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Effective Treatment With Oral Sulfonylureas in Patients With Diabetes Due to Sulfonylurea Receptor 1 (SUR1) Mutations

¹ Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, U.K
² St. George's University of London, London, U.K

Address correspondence and reprint requests to Professor Andrew T. Hattersley, Peninsula Medical School, Barrack Road, Exeter, EX2 5DW, U.K. E-mail: andrew.hattersley{at}pms.ac.uk

OBJECTIVE—Neonatal diabetes can result from mutations in the Kir6.2 or sulfonylurea receptor 1 (SUR1) subunits of the ATP-sensitive K⁺ 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 to compare it with Kir6.2 mutations.

RESEARCH DESIGN AND METHODS—We followed 27 patients with SUR1 mutations for at least 2 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, glycemic control before and after transfer, and treatment requirements in patients with SUR1 and Kir6.2 mutations.

RESULTS—Twenty-three patients (85%) successfully transferred onto sulfonylureas without significant side effects or increased hypoglycemia and did not need insulin injections. In these patients, median A1C fell from 7.2% (interquartile range 6.6–8.2%) on insulin to 5.5% (5.3–6.2%) on sulfonylureas (P = 0.01). When compared with Kir6.2 patients, SUR1 patients needed lower doses of both insulin before transfer (0.4 vs. 0.7 units · kg^–1 · day^–1; P = 0.002) and sulfonylureas after transfer (0.26 vs. 0.45 mg · kg^–1 · day^–1; 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 because they require lower doses of sulfonylureas than required by Kir6.2 patients.

Abbreviations: SUR1, sulfonylurea receptor 1

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