Klokwerk + study protocol: An observational study to the effects of night-shift work on body weight and infection susceptibility and the mechanisms underlying these health effects.

BACKGROUND: Night-shift work may cause severe disturbances in the worker's circadian rhythm, which has been associated with the onset of health problems and diseases. As a substantial part of the workforce is exposed to night-shift work, harmful aspects of night-shift work should not be overlooked. The aim of the Klokwerk + study is to study the effects of night-shift work on body weight and infection susceptibility and the mechanisms underlying these health effects. First, we will study the relation between night-shift work exposure and body weight and between night-shift work exposure and infection susceptibility. Second, we will examine the mechanisms linking night-shift work exposure to body weight and infection susceptibility, with a specific focus on sleep, physical activity, diet, light exposure, vitamin D level, and immunological factors. Lastly, we will focus on the identification of biomarkers for chronic circadian disturbance associated with night-shift work. METHODS/DESIGN: The design of this study is a prospective observational cohort study consisting of 1,960 health care workers aged 18-65 years. The study population will consist of a group of night-shift workers and an equally sized group of non-night-shift workers. During the study, there will be two measurement periods. As one of the main outcomes of this study is infection susceptibility, the measurement periods will take place at approximately the first (September/October) (T0) and the last month (April/May) (T1, after 6 months) of the flu season. The measurements will consist of questionnaires, anthropometric measurements, a smartphone application to determine infection susceptibility, food diaries, actigraphy, light sensors, and blood sample analyses. DISCUSSION: The Klokwerk + study will contribute to the current need for high-quality data on the health effects of night-shift work and its underlying behavioral and physiological mechanisms. The findings can be the starting point for the development of interventions that prevent negative health effects caused by night-shift work. In addition, the identification of biomarkers indicative of loss of homeostasis due to circadian disturbance may be an important asset in monitoring the effects of such interventions.

Weight fluctuation during childhood and cardiometabolic risk at young adulthood.

OBJECTIVES: To test the hypothesis that greater weight fluctuation between 2 and 6 years is associated with an increase in weight measures (such as body mass index [BMI]) and cardiometabolic risk in young adulthood. STUDY DESIGN: Weight fluctuation (determined by BMI SD scores) was measured at least 3 times between the ages of 2 and 6 years in 166 girls and 116 boys from the Terneuzen Birth Cohort. Cardiometabolic risk factors in young adulthood include components of the metabolic syndrome and weight. The extent of weight fluctuation was determined by assessing each individual's SE (or variation) around each individual's linear regression slope (or weight slope). The obtained variation scores were subsequently related to adult BMI, other weight measures, and cardiometabolic risk factors. RESULTS: In girls, greater weight fluctuation between 2 and 6 years was statistically significantly related to greater adult weight measures (1.08; 95% CI 1.01-1.15) and nonsignificantly with the metabolic syndrome. For boys weight fluctuation was not associated with adult weight (1.04; 95% CI 0.97-1.11), but weight slope was statistically significantly associated with adult overweight. CONCLUSIONS: The results suggest that weight fluctuations during early childhood are predictive for adult overweight in girls. For boys weight slope instead of weight fluctuation is predictive for adult overweight.

Associating night-shift work with lifetime use of sleep medication and sleep quality in a cohort of female nurses.

Night-shift workers often sleep at moments, not in sync with their circadian rhythm. Though the acute effects of night-shift work on sleep quality directly after a night shift are well described, less is known about the chronic effects of night-shift work on sleep. We associated ever-working night shifts and recently working night shifts (<4 wk) with lifetime use of sleep medication and melatonin, self-reported average sleep duration and sleep quality over the 4 wk preceding inclusion (measured using the Medical Outcomes Study Sleep scale). We explored trends in sleep outcomes with average frequency of night shifts per week, tenure of night-shift works in years, and time since last performed night work. This research was conducted within the Nightingale study which is a Dutch cohort study of 59,947 female registered nurses aged 18 to 65. Working night shifts was not associated with self-reported nonoptimal sleep length and sleep quality. However, we observed higher odds of lifetime use of sleep medication for nurses who ever-worked night shifts (OR 1.24; 95% CI 1.13, 1.35) and who recently worked night shifts (OR 1.13; 95% CI 1.05, 1.22); with night-shift work frequency and tenure being associated with lifetime use of sleep medication (P-value for trend < 0.001 for both). Odds for melatonin use were elevated for nurses who ever worked night shifts (OR 1.55; 95% CI 1.40, 1.71) and recently worked night shifts (OR 1.72; 95% CI 1.59, 1,86). The findings of this study have practical implications for healthcare organizations that employ nurses working night shifts. The observed associations between night-shift work and increased lifetime use of prescribed sleep medication and melatonin highlight the need for targeted support and interventions to address the potential long-term sleep problems faced by these nurses.

Effects of Nightshift Work on Blood Metabolites in Female Nurses and Paramedic Staff: A Cross-sectional Study.

Nightshift work disturbs the circadian rhythm, which might contribute to the development of cardio-metabolic disorders. In this cross-sectional study, we aimed to gain insight into perturbations of disease relevant metabolic pathways due to nightshift work. We characterized the metabolic profiles of 237 female nurses and paramedic staff participating in the Klokwerk study using the Nightingale Health platform. We performed analyses on plasma levels of 225 metabolites, including cholesterol, triglycerides, fatty acids, and amino acids. Using both principal component- and univariate-regression, we compared metabolic profiles of nightshift workers to metabolic profiles from workers that did not work night shifts (defined as day workers). We also assessed whether differential effects were observed between recently started versus more experienced workers. Within the group of nightshift workers, we compared metabolic profiles measured right after a nightshift with metabolic profiles measured on a day when no nightshift work was conducted. We observed evidence for an impact of nightshift work on the presence of unfavorable fatty acid profiles in blood. Amongst the fatty acids, effects were most prominent for PUFA/FA ratios (consistently decreased) and SFA/FA ratios (consistently elevated). This pattern of less favorable fatty acid profiles was also observed in samples collected directly after a night shift. Amino acid levels (histidine, glutamine, isoleucine, and leucine) and lipoproteins (especially HDL-cholesterol, VLDL-cholesterol, and triglycerides) were elevated when comparing nightshift workers with day workers. Amino acid levels were decreased in the samples that were collected directly after working a nightshift (compared to levels in samples that were collected during a non-nightshift period). The observed effects were generally more pronounced in samples collected directly after the nightshift and among recently started compared to more experienced nightshift workers. Our finding of a suggested impact of shift work on impaired lipid metabolism is in line with evidence that links disruption of circadian rhythmicity to obesity and metabolic disorders.

Diet, Physical Activity, and Daylight Exposure Patterns in Night-Shift Workers and Day Workers.

Background: Night-shift work has been reported to have an impact on nutrition, daylight exposure, and physical activity, which might play a role in observed health effects. Because these exposures show diurnal variation, and shift work has been related with disturbances in the circadian rhythm, the timing of assessment of these factors requires careful consideration. Our aim was to describe the changes in patterns of diet, physical activity, and daylight exposure associated with night-shift work. Methods: We conducted an observational study among female healthcare workers either regularly working night shifts or not working night shifts. We assessed physical activity and daylight exposure using continuous monitoring devices for 48 h. We logged dietary patterns (24 h) and other health- and work-associated characteristics. Two measurement sessions were conducted when participants did 'not' work night shifts, and one session was conducted during a night-shift period. Results: Our study included 69 night-shift workers and 21 day workers. On days in which they conduct work but no night work, night-shift workers had similar physical activity and 24-h caloric intake, yet higher overall daylight exposures than day workers and were more often exposed around noon instead of mainly around 1800h. Night-shift workers were less exposed to daylight during the night-shift session compared to the non-night-shift session. Total caloric intakes did not significantly differ between sessions, but we did observe a shorter maximum fasting interval, more eating moments, and a higher percentage of fat intake during the night-shift session. Conclusion: Observed differences in diet, physical activity, and exposure to daylight primarily manifested themselves through changes in exposure patterns, highlighting the importance of time-resolved measurements in night-shift-work research. Patterns in daylight exposure were primarily related to time of waking up and working schedule, whereas timing of dinner seemed primarily governed by social conventions.

Plasma sCD36 as non-circadian marker of chronic circadian disturbance in shift workers.

Shift work induces chronic circadian disturbance, which might result in increased health risks, including cardio-metabolic diseases. Previously, we identified sCD36 as a potential non-circadian biomarker of chronic circadian disturbance in mice. The aim of the current study (n = 232 individuals) was to identify whether sCD36 measured in plasma can be used as a non-circadian marker of chronic circadian disturbance in humans, which would allow its use to measure the effects of interventions and monitoring in large-scale studies. We compared levels of plasma sCD36 of day workers with recent (< 2 years) and experienced (> 5 years) night-shift workers within the Klokwerk study. We detected no differences in sCD36 levels between day workers and recent or experienced night-shift workers, measured during a day or afternoon shift. In addition, sCD36 levels measured directly after a night shift were not different from sCD36 levels measured during day or afternoon shifts, indicating no acute effect of night shifts on sCD36 levels in our study. In summary, our study does not show a relation between night-shift work experience (recent or long-term) and plasma levels of sCD36. Since we do not know if and for which time span night-shift work is associated with changes in sCD36 levels, and our study was relatively small and cross-sectional, further evidence for an association between chronic circadian disruption and this candidate biomarker sCD36 should be gathered from large cohort studies.

The Relationship Between Shift Work and Metabolic Risk Factors: A Systematic Review of Longitudinal Studies.

CONTEXT: Although the metabolic health effects of shift work have been extensively studied, a systematic synthesis of the available research is lacking. This review aimed to systematically summarize the available evidence of longitudinal studies linking shift work with metabolic risk factors. EVIDENCE ACQUISITION: A systematic literature search was performed in 2015. Studies were included if (1) they had a longitudinal design; (2) shift work was studied as the exposure; and (3) the outcome involved a metabolic risk factor, including anthropometric, blood glucose, blood lipid, or blood pressure measures. EVIDENCE SYNTHESIS: Eligible studies were assessed for their methodologic quality in 2015. A best-evidence synthesis was used to draw conclusions per outcome. Thirty-nine articles describing 22 studies were included. Strong evidence was found for a relation between shift work and increased body weight/BMI, risk for overweight, and impaired glucose tolerance. For the remaining outcomes, there was insufficient evidence. CONCLUSIONS: Shift work seems to be associated with body weight gain, risk for overweight, and impaired glucose tolerance. Overall, lack of high-methodologic quality studies and inconsistency in findings led to insufficient evidence in assessing the relation between shift work and other metabolic risk factors. To strengthen the evidence, more high-quality longitudinal studies that provide more information on the shift work schedule (e.g., frequency of night shifts, duration in years) are needed. Further, research to the (mediating) role of lifestyle behaviors in the health effects of shift work is recommended, as this may offer potential for preventive strategies.