J Korean Med Sci.  2007 Aug;22(4):616-620. 10.3346/jkms.2007.22.4.616.

Sulfonylurea Therapy in Two Korean Patients with Insulin-treated Neonatal Diabetes due to Heterozygous Mutations of the KCNJ11 Gene Encoding Kir6.2

• Kim MS
• Kim SY
• Kim GH
• Yoo HW
• Lee DW
• Lee DY

• KMID: 1127075
• DOI: http://doi.org/10.3346/jkms.2007.22.4.616

Abstract

Permanent neonatal diabetes (PND) is a rare form of diabetes characterized by insulin-requiring hyperglycemia diagnosed within the first three months of life. In most cases, the causes are not known. Recently, mutations in the KCNJ11 gene encoding the Kir6.2 subunit of the ATP-sensitive K(+) channel have been described in patients with PND. We report the first two Korean cases with PND due to a lysineto- arginine substitution at position 170 (K179R) and a valine-to-methionine substitution at position 59 (V59M) mutations of KCNJ11 encoding Kir6.2, respectively. After several years of insulin therapy, these patients were managed by oral glibenclamide therapy at a daily dose of 0.8-0.9 mg/kg. Their basal c-peptide levels increased after one week of glibenclamide therapy, and one month later, the insulin and c-peptide levels were in the normal ranges without any episodes of hyper- or hypoglycemia. These cases demonstrate that oral sulfonylurea may be the treatment of choice in PND patients with KCNJ11 mutations even at a young age.

Keyword

Neonatal Diabetes; Permanent; Korean; Sulfonylurea; Kir6.2 Channel; Mutation

MeSH Terms

Base Sequence
C-Peptide/blood
DNA Mutational Analysis
Diabetes Mellitus/blood/*drug therapy/genetics
Female
Glyburide/*therapeutic use
Hemoglobin A, Glycosylated/metabolism
Heterozygote
Humans
Hypoglycemic Agents/therapeutic use
Infant
Infant, Newborn
Insulin/blood/*therapeutic use
Korea
*Mutation
Potassium Channels, Inwardly Rectifying/*genetics
Sulfonylurea Compounds/therapeutic use
Treatment Outcome

Figure

• 

  Fig. 1 Direct DNA sequence analysis of two patients with permanent neonatal diabetes revealed mutations of the KCNJ11 gene encoding Kir6.2. Arrows indicate the nucleotide position affected by the mutation. Case 1 (A) had a nucleotide substitution with AAG to AGG at position 509 in the exon 3. Case 2 (B) had a nucleotide substitution with GTG to ATG at position 175 in the exon 2.

• 

  Fig. 2 A three representative 24-hr long recordings of glucose levels at one day before glibenclamide therapy (insulin therapy only, A) and one week (B) and one month (C) after glibenclamide therapy (only glibenclamide therapy), performed by continuous gluC cose monitoring system in case 1.

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