Improved diabetic control during oral sulfonylurea treatment in two children with permanent neonatal diabetes mellitus.
Permanent neonatal diabetes mellitus (PND), defined as diabetes diagnosed in the first 6 months of age and requiring life-long insulin therapy, is a rare disorder of unknown etiology. Activating mutations of the KCNJ11 gene, which encodes the Kir6.2 subunit of the ATP-dependent potassium channel in beta-cells, have been found to cause 30-58% of cases of PND. Sulfonylurea treatment in theses patients reduces or eliminates the need for exogenous insulin. We report two Taiwanese boys who were diagnosed with PND at 1 and 4.5 months of age. They had been treated with exogenous insulin for 6 and 15 years, respectively. In September 2006, they were both found to have a KCNJ11 mutation (valine-to-methionine at codon 59; V59M). Glibenclamide successfully increased the basal C-peptide level, lowered HbA(1c), and reduced blood sugar excursions. In one patient, the insulin dose was reduced to 0.2 U/kg/day, and the other was able to discontinue insulin altogether. These two cases from Taiwan add to the experience with similar mutations reported in Caucasians.
Wei-Hsin
WH
Ting
Chi-Yu
CY
Huang
Fu-Sung
FS
Lo
Hung-Chang
HC
Lee
Chong-Ling
CL
Lin
Wen-Ling
WL
Guo
Yann-Jinn
YJ
Lee
D000293:Adolescent; D001786:Blood Glucose / Q000187:drug effects; D002096:C-Peptide / Q000097:blood / Q000187:drug effects; D002648:Child; D004252:DNA Mutational Analysis; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D004359:Drug Therapy, Combination; D005215:Fasting; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000032:analysis / Q000187:drug effects; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000627:therapeutic use; D008297:Male; D017354:Point Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D016896:Treatment Outcome; D000099161:Kcnj11 Channel
D001786:Blood Glucose; D002096:C-Peptide; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel; C517652:hemoglobin A1c protein, human