Comparison of Antigenicity of Hoechst 21PH Insulin Using Either Implantable Intraperitoneal Pump or Subcutaneous External Pump Infusion in Type 1 Diabetic Patients

Abstract

OBJECTIVE—To assess the antigenicity of the insulin Hoechst 21PH (Hoe21PH) using continuous subcutaneous insulin infusion (CSII) and to compare the antigenicity of this insulin when administered intraperitoneally or subcutaneously. RESEARCH DESIGN AND METHODS—Peritoneal administration of Hoe21PH (Hoechst-Roussel, Somerville, NJ) insulin using implantable devices (continuous peritoneal insulin infusion [CPII]) increases anti-insulin antibody (AIA) levels in type 1 diabetic patients. Intraperitoneal administration, addition of a stabilizer (polyethylene polypropylene glycol), or insulin modifications due to storage in the pump may be involved in this antigenicity. In this nonrandomized study, 24 type 1 diabetic patients were treated with either CSII (n = 11, group 1) or CPII (n = 13, group 2). AIA levels were measured by radioimmunoassay (RIA) or enzyme-linked immunosorbent assay (ELISA) before starting patients on Hoe21PH and again after 3 and 6 months. RESULTS—Patients were comparable in the two groups. AIA levels (RIA) remained stable (24.3 ± 8.5% [month 0] to 24.9 ± 8.5.5% [month 6]) in group 1 and increased (21.8 ± 6.7% [month 0] to 41.8 ± 6.9% [month 6]) in group 2 (P = 0.005, Wilcoxon’s rank-sum test). Using ELISA, AIA remained stable in the patients in group 1 (n = 9; 3.8 ± 0.8 units/ml [month 0] and 4.1 ± 1.0 units/ml [month 6]) and tended to increase in the patients in group 2 (n = 12; 4.1 ± 0.7 units/ml [month 0] to 17.5 ± 4.6 units/ml [month 6]) (P = 0.07). Comparison of the evolution of AIA formation between the two groups, using RIA at months 0, 3, and 6 showed a significant difference (analysis of variance, P = 0.009). CONCLUSIONS—No increase in AIA levels was demonstrated when Hoe21PH insulin was administered subcutaneously as assessed by two different assays. CPII is proven to be more antigenic than CSII, and this is not related to a specific antigenicity of Hoe21PH insulin. The intraperitoneal route of administration or insulin modifications due to insulin storage in implantable devices might explain this antigenicity.