title: Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds.
abstract: OBJECTIVE
  The pathogenic base of neonatal diabetes mellitus (NDM) is highly heterogeneous. Sulfonylurea (SU) has been successfully applied in majority of NDM patients with KATP channel mutations; however, its rationality and effectiveness among patients with NDM stemmed from other genetic mutations have not been established. The objective of the present study was to investigate the effectiveness of SU therapy in NDM patients with heterogeneous genetic backgrounds.
  
  
  METHODS
  We identified 16 patients with NDM. These patients underwent SU titration and were followed after successful SU monotherapy. All patients were sequenced for all exons and adjacent intron-exon junctions of ABCC8, KCNJ11, and INS, and analyzed for 6q24 methylation defects. SU regimens were applied and glycemic status was evaluated in each patient.
  
  
  RESULTS
  Of the 16 patients, 15 (94%) reached glycemic goal (7-10 mmol/L) after SU monotherapy except one patient with the INS mutation. No significant side effects or organ damage were found in any of the 16 patients. Among these patients, five were found to harbor ABCC8 mutations, another five had mutations in KCNJ11, two had INS gene mutations, one with 6q24 hypomethylation, and three were absent for defects in genes tested.
  
  
  CONCLUSIONS
  Our study showed that SU monotherapy resulted in satisfactory glycemic control in most of the patients with NDM whose genetic defects are heterogeneous. The usage of SU may be considered as first-line therapy for patients with NDM in developing countries where effective genetic screening is not established.
authors.forename: Miaoying
authors.initials: M
authors.lastname: Zhang
authors.forename: Xiuli
authors.initials: X
authors.lastname: Chen
authors.forename: Shuixian
authors.initials: S
authors.lastname: Shen
authors.forename: Tang
authors.initials: T
authors.lastname: Li
authors.forename: Linqi
authors.initials: L
authors.lastname: Chen
authors.forename: Min
authors.initials: M
authors.lastname: Hu
authors.forename: Lingfeng
authors.initials: L
authors.lastname: Cao
authors.forename: Ruoqian
authors.initials: R
authors.lastname: Cheng
authors.forename: Zhuhui
authors.initials: Z
authors.lastname: Zhao
authors.forename: Feihong
authors.initials: F
authors.lastname: Luo
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D002648:Child; D002675:Child, Preschool; D003920:Diabetes Mellitus / Q000188:drug therapy* / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D000068617:Genetic Background; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000188:drug therapy / Q000235:genetics; D007328:Insulin / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics*; D011379:Prognosis; D013453:Sulfonylurea Compounds / Q000627:therapeutic use*; D064233:Sulfonylurea Receptors / Q000235:genetics*; D000099161:Kcnj11 Channel
chemical_list: D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D013453:Sulfonylurea Compounds; D064233:Sulfonylurea Receptors; D000099161:Kcnj11 Channel; C577507:ABCC8 protein, human