Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy
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 , _ _ , _ _ , Aloe Monica , Amadeo Simona , Arnaldi Claudia , Bassi Marta , Beccaria Luciano , Benelli Marzia , Maria Berioloi Giulia , Bertelli Enrica , Biagioni Martina , Bobbio Adriana , Boccato Stefano , Bologna Oriana , Bontempi Franco , Bonura Clara , Bracciolini Giulia , Brufani Claudia , Bruzzi Patrizia , Buono Pietro , Calcaterra Valeria , Cardani Roberta , Cardinale Giuliana , Casertano Alberto , Cristina Castiglione Maria , Cauvin Vittoria , Cherubini Valentino , Chiarelli Franco , Chiari Giovanni , Cianfarani Stefano , Cirillo Dante , Citriniti Felice , Coccioli Susanna , Cogliardi Anna , Confetto Santino , Contreas Giovanna , Corò Anna , Corsini Elisa , Cresta Nicoletta , De Berardinis Fiorella , De Donno Valeria , De Filippo Giampaolo , De Marco Rosaria , Deodati Annalisa , Faleschini Elena , Fattorusso Valentina , Favalli Valeria , Felappi Barbara , Ferrito Lucia , Fichera Graziella , Fontana Franco , Fornari Elena , Franceschi Roberto , Franco Francesca , Franzese Adriana , Paola Frongia Anna , Gaiero Alberto , Gallo Francesco , Gargantini Luigi , Giani Elisa , Giorgetti Chiara , Bianchi Giulia , Graziani Vanna , Gualtieri Antonella , Guasti Monica , Iannicelli Gennaro , Iannilli Antonio , Giovanna Ignaccolo , Ingletto Dario , Innaurato Stefania , Inzaghi Elena , Iovane Brunella , Kaufmann Peter , La Loggia Alfonso , Lapolla Rosa , Lasagni Anna , Lazzaro Nicola , Lenzi Lorenzo , Lera Riccardo , Levantini Gabriella , Lombardo Fortunato , Lonero Antonella , Longhi Silvia , Lucchesi Sonia , Paola Guerraggio Lucia , Lucieri Sergio , Macellaro Patrizia , Maffeis Claudio , Mainetti Bendetta , Maltoni Giulio , Mameli Chiara , Mammì Francesco , Luisa Manca-Bitti Maria , Manco Melania , Marino Monica , Mariano Matteo , Marigliano Marco , Marsciani Alberto , Mastrangelo Costanzo , Cristina Matteoli Maria , Mazzali Elena , Meschi Franco , MIgliaccio Antonella , Morandi Anita , Morganti Gianfranco , Mozzillo Enza , Musolino Gianluca , Nugnes Rosa , Ortolani Federica , Pardi Daniela , Pascarella Filomena , Passanisi Stefano , Pedini Annalisa , Pennati Cristina , Perrotta Angelo , Peruzzi Sonia , Peverelli Paola , Pezzino Giulia , Claudia Piona Anita , Piredda Gavina , Pistone Carmelo , Prandi Elena , Pedieri Barbara , Di Bonito Procolo , Pulcina Anna , Quinci Maria , Randazzo Emioli , Ricciardi Rossella , Ripoli Carlo , Roppolo Rosanna , Rutigliano Irene , Sabbio Alberto , salardi Silvana , Salvatoni Alessandro , Saporiti Anna , Sardi Rita , Scanu Mariapiera , Scaramuzza Andrea , Eleonardo Schiven , , Secco Andrea , Sessa Linda , Sogno Valin Paola , Sordelli Silvia , Spallino Luisa , Stagi Stefano , Stamati Filomena , Suprani Tosca , Talarico Valentina , Timapanaro Tiziana , Tirendi Antonella , Tomaselli Letizia , Tornese Gianluca , Andrea Trettene Adolfo , Tumini Stefano , Valerio Giuliana , Ventrici Claudia , Viscardi Matteo , Zaffani Silvana , Zampolli Maria , Zanette Giorgio , Zecchino Clara , Antonietta Zedda Maria , Zonca Silvia , Zucchini Stefano 
Published: February 2021

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.