title: Improved long-term glucose control in neonatal diabetes mellitus after early sulfonylurea allergy.
abstract: BACKGROUND
  Activating mutations of the ABCC8 gene can lead to permanent neonatal diabetes mellitus (PNDM). Glucose variability in infants with NDM treated with insulin can be extreme. We report long-term glycemic control in a patient with PNDM on sulfonylurea therapy, despite initial allergic reaction.
  
  
  METHODS
  A Chinese girl presented on the first day of life with persistent hyperglycemia. Despite treatment with various insulin regimens, hemoglobin (Hb)A1c (normal 4.8%-6.3%) increased from 5.0% at 14 days of age to a peak of 9.7% at 15 months of age. Her average insulin dose was 0.5 units/kg/day. Genetic analysis revealed two novel ABCC8 gene activating mutations encoding the beta-cell sulfonylurea-1 receptor of the ATP-sensitive potassium channel. At age 3 years 2 months, transition from insulin to the oral sulfonylurea glyburide was initiated. After 8 days, she developed urticaria, palmar erythema, and a diffuse maculopapular rash, which resolved when medication was discontinued. At age 3 years 11 months, glyburide was reintroduced at a very low dose and was increased with concomitant weaning of insulin over the following 6 months.
  
  
  RESULTS
  Normoglycemia (HbA1c 5.6%) was achieved on glyburide without any further allergic reaction at the age of 4 years 5 months with improved metabolic control. For the next 3 years, HbA1c measurements, and glucose means and variability were significantly lower compared with values during insulin therapy.
  
  
  CONCLUSIONS
  As compared with subcutaneous insulin, oral sulfonylureas improved long-term metabolic control in a patient with NDM caused by novel activating mutations in the ABCC8 gene. Desensitization permitted safe oral sulfonylurea therapy in our patient with NDM despite initial allergic reaction. Fewer episodes of hypoglycemia occurred on sulfonylurea than on insulin therapy, which is an advantage in a very young child.
authors: Division of Pediatric Endocrinology, Department of Pediatrics, New York University Langone Medical Center, New York, NY 10016, USA. bina.shah@nyumc.org
authors: Bina
authors: B
authors: Shah
authors: Emily
authors: E
authors: Breidbart
authors: Melissa
authors: M
authors: Pawelczak
authors: Leslie
authors: L
authors: Lam
authors: Marion
authors: M
authors: Kessler
authors: Bonita
authors: B
authors: Franklin
mesh_terms: D018528:ATP-Binding Cassette Transporters / Q000235:genetics; D001786:Blood Glucose / Q000032:analysis; D002648:Child; D003920:Diabetes Mellitus / Q000151:congenital / Q000235:genetics / Q000517:prevention & control*; D005260:Female; D005905:Glyburide / Q000627:therapeutic use*; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007231:Infant, Newborn; D007328:Insulin / Q000008:administration & dosage; D009154:Mutation / Q000235:genetics; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011955:Receptors, Drug / Q000235:genetics; D064233:Sulfonylurea Receptors; D016896:Treatment Outcome
chemical_list: D018528:ATP-Binding Cassette Transporters; D001786:Blood Glucose; D005905:Glyburide; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D024661:Potassium Channels, Inwardly Rectifying; D011955:Receptors, Drug; D064233:Sulfonylurea Receptors