title: Development of insulin antibodies and changes in titers over a long-term period in patients with type 2 diabetes.
abstract: BACKGROUND
  Recently, insulin analogs have become widely used for the treatment of diabetes. The aim of this study was to determine differences in the antigenicity of insulin analogs and long-term changes in titers in patients with type 2 diabetes.
  
  
  METHODS
  Insulin antibodies were examined using polyethylene glycol and protein G methods in 381 patients with type 2 diabetes.
  
  
  RESULTS
  Insulin antibodies were detected in 48 of 118 patients (40.7%) who used insulin, and insulin glargine and aspart were more antigenic. Insulin antibodies were unexpectedly found in seven of 263 patients (2.7%) who had never used insulin. Serum insulin concentrations in patients with insulin antibodies were significantly higher than those without them. Two years after the initial evaluation, insulin antibodies were still positive in 92.7% of patients who used insulin; while, they disappeared in all patients who had never used insulin. A patient who stopped insulin injections 6years ago was found to be positive for insulin antibodies at the first evaluation as well as 2years later.
  
  
  CONCLUSIONS
  Insulin glargine and aspart induced insulin antibodies more frequently, and insulin antibodies remained in patients for a long time. Insulin antibodies should be suspected even in patients not currently on insulin therapy.
authors.affiliation: Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan. Electronic address: hattorin@fc.ritsumei.ac.jp.
authors.forename: Naoki
authors.initials: N
authors.lastname: Hattori
authors.affiliation: Department of Pharmaceutical Sciences, Ritsumeikan University, Shiga, Japan.
authors.forename: Maharani Retna
authors.initials: MR
authors.lastname: Duhita
authors.affiliation: Department of Medicine, Co-op Osaka Hospital, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Mukai
authors.affiliation: Department of Medicine, Co-op Osaka Hospital, Japan.
authors.forename: Megumi
authors.initials: M
authors.lastname: Matsueda
authors.affiliation: Clinical Research Institute, National Hospital Organization, Kyoto Medical Center, Kyoto, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Shimatsu
mesh_terms: D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000188:drug therapy* / Q000276:immunology; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood / Q000276:immunology / Q000627:therapeutic use; D007330:Insulin Antibodies / Q000097:blood* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D013997:Time Factors
chemical_list: D007328:Insulin; D007330:Insulin Antibodies
keywords: Aspart; Detemir; Glargine; Insulin antibodies; Lispro; Type 2 diabetes