title: Effects of human insulin on insulin binding antibody production in nondiabetic subjects.
abstract: OBJECTIVE
  To test the hypothesis that human insulin may have a low immunogenicity and that short-term exposure may not cause endogenous insulin antibody production.
  
  
  METHODS
  Randomized double-blind prospective study. Serum samples collected for insulin binding antibodies and measured by a sensitive immunochemical assay. Subjects were seven healthy nondiabetic patients who had never received exogenous insulin. Each subject received 6 separate monthly injections of human insulin. On four occasions, both regular and NPH insulin were administered. On the other two occasions, either NPH or regular insulin was administered alone.
  
  
  RESULTS
  Mean +/- SE basal insulin antibody levels (1.2 +/- 0.2 micrograms/L) increased to a maximal level of 4.5 +/- 0.8 micrograms/L after four injections. Thereafter, antibody levels declined to an end-of-study value of 2.5 +/- 0.3 micrograms/L. This represented a highly significant overall increase (P less than 0.001). A control group of six insulin-dependent diabetic subjects treated with human insulin over the same period as the test subjects demonstrated no change in insulin antibody concentrations (2.8 +/- 0.7-2.7 +/- 0.6 micrograms/L).
  
  
  CONCLUSIONS
  These results suggest that human insulin preparations, when administered subcutaneously, may be more immunogenic than previously considered. The antigenic response was rapid, because only four subcutaneous injections were sufficient to produce insulin antibody levels in nondiabetic patients similar to those observed in insulin-dependent diabetic patients receiving chronic insulin replacement therapy.
authors.affiliation: Department of Medicine, The Medical School, Newcastle upon Tyne, United Kingdom.
authors.forename: S N
authors.initials: SN
authors.lastname: Davis
authors.forename: C J
authors.initials: CJ
authors.lastname: Thompson
authors.forename: M
authors.initials: M
authors.lastname: Peak
authors.forename: M D
authors.initials: MD
authors.lastname: Brown
authors.forename: K G
authors.initials: KG
authors.lastname: Alberti
mesh_terms: D000328:Adult; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007330:Insulin Antibodies / Q000096:biosynthesis*; D011446:Prospective Studies; D011897:Random Allocation; D012016:Reference Values
chemical_list: D007328:Insulin; D007330:Insulin Antibodies