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Effective treatment with oral sulfonylureas in patients with diabetes due to SUR1 Mutations.

¹Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, UK
²St Georges University of London, London, UK
³Authors who contributed to this paper from the Neonatal Diabetes International Collaborative Group are listed in the appendix (alphabetical with institution)

Andrew.Hattersley{at}pms.ac.uk

ABSTRACT

Objective: Neonatal diabetes can result from mutations in the Kir6.2 or SUR1 subunits of the K_ATP channel. Transfer from insulin to oral sulfonylureas in patients with neonatal diabetes due to Kir6.2 mutations is well described, but less is known about changing therapy in patients with SUR1 mutations. We aimed to describe the response to sulfonylurea therapy in patients with SUR1 mutations and compare it with Kir6.2 mutations.

Research Design and Methods: We followed 27 patients with SUR1 mutations for at least two months after attempted transfer to sulfonylureas. Information was collected on clinical features, treatment before and after transfer and the transfer protocol used. We compared: successful and unsuccessful transfer patients, glycaemic control before and after transfer, and treatment requirements in patients with SUR1 and Kir6.2 mutations.

Results: 23 patients (85%) successfully transferred onto sulfonylureas without significant side effects or increased hypoglycaemia and did not need insulin injections. In these patients the median HbA1c fell from 7.2% (IQR 6.6-8.2%) on insulin to 5.5% (IQR 5.3–6.2%) on sulfonylureas P=0.01 . When compared to Kir6.2 patients, SUR1 patients needed lower doses of both insulin before transfer (0.4 vs 0.7u/kg/day, P=0.002) and sulfonylureas after transfer (0.26 vs 0.45 mg/kg/day, P=0.005).

Conclusions: Oral sulfonylurea therapy is safe and effective in the short-term in most patients with diabetes due to SUR1 mutations and may successfully replace treatment with insulin injections. A different treatment protocol needs to be developed for this group as they require lower doses of sulfonylureas than Kir6.2 patients.

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