Transition from insulin to sulfonylurea in a child with diabetes due to a mutation in KCNJ11 encoding Kir6.2--initial and long-term response to sulfonylurea therapy.
BACKGROUND
Mutations in the KCNJ11 gene encoding the adenosine triphosphate (ATP)-sensitive potassium channel (K(ATP)) subunit Kir6.2 are the most frequent cause of diabetes in infancy. Sulfonylurea (SU) treatment restores insulin secretion in patients with KCNJ11 mutations.


METHODS
We report a 9-year-old boy who presented at the age of three months with diabetic ketoacidosis. Results Sequencing of the KCNJ11 gene revealed an R201H mutation. Therefore, he was transferred from insulin to oral SU therapy. He required a high-threshold dose before insulin could be discontinued. After transition, a subsequent dose reduction was necessary to avoid hypoglycemia. Improved sustained metabolic control without complications was achieved on a low SU maintenance dose twice daily over 36 months.


CONCLUSIONS
SU therapy is safe for patients with diabetes due to KCNJ11 mutations. The mechanism of a threshold dose and the twice-daily requirement needs further attention.
Department of Pediatrics, Division of Pediatric Endocrinology and Diabetology, University of Lübeck, Lübeck, Germany. wagnerv@paedia.ukl.mu-luebeck.de
Verena M
VM
Wagner
Britta
B
Kremke
Olaf
O
Hiort
Sarah E
SE
Flanagan
Ewan R
ER
Pearson
D001786:Blood Glucose / Q000187:drug effects; D002648:Child; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000188:drug therapy* / Q000235:genetics*; D005905:Glyburide / Q000008:administration & dosage; D006442:Glycated Hemoglobin / Q000187:drug effects; D006579:Heterozygote; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007223:Infant; D007328:Insulin / Q000008:administration & dosage*; D054086:KATP Channels / Q000187:drug effects / Q000235:genetics; D008297:Male; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects / Q000235:genetics; D013453:Sulfonylurea Compounds / Q000008:administration & dosage*; D000099161:Kcnj11 Channel
D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D054086:KATP Channels; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel