Emergence of insulin resistance following empirical glibenclamide therapy: a case report of neonatal diabetes with a recessive INS gene mutation

J Pediatr Endocrinol Metab. 2018 Mar 28;31(3):345-348. doi: 10.1515/jpem-2017-0325.

Abstract

Background: As KATP channel mutations are the most common cause of neonatal diabetes mellitus (NDM) and patients with these mutations can be treated with oral sulfonylureas, empiric therapy is a common practice for NDM patients.

Case presentation: A non-syndromic, small for gestational age baby born to first-degree consanguineous parents was diagnosed with NDM. Because of hypo- and hyperglycemic episodes and variability in insulin requirement, we initiated a trial of glibenclamide, with a presumptive diagnosis of NDM caused by a KATP channel mutation. However, this empiric sulfonylurea trial did not improve the patient's glycemic control and resulted in resistance to exogenous insulin. Genetic testing identified a previously reported homozygous INS promoter mutation (c.-331C>G), which was not responsive to sulfonylurea therapy.

Conclusions: In light of our results, we recommend to confirm the genetic diagnosis as soon as possible and decide on sulfonylurea treatment after a genetic diagnosis is confirmed.

Keywords: insulin gene; neonatal diabetes mellitus; sulfonylurea.

Publication types

  • Case Reports

MeSH terms

  • Blood Glucose / analysis
  • Consanguinity
  • Diabetes Mellitus / drug therapy
  • Diabetes Mellitus / genetics*
  • Glyburide / adverse effects
  • Glyburide / therapeutic use*
  • Homozygote
  • Humans
  • Infant, Newborn
  • Infant, Newborn, Diseases / drug therapy
  • Infant, Newborn, Diseases / genetics*
  • Infant, Small for Gestational Age
  • Insulin / genetics*
  • Insulin / therapeutic use
  • Insulin Resistance / genetics*
  • Male
  • Mutation
  • Promoter Regions, Genetic / genetics

Substances

  • Blood Glucose
  • Insulin
  • Glyburide