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Sulphonylurea Transfer In Patients With KCNJ11 And ABCC8 Mutations – PNDM

Background

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 800 patients worldwide.

Downloads

PNDM transfer protocol

Contacts

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

References

Pearson ER, Flechtner I, Njølstad PR, Malecki MT, Flanagan SE, Larkin B, Ashcroft FM, Klimes I, Codner E, Iotova V, Slingerland AS, Shield J, Robert JJ, Holst JJ, Clark PM, Ellard S, Søvik O, Polak M, Hattersley AT; Neonatal Diabetes International Collaborative Group. Switching from insulin to oral sulfonylureas in patients with diabetes due to Kir6.2 mutations. N Engl J Med. 2006 Aug 3;355(5):467-77. doi: 10.1056/NEJMoa061759. 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).

Rafiq M, Flanagan SE, Patch AM, Shields BM, Ellard S, Hattersley AT; Neonatal Diabetes International Collaborative Group. Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations. Diabetes Care. 2008 Feb;31(2):204-9. doi: 10.2337/dc07-1785. Epub 2007 Nov 19. PMID: 18025408; PMCID: PMC7611807.

Bowman P, Sulen Å, Barbetti F, Beltrand J, Svalastoga P, Codner E, Tessmann EH, Juliusson PB, Skrivarhaug T, Pearson ER, Flanagan SE, Babiker T, Thomas NJ, Shepherd MH, Ellard S, Klimes I, Szopa M, Polak M, Iafusco D, Hattersley AT, Njølstad PR; Neonatal Diabetes International Collaborative Group. Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations: an international cohort study. Lancet Diabetes Endocrinol. 2018 Aug;6(8):637-646. doi: 10.1016/S2213-8587(18)30106-2. Epub 2018 Jun 4. Erratum in: Lancet Diabetes Endocrinol. 2018 Sep;6(9):e17. PMID: 29880308; PMCID: PMC6058077.

Bowman P, Mathews F, Barbetti F, Shepherd MH, Sanchez J, Piccini B, Beltrand J, Letourneau-Freiberg LR, Polak M, Greeley SAW, Rawlins E, Babiker T, Thomas NJ, De Franco E, Ellard S, Flanagan SE, Hattersley AT; Neonatal Diabetes International Collaborative Group. Long-term Follow-up of Glycemic and Neurological Outcomes in an International Series of Patients With Sulfonylurea-Treated ABCC8 Permanent Neonatal Diabetes. Diabetes Care. 2021 Jan;44(1):35-42. doi: 10.2337/dc20-1520. Epub 2020 Nov 12. PMID: 33184150; PMCID: PMC7783935.

de Gouveia Buff Passone C, Giani E, Vaivre-Douret L, Kariyawasam D, Berdugo M, Garcin L, Beltrand J, Bernardo WM, Polak M. Sulfonylurea for improving neurological features in neonatal diabetes: A systematic review and meta-analyses. Pediatr Diabetes. 2022 Sep;23(6):675-692. doi: 10.1111/pedi.13376. Epub 2022 Jun 24. Erratum in: Pediatr Diabetes. 2022 Aug 19;: PMID: 35657808.

Babiker T, Vedovato N, Patel K, Thomas N, Finn R, Männikkö R, Chakera AJ, Flanagan SE, Shepherd MH, Ellard S, Ashcroft FM, Hattersley AT. Successful transfer to sulfonylureas in KCNJ11 neonatal diabetes is determined by the mutation and duration of diabetes. Diabetologia. 2016 Jun;59(6):1162-6. doi: 10.1007/s00125-016-3921-8. Epub 2016 Mar 31. PMID: 27033559; PMCID: PMC4869695.

Thurber BW, Carmody D, Tadie EC, Pastore AN, Dickens JT, Wroblewski KE, Naylor RN, Philipson LH, Greeley SA; United States Neonatal Diabetes Working Group. Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes. Diabetologia. 2015 Jul;58(7):1430-5. doi: 10.1007/s00125-015-3593-9. Epub 2015 Apr 17. PMID: 25877689; PMCID: PMC4641523.

Garcin L, Mericq V, Fauret-Amsellem AL, Cave H, Polak M, Beltrand J. Neonatal diabetes due to potassium channel mutation: Response to sulfonylurea according to the genotype. Pediatr Diabetes. 2020 Sep;21(6):932-941. doi: 10.1111/pedi.13041. Epub 2020 Jul 20. PMID: 32418263.

Estevez P, Boscolo O, Quiroga E, Fernandez Penuto R, Buontempo F, Tripodi V, Lucangioli S. Development and stability study of glibenclamide oral liquid paediatric formulations for the treatment of permanent neonatal diabetes mellitus. Eur J Hosp Pharm. 2016 Jul;23(4):213-218. doi: 10.1136/ejhpharm-2015-000763. Epub 2015 Dec 16. PMID: 31156851; PMCID: PMC6451472.

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