Gene Study Sheds Light on Body Clock's Link to Diabetes

Researchers studying the link between diabetes and a hormone that affects your so-called "body clock" have identified a genetic mutation in the receptor for the hormone melatonin that may to boost the risk of the disease.

The finding could help improve assessment of a person's diabetes risk and could also lead to the development of personalized treatments.

The research team from Imperial College London found that people who have rare genetic mutations in the receptor for melatonin have a greatly increased risk for type 2 diabetes.

Melatonin controls the body's sleep-wake cycle. A previous study found that people with common variations in the gene for the melatonin receptor MT2 have a slightly increased risk for type 2 diabetes.

This new study discovered that having any of four rare mutations of the MT2 is associated with a six times increased risk of developing type 2 diabetes. Melatonin controls the release of insulin, which regulates blood sugar levels. Mutations in the MT2 gene may disrupt the connection between the body clock and insulin release, resulting in abnormal control of blood sugar, the researchers explained.

For their study, the investigators examined the MT2 gene in more than 7,000 people. They identified 40 variants associated with type 2 diabetes, four of which are very rare and make the receptor incapable of responding to melatonin. The effect of these four variants was then confirmed in an additional group of nearly 12,000 people.

"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," study leader Philippe Froguel, from the School of Public Health, said in an Imperial College London news release. "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. Cataloging these mutations will enable us to much more accurately assess a person's risk of disease based on their genetics," Froguel added.

While the study found a link between the mutation and diabetes risk, it did not find a cause-and-effect relationship.

Practice Pearls:

• Note that this study documents thirteen mutations that partially or completely shut down the receptor for melatonin and are associated with a high risk of type 2 diabetes.

• Note that the neurohormone melatonin is mainly secreted from the pineal gland in a circadian pattern, with higher levels being observed during the night.

Bonnefond A, et al "Rare MTNR1B variants impairing melatonin receptor 1B function contribute to type 2 diabetes" Nature Genetics 2012; DOI: 10.1038/ng.1053.