Sulfonylurea vs insulin therapy in individuals with sulfonylurea-sensitive permanent neonatal diabetes mellitus, attributable to a KCNJ11 mutation, and poor glycaemic control

Background: Therapy with sulfonylurea is preferable to insulin in the majority of individuals with KCNJ11 mutations, but not all of these people achieve target levels of HbA_1c in long-term follow-up. We aimed to compare sulfonylurea therapy with insulin treatment in two sulfonylurea-sensitive individuals with a KCNJ11 mutation who had poorly controlled permanent neonatal diabetes mellitus.

Case report: We report on two individuals with a KCNJ11 mutation (p.R201H) who are currently aged 35 (SVK1) and 21 years (SVK2). These individuals were switched from insulin to sulfonylurea in 2005. Data from the first 4 (SVK2) and 8 years (SVK1) of the follow-up showed improved diabetes control and increased quality of life for both individuals. During the following years, however, both individuals failed to retain good diabetes control (HbA_1c ≤ 53 mmol/mol; 7.0%). We therefore changed the therapy to a combination of insulin and sulfonylurea in both individuals, or to insulin monotherapy in SVK1, and compared the effects on HbA_1c with those of sulfonylurea monotherapy. HbA_1c levels in both individuals worsened after adding insulin to sulfonylurea [67 mmol/mol (8.3%) vs 77 mmol/mol (9.2%) in SVK1 and 106 mmol/mol (11.8%) vs 110±19 mmol/mol (12.2±1.7%) in SVK2], and after switching to only insulin therapy in SVK1 [57 mmol/mol (7.4%) vs 62 mmol/mol (7.8%)] when compared with sulfonylurea monotherapy.

Discussion: Our data show that sulfonylurea monotherapy might be preferable to insulin in people with permanent neonatal diabetes mellitus sensitive to sulfonylurea even when HbA_1c is above target.