BOVINE AND HUMAN NPH INSULINS AS T-CELL IMMUNOGENS

The aim of this study was to assess the immunocompetence of T cells fr om patients with poorly controlled diabetes with respect to Candida al bicans antigen and to compare the relative immunogenicity of human ins ulin, bovine insulin and protamine at the T-cell level during 6 months treatment with human or bovine NPH insulins. T-cell proliferation was measured in vitro in response to C albicans, bovine and human insulin , bovine and human NPH and protamine in 17 patients with newly-diagnos ed type 1 (insulin-dependent) and 12 with poorly-controlled type 2 (no n-insulin-dependent diabetes) before and after 0.5, 1, 3 and 6 months of treatment with either bovine or human NPH insulin. The following re sults were found: Baseline responses to C albicans (as a recall antige n) were similar for patients and controls despite marked hyperglycaemi a in the patients. No patient had a response greater than mean + 2 S.D . of controls to human or bovine insulin before starting treatment, or had insulin autoantibodies. Treatment with human NPH insulin did not induce T-cell responses to human or bovine insulin, but 3/13 (23%) pat ients treated with bovine NPH responded to bovine and human insulin af ter 6 months, of whom one responded exclusively to human. In contrast, 6 (46%) bovine and 3 (19%) human NPH-treated patients responded to pr otamine. It was concluded that there is no evidence of T-cell immunosu ppression in poorly-controlled diabetes or of T-cell autoimmunity to i nsulin in newly-diagnosed type 1 diabetes. Treatment with bovine NPH i nsulin immunizes T cells to insulin, but human NPH does not. Regardles s of insulin species the main immunogen in NPH insulins is protamine.