Diabetes Genes

Sulphonylurea Transfer In Patients With KCNJ11 And ABCC8 Mutations – PNDM


Most people (>90%) with permanent neonatal diabetes caused by a KCNJ11 or ABCC8 genetic change can stop insulin and achieve better glucose control with sulphonylurea tablets. The KCNJ11 and ABCC8 genetic changes affect the Kir6.2 and SUR1 subunits of the potassium channel which provide the link between the sensing of glucose (testing how high the blood glucose is) and the release of insulin from the pancreatic beta-cell. Sulphonylureas bind to the channel to enable the pancreatic beta-cell to respond by secreting insulin when food is eaten.

The Exeter team discovered that genetic changes in KCNJ11 and ABCC8 cause permanent neonatal diabetes and did the major studies on sulphonylurea treatment in patients with potassium channel diabetes.  This information about treating this rare condition is based on our experience since 2004 with more than 400 patients worldwide.


PNDM Kir6.2 over 1 year PNDM Kir6.2 under 1 year


For further information or support please contact Professor Andrew Hattersley a.t.hattersley@exeter.ac.uk or Dr Maggie Shepherd on 01392 408261 or m.shepherd1@nhs.net


Pearson ER et  al Switching from insulin to oral sulphonylurea in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006 Aug 3;355(5):467-77. PubMed PMID: 16885550.
This paper describes how sulphonylurea treated Kir6.2 (KCNJ11) patients do not respond to glucose given into a vein but do respond to oral glucose and that this is mediated through GLP-1.