title: Effect of long-term exposure to insulin lispro on the induction of antibody response in patients with type 1 or type 2 diabetes.
abstract: OBJECTIVE
  To determine the long-term effects of insulin lispro on inducing lispro-specific, insulin-specific, and cross-reactive (reactive with both insulin lispro and human insulin) antibodies.
  
  
  METHODS
  A multinational, multicenter combination of controlled and noncontrolled, open-label studies of 4.5 years' duration was designed to evaluate the long-term immunologic profile of subcutaneously administered insulin lispro. A total of 1,221 patients (men and women; 12-81 years of age) with type 1 or type 2 diabetes were enrolled. Circulating anti-insulin antibodies were measured using radioimmunoassays.
  
  
  RESULTS
  Insulin-specific and lispro-specific antibody responses were within the background noise levels of the assays. Significant elevations of antibody were confined to a cross-reactive antibody response. Antibody levels resulting from prior exposure to long- and short-acting insulins changed little after transfer to insulin lispro and remained within or near the baseline levels. De novo exposure to insulin lispro resulted in increases in cross-reactive but not insulin- or lispro-specific antibody levels. Cross-reactive insulin antibodies developed more readily in patients with type 1 diabetes than in those with type 2 diabetes. Long-term antibody responses tended to decrease over time and returned to baseline or near-baseline levels by the end of the long-term studies. No evidence of an anamnestic antibody response could be found in individuals treated intermittently with insulin lispro.
  
  
  CONCLUSIONS
  The immunogenic profile of patients treated with insulin lispro was comparable to that of patients treated with recombinant human insulin. Inductions of significant levels of specific or cross-reactive antibodies were not observed in patients who had received insulin previously. No significant antibody-dependent increases in insulin dosage requirements were noted in these patients. The incidence of insulin allergy was not different from that in patients treated with recombinant regular human insulin.
authors.affiliation: Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46285, USA.
authors.forename: S Edwin
authors.initials: SE
authors.lastname: Fineberg
authors.forename: Jie
authors.initials: J
authors.lastname: Huang
authors.forename: Rocco
authors.initials: R
authors.lastname: Brunelle
authors.forename: K S
authors.initials: KS
authors.lastname: Gulliya
authors.forename: James H
authors.initials: JH
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D003429:Cross Reactions; D018592:Cross-Over Studies; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology*; D004342:Drug Hypersensitivity / Q000453:epidemiology / Q000276:immunology; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000276:immunology; D015994:Incidence; D007328:Insulin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000276:immunology; D061268:Insulin Lispro; D008297:Male; D008875:Middle Aged
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D061268:Insulin Lispro