Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2021) 78 OC8.5 | DOI: 10.1530/endoabs.78.OC8.5

BSPED2021 Oral Communications Oral Communications 8 (9 abstracts)

Permanent neonatal diabetes due to KCNJ11 mutation: early successful transition to Glibenclamide and stable glucose profile with multiple daily dosing

Katherine Hawton 1,2 , Rebekah Adams 1 , Emily Dustan 1 & Dinesh Giri 1,2

1University Hospital Bristol NHS Foundation Trust, Bristol, United Kingdom; 2University of Bristol, Bristol, United Kingdom

Introduction: Neonatal diabetes (ND) usually presents before 6 months of age and 50% of cases are transient and 50% permanent with more than 20 known genetic causes. Early recognition and urgent genetic testing are important to enable appropriate, precise treatment. Mutations in KCNJ11 cause ND responsive to glibenclamide, alleviating the need for insulin administration, but there are limited reports of early successful transition.

Case: This infant was born at 37 weeks’ gestation weighing 2.07 kg (2nd centile). She had persistent hyperglycaemia (blood glucose >12 mmol/l) requiring intravenous insulin. Her father has diabetes due to a KCNJ11 mutation managed with glimepiride. The baby was started on glibenclamide early at 10 days of age (0.05 mg/kg/day), following which insulin was stopped. Subsequently, genetic results confirmed paternally inherited missense variant KCNJ11 p.(Arg201His). Glibenclamide was initially administered as crushed tablets dissolved in water as the only licenced suspension (Amglidia; 0.6 mg/ml) was not readily available and impractical due to small dose requirements. Multiple hypoglycaemias were noted despite reducing the dose to 0.02 mg/kg/day possibly indicating that crushed tablets were causing unreliable dose distribution. Continuous glucose monitoring (CGM) using Dexcom G6 was initiated at 3 weeks of age which also showed multiple hypoglycaemias. Therefore, an in-house suspension was urgently prepared by our local pharmacy at a concentration of 0.2 mg/ml. With this formulation, twice to thrice daily divided doses (0.5 mg/kg/day) were found to cause fluctuations in blood glucose (BG) levels with hypoglycaemia (<3 mmol/l) post-dose and hyperglycaemia (>15 mmol/l) before doses. Increasing the dose frequency to 5-times-daily achieved a stable BG profile without rapid excursions between doses or significant hypoglycaemia. Average BG on CGM improved to 7-8 mmol/l and HbA1c reduced from 58 mmol/mol to 44 mmol/mol. The patient is now 5 months and continues to gain weight (9th centile) with no current developmental concerns.

Discussion: Early commencement of glibenclamide is associated with better neurodevelopmental outcomes in ND. Crushed tablet forms are not ideal in neonates as they may have unreliable dose distribution but limited availability of glibenclamide suspension form may prove challenging. In ND, small frequent doses of suspension may reduce BG variability and enable a more stable profile than twice daily doses.

Volume 78

48th Meeting of the British Society for Paediatric Endocrinology and Diabetes

Online, Virtual
24 Nov 2021 - 26 Nov 2021

British Society for Paediatric Endocrinology and Diabetes 

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