Presence of anti-GAD in a non-diabetic population of adults; time dynamics and clinical influence: results from the HUNT study

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