Insulin autoimmune syndrome with insulin-resistant diabetes at the incipient stage prior to hypoglycemic attacks

Insulin autoimmune syndrome is characterized by spontaneous hypoglycemia, glucose intolerance, hyperinsulinemia and insulin-binding antibodies in serum without previous immunization. A 31-year-old man with Graves' disease developed insulin autoantibodies after therapy with methimazole. The patient was unique in that persistent hyperglycemia with polyuria and polydipsia had continued for several days before frequent hypoglycemic attacks appeared. We were able to extract a huge amount of immunoreactive insulin (116,000 microU/ml) with acid-ethanol from his serum obtained in the diabetic stage, and serum C-peptide immunoreactivity was as high as 268 ng/ml. The insulin-binding activity of his serum was quite potent, and when 1:5,000 diluted serum was incubated with 125I-porcine insulin, 71.2% of the label could be precipitated by polyethylene glycol. The insulin-binding protein was identified as mainly IgG with kappa light chains. Insulin-binding activity was not detected in serum obtained before methimazole therapy, suggesting that the drug was responsible for the induction of antibodies in this patient. The antibodies recognized porcine, sheep, bovine and horse insulins as well as human insulin. The mechanisms by which the antibodies produced hyper- and hypoglycemia have also been discussed.