QUANTITATION OF GLUTAMIC-ACID DECARBOXYLASE AUTOANTIBODY LEVELS IN PROSPECTIVELY EVALUATED RELATIVES OF PATIENTS WITH TYPE-I DIABETES

In this study, we demonstrate that levels of glutamic acid decarboxyla se (GAD) autoantibodies (GAAs) by radioassay differ between relatives with GAD-absorbable and GAD-nonabsorbable islet cell antibodies (ICAs) . Extremely high levels of GAAs are often found in relatives with GAD- absorbable ICAs (>1,800 cpm, >9 SD above normal control subjects; mean = 1,991 cpm), and lower levels (mean = 1,078 cpm) of GAAs were presen t in relatives with nonabsorbable ICAs (P < 10(-5)). The serum levels of GAAs were remarkably constant for relatives of both groups over tim e. The levels of GAAs were found to be inversely related to both the l evels of insulin autoantibodies and the rate of loss of intravenous gl ucose-stimulated insulin secretion (P < 10(-5) and P < 0.01, respectiv ely). Relatives with low positive levels of GAAs had more rapid loss o f insulin secretion and were at high risk to become diabetic (50% diab etic at 4 years) compared with relatives with higher levels (1,800 cpm ) of GAAs (10% diabetic at 4 years; P < 0.05). These data suggest that high levels of GAAs are associated with a decreased risk of progressi on to type I diabetes and extend the hypothesis that distinct subsets of ICAs and GAAs with differing prognostic significance can be identif ied.