Assessing the glycaemic and CNS response to sulphonylurea therapy in patients with KCNJ11 mutations
Neonatal diabetes is a rare condition that can be caused by a mutation in a gene called KCNJ11, and is treated with sulphonylureas. Dr Bowman plans to investigate the safety and effectiveness of sulphonylureas in more detail than has been carried out to date, to improve the treatment that people living with this condition receive.
Background to research
Neonatal diabetes is a rare form of diabetes that is diagnosed in babies before the age of six months. Babies with the condition have dangerously high blood glucose levels, because the pancreas doesn’t release insulin. Neonatal diabetes can be caused by a mutation (or change) in a gene called KCNJ11, which ‘switches off’ insulin release. The protein coded for by the KCNJ11 gene also exists in the brain, and the mutation can impact on neurological function (for example, delayed development, muscle weakness and attention problems). This type of diabetes can be treated with a drugs known as sulphonylureas, which ‘switch on’ insulin release. Sulphonylureas are used to treat Type 2 diabetes, but they begin to fail in around half of patients after five years, and can cause serious side effects. It’s believed that this is less common in people with neonatal diabetes, but it hasn’t been fully investigated. Some research suggests that sulphonylureas may also improve the neurological problems linked to neonatal diabetes, but a higher dose is needed to work in the brain, and the treatment may work better if the drugs are started as soon as possible. Again, this hasn’t yet been fully investigated.
Dr Bowman plans to investigate how sulphonylureas work in the pancreas and the brain of people diagnosed with neonatal diabetes (caused by the KCNJ11 mutation). She will take blood samples, to understand how different types of food influence insulin and glucose levels in these individuals. She will interview people, to investigate whether using higher doses or starting earlier with sulphonylurea treatment has a positive impact on neurological function. Finally, she will establish whether long-term treatment with sulphonylureas is safe and effective.
Potential benefit to people with diabetes
This research could have a real impact on the treatment and care that people living with this rare form of neonatal diabetes currently receive. If successful, the results could help healthcare professionals to prescribe the most effective treatments and give the best dietary advice.