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Body clock gene link to diabetes

Defective versions of a “body clock” gene greatly increase the risk of type 2 diabetes, a study has shown.

The discovery provides new evidence of a link between the body’s sleep cycle, governed by the hormone melatonin, and the disease.

Previous research has found that people who work night shifts are more at risk of type 2 diabetes and heart disease.

Volunteers who have their sleep disrupted repeatedly for three days also develop temporary diabetic symptoms.

The new study focused on a gene called MT2 which codes for the molecular cell receptor that allows melatonin to work. Carrying any of four rare mutations in the gene increased the risk of developing type 2 diabetes six times, the research showed. Faulty MT2 is thought to disrupt the link between the body clock and insulin release, leading to abnormal control of blood sugar and diabetes.

The findings are published today in the journal Nature genetics.

Study leader Professor Philippe Froguel, from Imperial College London, said: “Blood sugar control is one of the many processes regulated by the body’s biological clock. This study adds to our understanding of how the gene that carries the blueprint for a key component in the clock can influence people’s risk of diabetes.

“We found very rare variants of the MT2 gene that have a much larger effect than more common variants discovered before. Although each mutation is rare, they are common in the sense that everyone has a lot of very rare mutations in their DNA. Cataloguing these mutations will enable us to much more accurately assess a person’s risk of disease based on their genetics.”

More than two million people in the UK are known to suffer from type 2 diabetes, the most common form of the disease, which is linked to obesity and lifestyle.

The Imperial team and other scientists from the UK and France looked at the MT2 gene in the DNA of 7,632 people. They found 40 variants associated with type 2 diabetes, including four that were very rare and rendered the receptor completely incapable of responding to melatonin. The link with the four mutations was then confirmed in an even bigger sample of 11,854 people.

The scientists tested the effects of the defective genes in human cells in the laboratory. They found the mutations had a major impact on type 2 diabetes risk.

Frougel, F et al. (2012) Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes, Nature Genetics, Published online 29 January 2012.

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