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.

Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy / Bonfanti, R.; Iafusco, D.; Rabbone, I.; Diedenhofen, G.; Bizzarri, C.; Patera, P. I.; Reinstadler, P.; Costantino, F.; Calcaterra, V.; Iughetti, L.; Savastio, S.; Favia, A.; Cardella, F.; Lo Presti, D.; Girtler, Y.; Rabbiosi, S.; D'Annunzio, G.; Zanfardino, A.; Piscopo, A.; Casaburo, F.; Pintomalli, L.; Russo, L.; Grasso, V.; Minuto, N.; Mucciolo, M.; Novelli, A.; Marucci, A.; Piccini, B.; Toni, S.; Silvestri, F.; Carrera, P.; Rigamonti, A.; Frontino, G.; Trada, M.; Tinti, D.; Delvecchio, M.; Rapini, N.; Schiaffini, R.; Mammi, C.; Barbetti, F.. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 1479-683X. - 184:4(2021), pp. 575-585. [10.1530/EJE-20-1030]

Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy

Iughetti L.;
2021

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.
2021
184
4
575
585
Differences between transient neonatal diabetes mellitus subtypes can guide diagnosis and therapy / Bonfanti, R.; Iafusco, D.; Rabbone, I.; Diedenhofen, G.; Bizzarri, C.; Patera, P. I.; Reinstadler, P.; Costantino, F.; Calcaterra, V.; Iughetti, L.; Savastio, S.; Favia, A.; Cardella, F.; Lo Presti, D.; Girtler, Y.; Rabbiosi, S.; D'Annunzio, G.; Zanfardino, A.; Piscopo, A.; Casaburo, F.; Pintomalli, L.; Russo, L.; Grasso, V.; Minuto, N.; Mucciolo, M.; Novelli, A.; Marucci, A.; Piccini, B.; Toni, S.; Silvestri, F.; Carrera, P.; Rigamonti, A.; Frontino, G.; Trada, M.; Tinti, D.; Delvecchio, M.; Rapini, N.; Schiaffini, R.; Mammi, C.; Barbetti, F.. - In: EUROPEAN JOURNAL OF ENDOCRINOLOGY. - ISSN 1479-683X. - 184:4(2021), pp. 575-585. [10.1530/EJE-20-1030]
Bonfanti, R.; Iafusco, D.; Rabbone, I.; Diedenhofen, G.; Bizzarri, C.; Patera, P. I.; Reinstadler, P.; Costantino, F.; Calcaterra, V.; Iughetti, L.; S...espandi
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