Differences between Transient Neonatal Diabetes Mellitus Subtypes can Guide Diagnosis and Therapy

in European Journal of Endocrinology
View More View Less
  • 1 R Bonfanti, Pediatrics, San Raffaele Hospital, Milano, Italy
  • 2 D Iafusco, Pediatrics, University of Campania Luigi Vanvitelli School of Medicine and Surgery, Napoli, Italy
  • 3 I Rabbone, Pediatrics, University of Eastern Piedmont Amedeo Avogadro School of Medicine, Novara, Italy
  • 4 G Diedenhofen, Experimental Medicine, University of Rome Tor Vergata, Roma, Italy
  • 5 C Bizzarri, Pediatrics, Diabetes Unit, Bambino Gesu Pediatric Hospital, Roma, Italy
  • 6 P Patera, Pediatrics, Diabetes Unit, Bambino Gesu Pediatric Hospital, Roma, Italy
  • 7 P Reistadler, Pediatrics, Ospedale San Maurizio, Bolzano, Italy
  • 8 F Costantino, Pediatrics, University of Rome La Sapienza, Roma, Italy
  • 9 V Calcaterra, Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy
  • 10 L Iughetti, Department of Medical and Surgical Sciences, University of Modena and Reggio Emilia, Modena, Italy
  • 11 S Savastio, Division of Pediatrics, Department of Health Sciences, University of Piemonte Orientale, Novara, Italy
  • 12 A Favia, Pediatrics, Presidio Ospedale di Santa Maria degli Angeli di Pordenone, Pordenone, Italy
  • 13 F Cardella, Pediatrics, Giovanni Di Cristina Children's Hospital, Palermo, Italy
  • 14 D Lopresti, Pediatrics, Azienda Ospedaliero Universitaria Policlinico Vittorio Emanuele Catania, Catania, Italy
  • 15 Y Girtler, Pediatrics, Ospedale San Maurizio , Bolzano, Italy
  • 16 S Rabbiosi, Pediatrics, Ospedale San Maurizio, Bolzano, Italy
  • 17 G D'Annunzio, Pediatrics, Giannina Gaslini Institute, Genova, Italy
  • 18 A Zanfardino, Pediatrics, University of Campania Luigi Vanvitelli, Napoli, Italy
  • 19 A Piscopo, Pediatrics, University of Campania Luigi Vanvitelli School of Medicine and Surgery, Napoli, Italy
  • 20 F Casaburo, Pediatrics, University of Campania Luigi Vanvitelli School of Medicine and Surgery, Napoli, Italy
  • 21 L Pintomalli, Medical Genetics, Great Metropolitan Hospital, Reggio Calabria, Italy
  • 22 L Russo, Pediatrics, University of Michigan, Ann Arbor, United States
  • 23 V Grasso, Experimental Medicine, University of Rome Tor Vergata, Roma, Italy
  • 24 N Minuto, Pediatrics, Istituto Giannina Gaslini, Genova, Italy
  • 25 M Mucciolo, Translational Cytogenomics Research Unit, Bambino Gesu Pediatric Hospital, Roma, Italy
  • 26 A Novelli, Translational Cytogenomics Research Unit, Ospedale Pediatrico Bambino Gesù, Roma, Italy
  • 27 A Marucci, Diabetes and Endocrine Diseases, Fondazione IRCCS Casa Sollievo delle Sofferenza , San Giovanni Rotondo, Italy
  • 28 B Piccini, Pediatrics, Meyer University Children's Hospital, Florence, Italy
  • 29 S Toni, Pediatrics, Meyer University Children's Hospital, Florence, Italy
  • 30 F Silvestri, Pediatrics, University of Rome La Sapienza, Roma, Italy
  • 31 P Carrera, Center for Omics Science, San Raffaele Hospital, Milano, Italy
  • 32 A Rigamonti, Pediatrics, San Raffaele Hospital, Milano, Italy
  • 33 G Frontino, Pediatrics, San Raffaele Hospital, Milano, Italy
  • 34 M Trada, Pediatrics, University of Turin, Torino, Italy
  • 35 D Tinti, Pediatrics, University of Turin, Torino, Italy
  • 36 M Delvecchio, Pediatrics, Ospedale Pediatrico Giovanni XXIII, Bari, Italy
  • 37 N Rapini, Diabetes Unit, Bambino Gesù Children's Hospital, Rome, Italy
  • 38 R Schiaffini, Diabetes Unit, Bambino Gesu Pediatric Hospital, Roma, Italy
  • 39 C Mammì, Medical Genetics, Great Metropolitan Hospital, Reggio Calabria, Italy
  • 40 F Barbetti, Experimental Medicine, University of Rome Tor Vergata, Rome, 00134, Italy

Correspondence: Fabrizio Barbetti, Email: fabrizio.barbetti@uniroma2.it
Restricted access

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 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.

 

     European Society of Endocrinology

Sept 2018 onwards Past Year Past 30 Days
Abstract Views 170 170 170
Full Text Views 14 14 14
PDF Downloads 22 22 22