Pharma / Biotech

Neonatal diabetes due to potassium channel mutation: response to sulfonylurea according to the genotype.


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Neonatal diabetes due to potassium channel mutation: response to sulfonylurea according to the genotype.

Pediatr Diabetes. 2020 May 16;:

Authors: Garcin L, Mericq V, Fauret-Amsellem AL, Cave H, Polak M, Beltrand J

Abstract
OBJECTIVE: A precision medicine approach is used to improve treatment of patients with monogenic diabetes. Herein we searched SU efficiency according to the genotype-phenotype correlation, dosage used and side effects.
RESEARCH DESIGN AND METHODS: Systematic review conducted according the PRISMA control criteria identifying relevant studies evaluating the in vivo and in vitro sensitivity of ATP-dependent potassium channels according to the characteristics of genetic mutation.
RESULTS: 103 selected articles with complete data in 502 cases in whom 413 (82.3%) had mutations in KCNJ11 (#64) and 89 in ABCC8 (# 56). Successful transfer from insulin to SU was achieved in 91% and 86.5% patients, respectively at a mean age of 36.5 months (0-63 years). Among patients with KCNJ11 and ABCC8 mutations 64 & 46 were associated with constant success,5 & 5 to constant failure, and 10 and 4 to variable degrees of reported success rate, respectively. The glibenclamide dosage required for each genotype ranged from 0.017 to 2.8 mg / kg / day. Comparing both the in vivo and in vitro susceptibility results, some mutations appear more sensitive than others to sulfonylurea treatment. Side effects were reported in 17 /103 of the included articles: mild gastrointestinal symptoms and hypoglycaemia were the most common. One premature patient had an ulcerative necrotizing enterocolitis which association with SU is difficult to ascertain.
CONCLUSIONS: Sulfonylurea are an effective treatment for monogenic diabetes due to KCNJ11 and ABCC8 genes mutations. The success of the treatment is conditioned by differences in pharmacogenetics, younger age, pharmacokinetics, compliance and maximal dose used. This article is protected by copyright. All rights reserved.

PMID: 32418263 [PubMed – as supplied by publisher]

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