A longitudinal study of insulin antibodies and anti-insulin cytotoxicity in type I diabetes mellitus.

Insulin antibodies and T-cell lymphocyte cytotoxic reactivity against insulin and its related peptides were studied longitudinally in 3 groups of patients with type I diabetes mellitus (DM). Group 1 patients were those in whom the diagnosis was made within 1 week of the initiation diagnosis. They were subdivided into those receiving MC porcine (A) or MC bovine (B) insulin. Group 2 patients were those with a duration of DM for 2-6 years who were receiving either MC porcine (A) or MC bovine (B) insulins. Group 3 subjects were those who had been on conventional recrystallized insulin and then switched to MC porcine (A) or MC bovine (B) insulins for 2 weeks before the start of the study. The incidence of cytotoxic reactions and insulin antibodies were approximately 40-50% for group 1 (either 1A or 1B) at the initiation of the study. At 3-month follow up all patients in group 1B developed insulin antibodies (p less than 0.02) and a significant increase in the frequency of cytotoxic reactions (p less than 0.01). By contrast there was a decline in the frequency of cytotoxic reactions in group 1A (p less than 0.01 at 1 year) and the increase in insulin antibodies was non-significant. Group 2B had higher frequency in cytotoxic reactions (p less than 0.005) and of insulin antibodies (p less than 0.05) than group 2A. A significant decrease (p less than 0.01) in cytotoxic reactions was observed at 3 months following the switch of patients from conventional bovine insulin preparations to 'A' but not to 'B'. However in both subgroups insulin antibodies persisted for at least 12 months. Cross-reactivity between antibodies to human, porcine and bovine insulins was evident in all groups. The early cellular and humoral immune phenomena were positively correlated in both group 1A and 1B suggesting their common involvement in the pathogenesis of DM.