Insulin was first used in the treatment of diabetic patients in 1921 and the first immunological problem associated with its use was reported in 1922 [1]; a patient developed anaphylaxis after the injection of a porcine, but not of a bovine insulin preparation. At that time insulin preparations were very impure and the antigen was probably a contaminating substance rather than insulin. In subsequent years a small number of patients were found to have developed insulin resistance after treatment with insulin [2]. In