Long-term follow-up of glycemic and neurological outcomes in an international series of patients with sulfonylurea-treated ABCC8 permanent neonatal diabetes

Andrew T Hattersley,Barbara Piccini,Eamon Rawlins,Elisa De Franco,Fabrizio Barbetti,Frances Mathews,Jacques Beltrand,Janine Sanchez,Lisa R Letourneau-Freiberg,Maggie H Shepherd,Michel Polak,Nicholas J Thomas,Pamela Bowman,Sarah E Flanagan,Sian Ellard,Siri Atma W Greeley,Tarig Babiker,The Neonatal Diabetes International Collaborative Group

doi:10.2337/figshare.13053074

Abstract

Objective ABCC8 mutations cause neonatal diabetes that can be transient (TNDM) or less commonly permanent (PNDM); ~90% individuals can be treated with oral sulfonylureas instead of insulin. Previous studies suggested that people with ABCC8-PNDM require lower sulfonylurea doses and have milder neurological features than those with KCNJ11-PNDM. However, these studies were short-term and included combinations of permanent and transient forms of ABCC8-NDM. We aimed to assess the long-term glycemic and neurological outcomes in sulfonylurea-treated ABCC8-PNDM. Research Design and Methods We studied all 24 individuals with ABCC8-PNDM diagnosed in the UK, Italy, France or USA known to transfer from insulin to sulfonylureas before May 2010. Data on glycemic control, sulfonylurea dose, adverse effects including hypoglycemia, and neurological features were analysed using non-parametric statistical methods. Results Long-term data were obtained for 21/24 individuals (median follow-up 10.0 (4.1-13.2) years). 18/21 remained on sulfonylureas without insulin at most recent follow-up. Glycemic control improved on sulfonylureas (pre-sulfonylurea vs 1-year post-transfer HbA1c 7.2% vs 5.7%, p=0.0004) and remained excellent long-term (1-year vs. 10-year HbA1c 5.7% vs. 6.5%, p=0.04), n=16. Relatively high doses were used (1-year vs 10-year dose 0.37 vs 0.25mg/kg/day glyburide, p=0.50), without any severe hypoglycemia. Neurological features were reported in 13/21 individuals: these improved following sulfonylurea transfer in 7/13. The commonest features were learning difficulties (52%), developmental delay (48%), and ADHD (38%). Conclusions Sulfonylurea treatment of ABCC8-PNDM results in excellent long-term glycemic control. Overt neurological features frequently occur and may improve with sulfonylureas, supporting early, rapid genetic testing to guide appropriate treatment and neurodevelopmental assessment.

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