Affinity of IgG-Insulin Antibodies to Human (recombinant DNA) Insulin and Porcine Insulin in Insulin-treated Diabetic Individuals With and Without Insulin Resistance

The affinity of human (recombinant DNA) insulin and porcine insulin to preformed IgG-insulin antibodies of insulin-treated diabetic individuals was studied in 29 insulin-treated diabetic patients. The binding of 125I-human insulin and 125I-porcine insulin with antibodies was similar in the group of patients without insulin resistance (N = 25). The sera of insulin-resistant diabetic patients (N = 4), containing very high IgG-insulin immunoglobulins, showed a significantly lower affinity for human insulin compared with porcine insulin (P less than 0.01). All four patients with insulin-antibody-mediated insulin resistance were positive for HLA-DR4, but negative for -DR3, supporting the concept of an immunogenetically transferred anti-insulin immune response in insulin-treated diabetic individuals. Based on the reduced binding of human insulin to IgG-antibodies of very high titers in patients with insulin resistance, a potential therapeutic advantage of human insulin therapy can be expected in such infrequent cases of immunologic insulin resistance.