonin levels would be high. Stars representing differences in glucose levels for the circadian glucose rhythm between scheduled wakefulness and sleep (p <0.05) are placed once between 180 to 180 degrees as the glucose data are double plotted. Data represent mean values (±SEM).

Circadian rhythm in glucose levels

Hourly glucose levels averaged by circadian phase (and thus independent of hours into 42.85h forced desynchrony day) are displayed in Figure 2b and demonstrate a significant effect of circadian phase (p<0.0001). Glucose levels were lowest prior to the beginning of the biological night, rose across the biological night, peaked in the biological morning, and decreased across the remainder of the biological day. When plotted separately for scheduled wakefulness and scheduled sleep (Figure 2c), wakefulness glucose levels were higher than observed during scheduled sleep at nearly every circadian phase (interaction effect of sleep-wakefulness state x circadian phase, p < 0.001). Glucose levels during scheduled sleep displayed a circadian rhythm similar to that shown in figure 2b, such that levels were lowest prior to the beginning of the biological night, rose during the biological night, showed a fitted peak in the biological morning at 94.4±13.5 circadian degrees, and decreased across the remainder of the biological day. Glucose levels during scheduled wakefulness also displayed a circadian rhythm such that levels were lowest prior to the beginning of the biological night, peaked during the biological night near 32.3±8.1 circadian degrees and decreased thereafter. The peak circadian phase of the glucose rhythm was significantly later during scheduled sleep versus wakefulness (p<0.05), whereas the circadian amplitudes of the glucose rhythm were not significantly different during scheduled sleep (8.1±1.3 mg/dl) versus wakefulness (6.5±1.2 mg/dl; p=0.15).

Hours into the forced desynchrony day and daily glucose levels

We next examined glucose levels for each 42.85h forced desynchrony day. Figure 3A shows hourly glucose levels on forced desynchrony day 1 when wakefulness began at a typical time of day compared to baseline and on forced desynchrony day 2 when wakefulness began during the biological night. On forced desynchrony day 2, glucose levels increased rapidly during combined extended wakefulness and circadian misalignment compared to forced desynchrony day 1. Glucose excursions that were on average above 140 mg/dl were seen on forced desynchrony day 2 after meals 1, 3, 4, and 6 whereas no such excursions occurred on forced desynchrony day 1. Glucose levels were also higher during the first two-thirds of the sleep episode on forced desynchrony day 2 versus forced desynchrony day 1. Figure 3B shows hourly glucose levels on forced desynchrony days 1, 6, and 10 when wakefulness began at a more similar time of day compared to baseline (in this case near habitual waketime) and as can be seen glucose levels were more similar. Glucose profiles for all other forced desynchrony days plotted for those that began at a more similar times of day are shown in Supplemental Figure 1.

Figure 3. Impact of extended wakefulness and circadian misalignment on glucose AUC.

Figure 3.

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Glucose is plotted hourly across the first and second (A) and first, sixth and tenth (B) 42.85h forced desynchrony days. Glucose AUC (C) is plotted for each of the fourteen 42.85h forced desynchrony days. (FD, Forced Desynchrony). Data represent mean values (±SEM).

Glucose AUC for each 42.85h forced desynchrony day is shown in Figure 3C. A significant main effect of forced desynchrony day (p<0.01) was observed with highest glucose AUC on day 2. Following forced desynchrony day 2, glucose AUC returned to levels more similar to those on forced desynchrony day 1.

Discussion

Findings from this study indicate both hours into 42.85h forced desynchrony day and circadian phase modulate glucose levels, with differential effects of sleep and wakefulness on the timing of the circadian rhythm of glucose. Moreover, glucose levels rapidly increased after the first 42.85h forced desynchrony day of combined extended wakefulness and circadian misalignment, followed by a return to forced desynchrony day 1 levels.

This study extends previous findings that plasma glucose oscillates in a circadian manner. Our finding of a circadian peak in glucose levels during the biological night when participants were awake is consistent with the majority of findings from circadian constant routine (28–31, 39) and forced desynchrony protocols (33, 34), whereas our finding of a circadian peak in glucose levels later during the biological morning when participants were asleep is consistent with findings from a prior constant routine study (32). The circadian rhythm in glucose during wakefulness is likely the most relevant for circadian misalignment-induced metabolic dysregulation, given that it largely reflects responses to food intake. It is possible, however, that the sleeping/fasting peak of the circadian rhythm in glucose represents circadian phase differences in other glucose regulatory mechanisms that can be disturbed during sleep when circadian misaligned. Potential mechanisms driving the observed circadian rhythms in glucose, especially during scheduled sleep/fasting, are not entirely clear. For example, a rhythm in hepatic glucose production and its potential involvement in the day-night regulation of glucose homeostasis in humans is largely unknown. Some investigations suggest an impact of sleep itself on hepatic glucose production given the observation of an acute sleep-onset decline in hepatic glucose production (40). However, other reports suggest a lack of day-night rhythm in 24h fasting hepatic glucose production (41). Glucagon is released in response to low blood glucose by pancreatic alpha cells to stimulate hepatic glucose production; however, the rhythm of glucagon has not been examined in a constant routine or forced desynchrony protocol and the available evidence suggests that glucagon is strongly regulated by the wakefulness-sleep/eating-fasting cycle (7). Insulin is another factor regulating plasma glucose levels by inhibiting hepatic glucose production and stimulating glucose uptake by insulin sensitive tissues (11). A day-night variation in insulin sensitivity has been consistently reported in healthy volunteers with higher afternoon and evening blood glucose levels observed following glucose administration, compared to when glucose is administered in the morning (11). Further, the central circadian clock likely plays an important role in glucose rhythm generation, as lesioning the SCN in rats results in the disappearance of a daily fluctuation in food intake, glucose uptake, and insulin sensitivity (42). Additionally, the molecular clock plays a role in glucose metabolism (43). Taken together, the underlying mechanism regulating circadian glucose rhythms remains to be elucidated.

Food intake in humans possesses a robust daily rhythm with eating localized to the daytime/light phase and fasting occurring in the night/dark phase. For some time, it has been recognized that eating during the biological night in humans is associated with metabolic impairments (5–7, 44–47). More recently, eating later in the day (48, 49) or early in the morning (44, 45) is also associated with metabolic dysfunction. For example, a study of food timing in 110 young adults over the course of one week revealed that timing of food intake relative to melatonin onset, which represents the beginning of the biological night, was associated with percent body fat and body mass index (48). Energy intake in the morning when melatonin levels are high is associated with impaired insulin sensitivity (44, 45). Furthermore, when eating at night is prevented during circadian misalignment, glucose tolerance is reported to be largely maintained (30, 50) . Finally, mice lacking whole body (Cry1;Cry2 knock-out) or liver-specific (Bmal1 and Rev-erba/b knock-out) clock function rapidly gain weight and display metabolic impairments when fed an ad libitum diet. However, when fed the same diet but with food access restricted to a 10h interval during the active phase, mice are protected from excessive weight gain and metabolic disease (51). Thus, our findings also are consistent with the hypothesis that circadian misalignment disturbs metabolic homeostasis due to food intake at an adverse circadian phase. Further studies are necessary to determine whether eating at night per se is a contributor to metabolic impairment during circadian misalignment.

Consistent with previous reports of alterations in glucose homeostasis during sleep and circadian disruption, we further observed an acute elevation in glucose levels after the first forced desynchrony day of combined extended wakefulness and circadian misalignment. These data support the notion that sleep and circadian disruption lead to immediate and clinically relevant elevations in glucose levels (i.e., excursions above 140 mg/dl). Specifically, the magnitude of glucose increase on forced desynchrony day 2 is comparable to the glucose differences between people with normal versus impaired glucose tolerance (52). How changes in glucose counterregulatory hormones may contribute to the higher glucose levels in this case is unknown and requires follow-up studies during sleep loss and circadian misalignment. Further, it is unknown why glucose levels returned to forced desynchrony day 1 levels after forced desynchrony day 2 and remained similar to forced desynchrony day 1 levels for the rest of the protocol. Findings from prior studies of circadian misalignment have shown a rapid concomitant increases in insulin levels when food intake occurs during the biological nighttime (7, 46). As we tested healthy adults, it is possible that there was a compensatory increase in insulin secretion after the second forced desynchrony day in the current study reflecting a physiological adaptation to maintain healthy glucose levels. Indeed, insufficient sleep and morning circadian misalignment has been found to be associated with impaired insulin sensitivity that is compensated by an increased insulin response to glucose, which may reflect an initial physiological adaptation to maintain normal blood sugar levels (44). We could not measure insulin levels in the current study due to the limited sample volume available for our analysis and this is a limitation of the study. Sleep is not equivalent across all circadian phases during the forced desynchrony even when the number, timing, and duration of sleep opportunities are tightly controlled (26, 53) and this could contribute to our findings. We studied a relatively small number of healthy young adults and follow-up studies should consider other populations (e.g., middle-aged and older adults, individuals with pre-diabetes, and shift workers).

In conclusion, our data confirm the circadian regulation of glucose, as well as dissect the differential impact of sleep and wakefulness across the circadian cycle on glucose levels and rhythms. Furthermore, we report the impact of extended wakefulness and circadian misalignment on glucose levels acutely and over the course of an extended wakefulness circadian misalignment inpatient protocol, similar in duration to extended duty and nighttime work hours commonly encountered by military personnel, emergency responders, and medical house staff. Our findings have important implications for understanding factors contributing to altered glucose metabolism during sleep loss and circadian misalignment, and for adaptation of metabolic physiology. The mechanism(s) underlying the observations of the present study are not known but may be of relevance regarding metabolic disease risk in individuals who routinely curtail their sleep, as well as have variable sleep-wake schedules and/or suffer from repeated bouts of circadian misalignment.

Supplementary Material

MMC1

Supplemental Figure 1. Impact of extended wakefulness and circadian misalignment on glucose profiles as derived from the forced desynchrony protocol. Glucose was averaged across the fourteen 42.85h forced desynchrony days and profiles are expressed as a function of hours into the 42.85h forced desynchrony day for days with similar waketimes (A-D). Data represent mean values (±SEM).

Acknowledgments

This research was supported by NIH K01DK110138 to J.L.B, US AFOSR F49620-00-1-0266 to C.A.C. J.M.R. and K.P.W., Office of Naval Research MURI grant N00014-15-1-2809 to KPW, and the University of Colorado Boulder Undergraduate Research Opportunities Grant to BKH. This study was conducted in the General Clinical Research Center (GCRC, supported by NIH Grant NCRR-GCRC-M01 RR02635) of the Brigham and Women’s Hospital. This study also received financial support from Cephalon, Inc.

Footnotes

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Statement of Dr. Czeisler’s contributions to this work

In addition to Dr. Czeisler being a corresponding co-author on this manuscript, prior work from him and his colleagues provided foundational knowledge on the use of the forced desynchrony protocol to elucidate the circadian period in humans as well as homeostatic versus circadian impacts on human physiology and behavior (e.g., (26, 35, 36, 38, 53)), including impacts on metabolic health outcomes (6, 8).

Public Health Relevance statement

Sleep loss and circadian misalignment negatively and rapidly impact metabolic physiology. Our findings show immediate and clinically relevant elevations in glucose levels and apparent rapid physiological adaptation.

Disclosure statement

Dr. Broussard reports consulting fees from Everlywell, Inc, Marketing Your Science LLC, and Cellular Longevity, Inc., outside the submitted work. Mr. Knud-Hansen, Dr. Grady and Mr. Knauer have nothing to disclose. Mr. Ronda reports grants from Airforce Office of Scientific Research, grants from Cephalon Inc. during the conduct of the study. Dr Aeschbach reports grants from Airforce Office of Scientific Research, grants from Cephalon Inc., during the conduct of the study; other from German Aerospace Center, outside the submitted work; Dr. Czeisler reports grants from Airforce Office of Scientific Research, grants from Cephalon Inc.; serves as the incumbent of an endowed professorship provided to Harvard Medical School by Cephalon, Inc. Dr, Czeisler reports institutional support for a Quality Improvement Initiative from Delta Airlines and Puget Sound Pilots outside the submitted work; education support to Harvard Medical School Division of Sleep Medicine and support to Brigham and Women’s Hospital from: Jazz Pharmaceuticals PLC, Inc, Philips Respironics, Inc., Optum, and ResMed, Inc. outside the submitted work; research support to Brigham and Women’s Hospital from Axome Therapeutics, Inc., Dayzz Ltd., Peter Brown and Margaret Hamburg, Regeneron Pharmaceuticals, Sanofi SA, Casey Feldman Foundation, Summus, Inc., Takeda Pharmaceutical Co., LTD, Abbaszadeh Foundation, CDC Foundation outside the submitted work; educational funding to the Sleep and Health Education Program of the Harvard Medical School Division of Sleep Medicine from ResMed, Inc., Teva Pharmaceuticals Industries, Ltd., and Vanda Pharmaceuticals outside the submitted work; personal royalty payments on sales of the Actiwatch-2 and Actiwatch-Spectrum devices from Philips Respironics, Inc outside the submitted work; personal consulting fees from Axome, Inc., Bryte Foundation, With Deep, Inc. and Vanda Pharmaceuticals; honoraria from the Associated Professional Sleep Societies, LLC for the Thomas Roth Lecture of Excellence at SLEEP 2022, from the Massachusetts Medical Society for a New England Journal of Medicine Perspective article, from the National Council for Mental Wellbeing, from the National Sleep Foundation for serving as chair of the Sleep Timing and Variability Consensus Panel, for lecture fees from Teva Pharma Australia PTY Ltd. and Emory University, and for serving as an advisory board member for the Institute of Digital Media and Child Development, the Klarman Family Foundation, and the UK Biotechnology and Biological Sciences Research Council outside the submitted work. Dr. Czeisler has received personal fees for serving as an expert witness on a number of civil matters, criminal matters, and arbitration cases, including those involving the following commercial and government entities: Amtrak; Bombardier, Inc.; C&J Energy Services; Dallas Police Association; Delta Airlines/Comair; Enterprise Rent-A-Car; FedEx; Greyhound Lines, Inc./Motor Coach Industries/FirstGroup America; PAR Electrical Contractors, Inc.; Puget Sound Pilots; and the San Francisco Sheriff’s Department; Schlumberger Technology Corp.; Union Pacific Railroad; United Parcel Service; Vanda Pharmaceuticals. CAC has received travel support from the Stanley Ho Medical Development Foundation for travel to Macao and Hong Kong; equity interest in Vanda Pharmaceuticals, With Deep, Inc, and Signos, Inc. outside the submitted work; and institutional educational gifts to Brigham and Women’s Hospital from Johnson & Johnson, Mary Ann and Stanley Snider via Combined Jewish Philanthropies, Alexandra Drane, DR Capital, Harmony Biosciences, LLC, San Francisco Bar Pilots, Whoop, Inc., Eisai Co., LTD, Idorsia Pharmaceuticals LTD, Sleep Number Corp., Apnimed, Inc., Avadel Pharmaceuticals, Bryte Foundation, f.lux Software, LLC, Stuart F. and Diana L. Quan Charitable Fund outside the submitted work. Dr Czeisler’s interests were reviewed and are managed by the Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of interest policies. Dr. Wright reports grants from Airforce Office of Scientific Research, grants from Cephalon Inc. Dr. Wright reports consulting fees from or served as a paid member of scientific advisory boards for the Sleep Disorders Research Advisory Board-National Heart, Lung and Blood Institute, CurAegis Technologies, Circadian Therapeutics,LTD, Circadian Biotherapies, Inc., and the U.S. Army Medical Research and Materiel Command–Walter Reed Army Institute of Research outside the submitted work; research support/donated materials: DuPont Nutrition & Biosciences, Grain Processing Corporation, and Friesland Campina Innovation Centre outside the submitted work.

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Associated Data

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Supplementary Materials

MMC1

Supplemental Figure 1. Impact of extended wakefulness and circadian misalignment on glucose profiles as derived from the forced desynchrony protocol. Glucose was averaged across the fourteen 42.85h forced desynchrony days and profiles are expressed as a function of hours into the 42.85h forced desynchrony day for days with similar waketimes (A-D). Data represent mean values (±SEM).

NIHMS1947417-supplement-MMC1.pptx (99KB, pptx)

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