title: Type 1 diabetes and interferon therapy: a nationwide survey in Japan.
abstract: OBJECTIVE
  Interferon therapy can trigger induction of several autoimmune diseases, including type 1 diabetes. To assess the clinical, immunologic, and genetic characteristics of type 1 diabetes induced by interferon therapy, we conducted a nationwide cross-sectional survey.
  
  
  METHODS
  Clinical characteristics, anti-islet autoantibodies, and HLA-DR typing were examined in 91 patients for whom type 1 diabetes developed during or shortly after interferon therapy.
  
  
  RESULTS
  Median age at the onset of type 1 diabetes was 56 (interquartile range 48-63) years and mean ± SD BMI was 20.8 ± 2.7 kg/m(2). The time period from the initiation of interferon therapy to type 1 diabetes onset in patients receiving pegylated interferon and ribavirin was significantly shorter than that in patients with nonpegylated interferon single therapy (P < 0.05). Anti-islet autoantibodies were detected in 94.5% of patients at diabetes onset. Type 1 diabetes susceptibility HLA-DRs in the Japanese population, DR4 and DR9, were also associated with interferon treatment-related type 1 diabetes. Furthermore, the prevalence of HLA-DR13 was significantly higher in interferon treatment-related type 1 diabetes than in healthy control subjects (odds ratio 3.80 [95% CI 2.20-7.55]; P < 0.0001) and classical type 1 diabetes (2.15 [1.17-3.93]; P < 0.05).
  
  
  CONCLUSIONS
  Anti-islet autoantibodies should be investigated before and during interferon therapy to identify subjects at high risk of type 1 diabetes. Stronger antiviral treatment may induce earlier development of type 1 diabetes. Furthermore, patients who develop interferon-induced type 1 diabetes are genetically susceptible.
authors.affiliation: Department of Metabolism/Diabetes and Clinical Nutrition, Nagasaki University Hospital, Nagasaki, Japan.
authors.forename: Kan
authors.initials: K
authors.lastname: Nakamura
authors.forename: Eiji
authors.initials: E
authors.lastname: Kawasaki
authors.forename: Akihisa
authors.initials: A
authors.lastname: Imagawa
authors.forename: Takuya
authors.initials: T
authors.lastname: Awata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ikegami
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Uchigata
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Kobayashi
authors.forename: Akira
authors.initials: A
authors.lastname: Shimada
authors.forename: Koji
authors.initials: K
authors.lastname: Nakanishi
authors.forename: Hideichi
authors.initials: H
authors.lastname: Makino
authors.forename: Taro
authors.initials: T
authors.lastname: Maruyama
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Hanafusa
mesh_terms: D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced* / Q000378:metabolism; D005260:Female; D059810:HLA-DR Serological Subtypes / Q000378:metabolism; D015804:HLA-DR4 Antigen / Q000378:metabolism; D006801:Humans; D007372:Interferons / Q000009:adverse effects* / Q000627:therapeutic use; D007564:Japan; D008297:Male; D008875:Middle Aged; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D059810:HLA-DR Serological Subtypes; C097337:HLA-DR13 antigen; D015804:HLA-DR4 Antigen; C038988:HLA-DR9 antigen; D012254:Ribavirin; D007372:Interferons