This study investigated the potential relationship between shift work and T2DM with the RBP4 level. Similar to previous research findings, we found that shift workers (OR=2.055, 95%CI: 1.274-3.317) had a 106% increased risk of T2DM compared to non-shift workers. The association remained even after full adjustment for multiple potential confounding factors. Inconsistent with previous studies, we observed the association between shift work and RBP4 levels. We found that RBP4 levels varied by shift work. RBP4 levels in shift workers were higher than those of non-shift workers. Shift work exposure was a significant predictor of the outcome of RBP4 concentration throughout the models adjusted for different variables.
Diabetes was the most common disease reported by shift workers [26]. Shift workers needed to rotate in different shifts, resulting in a certain "conflict" between working time and social time, which disturbed the normal biological rhythm, leaded to changes in sleep, diet, exercise habits, etc., and disturbed the normal glucose and lipid metabolism. At the same time, with the accumulation of shift time and the frequent occurrence of biological rhythm disorders, glucose homeostasis imbalance and IR would be caused. And this eventually leaded to chronic diseases such as T2DM.
The Atlantic Path Cohort study showed that shift workers were 27% more likely to develop diabetes than non-shift workers (95%CI: 8-51) [27]. Anne [28] et al. followed up 19873 nurses in Denmark for 15 years to study the relationship between shift work and diabetes incidence rate. They found that after adjusting BMI, the risk of nurses suffering from diabetes on night shift was 1.58 times to those on day shift (95% CI: 1.25-1.99). A meta-analysis based on 38 meta-analyses and 24 systematic reviews reported a meta-relative risk ranged from 1.09 to 1.40 in shift workers [29]. There are population [30] and gender [31] differences between shift work and the risk of T2DM. This study investigated oil workers in Western China and found that the risk of diabetes in shift workers was 2.055 times higher than that in non-shift workers (95% CI: 1.274-3.317). Overweight and (or) obesity was one of the influencing factors of T2DM. Shift workers were more likely to be overweight than day shift workers [32]. After adjusting for age, gender, and BMI, we found that shift workers were 94.2% more likely to develop diabetes (95% CI: 1.197-3.152). Adverse health behaviors caused by shift work, such as changes in living habits, smoking and poor sleep quality [33], coupled with the destruction of biological rhythm, could produce adverse metabolic phenotypes. After adjusting for age, gender, BMI, smoking, drinking and family income, our study found that shift work was still a risk factor for diabetes (OR=1.912, 95% CI: 1.168-3.131).
Because the working hours of shift workers were not in accordance with their physiological or social circadian rhythm, they seemed to be susceptible to sleep disorders which consistented with excessive sleepiness and / or insomnia associated with shift work [34, 35]. This study also found that shift work had a negative impact on sleep quality. Although the subjects had different degrees of sleep disorders, compared with the non-shift work group, the total PSQI score of the reverse group was higher which indicating that the sleep disorders were more serious. At the same time, compared with the white team, the subjective sleep quality of the shift team was worse, the sleep time was longer, the sleep time was shorter, the sleep efficiency was worse, the sleep disorder was more serious, and the daytime dysfunction was more serious. Zhang et al. [36] found that current shift work and previous shift work were major factors that affected sleep quality. And it was found that the current shift work was significantly correlated with sleep efficiency, sleep quality and daily dysfunction. Hwanjin Park et al [37] found that the PSQI score of shift workers was significantly higher than that of day workers. Yu Zhang et al. [38] found that the prevalence of sleep disorders in workers on shift was noticeably higher than that on day workers. A cohort study found that, the risk of sleep disorders was higher in those with irregular working hours compared with daytime work [39]. The synchronization of circadian rhythm to the 24 hours cycle is largely preserved by external and environmental factors. And shift work will make sleep wake rhythm which are natural, endogenous sleep and wakefulness conflict. Then this would have a negative impact on both sleep and wakefulness. Night shift workers often sleep during the day when the circadian alarm signal is strongest, and the sleep time during the day is short and scattered, which leads to insufficient homeostatic sleep and delayed awakening of the circadian rhythm at night. Shift workers need to stay awake and work at night when the circadian alarm signal is the lowest and sleepiness is the most serious. However, there are often some lower stimuli (for example, darker light, quieter, less busy) at night [40]. Sleep is a major part of lifestyle. Controlled laboratory studies have shown that sleep restriction could lead to impaired glucose tolerance [41], which is closely related to the onset of diabetes. However, in the mediating effect analysis of the impact of sleep on diabetes during shift work in this study, no positive research results were obtained (because the data are meaningless, not listed), which may be due to the varying prevalence of sleep disorders among the subjects.
RBP4 promotes the occurrence of IR in tissues and organs by affecting the intake of glucose and the regulation of gluconeogenesis. Thus RBP4 plays a key role in the occurrence and development of diabetes and other related diseases. We found that shift exposure was a risk factor for changes in RBP4 concentration in models that adjusted for different variables. With the same age, gender, BMI, diabetes, PSQI, family income, smoking and drinking, the RBP4 level of shift workers increased by an average of 9.51μg/mL compared with the non-shift workers. To our knowledge, this is the first research on the relationship between shift work and RBP4 among oil workers. RBP-4 might be a predictor for the onset of diabetes in coming future. Bose et al. [42] found that higher serum RBP-4 had a positive correlation with Insulin, glucose, and HOMA-IR in healthy non diabetic participants with family history of diabetes. In a 10-year prospective study, it was found that NGT with higher serum RBP4 was associated with new-onset prediabetes and T2DM [43]. Animal experiments also found that the knockout of GLUT4 in adipose tissue could cause the high expression of RBP4 level, and finally promote the production of T2DM [44]. Laparoscopic sleeve gastrectomy may bring a decline in the level of RBP4 and improve IR in obese patients [45]. RBP4 could cause changes in downstream gene expression and signal transduction pathways through STRA6 -JAK / STAT [46] and MAPK signal transduction pathway, and finally induce IR and accelerate the production of T2DM [22, 24, 47]. Norseen et al. [23] and Moraes Vieira et al. [48, 49] found that RBP4 could also cause IR through immune related pathways. Ma x et al. [50] proposed that RBP4 was a gene controlled by circadian rhythm. The circadian clock gene BMAL1 in mouse liver drives RBP4 to regulate glucose metabolism through its direct target DBP. This not only provided a new mechanism for the circadian regulation of RBP4, but also revealed the key role of RBP4 in regulating glucose metabolism through the biological clock, as well as the time-dependent association between RBP4 and mouse IR, which had potential importance in the clinical prognosis of T2DM and metabolic syndrome with IR. However, this requires further research.
However, some limitations in this study should be considered in future research. First, we can only describe the relationships among shift work, RBP4 and T2DM though a cross- sectional study, but cannot explain the temporality and casual relationships among the three. Understanding the correlation between work-related environment and diabetes biomarkers could conduce to enforcing intervention and prevention strategies aimed at improving the working conditions and the health of individual workers. Second, the covariates and sleep quality were obtained through the self-report questionnaire that may lead to recall bias. Only the international PSQI scale was used in the measurement of sleep disorders. In the future, sleep diary, activity recorder, and the Bergen shift work sleep questionnaire (BSWSQ) [51] and the shift work disorder questionnaire (SWDQ) [52] which evaluated insomnia and sleepiness symptoms related to sleep wake disorder caused by shift work could be considered to reduce subjective impact. Finally, some confounding factors were not addressed in this study. Studies, especially cohort study aiming to research other potential risk factors between shift work and RBP4 and T2DM should also be conducted to reduce the risk of diabetes in shift workers. Therefore, the findings of our study should be regarded as preliminary results, more research is needed in the field.