title: High frequency of persisting or increasing islet-specific autoantibody levels after diagnosis of type 1 diabetes presenting before 40 years of age. The Belgian Diabetes Registry.
abstract: OBJECTIVE
  To study the presence and levels of GAD65 antibodies (GADA), IA-2 antibodies (IA-2-A), and islet cell antibodies (ICA) during the first years after clinical onset of type 1 diabetes in relation to age at diagnosis.
  
  
  METHODS
  Type 1 diabetic patients (n = 194) <40 years of age were consecutively recruited at the time of diagnosis by the Belgian Diabetes Registry and followed during the first 4 years of insulin treatment. ICA were determined by indirect immunofluorescence assay and IA-2-A, GADA, and insulin autoantibodies by a radioligand assay.
  
  
  RESULTS
  Overall, 94% of initially antibody-positive patients (n = 180) remained positive for at least 1 antibody type 4 years after diagnosis. In the case of diagnosis after 7 years of age, GADA, IA-2-A, and ICA persisted in 91, 88, and 71%, respectively, of the initially antibody-positive patients. Antibody persistence was lower in those diagnosed at <7 years of age, amounting to 60% for GADA, 71% for IA-2-A, and 39% for ICA. In 57% of the initially antibody-positive patients, at least 1 type of autoantibody reached peak values after diagnosis. This occurred more frequently for clinical onset after 7 years of age and more often for GADA (49%) than for IA-2-A (29%) or ICA (19%). Of the patients, 24% that were negative for GADA at onset became GADA-positive during the following 4 years. Among the 7% initially antibody-negative patients, 2 of 14 subjects developed antibodies after clinical onset.
  
  
  CONCLUSIONS
  In particular, for diagnosis after 7 years of age, islet cell-specific autoantibodies generally persist for many years after diagnosis. There is also a high frequency of increasing antibody levels and of conversion to antibody positivity in the first 4 years after diagnosis and start of insulin treatment. Thus, determination of antibodies at diagnosis can underestimate the number of cases with autoimmune type 1 diabetes, in particular with assays of lower sensitivity. The divergent temporal patterns of ICA, GADA, and IA-2-A suggest that the ICA test recognizes other antibody specificities besides GADA and IA-2-A and reflects other autoimmune processes; it also indicates that GADA assays have a higher diagnostic sensitivity in the period after clinical onset.
authors.affiliation: Diabetes Research Center, Academic Hospital, Vrije University Brussel, Brussels, Belgium.
authors.forename: K
authors.initials: K
authors.lastname: Decochez
authors.forename: J
authors.initials: J
authors.lastname: Tits
authors.forename: J L
authors.initials: JL
authors.lastname: Coolens
authors.forename: L
authors.initials: L
authors.lastname: Van Gaal
authors.forename: G
authors.initials: G
authors.lastname: Krzentowski
authors.forename: F
authors.initials: F
authors.lastname: Winnock
authors.forename: E
authors.initials: E
authors.lastname: Anckaert
authors.forename: I
authors.initials: I
authors.lastname: Weets
authors.forename: D G
authors.initials: DG
authors.lastname: Pipeleers
authors.forename: F K
authors.initials: FK
authors.lastname: Gorus
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D001323:Autoantibodies / Q000097:blood*; D001530:Belgium; D002096:C-Peptide / Q000097:blood; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology; D006801:Humans; D007223:Infant; D008297:Male; D012042:Registries; D044465:White People
chemical_list: D001323:Autoantibodies; D002096:C-Peptide; C024211:islet cell antibody; D005968:Glutamate Decarboxylase