Researchers discover gene responsible for neonatal diabetes

Researchers at Oxford University and the Peninsula Medical School in Exeter have located a gene responsible for around a third of cases of neonatal diabetes. Their findings are likely to lead to treatment of the condition by means of a tablet rather than injections, improving the quality of life of both patients and their parents.

Approximately one in 400,000 babies is diagnosed with diabetes within three months of being born, and currently these children have to be given daily insulin injections for the rest of their lives. The paper published in the New England Journal of Medicine by researchers at Oxford University and the Peninsula Medical School shows that mutations in a gene called Kir6.2 are a common cause of this kind of childhood diabetes.

Kir6.2 regulates the secretion of insulin from the beta-cells of the pancreas. In healthy people, it responds to increased levels of glucose in the blood (for example after a meal) by causing the beta-cell to release insulin, a hormone that lowers the blood sugar. In individuals with Kir6.2 mutations, the protein no longer works correctly, so that insulin is no longer released and blood sugar levels rise too high. This inability to control glucose levels produces diabetes, with its associated risks of blindness, heart problems, amputations and early death.

In order to control their blood glucose levels, children with this type of diabetes currently have to take insulin injections for the rest of their lives. However, identification of the gene responsible may enable them to be treated with oral drugs that regulate the beta-cell function, avoiding the need for insulin to be administered by injection.

Dr Anna Gloyn, who is lead author on the paper and carried out her studies whilst at the Peninsula Medical School but is now at Oxford's Centre for Diabetes, Endocrinology and Metabolism, said: 'We have shown that over one third of patients diagnosed with diabetes before the age of six months will have diabetes because of a defect in Kir6.2 gene. It is a very exciting finding that the cause of diabetes in these children has resulted in the real possibility of stopping insulin injections.'

The Exeter team, led by Professor Andrew Hattersley, working in concert with clinicians and patients from around the world, identified the mutations in Kir6.2. The Oxford team, led by Professor Frances Ashcroft FRS, then determined how they impair the protein function and lead to diabetes.

The paper, 'Activating Mutations in the Gene Encoding the ATP-Sensitive Potassium-Channel Subunit Kir6.2 and Permanent Neonatal Diabetes', can be read in full at the New England Journal of Medicinewebsite. http://content.nejm.org/cgi/content/short/350/18/1838