Insulin antibodies in the pathogenesis of insulin allergy and resistance

Insulin allergy developed in a patient treated with beef/pork insulin. Desensitization therapy led to cessation of the allergy, but it was associated with the development of diabetic ketoacidosis with apparent insulin resistance which was successfully treated with fish insulin. The patient's initial serum contained a high titer of anti-insulin immunoglobulin E (IgE) antibody directed primarily against beef insulin. Desensitization therapy with pork insulin was associated with the production of anti-insulin immunoglobulin G (IgG) antibody with highest immunologic reactivity to pork insulin. This IgG antibody may have blocked the interaction of insulin with tissue-fixed IgE antibody but, in addition, led to significant increases in total serum insulin-binding capacity and transient insulin resistance. The favorable clinical response to fish insulin was likely due to the negligible immunologic reactivity of this patient's anti-insulin antibodies with fish insulin. This report suggests that desensitization therapy for insulin allergy can lead to insulin resistance of the immune type.