title: Efficacy and safety of sulfonylurea use in permanent neonatal diabetes due to KCNJ11 gene mutations: 34-month median follow-up.
abstract: BACKGROUND
  Recently, many patients with Kir6.2-related permanent neonatal diabetes mellitus (PNDM) have been successfully transferred from insulin therapy to sulfonylurea (SU) treatment. The long-term efficacy and safety of SU treatment in PNDM patients, however, have not yet been determined.
  
  
  METHODS
  We monitored glycemic control and the occurrence of potential side effects in 14 Kir6.2-related PNDM patients from Poland (median age, 12.0 years; range, 5-50 years) who were transferred to SU therapy at least 2 years ago. Three of the 14 patients were lost to follow-up, whereas for the remaining 11 individuals the median follow-up was 34 months (range, 27-51 months).
  
  
  RESULTS
  The initial reduction of glycated hemoglobin (HbA1c) after the switch to SU (approximately 3-6 months post-transfer) was 1.68% (range, 0.3-3.7%), and good metabolic control was maintained over the entire period of observation with an average HbA1c level of 6.0% (range, 5.3-6.7%) at the last visit. This was accompanied by a substantial drop in SU dose by 0.24 mg/kg, which constituted a 38.0% decrease. A rapid progression of retinal changes was observed in one patient, a 34-year-old woman at the beginning of the observation, with preexisting proliferative diabetic retinopathy. No causal relationship between these changes and SU treatment could be proven. Neither serious side effects nor progression of diabetes complications was observed in any other patients. No detrimental effect on growth in the observed minors was recorded.
  
  
  CONCLUSIONS
  In summary, the switch from insulin therapy to SU treatment in PNDM related to KCNJ11 mutations was found to be an efficient and safe therapeutic method over a period of 34-month median follow-up. Although no serious side effects were associated with SU treatment, their use in Kir6.2 PNDM requires further attention, particularly in children, adolescents, and patients with advanced chronic diabetes complications.
authors.affiliation: Department of Metabolic Diseases, Jagiellonian University Medical College , Krakow, Poland.
authors.forename: Tomasz
authors.initials: T
authors.lastname: Klupa
authors.forename: Jan
authors.initials: J
authors.lastname: Skupien
authors.forename: Barbara
authors.initials: B
authors.lastname: Mirkiewicz-Sieradzka
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Gach
authors.forename: Anna
authors.initials: A
authors.lastname: Noczynska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Zubkiewicz-Kucharska
authors.forename: Mieczyslaw
authors.initials: M
authors.lastname: Szalecki
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Kozek
authors.forename: Joanna
authors.initials: J
authors.lastname: Nazim
authors.forename: Wojciech
authors.initials: W
authors.lastname: Mlynarski
authors.forename: Maciej T
authors.initials: MT
authors.lastname: Malecki
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009154:Mutation; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome; D000099161:Kcnj11 Channel
chemical_list: D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel