Permanent neonatal diabetes by a new mutation in KCNJ11: unsuccessful switch to sulfonylurea

• Type: Article in International Scientific Journal
• Date: 2015

Authors

Lau, E (Author) FMUP; C Correia (Author) FMUP; Freitas, P (Author) FMUP; Nogueira, C (Author) Other; mascarenhas, t (Author) FMUP; Saavedra, A (Author) Other; Costa, C (Author) FMUP; Carvalho, Davide (Author) FMUP; Fontoura M (Author) FMUP

Journal

Title: Arquivos Brasileiros de Endocrinologia e Metabologia

Vol. 59

Pages: 559-561

ISSN: 0004-2730

Publisher: Universidade de São Paulo

Indexing

ISI Web of Knowledge - 5 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-00K-4QK

DOI: 10.1590/2359-3997000000076

Abstract (EN): Permanent neonatal diabetes (PNDM) can result from activating heterozygous mutations in KCNJ11 gene, encoding the Kir6.2 subunit of the pancreatic ATP-sensitive potassium channels (K-ATP). Sulfonylureas promote K-ATP closure and stimulate insulin secretion, being an alternative therapy in PNDM, instead of insulin. Male, 20 years old, diagnosed with diabetes at 3 months of age. The genetic study identified a novel heterozygous mutation in exon 1 of the KCNJ11 gene - KCNJ11:c1001G>7 (p.Gly334Val) - and confirmed the diagnosis of PNDM. Therefore it was attempted to switch from insulin therapy to sulfonylurea. During glibenclamide institution C-peptide levels increased, however the suboptimal glycemic control lead us to restart an intensive insulin scheme. This new variant of KCNJ11 mutation had a phenotypic lack of response to sulfonylurea therapy. Age, prior poor metabolic control and functional change of K-ATP channel induced by this specific mutation may explain the observed unsuccessful switch to sulfonylurea. Interestingly, C-peptide levels raise during glibenclamide administration support some degree of improvement in insulin secretory capacity induced by the treatment. Understanding the response to sulfonylurea is crucial as successful treatment may be life-changing in these patients.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 3