Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations : an international cohort study

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Neonatal Diabet Int Collaborative , Bowman , P & Tuomi , T 2018 , ' Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations : an international cohort study ' , The Lancet diabetes & endocrinology , vol. 6 , no. 8 , pp. 637-646 . https://doi.org/10.1016/S2213-8587(18)30106-2

Title: Effectiveness and safety of long-term treatment with sulfonylureas in patients with neonatal diabetes due to KCNJ11 mutations : an international cohort study
Author: Neonatal Diabet Int Collaborative; Bowman, Pamela; Tuomi, Tiinamaija
Contributor: University of Helsinki, Centre of Excellence in Complex Disease Genetics
Date: 2018-08
Language: eng
Number of pages: 10
Belongs to series: The Lancet diabetes & endocrinology
ISSN: 2213-8587
URI: http://hdl.handle.net/10138/299283
Abstract: Background KCNJ11 mutations cause permanent neonatal diabetes through pancreatic ATP-sensitive potassium channel activation. 90% of patients successfully transfer from insulin to oral sulfonylureas with excellent initial glycaemic control; however, whether this control is maintained in the long term is unclear. Sulfonylurea failure is seen in about 44% of people with type 2 diabetes after 5 years of treatment. Therefore, we did a 10-year multicentre follow-up study of a large international cohort of patients with KCNJ11 permanent neonatal diabetes to address the key questions relating to long-term efficacy and safety of sulfonylureas in these patients. Methods In this multicentre, international cohort study, all patients diagnosed with KCNJ11 permanent neonatal diabetes at five laboratories in Exeter (UK), Rome (Italy), Bergen (Norway), Paris (France), and Krakow (Poland), who transferred from insulin to oral sulfonylureas before Nov 30, 2006, were eligible for inclusion. Clinicians collected clinical characteristics and annual data relating to glycaemic control, sulfonylurea dose, severe hypoglycaemia, side-effects, diabetes complications, and growth. The main outcomes of interest were sulfonylurea failure, defined as permanent reintroduction of daily insulin, and metabolic control, specifically HbA(1c) and sulfonylurea dose. Neurological features associated with KCNJ11 permanent neonatal diabetes were also assessed. Findings 90 patients were identified as being eligible for inclusion and 81 were enrolled in the study and provided long-term (>5.5 years cut-off) outcome data. Median follow-up duration for the whole cohort was 10.2 years (IQR 9.3-10.8). At most recent follow-up (between Dec 1, 2012, and Oct 4, 2016), 75 (93%) of 81 participants remained on sulfonylurea therapy alone. Excellent glycaemic control was maintained for patients for whom we had paired data on HbA(1c) and sulfonylurea at all time points (ie, pre-transfer [for HbA(1c)], year 1, and most recent followup; n=64)-median HbA(1c) was 8.1% (IQR 7.2-9.2; 65.0 mmol/mol [55.2-77.1]) before transfer to sulfonylureas, 5.9% (5.4-6.5; 41.0 mmol/mol [35.5-47.5]; p Interpretation High-dose sulfonylurea therapy is an appropriate treatment for patients with KCNJ11 permanent neonatal diabetes from diagnosis. This therapy is safe and highly effective, maintaining excellent glycaemic control for at least 10 years. Copyright (C) 2018 The Author(s). This is an Open Access article under the CC BY 4.0 license.
Subject: ACTIVATING MUTATIONS
KIR6.2
CHILDREN
THERAPY
INSULIN
GENE
HYPOGLYCEMIA
ADOLESCENTS
DYSFUNCTION
MELLITUS
3121 General medicine, internal medicine and other clinical medicine
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