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

Archives of Endocrinology and Metabolism
Eva LauManuel Fontoura

Abstract

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 (KATP). Sulfonylureas promote KATP 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 KATP 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 s...Continue Reading

References

Nov 9, 2004·The Journal of Clinical Endocrinology and Metabolism·Amnon ZungZvi Zadik
Dec 8, 2004·Proceedings of the National Academy of Sciences of the United States of America·Peter ProksFrances M Ashcroft
Feb 19, 2005·Human Molecular Genetics·Anna L GloynAndrew T Hattersley
Aug 4, 2006·The New England Journal of Medicine·Ewan R PearsonUNKNOWN Neonatal Diabetes International Collaborative Group
Mar 14, 2007·Orphanet Journal of Rare Diseases·Michel Polak, Hélène Cavé
Jul 30, 2008·Pediatric Diabetes·Julie StøyUNKNOWN United States Neonatal Diabetes Working Group
Mar 4, 2010·Cell Metabolism·Frances M Ashcroft
Oct 14, 2014·Diabetes Research and Clinical Practice·Yotsapon ThewjitcharoenAndrew T Hattersley

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Citations

Jun 1, 2016·Frontiers in Pharmacology·Paola ImbriciDiana Conte
Jun 14, 2018·Diabetic Medicine : a Journal of the British Diabetic Association·S MisraN S Oliver

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