A pitfall in diagnosing type B insulin resistance syndrome: Suspected antibody interference in a patient with insulin allergy

The patient was a 73-year-old man with diabetes who developed marked hyperglycemia after several years of insulin therapy. Investigations showed marked hyperinsulinemia, positive insulin antibodies with low affinity/high binding capacity, insulin-specific IgE and eosinophil infiltration on skin biopsy, confirming insulin allergy. Positivity for insulin receptor autoantibodies (IRAb) initially led to a diagnosis of type B insulin resistance syndrome. However, a relatively low C-peptide level (1.57 ng/mL) despite severe hyperinsulinemia (1231.9 μU/mL) was key for differentiation. After cessation of insulin and initiating a multi-drug anti-diabetes regimen, the patient's glycemic control improved markedly, with a decrease in HbA_1c from 12.3 to 6.7%. His serum insulin level decreased, and his IRAb test turned negative. This case highlights the fact that a high insulin antibody titer can cause a false-positive IRAb result. A disproportionately low C-peptide level in the presence of hyperinsulinemia may aid differentiation between insulin allergy and type B insulin resistance syndrome.