Is there a link between sleep and type 2 diabetes? That's one implication of a new study, which has found that variants in a gene that helps regulate the body's daily rhythms increase the chance of developing the disease. The find, reported online yesterday in three papers in Nature Genetics, may suggest new ways to treat or prevent the ever more common disorder.
The body's internal clock--or circadian rhythm--is kept accurate by a hormone called melatonin, whose levels fall during the day and rise at night. Melatonin helps regulate sleep patterns, and in recent years, scientists have found that these patterns are tied to metabolism. For example, people who sleep less have a higher risk of obesity and diabetes. And experimental mice with disrupted circadian rhythms tend to gain weight.
Researchers suspect the link has something to do with another hormone, insulin: Melatonin appears to regulate the body's levels of insulin, which helps cells take up the sugar glucose from the blood. (In type 2 diabetes, the system doesn't work properly, and blood glucose is too high, damaging various organs.)
The new studies back up this link. Three groups found that people with certain variations in the so-called melatonin receptor 2 gene have higher levels of blood glucose first thing in the morning. Such high fasting glucose levels are one warning sign for type 2 diabetes. Gonçalo Abecasis of the University of Michigan, Ann Arbor, and his colleagues used data from 10 genome-wide studies involving 36,610 individuals to look for genetic variations that correlated with fasting glucose concentrations. They pinpointed a common variation in the gene called MTNR1B, which codes for one of the body's two known melatonin receptors. A study led by Leif Groop of Lund University in Sweden, using data from two long-term health studies, confirmed that result and also found that people carrying the high-blood-sugar gene variant have an increased risk of developing type 2 diabetes. Philippe Froguel of Imperial College London and his colleagues, looking at data from 2154 individuals in France, found a similar association with a different genetic variation very near the same gene.
Although previous work had suggested a connection between metabolism and circadian rhythm control, the find "will come as a big surprise to 99% of people involved in diabetes research," says Eve Van Cauter of the University of Chicago in Illinois, an expert on sleep and metabolism who was not involved in the studies. The exact biological explanation is not yet clear; however, she says one possibility is that people with the high-risk gene variant have an insulin-production system that is overly sensitive to melatonin. Understanding exactly what effect the variations have could help design more effective treatments for diabetics, says Froguel.
