Antibody-Mediated Extreme Insulin Resistance: A Report of Three Cases

Am J Med. 2018 Jan;131(1):102-106. doi: 10.1016/j.amjmed.2017.08.004. Epub 2017 Aug 16.

Abstract

Background: Type 2 diabetes mellitus is characterized by relative insulin deficiency and insulin resistance. Features suggesting severe insulin resistance include acanthosis nigricans, hyperandrogenism, weight loss, and recurrent hospital admissions for diabetic ketoacidosis. In rare circumstances, hyperglycemia persists despite administration of massive doses of insulin. In these cases, it is important to consider autoimmune etiologies for insulin resistance, such as type B insulin resistance and insulin antibody-mediated extreme insulin resistance, which carry high morbidity and mortality if untreated. Encouragingly, immunomodulatory regimens have recently been published that induce remission at high rates.

Methods/results: We describe 3 cases of extreme insulin resistance mediated by anti-insulin receptor autoantibodies or insulin autoantibodies. All cases were effectively treated with an immunomodulatory regimen.

Conclusion: Although cases of extreme insulin resistance are rare, it is important to be aware of autoimmune causes, recognize suggestive signs and symptoms, and pursue appropriate diagnostic evaluation. Prompt treatment with immunomodulators is key to restoring euglycemia in patients with autoimmune etiologies of insulin resistance.

Keywords: Extreme insulin resistance; Insulin antibody-mediated extreme insulin resistance; Insulin receptor antibody; Type B insulin resistance.

Publication types

  • Case Reports

MeSH terms

  • Antibodies / immunology*
  • Azathioprine / administration & dosage
  • Azathioprine / therapeutic use
  • Cyclophosphamide / administration & dosage
  • Cyclophosphamide / therapeutic use
  • Dexamethasone / administration & dosage
  • Dexamethasone / therapeutic use
  • Diabetes Mellitus, Type 2 / immunology*
  • Drug Therapy, Combination
  • Female
  • Glucocorticoids / administration & dosage
  • Glucocorticoids / therapeutic use
  • Humans
  • Immunologic Factors / administration & dosage
  • Immunologic Factors / therapeutic use
  • Immunosuppressive Agents / administration & dosage
  • Immunosuppressive Agents / therapeutic use
  • Insulin / administration & dosage
  • Insulin / immunology
  • Insulin / therapeutic use*
  • Insulin Resistance / immunology*
  • Male
  • Middle Aged
  • Receptor, Insulin / immunology*
  • Rituximab / administration & dosage
  • Rituximab / therapeutic use

Substances

  • Antibodies
  • Glucocorticoids
  • Immunologic Factors
  • Immunosuppressive Agents
  • Insulin
  • Rituximab
  • Dexamethasone
  • Cyclophosphamide
  • Receptor, Insulin
  • Azathioprine