DO GLUTAMIC-ACID DECARBOXYLASE ANTIBODIES IMPROVE THE PREDICTION OF IDDM-I IN FIRST-DEGREE RELATIVES AT RISK FOR IDDM

To determine whether the predictive value of islet cell antibodies (IC A) and insulin autoantibodies (IAA) is increased by measurement of glu tamic acid decarboxylase antibodies (GADAb) in first-degree relatives of patients with insulin-dependent diabetes mellitus (IDDM), we measur ed GADAb in those developing IDDM and in relatives found to be ICA- or IAA-positive in our family screening study. First-degree relatives (n =2904) were followed for 2.4 (median, range 0.04-5.8) years. Of the su bjects developing IDDM, 11/14 (78%) had ICA greater than or equal to 2 0JDF units, 1/14 (7%) had IAA greater than or equal to 100 nU/ml and 6 /14 (43%) had GADAb (greater than or equal to 460nU/ml, measured by pr ecipitation of enzymatic activity). Of the four subjects with ICA<Z0 a nd IAA<100 nU/ml who developed IDDM, one had elevated GADAb. Significa nt inhibition of GAD enzymatic activity by serum immunoglobulins, a po tential cause of false-negative results in our immunoprecipitation ass ay, was not detected in seven subjects who developed IDDM in the absen ce of GADAb. Sixty-nine of the 2904 subjects with ICA greater than or equal to 20 or IAA greater than or equal to 100 were followed for 3.1 (median range 0.1-5.4) years. Survival analysis showed that diabetes-f ree survival in this group was not influenced significantly by GADAb p ositivity. In conclusion, GADAb in the absence of ICA and IAA are unco mmon in first-degree relatives who progress to IDDM and the presence o f GADAb does not increase the risk for IDDM in ICA- or IAA-positive re latives.