New research published in Nature Genetics has identified a substantially increased risk of type 2 diabetes for people with rare genetic mutations in the melatonin receptor 1B gene, MTNR1B.
Melatonin is known as the ‘body clock’ hormone; it controls the cycle of sleep and wakefulness via processes including the control of insulin release and blood sugar levels.
Previous research had shown an increased risk for type 2 diabetes among carriers of certain common variants in the MTNR1B gene. Now, a much greater effect has been seen for rarer mutations; forty different different mutations were identified in a sample of nearly 8,000 people, of which four were severe, completely disabling the receptor.
These mutations were analysed in a further sample of nearly 12,000 people. Overall, over 8,000 people with type 2 diabetes and 10,000 without the disease were examined for these four mutations. The presence of any one mutation was found to increase the risk of type 2 diabetes six-fold.
Comment: It is suggested that these mutations may interfere with the effect of melatonin on the release of insulin (and hence normal control of blood glucose levels), or on control of normal circadian rhythms. Drugs that stimulate the melatonin receptor, currently used to treat sleep disorders and depression, may therefore be beneficial for type 2 diabetes. Researchers also hope that understanding such mutations may lead to improved disease risk assessment by incorporating genetic data.