Glutamic acid decarboxylase and islet cell antibodies in healthy Estonian children

The prevalence of antibodies to the 65 kDa isoform of glutamic acid decarbo xylase (GADA) was compared with that of islet cell antibodies (ICA) in 614 non-diabetic Estonian children (314 males) aged 3-18 years representing the general population. GADA were analyzed with a radioligand assay, and ICA w ith a standard immunofluorescence method with a detection limit of 2.5 Juve nile Diabetes Foundation (JDF) units. Fourteen subjects (2.3%, 95% confiden ce interval [CI] 1.1-3.5%) tested positive for GADA (median level 10.8 rela tive units [RU], range 7.7-154.2 RU), while 10 (1.6%, CI 0.6-2.6%) had ICA (median levels 34 JDF units, range 3-97 JDF units), Five subjects (0.8%, CI 0.1-1.5%; p=0.03 vs GADA and 0.15 vs ICA) were double positive. The indivi dual with the second highest GADA level (129.3 RU) and the highest ICA leve l (97 JDF units) presented with type 1 diabetes 4 months later. A follow-up sample was obtained approximately 3-4 years after the first sampling in 14 subjects initially positive for ICA and/or GADA, Four of the nine initiall y ICA-positive children remained positive, but their levels decreased from a median of 42 to 18 JDF units (p=0.06). Only two of the nine retested subj ects initially positive for GADA remained positive in the second sample. Th ese observations suggest that the prevalence of GADA in non-diabetic childr en is of the same magnitude as that of ICA, Combined positivity for both GA DA and ICA is less prevalent than single antibody specificities, indicating that double autoantibody positivity may have a higher predictive value for future type 1 diabetes in the general population than either antibody sepa rately. The evanescent character of diabetes-associated autoantibodies in a proportion of the unaffected children implies that more subjects may exper ience self-restricted beta-cell damage than the number progressing to actua l disease.