title: Interaction of onset and duration of diabetes on the percent of GAD and IA-2 antibody-positive subjects in the type 1 diabetes genetics consortium database.
abstract: OBJECTIVE
  GAD antibodies (GADA) are more common in type 1 diabetic subjects diagnosed at an older age, whereas insulinoma-antigen 2 antibodies (IA-2A) are more common in subjects with younger onset. The prevalence of both antibodies decreases with longer duration of type 1 diabetes. We evaluated the interaction between age of diagnosis (onset) and duration of diabetes on the percentage of GADA- and IA-2A-positive subjects.
  
  
  METHODS
  Data were used from 5,020 individuals with type 1 diabetes obtained from the Type 1 Diabetes Genetics Consortium dataset. The percentages of GADA- and IA-2A-positive subjects were modeled with duration as the continuous independent variable using a modified spline.
  
  
  RESULTS
  Within the first 5 years from diagnosis, 19.4% of individuals (median age 13 years) had neither GADA nor IA-2A, and by 6 to 13 years after diagnosis (median age 18 years), 31.7% were antibody-negative. There was no significant interaction between onset of disease and duration of diabetes for IA-2A (P = 0.30). The interaction was significant for GADA (P = 0.0002), resulting from differences in subjects diagnosed at or older than age 14. For these individuals, there was no apparent effect of duration of disease on the percentage of GADA-positive subjects within the first 5 years of diagnosis.
  
  
  CONCLUSIONS
  Onset and duration of diabetes both have an important effect on antibody status. The interaction of onset and duration on GADA positivity, but not on IA-2A, suggests differences in biology. These data provide a context for clinicians to interpret results of autoantibody testing in clinical practice.
authors.affiliation: Division of Metabolism, Endocrinology and Nutrition, University of Washington, Seattle, Washington, USA. dtridgell@benaroyaresearch.org
authors.forename: David M
authors.initials: DM
authors.lastname: Tridgell
authors.forename: Charles
authors.initials: C
authors.lastname: Spiekerman
authors.forename: Richard S
authors.initials: RS
authors.lastname: Wang
authors.forename: Carla J
authors.initials: CJ
authors.lastname: Greenbaum
mesh_terms: D000293:Adolescent; D000328:Adult; D001323:Autoantibodies / Q000096:biosynthesis / Q000378:metabolism*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000201:enzymology / Q000276:immunology*; D005260:Female; D005968:Glutamate Decarboxylase / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D013997:Time Factors; D055815:Young Adult
chemical_list: D001323:Autoantibodies; C096322:ICA512 autoantibody; D005968:Glutamate Decarboxylase