Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy. Issue 4 (April 2021)

• Record Type: Journal Article
• Authors: Bonfanti, Riccardo; Iafusco, Dario; Rabbone, Ivana; Diedenhofen, Giacomo; Bizzarri, Carla; Patera, Patrizia Ippolita; Reinstadler, Petra; Costantino, Francesco; Calcaterra, Valeria; Iughetti, Lorenzo; Savastio, Silvia; Favia, Anna; Cardella, Francesca; Lo Presti, Donatella; Girtler, Ylenia; Rabbiosi, Sarah; D'Annunzio, Giuseppe; Zanfardino, Angela; Piscopo, Alessia; Casaburo, Francesca; Pintomalli, Letizia; Russo, Lucia; Grasso, Valeria; Minuto, Nicola; Mucciolo, Mafalda; Novelli, Antonio; Marucci, Antonella; Piccini, Barbara; Toni, Sonia; Silvestri, Francesca; Carrera, Paola; Rigamonti, Andrea; Frontino, Giulio; Trada, Michela; Tinti, Davide; Delvecchio, Maurizio; Rapini, Novella; Schiaffini, Riccardo; Mammì, Corrado; Barbetti, Fabrizio;
• Is Part Of: European journal of endocrinology. Volume 184:Issue 4(2021)
• Page Start: 575
• Page End: 585
• Publication Date: 2021-04
• Subjects: Endocrinology -- Periodicals; 616.4005
• DOI: 10.1530/EJE-20-1030
• Languages: English
• ISSNs: 0804-4643

Abstract

Abstract : Objective: Transient neonatal diabetes mellitus (TNDM) is caused by activating mutations in ABCC8 and KCNJ11 genes (KATP /TNDM) or by chromosome 6q24 abnormalities (6q24/TNDM). We wanted to assess whether these different genetic aetiologies result in distinct clinical features. Design: Retrospective analysis of the Italian data set of patients with TNDM. Methods: Clinical features and treatment of 22 KATP /TNDM patients and 12 6q24/TNDM patients were compared. Results: Fourteen KATP /TNDM probands had a carrier parent with abnormal glucose values, four patients with 6q24 showed macroglossia and/or umbilical hernia. Median age at diabetes onset and birth weight were lower in patients with 6q24 (1 week; −2.27 SD) than those with KATP mutations (4.0 weeks; −1.04 SD) ( P = 0.009 and P = 0.007, respectively). Median time to remission was longer in KATP /TNDM than 6q24/TNDM (21.5 weeks vs 12 weeks) ( P = 0.002). Two KATP /TNDM patients entered diabetes remission without pharmacological therapy. A proband with the ABCC8 /L225P variant previously associated with permanent neonatal diabetes entered 7-year long remission after 1 year of sulfonylurea therapy. Seven diabetic individuals with KATP mutations were successfully treated with sulfonylurea monotherapy; four cases with relapsing 6q24/TNDM were treated with insulin, metformin or combination therapy. Conclusions: If TNDM is suspected, KATP genes should be analyzed first with the exception of patients with macroglossia and/or umbilical hernia. Remission of diabetes without pharmacological therapy should not preclude genetic analysis. Early treatment with sulfonylurea may induce long-lasting remission of diabetes in patients with KATP mutations associated with PNDM. Adult patients carrying KATP /TNDM mutations respond favourably to sulfonylurea monotherapy.