title: Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2.
abstract: Permanent neonatal diabetes mellitus (PNDM) is a rare form of diabetes characterized by insulin-requiring hyperglycemia that is diagnosed within the first months of life. Recently, activating mutations in the gene encoding the ATP-sensitive potassium-channel subunit Kir6.2 were identified in 10 PNDM patients. Tolbutamide-stimulated insulin secretion, demonstrated in 3 of these patients suggested that some PNDM patients may respond to oral sulfonylurea treatment. In this report, we describe an infant with PNDM due to an arginine-to-histidine substitution at position 201 (R201H) of the gene encoding Kir6.2. After insulin pump therapy for six months, he was shifted to oral glybenclamide therapy at a daily dose of 0.8 mg/kg. Basal c-peptide level increased by two fold during glybenclamide treatment, but no further elevation was observed following intravenous glucose administration. Outpatient, continuous glucose monitoring while on a normal infant diet demonstrated a marked improvement in glycemic control. This study demonstrates the feasibility of oral sulfonylurea treatment in PNDM patients with Kir6.2 mutations even during infancy, and the superiority of this approach over insulin administration.
authors.affiliation: Pediatric Endocrinology Unit, Kaplan Medical Center, Affiliated with Hadassah Medical School, The Hebrew University of Jerusalem, Rehovot 76100, Israel. amzung2@bezeqint.net.
authors.forename: Amnon
authors.initials: A
authors.lastname: Zung
authors.forename: Benjamin
authors.initials: B
authors.lastname: Glaser
authors.forename: Revital
authors.initials: R
authors.lastname: Nimri
authors.forename: Zvi
authors.initials: Z
authors.lastname: Zadik
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D003920:Diabetes Mellitus / Q000097:blood / Q000188:drug therapy* / Q000235:genetics; D005905:Glyburide / Q000627:therapeutic use*; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D008297:Male; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D000099161:Kcnj11 Channel
chemical_list: D001786:Blood Glucose; D005905:Glyburide; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel