Effective treatment with oral sulfonylureas in patients with diabetes due to sulfonylurea receptor 1 (SUR1) mutations

Abstract

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 x kg(-1) x day(-1); P = 0.002) and sulfonylureas after transfer (0.26 vs. 0.45 mg x kg(-1) x 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.

Figures

Figure 1. Initial reduction in glycated haemoglobin levels following transfer from insulin to sulfonylurea.

Panel A shows glycated haemoglobin values (HbA1c) for 10 patients (all those with full data) who had HbA1c measured when on insulin treatment and also at least 4 weeks after (median 15) weeks after successful transfer onto sulfonylurea medication. The thick horizontal lines represent the mean HbA1c with insulin and sulfonylurea treatment. Panel B shows mean glycated haemoglobin values and sulfonylurea doses for 5 patients for whom data were available for at least 6 months after transfer onto sulfonylureas. The solid line represents mean glycated haemoglobin values. The bars show 95% confidence intervals and the dashed line represents the mean equivalent dose of glyburide in mg/kg/day.

Figure 2. Lower treatment doses are needed in patients with SUR1 mutations compared to patients with Kir6.2 mutations.

Black bars = Kir6.2 patients, White bars = SUR1 patients. Median insulin and sulfonylurea doses are shown for 21 patients with SUR1 mutations and 44 with Kir6.2 mutations who successfully transferred from insulin to sulfonylurea therapy.