Immunologic improvement resulting from the transfer of animal insulin-treated diabetic subjects to human insulin (recombinant DNA)

Abstract

To study the immunologic effects of transfer of patients from animal insulins to human insulin (recombinant DNA), a double-blind comparative trial was begun in over 300 patients. Preliminary results are reported in 116 individuals. After maintenance on purified pork or mixed beef-pork insulins (PPI or MBP) for a minimum of 6 mo, 116 patients were either switched to human insulin or maintained on their previous insulin. Antibody levels were assessed at a baseline visit and then monthly. In PPI-maintained individuals as well as those switched to human insulin there was a significant decrease in qualitative antibody binding as indicated by species-specific binding of 125I beef and human insulins (SBB and SBH), both P less than 0.005. Quantitative binding, as indicated by bound insulin levels, decreased to a much greater extent in patients switched to human insulin, 52% versus 31%, P less than 0.005. Parameters derived from formal antibody titration did not change. In patients maintained on MBP, bound insulin decreased (-36% at 6 mo, P less than 0.002). When switched from MBP to human insulin, there was a marked reduction in all parameters of binding, both qualitative and quantitative: SBP, -68%; SBH, -61%; SBB, -57%; bound insulin, -67% (all P less than 0.001) and decreases in high- and low-affinity binding capacities (P less than 0.02). Thus, for patients treated previously with nonhomologous insulins, transfer to human insulin may result in significant immunologic improvement in anti-insulin antibody levels.