The Pharmaceutical Journal
Vol 277 No 7412 p153
5 August 2006

This article
Reprint   Photocopy

  Acrobat Reader

News summary

Sulphonylureas for infantile onset diabetes

Up to half of patients with diabetes caused by mutations in the KCNJ11 gene (the most common cause of permanent neonatal diabetes mellitus) can replace their insulin injections with oral sulphonylurea therapy.

Ewan Pearson from the Peninsula Medical School in Exeter and colleagues from the Neonatal Diabetes International Collaborative Group studied the effect of switching from insulin to sulphonylurea therapy in 49 patients diagnosed with this form of diabetes (New England Journal of Medicine 2006;355:467).

The researchers say that mutations in the KCNJ11 gene, which encodes a subunit of the K_ATP channel called Kir6.2, have recently been found to cause diabetes in the neonatal period or early infancy. “Such mutations account for 30 to 58 per cent of cases of permanent diabetes diagnosed in patients under six months of age,” they say.

Of the 49 patients treated with sulfonyl-ureas (mainly glyburide, but also glipizide, gliclazide, tolbutamide and glimepiride) 44 were able to stop insulin treatment and glycaemic control was improved in all patients tested (mean glycated haemoglobin fell from 8.1 per cent to 6.4 per cent after 12 weeks of treatment, P<0.001). Five patients had transitory diarrhoea, but no other side effects were reported.

The researchers explain that patients with KCNJ11 mutations have K_ATP channels with decreased sensitivity to ATP inhibition. “Consequently, their channels remain open in the presence of glucose, thereby reducing insulin secretion.” They add that sulphonylureas close K_ATP channels by an ATP-independent route, thereby causing insulin secretion.

The researchers conclude: “We recommend early molecular genetic diagnosis in all patients with diabetes whose disease was diagnosed before the age of six months, whatever their current age, since the identification of patients with Kir6.2 mutations has important therapeutic implications.”

Commenting on the study, Angela Wilson, director of research at Diabetes UK, said: “Although the condition is rare, there could still be more people who are enduring a life of daily injections who do not need to. I would urge anyone diagnosed with diabetes in the first six months of life to be tested.”