title: Age at the time of sulfonylurea initiation influences treatment outcomes in KCNJ11-related neonatal diabetes.
abstract: OBJECTIVE
  Individuals with heterozygous activating mutations of the KCNJ11 gene encoding a subunit of the ATP-sensitive potassium channel (KATP) can usually be treated with oral sulfonylurea (SU) pills in lieu of insulin injections. The aim of this study was to test our hypothesis that younger age at the time of initiation of SU therapy is correlated with lower required doses of SU therapy, shorter transition time and decreased likelihood of requiring additional diabetes medications.
  
  
  METHODS
  We performed a retrospective cohort study using data on 58 individuals with neonatal diabetes due to KCNJ11 mutations identified through the University of Chicago Monogenic Diabetes Registry ( http://monogenicdiabetes.uchicago.edu/registry ). We assessed the influence of age at initiation of SU therapy on treatment outcomes.
  
  
  RESULTS
  HbA1c fell from an average of 8.5% (69 mmol/mol) before transition to 6.2% (44 mmol/mol) after SU therapy (p < 0.001). Age of initiation of SU correlated with the dose (mg kg(-1) day(-1)) of SU required at follow-up (r = 0.80, p < 0.001). Similar associations were observed across mutation subtypes. Ten participants required additional glucose-lowering medications and all had initiated SU at age 13 years or older. No serious adverse events were reported.
  
  
  CONCLUSIONS
  Earlier age at initiation of SU treatment is associated with improved response to SU therapy. Declining sensitivity to SU may be due to loss of beta cell mass over time in those treated with insulin. Our data support the need for early genetic diagnosis and appropriate personalised treatment in all cases of neonatal diabetes.
authors: Departments of Pediatrics and Medicine, Section of Adult and Pediatric Endocrinology, Diabetes, & Metabolism, University of Chicago, 5841 S. Maryland Ave., MC 1027, Chicago, IL, 60637, USA.
authors: Brian W
authors: BW
authors: Thurber
authors: David
authors: D
authors: Carmody
authors: Elizabeth C
authors: EC
authors: Tadie
authors: Ashley N
authors: AN
authors: Pastore
authors: Jazzmyne T
authors: JT
authors: Dickens
authors: Kristen E
authors: KE
authors: Wroblewski
authors: Rochelle N
authors: RN
authors: Naylor
authors: Louis H
authors: LH
authors: Philipson
authors: Siri Atma W
authors: SA
authors: Greeley
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D017668:Age of Onset; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000151:congenital* / Q000188:drug therapy*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005905:Glyburide / Q000627:therapeutic use; D006442:Glycated Hemoglobin / Q000032:analysis; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D009154:Mutation / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D012189:Retrospective Studies; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D016896:Treatment Outcome; D055815:Young Adult; D000099161:Kcnj11 Channel
chemical_list: D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D000099161:Kcnj11 Channel