ISSN 1662-4009 (Online)

ESPE Yearbook of Paediatric Endocrinology (2019) 16 2.8 | DOI: 10.1530/ey.16.2.8

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

Bowman P, Sulen Å, Barbetti F, Beltrand J, Svalastoga P, Codner E, Tessmann EH, Juliusson PB, Skrivarhaug T, Pearson ER, Flanagan SE, Babiker T, Thomas NJ, Shepherd MH, Ellard S, Klimes I, Szopa M, Polak M, Iafusco D, Hattersley AT, Njølstad PR & Neonatal Diabetes International Collaborative Group. Collaborators (113)

To read the full abstract: Lancet Diabetes Endocrinol. 2018 Aug;6(8)

This study describes a 10-year follow-up of a large international multicenter cohort of patients with KCNJ11 permanent neonatal diabetes. It addresses key questions relating to long-term efficacy and safety of sulfonylureas in these patients.

The discovery that mutations in the KCNJ11 gene lead to neonatal diabetes mellitus in some patients transformed the care of these patients by switching from subcutaneous insulin injections to oral sulphonylureas. Although most patients respond to sulphonylureas in the short-term, there are no data on long-term follow up and whether these patients show decreasing responses to sulphonylureas over the long-term, as happens for example in patients with Type 2 diabetes.

In this international multicenter study, all patients who were diagnosed with neonatal diabetes mellitus due to KCNJ11 mutations and switched over to oral sulphonylureas before 30th of November 2006 were recruited and their long-term glycemic control and sulphonylurea safety were assessed over 10 years. The study showed that sulfonylurea failure, which is commonly seen in Type 2 diabetes, is not a feature in neonatal diabetes patients with mutations due of KCNJ11. Sulfonylureas were found to be safe in the long term, even in high doses, in this unique group of patients and there was excellent glycemic control maintained over the 10 year follow up period. In the short term there was some improvement in the neurological features, but unfortunately this did not continue in the long-term.

The key message from this study is that all infants diagnosed with neonatal diabetes aged less than 6 months old should undergo rapid genetic testing to facilitate early transfer of those with KCNJ11 mutations to sulfonylureas as first-line treatment. This action should result in safe and long-lasting excellent glycemic control for at least 10 years. Neurological features might show initial improvement but are likely to persist. Further research is needed to establish the effect of very early transfer and high-dose sulfonylurea therapy on neurological features.

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