SFEIES24 Oral Communications Case Report Oral Communications (6 abstracts)
1Mater Miseridordiae University Hospital, Dublin, Ireland; 2Childrens Health Ireland at Temple Street, Dublin, Ireland; 3Institute of Biomedical and Clinical Science, University of Exeter Medical School, Exeter, United Kingdom
Heterozygous activating mutations of the KCNJ11 gene are the most common cause of permanent neonatal diabetes. High dose sulphonylurea (SU) therapy usually results in long-term glycaemic control. A 32-year-old woman presented at four weeks old with hyperglycaemia, ketonuria and acidosis. She was treated with insulin throughout childhood and adolescence. She was later diagnosed with a KCNJ11 mutation (R201H, c.601C>A). She successfully transitioned to SU on a second attempt at age 24; transferring from 50units of insulin to glibenclamide 0.44 mg/kg/day with improved glycaemic control and HbA1c of 44mmol/mol. After seven years of SU therapy, HbA1c was 71mmol/mol despite incremental glibenclamide dose increase to 40 mg twice daily (1.3 mg/kg/day). This was in the context of a busy job, stable weight and BMI 26.7kg/m2. HbA1c worsened despite a trial of bolus insulin aspart 4units with breakfast. Liraglutide 0.3 mg daily was commenced at age 32 and increased to 0.6 mg. She switched to semaglutide 0.25 mg which was then up titrated to 0.5 mg for convenience. Bolus insulin was stopped and glibenclamide was reduced to 35 mg/day (0.6 mg/kg/day) to offset nocturnal hypoglycaemia post-exertion. HbA1c reduced to 44mmol/mol at six months and 47mmol/mol at twelve month follow up. Weight reduced from 64.2kg to 58kg and BMI was normal at 24.2kg/m2. SUs act downstream of the SU receptor and activate the KATP < channel through a route independent of ATP to stimulate insulin release. Glucagon-like peptide 1 agonists (GLP1a) bypass the SUR receptor to secrete insulin but are dependent on cAMP. Sufficient levels of cAMP are only achieved in KCNJ11 diabetes with SUs. Concomitant GLP1a treatment augments the glucose lowering effect of SU in the KCNJ11 R201H mutation.