• Han Na Kim, Betiel Fesseha, Laura Anzaldi, Allison Tsao, Panagis Galiatsatos, and Aniket Sidhaye.
• Division of Endocrinology, Diabetes, & Metabolism, Department of MedicineThe Johns Hopkins University School of Medicine, Baltimore, Md.
• Am. J. Med. 2018 Jan 1; 131 (1): 102-106.

BackgroundType 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/ResultsWe 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.ConclusionAlthough 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.Copyright © 2018 Elsevier Inc. All rights reserved.

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