Disrupted body clock may cause type 2 diabetes

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 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.