Adverse metabolic and cardiovascular consequences of circadian misalignment

Division of Sleep Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
Proceedings of the National Academy of Sciences (Impact Factor: 9.67). 04/2009; 106(11):4453-8. DOI: 10.1073/pnas.0808180106
Source: PubMed


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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Available from: Frank A. J. L. Scheer,
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    • "Living in modern societies and different work/social schedules often lead to mismatch in timing and circadian misalignment [19]. Scheer et al. studied 10 healthy adults under experimentally induced circadian misalignment and found that eating and sleeping 12 h after habitual times were associated with a 6% increase in plasma glucose levels [34]. Furthermore, Suwazono et al. in a longitudinal study among Japanese workers have found 1.35 times increased risk of diabetes in the alternating shift work compared with the dayshift work [35]. "
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    ABSTRACT: Aims. It is known that sleep has a major role in the regulation of endocrine functions and glucose metabolism. However, it is not clear whether the sleep pattern is affected at or prior to the onset of diabetes, among those with prediabetes. The purpose of this study was to determine the association of sleep patterns and prediabetes in Qazvin, Iran. Methods. A representative sample of residents of Qazvin was selected by multistage cluster random sampling method in 2011. Plasma glucose level and sleep quality were measured cross-sectionally as well as demographic characteristics. A logistic regression analysis was used to examine the association of sleep status and prediabetes. Results. Mean age was 39.3 ± 10.1 years. Of 958, 474 (49.47%) were female. Poor sleep quality was associated with 2.197-fold increased risk of prediabetes after adjustment for age, gender, body mass index, and metabolic syndrome. Conclusion. This study provides evidences that subjects with poor sleep quality are more likely to develop prediabetes than people with good sleep quality.
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    • "Increased fatigue is among the negative consequences of reduced sleep length, disturbed patterns of sleep and impaired sleep quality among shift-workers, thereby affecting the ability to meet the work demands (Di Lorenzo et al., 2003; Costa, 2010). Moreover, sleep disturbances have been associated with an imbalance in appetite hormones that increase feelings of hunger and metabolic changes (Scheer et al., 2009). Hence, the aim of this study was to examine the association of overweight and obesity with WF, and to determine if the associations differ for workers with different working-time arrangements (i.e. "
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    ABSTRACT: Background Obesity is associated with productivity loss, but little is known about how obese workers function at work and also the role of working-time arrangements on this association is lacking. Therefore, the aim of this study was to examine the association of overweight and obesity with work functioning (WF), and to determine whether the associations differ between workers with different working-time arrangements. Methods A cross-sectional study was conducted within the sampling frame of the ‘Shift Your Work’ study that examined the effect of irregular working-times in relation to health and functioning at work. We included N = 622 Dutch employees, of which N = 384 (62%) were shift-workers, N = 171 (27%) on-call workers and N = 67 (11%) day-workers. Overweight and obesity were defined as BMI 25–30 and ≥30, respectively. WF was assessed using the Work-Role Functioning Questionnaire. Results The prevalences of overweight and obesity were 48% and 10% in all workers, 49% and 11% in shift-workers, 45% and 10% in on-call workers, and 49% and 6% in day workers, respectively. In all workers, obesity was associated with lower WF scores for physical demands (adjusted estimate, aB = −5.5). In shift-workers, obesity was associated with lower WF scores for output and physical demands (aB = −8.8 and −6.8, respectively). In day and on-call workers, overweight and obesity were not associated with WF. Conclusions Overweight and obesity are highly prevalent in the working population. Obesity might reduce the executive function performance beyond physical limitations, and limit the ability to accomplish tasks successfully, especially in shift workers.
    Applied Ergonomics 07/2015; DOI:10.1016/j.apergo.2015.07.016 · 2.02 Impact Factor
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    • "However, recent studies have shown that circadian disruption can abolish diurnal oscillation of plasma Leptin in both humans and animal models Cell Metabolism 22, 1–12, September 1, 2015 ª2015 Elsevier Inc. 1 Please cite this article in press as: Kettner et al., Circadian Dysfunction Induces Leptin Resistance in Mice, Cell Metabolism (2015), 10.1016/j.cmet.2015.06.005 without changes in external food cues ( Kalsbeek et al., 2001 ; Scheer et al., 2009 ; Shea et al . , 2005 ; Simon et al. , 1998 ) . "
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    ABSTRACT: Circadian disruption is associated with obesity, implicating the central clock in body weight control. Our comprehensive screen of wild-type and three circadian mutant mouse models, with or without chronic jet lag, shows that distinct genetic and physiologic interventions differentially disrupt overall energy homeostasis and Leptin signaling. We found that BMAL1/CLOCK generates circadian rhythm of C/EBPα-mediated leptin transcription in adipose. Per and Cry mutant mice show similar disruption of peripheral clock and deregulation of leptin in fat, but opposite body weight and composition phenotypes that correlate with their distinct patterns of POMC neuron deregulation in the arcuate nucleus. Chronic jet lag is sufficient to disrupt the endogenous adipose clock and also induce central Leptin resistance in wild-type mice. Thus, coupling of the central and peripheral clocks controls Leptin endocrine feedback homeostasis. We propose that Leptin resistance, a hallmark of obesity in humans, plays a key role in circadian dysfunction-induced obesity and metabolic syndromes. Copyright © 2015 Elsevier Inc. All rights reserved.
    Cell metabolism 07/2015; DOI:10.1016/j.cmet.2015.06.005 · 17.57 Impact Factor
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