EURHYTHDIA

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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 Obiettivo del progetto (Objective)

'Modern lifestyle has dramatically changed the daily rhythms of life. Physical activity, diet and light exposure are no longer restricted to daytime hours, as technical and economical de-mands fuel the necessity to work outside usual working hours. Recent studies show that al-tered light exposure, shifted exercise patterns and untimely food intake following extended active periods into the night disturb the circadian clocks and severely disrupt endocrine and metabolic processes, contributing to an increased risk of type 2 diabetes/obesity. Especially shift workers constituting 20% of the European working population are affected by this prob-lem. Until now only few studies investigating circadian rhythm disturbances in the context of type 2 diabetes/obesity have been conducted in man. Within EuRhythDia a consortium of leading scientists supported by research-intensive SMEs aims to close this gap. The objective of the project is to achieve breakthroughs in the understanding of the causality between inner clock rhythm disturbances and the development of type 2 diabetes/obesity, and to verify whether re-setting the circadian clock through lifestyle interventions (exercise, diet, light exposure and melatonin intake) alters cardiometabolic risk to a clinically relevant degree. The project is based on shift workers as a model and combines genetic, epigenetic, proteomic, metabolomic, physiological, and clinical approaches. The consortium has direct access to well characterised human data incl. individuals predisposed to type 2 diabetes via LUPS co-hort. Additional small interventional and validation cohorts of shift workers and high risk juveniles will be recruited, and supportive animal studies will be conducted. Through the de-velopment of novel diagnostic assays enabling identification of patients at risk and elaboration of targeted prevention guidelines focusing on shift workers and juveniles, EuRhythDia will contribute to a positive impact on European citizens` health.'

Descrizione progetto (Article)

Emerging evidence indicates that irregular sleeping, eating and exercise regimens may disrupt the endogenous circadian clock and predispose individuals to obesity and T2D. This is believed to be due to an imbalance between metabolism and energy needs.

The causative role of clock genes in the development of T2D remains to be proven, but epidemiological data indicates that shift workers are at increased risk for T2D. The EU-funded project http://eurhythdia.eu (EURHYTHDIA) (Chronotherapeutic lifestyle intervention for diabetes and obesity to reset the circadian rhythm and improve cardiometabolic risk in the European working population) is working on understanding the link between circadian regulation and metabolism as well as the development of T2D. The consortium will also test the validity of lifestyle interventions to prevent disease development using suitable cohorts.

Researchers comprehensively analysed metabolite patterns and epigenomic modifications in clock genes to identify any association between night shift work and disrupted metabolic homeostasis. Bioinformatics studies are ongoing to identify novel biomarkers of circadian disruption for early diagnosis and intervention.

Intervention studies in night shift workers and in first-degree relatives of patients with T2D have already started through controlled clinical studies. Researchers are working on assessing the effect of resetting the circadian clock using light therapy, circadian-timed exercise and melatonin treatment in night shift workers. Circadian intervention with melatonin is being assessed in relatives of patients with T2D.

Ongoing animal experiments reveal that certain circadian regulatory target genes play a major role in regulating metabolic state and thereby glucose homeostasis.

Another major achievement is the development and validation of a zebrafish model of circadian disorder. This will be used to elucidate the changes occurring at the molecular level with and without circadian interventions.

The translational EURHYTHDIA project has already uncovered some new diagnostic tools and compounds for assessing circadian rhythm and metabolism. Besides providing drug targets for therapeutic intervention in diabetes, preventive measures such as lifestyle changes can benefit individuals at risk of metabolic disorders.