title: HLA genes, islet autoantibodies and residual C-peptide at the clinical onset of type 1 diabetes mellitus and the risk of retinopathy 15 years later.
abstract: OBJECTIVE
  HLA genes, islet autoantibodies and residual C-peptide were studied to determine the independent association of each exposure with diabetic retinopathy (DR), 15 years after the clinical onset of type 1 diabetes in 15-34 year old individuals.
  
  
  METHODS
  The cohort was identified in 1992 and 1993 by the Diabetes Incidence Study in Sweden (DISS), which investigates incident cases of diabetes for patients between 15 and 34 years of age. Blood samples at diagnosis were analyzed to determine HLA genotype, islet autoantibodies and serum C-peptide. In 2009, fundus photographs were obtained from patient records. Study measures were supplemented with data from the Swedish National Diabetes Registry.
  
  
  RESULTS
  The prevalence of DR was 60.2% (148/246). Autoantibodies against the 65 kD isoform of glutamate decarboxylase (GADA) at the onset of clinical diabetes increased the risk of DR 15 years later, relative risk 1.12 for each 100 WHO units/ml, [95% CI 1.02 to 1.23]. This equates to risk estimates of 1.27, [95% CI 1.04 to 1.62] and 1.43, [95% CI 1.06 to 1.94] for participants in the highest 25(th) (GADA>233 WHO units/ml) and 5(th) percentile (GADA>319 WHO units/ml) of GADA, respectively. These were adjusted for duration of diabetes, HbA(1c), treated hypertension, sex, age at diagnosis, HLA and C-peptide. Islet cell autoantibodies, insulinoma-antigen 2 autoantibodies, residual C-peptide and the type 1 diabetes associated haplotypes DQ2, DQ8 and DQ6 were not associated with DR.
  
  
  CONCLUSIONS
  Increased levels of GADA at the onset of type 1 diabetes were associated with DR 15 years later. These results, if confirmed, could provide additional insights into the pathogenesis of the most common microvascular complication of diabetes and lead to better risk stratification for both patient screenings and DR treatment trials.
authors.affiliation: Cardiovascular Health Research Unit, School of Medicine, and the Department of Epidemiology, School of Public Health, University of Washington, Seattle, Washington, United States of America. richaj@uw.edu
authors.forename: Richard A
authors.initials: RA
authors.lastname: Jensen
authors.forename: Elisabet
authors.initials: E
authors.lastname: Agardh
authors.forename: Ake
authors.initials: A
authors.lastname: Lernmark
authors.forename: Soffia
authors.initials: S
authors.lastname: Gudbjörnsdottir
authors.forename: Nicholas L
authors.initials: NL
authors.lastname: Smith
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Carina
authors.initials: C
authors.lastname: Törn
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000276:immunology*; D002096:C-Peptide / Q000276:immunology*; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology*; D003930:Diabetic Retinopathy / Q000453:epidemiology* / Q000276:immunology*; D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000235:genetics*; D006801:Humans; D007515:Islets of Langerhans / Q000276:immunology*; D008297:Male; D012044:Regression Analysis; D012307:Risk Factors; D013548:Sweden / Q000453:epidemiology; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; D006680:HLA Antigens