Protamine antibody production in diabetic subjects treated with NPH insulin.

Treatment with neutral protamine Hagedorn (NPH) insulin predisposes individuals with diabetes to anaphylactoid reactions when given bolus protamine for heparin reversal during cardiovascular procedures. To prospectively examine production of protamine antibodies, 30 patients with non-insulin dependent diabetes were followed for 12 months from initiation of therapy with porcine NPH or Lente insulin. Twenty-one subjects were randomly assigned to NPH (protamine containing) and nine controls to Lente (protamine free) insulin. Protamine specific IgG antibody was produced by 6/21 (29%) of NPH-treated subjects and 0/9 controls. Among NPH treated subjects, there was no difference between protamine antibody producers and non-producers with regard to age, race, weight, or pre-treatment glycosylated hemoglobin. Both producer and non-producer groups received similar amounts of insulin and protamine and achieved similar glycemic control. Insulin antibodies were made by 4/6 (67%) of protamine antibody producers and by 6/15 (40%) of non-producers (NS). The authors conclude that one of three new diabetics who are treated with porcine NPH insulin will make IgG protamine antibodies. These antibodies do not affect insulin requirements, glycemic control, or insulin antibody production. Because of the frequency of protamine antibody production and the risk of anaphylaxis to bolus protamine administration in NPH treated diabetics, the authors suggest that NPH insulin-treated individuals should avoid heparin reversal by protamine.