A case of a non-insulin dependent diabetic patient with regular spontaneous hypoglycemic attacks, which were due to insulin-binding antibodies induced by human insulin therapy.

A 74-year-old diabetic patient had been treated with oral hypoglycemic agents from the age of 40 years until the age of 72, when his treatment regimen was changed to human insulin. He began experiencing hypoglycemic attacks 14 months after the initiation of insulin therapy. He continued to experience hyperglycemia every morning and hypoglycemia every day at 5:30 p.m. even after insulin therapy was withdrawn. His plasma levels of C-peptide immunoreactivity, total and free immunoreactive insulins were 4.2 ng/ ml, 740 microU/ml and 141.8 microU/ml, respectively. His 125I-insulin binding rate was 94.4%. These findings suggest that his hypoglycemic attacks may have been due to insulin antibodies. Analysis revealed that insulin binding antibodies belonged to IgG with kappa light chains. The patient's genotype was HLA-DR4. He had not received animal insulin or any medications containing a sulfhydryl group. Although the IgG antibody was produced against injected human insulin, his HLA type and the characteristics of his antibodies resembled those of a patient with insulin autoimmune syndrome (IAS). We hypothesize that this patient represented a rare instance of a patient constitutionally similar to a patient with IAS, but whose hypoglycemic attacks resulted from the antibodies induced by the administration of human insulin. This case seems to be the first one with hypoglycemic attacks due to anti-human insulin antibody produced by human insulin therapy.