title: Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study.
abstract: BACKGROUND
  It is well known that anti-GAD (glutamic acid decarboxylase) serves as a marker for development of autoimmune diabetes in adults. On the other hand, the clinical implications of anti-GAD positivity in persistently non-diabetic (PND) adults are poorly elucidated. Our aim was to establish the frequency of anti-GAD in PNDs in an all-population-based cohort from the Nord-Trøndelag health study (HUNT) and to prospectively test for associations with glucose tolerance and thyroid autoimmunity.
  
  
  METHODS
  We formed a primary study population (4496 individuals), selected randomly from the age group 20-90 years (50% men/women), who were non-diabetic both at HUNT2 (1995-1997) and HUNT3 (2006-2008). Anti-GAD-positive individuals at HUNT2, together with anti-GAD-negative individuals aged 20-29 years, were retested for anti-GAD positivity at HUNT3. A secondary study population consisted of individuals with type 2 diabetes (T2D, n=349) at HUNT3 who developed diabetes between HUNT2 and HUNT3.
  
  
  RESULTS
  The frequency of anti-GAD positivity in PND was 1.7% (n=76) at HUNT2. Positivity did not associate with gender, family history of diabetes, or glucose levels, but was associated with thyroid-associated autoimmunity (increased frequency of positivity for anti-TPO (thyroid peroxidase), p<0.002). HLA-DQA1/DQB1, a risk haplotype for autoimmunity, was also associated with anti-GAD positivity in PND. The incidence of anti-GAD positivity was low (0.4%) in the subsample of individuals who were anti-GAD negative in HUNT2. Anti-GAD positivity in PNDs was frequently evanescent, with 54% losing, usually low-grade, positivity between HUNT2 and HUNT3. An evanescent state of autoimmunity as assessed by anti-GAD positivity during "pre-diabetes" in individuals later diagnosed with T2D could, however, not be affirmed.
  
  
  CONCLUSIONS
  Anti-GAD positivity in PND is associated with HLA risk haplotypes and thyroid autoimmunity but not with clinical parameters of diabetes. Fleeting anti-GAD positivity is common; however, results do not support the notion of a history of autoimmunity in T2D in the present cohort.
authors.affiliation: Department of Public Health and General Practice, Faculty of Medicine , HUNT Research Centre, The Norwegian University of Science and Technology , Levanger , Norway.
authors.forename: Elin Pettersen
authors.initials: EP
authors.lastname: Sørgjerd
authors.affiliation: Hormone Laboratory, Department of Medical Biochemistry , Oslo University Hospital , Oslo , Norway.
authors.forename: Per M
authors.initials: PM
authors.lastname: Thorsby
authors.affiliation: Hormone Laboratory, Department of Medical Biochemistry , Oslo University Hospital , Oslo , Norway.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Torjesen
authors.affiliation: Department of Laboratory Medicine, Children's and Women's Health, Faculty of Medicine , The Norwegian University of Science and Technology , Trondheim , Norway.
authors.forename: Frank
authors.initials: F
authors.lastname: Skorpen
authors.affiliation: Department of Public Health and General Practice, Faculty of Medicine , HUNT Research Centre, The Norwegian University of Science and Technology , Levanger , Norway.
authors.forename: Kirsti
authors.initials: K
authors.lastname: Kvaløy
authors.affiliation: Department of Cancer Research and Molecular Medicine, Faculty of Medicine , The Norwegian University of Science and Technology , Trondheim , Norway ; Department of Endocrinology , St. Olav University Hospital , Trondheim , Norway.
authors.forename: Valdemar
authors.initials: V
authors.lastname: Grill
keywords: Adult Diabetes; Autoantibodies; Autoimmunity