Gene Mutation Alters Circadian Rhythm and Elevates Diabetes Risk

Scientists working on a genome-wide association study have linked a gene alteration to abnormalities in a person’s body clock and sleep patterns, suggesting that diabetes and higher than normal blood sugar levels could partly be tackled by treating sleep problems.

The paper details a mutation called rs1387153, near the MTNR1B gene associated with an increased average blood sugar level and around a 20% elevated risk of developing type 2 diabetes.

MTNR1B forms part of a signaling pathway that controls the action of the hormone melatonin. This hormone regulates the body's circadian rhythm. In healthy people, blood sugar levels are kept under control by insulin. But the researchers suggest that when there is a genetic abnormality that affects melatonin levels and sleep patterns this may also disturb the levels of insulin in the blood, preventing the body from maintaining control of blood sugar levels.

The team analyzed the genetic makeup of 2,151 nondiabetic French people (comprising 715 lean adults, 614 lean children, 247 obese adults and 575 obese children) and identified the rs1387153 mutation as being associated with high blood sugar levels. They confirmed their findings by looking at the genetic makeup of more than 16,000 nondiabetic people from different groups in France, Denmark, and Finland.

Investigators then determined that the presence of the rs1387153 increased the risk of type 2 diabetes by comparing the genetic makeup of 6,332 French and Danish diabetic subjects with that of a group of 9,132 French and Danish people with normal blood sugar levels. The researchers found the same links between rs1387153 and a risk of diabetes in all the European populations they studied.

The study appears today in the journal Nature Genetics. Researchers from Imperial College London, the French National Research Institute CNRS, Lille University, McGill University, Steno Diabetes Center and others collaborated on the study.