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Chronotherapeutic lifestyle intervention for diabetes and obesity to reset the circadian rhythm and improve cardiometabolic risk in the European working population

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First in-man studies demonstrate high prevalence of diabetes and cardiovascular disease in shift workers

Existing epidemiological studies have shown a correlation between shift working and a higher prevalence of type 2 diabetes and cardiovascular disease. The EURHYTHDIA project has developed predictive biomarkers and prevention strategies that should help identify and protect patients at risk.

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The circadian clock, more specifically its so-called clock genes, is basically the programme that tells us when to sleep, wake up or eat. In shift workers, however, this body clock is deeply challenged, to the point where it may lead to diabetes and cardiovascular disease, as well as insulin resistance and disturbances in glucose metabolism. With no existing study in human subjects, the EURHYTHDIA (Chronotherapeutic lifestyle intervention for diabetes and obesity to reset the circadian rhythm and improve cardiometabolic risk in the European working population) team was left with two questions to answer: What’s the causality between inner clock rhythm disturbances and the development of type 2 diabetes? Does the re-setting of the circadian clock through the likes of exercise, diet, light exposure and melatonin intake alter cardiometabolic risk to a clinically relevant degree? ‘At the beginning of the project, it remained unclear to what extent shift work may directly influence gene expression of the clock system and whether certain markers may be predictive for the development of diabetes and cardiovascular disease in shift workers,’ Prof. Rainer Böger, coordinator of the project and director of UKE Hamburg, recalls. To close this gap in knowledge, EURHYTHDIA aimed to establish novel predictive markers for the development of diabetes and cardiovascular disease in shift workers. The team also tested whether interventional strategies such as light therapy, melatonin or physical activity may reset the clock system, and whether similar strategies may have an impact on the conversion from pre-diabetes to diabetes in patients at risk. Tests were run on healthy night shift workers, whilst people with a history of metabolic syndrome or diabetes were excluded. ‘Evidence from the cross-sectional study on night shift nurses in Italy identified early metabolism and vascular alterations compared to the control group,’ Prof. Böger explains. ‘The analysis showed that even after stopping working on the night shifts for a few years, the same defects were found among these nurses, potentially suggesting the maintenance of metabolic memory even post night shift work. Other factors such as epigenetics and other mechanisms are being investigated.’ In a clinical trial, light therapy was demonstrated to have no effect on glucose metabolism among nurses, at least for a short intervention period of three months. Towards early detection in patients Pre-clinical studies on mice were more fruitful, as Prof. Böger emphasizes: ‘Our team in Lille demonstrated that Rev-erb-α, a regulator of the circadian clock, is also a pharmacological target for restoring circadian rhythms, thereby improving metabolic homeostasis and reducing inflammation. This may have important clinical implications in diabetes and atherosclerosis.’ In Helsinki, another project team validated zebra fish larvae as a reliable and cost-effective animal model for sleep and circadian studies. This should allow for faster response to specific research questions related, for instance, to the additive effects of lighting conditions, sleep deprivation and nutritional factors on the behaviour and physiological functions of larvae. ‘The results can help recognise potentially identical effects in humans. When necessary, the model can also provide recommendations for arranging work shifts, nutrition and light schedules in a way that would induce minimum harmful effects on workers.’ All in all, EURHYTHDIA may lay the foundations for future research and general recommendations for shift workers. It also paves the way for future clinical studies to identify effective strategies to reduce cardiovascular morbidity and mortality in shift workers.


EURHYTHDIA, diabetes, cardiovascular disease, biomarkers, circadian clock, shift workers, predictive marker, nurses, light therapy, glucose, atherosclerosis

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