Transfer to Sulphonylurea Therapy in Adult Subjects With Permanent Neonatal Diabetes Due to KCNJ11-Activating Mutations

Abstract

Activating mutations in the KCJN11 gene encoding in the ATP-sensitive K+ channel (KATP channel) subunit Kir6.2 were reported (1) as the most common cause of permanent neonatal diabetes (PND). Recently, it has been shown that most subjects with Kir6.2 mutations could be switched from insulin to sulfonylurea and that such treatment is both safe and highly effective, at least in the short term (2,3). Notably, the majority of reported successfully transferred patients were children. Data on adults are very scarce, and there are few mutation carriers transferred off insulin (2,4). Moreover, some adult subjects are unable to switch from insulin to sulfonylurea (2). We have recently identified four adult carriers of a Kir6.2 mutation and provided evidence that they, before the sulfonylurea exposure, were characterized by decreased insulin sensitivity (5). Here, we report their successful transfer to sulfonylurea. To dissect the genetic background of PND in Poland, the Nationwide Registry has recently been established. Four adult subjects with Kir6.2-activating mutations were identified by the end of 2005. Three subjects carried the R210H mutation, while one individual had the K170N substitution. They were included in the current project, which aimed to switch from insulin to sulfonylurea and to assess, by hyperinsulinemic-euglycemic clamp, whether the alteration in insulin action occurs after this transfer. The study protocol and informed-consent procedures were approved by the ethics committee of Jagiellonian University. The project was conducted according to the …