Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes

• DOI: 10.1007/s00125-016-3921-8
• Publication Date: 2016-03-31T11:17:11Z
• Authors: Tarig Babiker; Natascia Vedovato; Kashyap Patel; Nicholas Thomas; Roisin Finn; Roope Männikkö; Ali J. Chakera; Sarah E. Flanagan; Maggie H. Shepherd; Sian Ellard; Frances M. Ashcroft; Andrew T. Hattersley
• Keywords: Tolbutamide; Kir6.2; Sulfonylurea

The finding that patients with diabetes due to potassium channel mutations can transfer from insulin sulfonylureas has revolutionised the management of permanent neonatal diabetes. extent which in vitro characteristics mutation predict a successful is not known. Our aim was identify factors associated KCNJ11 (which encodes inwardly rectifying Kir6.2). We retrospectively analysed clinical data on 127 who attempted sulfonylureas. considered when completely discontinued whilst All unsuccessful transfers received ≥0.8 mg kg−1 day−1 glibenclamide (or equivalent) for >4 weeks. response mutant Kir6.2/SUR1 channels tolbutamide assessed Xenopus oocytes. For some specific mutations, all individuals carrying were able successfully; we therefore investigated features could transfer. In all, 112 out (88%) successfully transferred an improvement HbA1c 8.2% (66 mmol/mol) insulin, 5.9% (41 sulphonylureas (p = 0.001). determined likelihood transfer: block <63% p.C166Y, p.I296L, p.L164P or p.T293N and no these transferred. However, most >73% did successfully. few had longer duration than those (18.2 vs 3.4 years, p 0.032). There difference pre-transfer 0.87), weight-for-age z scores (SD score; 0.12) sex 0.17). Transfer best predicted by Knowledge help whether likely. This result supports early genetic testing treatment aged under 6 months.