Adverse metabolic and cardiovascular consequences of circadian misalignment
Open accessAbstract
There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h "day." Subjects ate 4 isocaloric meals each 28-h "day." For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling approximately 1,000 assays/subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept approximately 12 h out of phase from their habitual times, systematically decreased leptin (-17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (-20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work.
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The postprandial responses of some healthy individuals during the biological night are equivalent to the responses of individuals with prediabetes.
“The postprandial responses of some healthy individuals during the biological night are equivalent to the responses of individuals with prediabetes (9).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [9]
It is possible that glucose impairments persist for several hours in the LE condition.
“Whereas our study was limited to 2-h assessments, it is possible that glucose impairments persist for several hours in the LE condition (9).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [9]
Studies in highly controlled laboratory conditions have found that eating during the biological night causes metabolic changes, including increased postprandial glucose.
“Studies performed in highly controlled laboratory conditions have found that eating during the biological night causes metabolic changes, including increased postprandial glucose (3,8,9).”
From Interplay of Dinner Timing and <i>MTNR1B</i> Type 2 Diabetes Risk Variant on Glucose Tolerance and Insulin Secretion: A Randomized Crossover Trial (2022) · cites this paper as [9]
Two recent laboratory studies provided causative evidence that circadian misalignment associated with reductions in total sleep time has a deleterious effect on diabetes risk and cardiovascular function.
“Two recent laboratory studies in which healthy participants were exposed to circadian misalignment associated with reductions in total sleep time provided causative evidence for a deleterious effect on diabetes risk and cardiovascular function (14,15).”
From Circadian Misalignment Augments Markers of Insulin Resistance and Inflammation, Independently of Sleep Loss (2014) · cites this paper as [14]
In a previous study, total sleep time varied according to the degree of misalignment, and the conclusion relied on statistical significance while controlling for sleep efficiency.
“In this previous study, total sleep time varied according to the degree of misalignment, and the conclusion that circadian misalignment has adverse cardiometabolic consequences relied on the statistical significance of alignment versus misalignment while controlling for sleep efficiency as a covariate in the statistical analysis.”
From Circadian Misalignment Augments Markers of Insulin Resistance and Inflammation, Independently of Sleep Loss (2014) · cites this paper as [14]
Circadian misalignment may lead to central and peripheral deleterious consequences, such as memory deficit and insulin resistance.
“Circadian misalignment may lead to central and peripheral deleterious consequences, such as memory deficit and insulin resistance [69–71].”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [71]
During circadian misalignment, sleep efficiency was reduced to 67% versus 84% at baseline, and glucose and insulin responses to breakfast were increased.
“sleep efficiency was reduced to 67% at the peak of circadian misalignment (versus 84% at baseline), and the glucose and insulin responses to breakfast were increased [35].”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [35]
Young healthy men and women in a forced desynchrony protocol exhibited lower leptin levels when they ate and slept 12h out of phase from their usual schedule.
“Lastly, young healthy men and women studied on in a forced desynchrony protocol involving a 28-h sleep-wake and dark-light cycle with 4 isocaloric meals exhibited lower leptin levels when they ate and slept 12h out of phase from their usual schedule [35].”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [35]
In one study, circadian misalignment led some subjects to exhibit postprandial glucose responses akin to the range observed in prediabetes.
“In one particular study, circadian misalignment led some subjects to exhibit postprandial glucose responses akin to the range observed in prediabetes (111).”
From Chronotype: Implications for Epidemiologic Studies on Chrono-Nutrition and Cardiometabolic Health (2019) · cites this paper as [111]
Laboratory studies examining the impact of circadian and/or sleep disruption on glucose homeostasis under controlled conditions support the epidemiological findings linking circadian/sleep disruption to type 2 diabetes.
“a number of laboratory studies examining the impact of circadian and/or sleep disruption on glucose homeostasis under controlled conditions, support the above mentioned epidemiological findings [144–147].”
From Circadian control of glucose metabolism (2014) · cites this paper as [146]
Disruption of the circadian clock, because of shift-work or bad sleeping habits, can cause severe disturbances in endocrine rhythms.
“Disruption of the circadian clock, because of shift-work or bad sleeping habits, can cause severe disturbances in these rhythms [146].”
From Circadian control of glucose metabolism (2014) · cites this paper as [146]
Healthy adults asked to eat and sleep 12 hours out of phase from their regular schedules exhibited vascular and endocrine abnormalities, such as increased arterial pressure, reversed daily cortisol rhythm, and postprandial glucose levels in the prediabetic range.
“healthy adults asked to eat and sleep 12 hours out of phase from their regular schedules exhibited vascular and endocrine abnormalities, such as increased arterial pressure, a reversed daily cortisol rhythm, and postprandial glucose levels in the range of a prediabetic state (8).”
From Social jetlag, chronotype, and cardiometabolic risk (2015) · cites this paper as [8]
The report extends findings from acute circadian misalignment paradigms and prospective shift-work studies by demonstrating a link between social jetlag and metabolic abnormalities.
“Our report extends findings from both acute circadian misalignment paradigms and prospective shift-work studies by demonstrating a link between SJL and metabolic abnormalities (8,11).”
From Social jetlag, chronotype, and cardiometabolic risk (2015) · cites this paper as [8]
The effects of circadian misalignment were already observed after just a few days.
“The effects were already observed after just a few days of circadian misalignment.”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [69]
Circadian misalignment causes decreased glucose tolerance, decreased concentrations of the satiety hormone leptin, and increased wake time blood pressure.
“In an initial study, we showed that circadian misalignment causes decreased glucose tolerance, decreased concentrations of the satiety hormone leptin, and increased wake time blood pressure (69).”
From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [69]
In humans, resting plasma epinephrine and norepinephrine levels exhibit endogenous circadian rhythmicity with a broad peak during the middle of the biological day.
“In humans, resting plasma epinephrine and norepinephrine levels—markers of sympathetic nervous activity—exhibit endogenous circadian rhythmicity with a broad peak during the middle of the biological day”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2009
Circadian misalignment, defined as desynchrony between the circadian timing system and behaviors, increases wake time blood pressure.
“Scheer et al. (2009) demonstrated that circadian misalignment (i.e., desynchrony between the circadian timing system and behaviors) increases wake time blood pressure.”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2009
The effect of circadian misalignment on leptin is likely to be at least in part independent of concurrent decreases in sleep efficiency.
“A covariance analysis performed by Scheer et al. (2009) suggests that the effect of circadian misalignment on leptin is likely to be at least in part independent of concurrent decreases in sleep efficiency.”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2009
Short-term exposure (after 3 days) to circadian misalignment per se increases postprandial responses of glucose and insulin, demonstrating reduced glucose tolerance and suggesting reduced insulin sensitivity.
“Scheer et al. (2009), utilizing a forced desynchrony protocol, demonstrated that short-term exposure (after 3 days) to circadian misalignment per se increases the postprandial responses of glucose and insulin, demonstrating reduced glucose tolerance and suggesting reduced insulin sensitivity under these conditions (Fig. 4).”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2009
Short-term circadian misalignment while subjects consume isocaloric meals decreases circulating levels of leptin.
“Short-term circadian misalignment while subjects consume isocaloric meals also decreases circulating levels of leptin (Fig. 4; Scheer et al., 2009).”
From The impact of the circadian timing system on cardiovascular and metabolic function (2012) · cites this paper as Scheer et al., 2009
Circadian misalignment has been found to result in adverse metabolic and cardiovascular consequences, including decreased leptin, increased glucose and insulin, increased mean arterial blood pressure, and reduced sleep efficiency.
“This circadian misalignment has been found to result in adverse metabolic and cardiovascular consequences, including a decrease in leptin, an increase in glucose and insulin, an increase in mean arterial blood pressure, and reduced sleep efficiency [17].”
From Rotating Night Shift Work and Risk of Type 2 Diabetes: Two Prospective Cohort Studies in Women (2011) · cites this paper as [17]
The increase in glucose associated with circadian misalignment seems to be the result of an exaggerated postprandial glucose response.
“Furthermore, the increase in glucose seems to be the result of an exaggerated postprandial glucose response [17].”
From Rotating Night Shift Work and Risk of Type 2 Diabetes: Two Prospective Cohort Studies in Women (2011) · cites this paper as [17]
Rotating night shift work is generally associated with chronic misalignment between the endogenous circadian timing system and behavior cycles.
“Rotating night shift work is generally associated with chronic misalignment between the endogenous circadian timing system and the behavior cycles.”
From Rotating Night Shift Work and Risk of Type 2 Diabetes: Two Prospective Cohort Studies in Women (2011) · cites this paper as [17]
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BackgroundResultMeal timing regulates the human circadian system
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- Authors
- Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A.
- Affiliations
- Brigham and Women's Hospital (US)
- Beth Israel Deaconess Medical Center (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2009-03-17
- Volume
- 106
- Issue
- 11
- Pages
- 4453-4458
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC2657421
- OpenAlex
- W2091912666
- Cited by
- 2,351
- References
- 52
- Citations by year
- 2026: 180 · 2025: 148 · 2024: 129 · 2023: 152 · 2022: 162 · 2021: 166 · 2020: 185 · 2019: 151 · 2018: 138 · 2017: 142 · 2016: 134 · 2015: 144 · 2014: 135 · 2013: 113 · 2012: 107
- FWCI
- 40.08
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Brigham and Women's Hospital
- U.S. Public Health Service (NIDDK R01-57875)
- National Heart, Lung, and Blood Institute (K24-HL76446, K24HL076446, R01HL076409, R01HL064815, R01 HL64815)
- National Institute of Diabetes and Digestive and Kidney Diseases
- National Center for Complementary and Alternative Medicine
- National Center for Research Resources (M01RR002635, MO1 RR 02635)
- National Center for Complementary and Integrative Health (R21AT002713)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Keywords
- circadian misalignment, shift work, jet lag, obesity, diabetes mellitus, cardiovascular risk, leptin, insulin, cortisol rhythm, postprandial blood glucose, catecholamines, sleep efficiency, blood pressure, cardiac vagal modulation, core body temperature, cardiometabolic risk
- MeSH terms
- Adult, Cardiovascular Diseases, Circadian Rhythm, Eating, Fasting, Female, Humans, Male, Metabolic Diseases, Prediabetic State, Sleep, Wakefulness, Postprandial Period, Chronobiology Disorders
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.
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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