Night shift work increases risk of metabolic disorders, particularly obesity and insulin resistance. While the underlying mechanisms are unknown, evidence points to misalignment of peripheral ...oscillators causing metabolic disturbances. A pathway conveying such misalignment may involve exosome-based intercellular communication. Fourteen volunteers were assigned to a simulated day shift (DS) or night shift (NS) condition. After 3 days on the simulated shift schedule, blood samples were collected during a 24-h constant routine protocol. Exosomes were isolated from the plasma samples from each of the blood draws. Exosomes were added to naïve differentiated adipocytes, and insulin-induced pAkt/Akt expression changes were assessed. ChIP-Seq analyses for BMAL1 protein, mRNA microarrays and exosomal miRNA arrays combined with bioinformatics and functional effects of agomirs and antagomirs targeting miRNAs in NS and DS exosomal cargo were examined. Human adipocytes treated with exosomes from the NS condition showed altered Akt phosphorylation responses to insulin in comparison to those treated with exosomes from the DS condition. BMAL1 ChIP-Seq of exosome-treated adipocytes showed 42,037 binding sites in the DS condition and 5538 sites in the NS condition, with a large proportion of BMAL1 targets including genes encoding for metabolic regulators. A significant and restricted miRNA exosomal signature emerged after exposure to the NS condition. Among the exosomal miRNAs regulated differentially after 3 days of simulated NS versus DS, proof-of-concept validation of circadian misalignment signaling was demonstrated with hsa-mir-3614-5p. Exosomes from the NS condition markedly altered expression of key genes related to circadian rhythm in several cultured cell types, including adipocytes, myocytes, and hepatocytes, along with significant changes in 29 genes and downstream gene network interactions. Our results indicate that a simulated NS schedule leads to changes in exosomal cargo in the circulation. These changes promote reduction of insulin sensitivity of adipocytes in vitro and alter the expression of core clock genes in peripheral tissues. Circulating exosomal miRNAs may play an important role in metabolic dysfunction in NS workers by serving as messengers of circadian misalignment to peripheral tissues.
Circadian rhythm proteins participate in regulating multiple physiological activities, including immune responses. The day-night shift rotation (DNSR) affects the circadian rhythm. The influence of ...circadian rhythm disturbance associated with DNSR on the regulatory functions of B cells remains to be studied. In this study, Blood samples were collected from 30 nurses engaging DNSR. The B cells were isolated from blood samples through magnetic cell separation. The regulatory function of IL-10 B cells (B10 cells) was evaluated using immunological assays. The results showed that the IL-10 expression was significantly reduced in B10 cells in nurses after DNSR. The capacity of inducing type 1 regulatory T cells (Tr1 cells) in B10 cells was down regulated. The circadian locomotor output cycles kaput (CLOCK) was increased in B10 cells, which was negatively correlated with the reduction of IL-10 expression in B10 cells. CLOCK formed a complex with c-Maf inducing protein (CMIP) to induce CMIP degradation; this restricted the IL10 gene transcription in B10 cells. B10 cells collected from nurses after DNSR were ineffective in suppressing T-cell proliferation and inducing Tr1 cells. In summary, DNSR affects the immune regulating function of B10 cells by disturbing the circadian rhythm.
•Day–night-shift rotation increases the expression of the circadian rhythm CLOCK protein in B10 cells.•CLOCK physically contactes CMIP (c-Maf inducing protein) to induce CMIP degradation•Day–night-shift rotation attenuates IL-10 expression in B10 cells.
Abstract
Background
Night work has been increasing in the last decades due to new working arrangements for good and services production. Numerous studies have shown that night shift work causes ...disruptions in circadian rhythms that may affect health. In 2019, night shift work was classified as probably carcinogenic to humans by the International Agency for Research on Cancer, and may contribute to other health disorders. In this context, we assessed the number and proportion of workers exposed to night work today and investigated time trends by occupation and industry in France since 1982 in terms of prevention.
Methods
Using the data on work time schedules collected in the French Labour Force Surveys, sex- and period-specific job-exposure matrices (JEMs) to night work (working between midnight and 5 AM) were developed. After linkage of the JEMs with data of the national censuses of 1982, 1990, 1999, 2007 and 2015, the numbers and proportions of workers usually or occasionally exposed to night work were estimated.
Results
The number of night workers (usual and occasional) increased from 3.67 million in 1982 to 4.37 million in 2015 (15.8% vs 16.4%). Night work was more common in men than in women (e.g. 22.4% vs 10.0% in 2015), and usual night work largely increased after 2000 (4.4% in 1999, 7.2% in 2007). In 2015, 1.29 million men worked usually at night, including 882,000 workers in the service sector (63%) and 360,000 in the manufacturing and extracting industries (28%). For the same period, 581,000 women were usual night workers, most of them being employed in the service sector (90%). Among women, a 97% increase of usual night work was observed between 1982 and 2015.
Conclusions
This study shows that night work involves a growing number of workers in France, particularly in women in the service sector. These results raise concern about the public health impact of night work and particularly about the numbers of outcomes attributable to this exposure such as breast or prostate cancers.
This study aimed to evaluate effects of night and shift work patterns on type 2 diabetes (T2D) and hypertension in a longitudinal study, with detailed information on working hours.
The cohort ...comprised about 28 000 nurses and nursing assistants employed for more than one year 2008-2016 in Stockholm, Sweden. The employee register held detailed individual information on daily working hours. Information on diagnoses came from national and regional registers. Hazard ratios (HR) and confidence intervals (CI) were estimated by discrete-time proportional hazard models, adjusting for sex, age, country of birth, and profession.
During follow-up in 2013-2017, we identified 232 cases of T2D and 875 of hypertension. We observed an increased risk of T2D, but not hypertension, among employees who worked only night shifts the previous year (HR 1.59, 95% CI 1.02-2.43) and those with intensive shift work (>120 afternoon and/or night shifts the previous year: HR 1.67, 95% CI 1.11-2.48) compared to only day work. There was a non-significantly increased risk of T2D related to mixed day and afternoon shifts (HR 1.34, 95% CI 0.97-1.88). We observed tendencies in increased risk of T2D related to frequent spells of ≥3 consecutive night shifts and with number of years with exclusive (but not mixed) night work.
Permanent night work and frequent afternoon and/or night shifts were associated with an increased risk of T2D the following year, but not hypertension. The T2D risk was, to some extent, affected by frequent spells of several night shifts in a row and by cumulative years with permanent night work.
Background and purpose
Efforts to improve nurses’ physical and mental health are critical to ensuring the safety and quality of the healthcare system. Long-term studies targeting the relevancy of ...nurses’ occupation characteristics with health conditions remain insufficient. This study aimed to examine the relationship between nurses’ night shift and sleep problems and metabolic abnormalities risk.
Methods
This study was a part of the National Nurse Health Study, an ambispective cohort study in China, in 2021. Based on an integration physical examination data system, this study carried out a retrospective analysis of 730 nurses from 2018 to 2020 and combined with a questionnaire survey in 2021. The STROBE guidelines were adopted for reporting.
Results
In the 23 (23.0, 24.0) months follow-up, higher night shift load was associated with more sleep problems such as shortened sleep duration, sleep disorders, poor sleep quality, and sleep deprivation. Moreover, night shift load was associated with chronic diseases risk factors, increasing body mass index and body fat, with more night shift density, increasing the occurrence of low levels of high-density lipoprotein cholesterol, high triglyceride, triglyceride/high-density lipoprotein cholesterol ratio, and serum uric acid.
Conclusion
The night shift load has become an occupational health concern, contributing to chronic diseases relevant metabolic risk factors and negative influence on sleep health. Focus on the strategies to improve the sleep quality of nurses undergoing night shift work, optimize work scheduling and ongoing monitor the relevant risk factors are essential to enhance the stability and well-being of the nursing workforce.
Clinical Trials
registration information:
NCT04572347, on October 1, 2020.
https://www.clinicaltrials.gov/ct2/show/NCT04572347
Night-shift workers are exposed to nocturnal light and are more prone to circadian rhythm disorders. Although night-shift work is thought to be associated with the decrease in melatonin secretion, ...studies have shown inconsistent results.
This systematic review and meta-analysis studied the association between night-shift work and melatonin levels. Pubmed and Embase databases were used for literature searching. The pooled standardized mean differences (SMDs) and 95% confidence intervals (CIs) were used to compare the differences between night-shift workers and the controls.
Thirty-three studies reported in 25 articles (1845 night-shift workers and 3414 controls, mean age 45.12 years) were included after a systematic literature review. Data of circulating melatonin levels and its metabolites, 6-sulfatoxymelatonin (aMT6s) in urine were collected for meta-analysis. The results showed that the first morning-void aMT6s level in night-shift workers was significantly lower than in day workers (SMD = −0.101, 95% CI = −0.179 to −0.022, P = 0.012). The level of mean 24-h urinary aMT6s was lower in night-shift workers than day workers (SMD: −0.264, 95% CI: −0.473 to −0.056, P = 0.013). Among fixed night-shift workers, the level of circulating melatonin, as well as first morning-void aMT6s was lower than that of day workers.
Our findings indicate that experience of night-shift work is associated with suppression of melatonin production, especially among fixed night-shift workers.
•Night-shift work is a highly prevalent experience, introducing nocturnal light and circadian rhythm disorder to the workers.•Our study evidences that night-shift work leads to a decrease in melatonin levels measured by urinary 6-sulfatoxymelatonin.•Preventive measures for reduction of long-term night-shift work may prevent disruption of melatonin synthesis.
Objectives Rotating shift work is associated with adverse outcomes due to circadian misalignment, sleep curtailment, work-family conflicts, and other factors. We tested a bright light countermeasure ...to enhance circadian adaptation on a counterclockwise rotation schedule. Methods Twenty-nine adults (aged 20-40 years; 15 women) participated in a 4-week laboratory simulation with weekly counterclockwise transitions from day, to night, to evening, to day shifts. Each week consisted of five 8-hour workdays including psychomotor vigilance tests, two days off, designated 8-hour sleep episodes every day, and an assessment of circadian melatonin secretion. Participants were randomized to a treatment group (N=14), receiving intermittent bright light during work designed to facilitate circadian adaptation, or a control group (N=15) working in indoor light. Adaptation was measured by how much of the melatonin secretion episode overlapped with scheduled sleep timing. Results On the last night shift, there was a greater overlap between melatonin secretion and scheduled sleep time in the treatment group mean 4.90, standard deviation (SD) 2.8 hours compared to the control group (2.62, SD 2.8 hours; P=0.002), with night shift adaptation strongly influenced by baseline melatonin timing (r
=-0.71, P=0.01). While the control group exhibited cognitive deficits on the last night shift, the treatment group's cognitive deficits on the last night and evening shifts were minimized. Conclusions In this laboratory setting, intermittent bright light during work hours enhanced adaptation to night work and subsequent readaptation to evening and day work. Light regimens scheduled to shift circadian timing should be tested in actual shift workers on counterclockwise schedules as a workplace intervention.
The various non-standard schedules required of shift workers force abrupt changes in the timing of sleep and light-dark exposure. These changes result in disturbances of the endogenous circadian ...system and its misalignment with the environment. Simulated night-shift experiments and field-based studies with shift workers both indicate that the circadian system is resistant to adaptation from a day- to a night-oriented schedule, as determined by a lack of substantial phase shifts over multiple days in centrally controlled rhythms, such as those of melatonin and cortisol. There is evidence that disruption of the circadian system caused by night-shift work results not only in a misalignment between the circadian system and the external light-dark cycle, but also in a state of internal desynchronization between various levels of the circadian system. This is the case between rhythms controlled by the central circadian pacemaker and clock genes expression in tissues such as peripheral blood mononuclear cells, hair follicle cells, and oral mucosa cells. The disruptive effects of atypical work schedules extend beyond the expression profile of canonical circadian clock genes and affects other transcripts of the human genome. In general, after several days of living at night, most rhythmic transcripts in the human genome remain adjusted to a day-oriented schedule, with dampened group amplitudes. In contrast to circadian clock genes and rhythmic transcripts, metabolomics studies revealed that most metabolites shift by several hours when working nights, thus leading to their misalignment with the circadian system. Altogether, these circadian and sleep-wake disturbances emphasize the all-encompassing impact of night-shift work, and can contribute to the increased risk of various medical conditions. Here, we review the latest scientific evidence regarding the effects of atypical work schedules on the circadian system, sleep and alertness of shift-working populations, and discuss their potential clinical impacts.
Objectives: The aim of this study was to examine whether changes in work shifts and shift intensity are related to changes in difficulties to fall asleep, fatigue, and sleep length. Methods: ...Questionnaire responses of hospital employees (N=7727, 93% women) in 2008, 2012, 2014 and 2015 were linked to daily-based records of working hours during three months preceding each survey. We used conditional logistic regression and longitudinal fixed-effects analyses to investigate odds ratios (OR) and 95% confidence intervals (CI) for each 25% within-individual change in the proportion of working hour characteristics in relation to changes in fatigue, difficulties to fall asleep, and 24-hour sleep length. Results: Change in night but not in morning or evening shifts was associated with parallel changes in odds for longer sleep length (OR 1.45, 95% CI 1.28-1.64) and fatigue during free days (OR 1.38, 95% CI 1.16-1.64). Similarly, short shift intervals and having ＞2 but not ＞4 consecutive night shifts were associated with increased odds of fatigue during work and difficulties to fall asleep (OR 1.42, 95% CI 1.19-1.72 and OR 1.10, 95% CI 1.05-1.19, respectively). Among workers aged ≥50 years, the associations were the strongest between night shifts and longer sleep (OR 2.24, 95% CI 1.52-3.81) and between higher proportion of short shift intervals and fatigue during free days (OR 1.68, 95% CI 1.10-2.54). Conclusions: Among shift workers with fatigue or sleep problems, decreasing the proportion of night shifts and quick returns and giving preference to quickly forward-rotating shift systems may reduce fatigue.
The purpose of this study is to investigate the association of rotating night shift work, CLOCK, MTNR1A, MTNR1B genes polymorphisms and their interactions with type 2 diabetes among steelworkers.
A ...case-control study was conducted in the Tangsteel company in Tangshan, China. The sample sizes of the case group and control group were 251 and 451, respectively. The logistic regression, log-linear model and generalized multifactor dimensionality (GMDR) method were used to investigate the interaction between circadian clock gene, melatonin receptor genes and rotating night shift work on type 2 diabetes among steelworkers. Relative excess risk due to interaction (RERI) and attributable proportions (AP) were used to evaluate additive interactions.
Rotating night shift work, current shift status, duration of night shifts, and average frequency of night shifts were associated with an increased risk of type 2 diabetes after adjustment for confounders. Rs1387153 variants in MTNR1B was found to be associated with an increased risk of type 2 diabetes, which was not found between MTNR1A gene rs2119882 locus, CLOCK gene rs1801260 locus and the risk of type 2 diabetes. The association between rotating night shift work and risk of type 2 diabetes appeared to be modified by MTNR1B gene rs1387153 locus (RERI = 0.98, (95% CI, 0.40-1.55); AP = 0.60, (95% CI, 0.07-1.12)). The interaction between MTNR1A gene rs2119882 locus and CLOCK gene rs1801260 locus was associated with the risk of type 2 diabetes (RERI = 1.07, (95% CI, 0.23-1.91); AP = 0.77, (95% CI, 0.36-1.17)). The complex interaction of the MTNR1A-MTNR1B-CLOCK-rotating night shift work model based on the GMDR methods may increase the risk of type 2 diabetes (P = 0.011).
Rotating night shift work and rs1387153 variants in MTNR1B were associated with an increased risk of type 2 diabetes among steelworkers. The complex interaction of MTNR1A-MTNR1B-CLOCK-rotating night shift work may increase the risk of type 2 diabetes.
PDF
