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



      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.


      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.


      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.


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        • Arioglu E.
        • Andewelt A.
        • Diabo C.
        • et al.
        Clinical course of the syndrome of autoantibodies to the insulin receptor (type B insulin resistance): a 28-year perspective.
        Medicine (Baltimore). 2002; 81: 87-100
        • Malek R.
        • Chong A.Y.
        • Lupsa B.C.
        • et al.
        Treatment of type B insulin resistance: a novel approach to reduce insulin receptor autoantibodies.
        J Clin Endocrinol Metab. 2010; 95: 3641-3647
        • Semple R.K.
        • Cochran E.K.
        • Soos M.A.
        • et al.
        Plasma adiponectin as a marker of insulin receptor dysfunction: clinical utility in severe insulin resistance.
        Diabetes Care. 2008; 31: 977-979
        • Mianowska B.
        • Szadkowska A.
        • Pietrzak I.
        • et al.
        Immunogenicity of different brands of human insulin and rapid-acting insulin analogs in insulin-naive children with type 1 diabetes.
        Pediatr Diabetes. 2011; 12: 78-84
        • Asai M.
        • Kodera T.
        • Ishizeki K.
        • et al.
        Insulin lispro reduces insulin antibodies in a patient with type 2 diabetes with immunological insulin resistance.
        Diabetes Res Clin Pract. 2003; 61: 89-92
        • Lahtela J.T.
        • Knip M.
        • Paul R.
        • et al.
        Severe antibody-mediated human insulin resistance: successful treatment with the insulin analog lispro. A case report.
        Diabetes Care. 1997; 20: 71-73