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BMJ 2006; 333 doi: (Published 10 August 2006) Cite this as: BMJ 2006;333:344
  1. Kristina Fister, associate editor (

    Sulphonylurea can step in for insulin in diabetes with mutated KCNJ11

    It seems that nine out of 10 people whose diabetes is caused by a mutation in the KCNJ11 gene could safely switch from injecting insulin to taking oral sulphonylurea. People with this rare mutation are born with impaired insulin secretion, and are usually diagnosed with diabetes before 6 months of age. They were, until recently, thought to need insulin treatment all their lives.

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    Credit: N ENGL J MED

    In a multicentre study that enrolled 49 consecutive patients with the mutation who were between 3 months and 36 years old, 44 patients were able to switch. Glycaemic control was not only good with sulphonylurea, but was improved compared with insulin. The effects lasted for up to two years, until the study ended. The only side effect of sulphonylurea was transitory diarrhoea without pyrexia. It was recorded in five patients, lasted up to four days, and didn't alter the course of treatment.

    Mutations in the KCNJ11 gene impair ATP sensitive potassium channels in pancreatic β cells, so insulin is not secreted into the bloodstream. Sulphonylurea remedies this by mechanisms independent of ATP. In physiological studies on subgroups of patients, sulphonylurea restored insulin secretion in response to intravenous glucose, and even more so to oral glucose or a mixed meal. In vitro, sulphonylurea was able to close mutant potassium channels to the extent corresponding to the findings in vivo.

    The authors argue for genetic testing of all patients who had diabetes diagnosed early in life, whatever their age now, since they have a good chance of switching from injecting insulin to oral treatment. The accompanying editorial (p 507) highlights the need for routine screening of newborns for neonatal diabetes and discusses other implications of the findings.

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