ESPE2016 Free Communications Management of Disorders of Insulin Secretion (6 abstracts)
Persistent Beneficial Metabolic Effect after Five Years in a Cohort of 28 Subjects with Neonatal Diabetes owing to Potassium Channel Mutation and Transferred from Insulin to Sulfonylureas
Marie Hoarau a , Anne-Laure Fauret e , Kanetee Busiah a, , Cécile Godot a , Sandra Colas c , Jean-Marc Tréluyer b, , Raphael Scharfmann d , Hélène Cavé e , Michel Polak a, & Jacques Beltrand a,
aUnité d’endocrinologie, gynécologie et diabétologie pédiatrique, Hôpital Necker Enfants Malades, Assistance Publique-Hôpitaux de Paris, Paris, France; bFaculté de médecine Paris Descartes, Université Sorbonne Paris Cité, Paris, France; cUnité de recherche clinique, centre d’investigation Clinique, Hôpital universitaire Necker Enfants Malades Paris, Assistance Publique-Hôpitaux de Paris, Paris, France; dInserm U1016, Institut Cochin, Paris, France; eDépartement de génétique, Assistance Publique-Hôpitaux de Paris, Hôpital Universitaire Robert Debré, Paris, France
Background: Sulfonylureas (SU) have proven to be effective in patients with monogenic diabetes owing to potassium channel mutation. They allow the discontinuation of insulin and a good metabolic control. Long-term data arguing for a persistent beneficial effect of SU are missing.
Objective and hypotheses: SU provide a good metabolic control maintained over time in patients with neonatal diabetes.
Method: From a French cohort of 34 patients (GENEODIA study – French Neonatal Glibenclamide Study Group), we selected patients transferred successfully (no insulin during the 12 months after the switch) for more than five years (before 2010). Data recorded retrospectively: safety, diabetes complication, SU dosage and HbA1C before switch and at last follow-up visit.
Results: About 28 patients were eligible (18 boys – 24 KCNJ11 mutations – 4 ABCC8 mutations). Complete data before switch were available for 24 patients and after switch for 17 patients. Median time till SU start was 9.32 years (5.8–12.15) and median follow-up time 6.6 years (1.4–11.5 years). Median age at transfer from insulin to SU was 4.9 years (0.23–36.5). Median HbA1C before transfer was 7.4% (5.3–10.3) and 6.1% (5.1–8.1%) at last visit. Median change was −1.4% (−4 to +0.3%), P<0.001. Median glibenclamide dosage was 0.16 mg/kg/day (0.025–0.66) at last visit. Safety was good; no episodes of renal or hepatic failure and no development of retinopathy or nephropathy were reported. Insulin was re introduced permanently in 1 patient (3 years after SU transfer) and transiently in another (1 year after transfer and during 4 years).
Conclusion: While prescribed off label, SU display a beneficial metabolic effect maintained over time with an extremely good safety profile in patients with neonatal diabetes owing to potassium channel mutation.
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