VALUE OF ANTIBODIES TO GAD(65) COMBINED WITH ISLET-CELL CYTOPLASMIC ANTIBODIES FOR PREDICTING IDDM IN A CHILDHOOD POPULATION

The value of a test for islet cell cytoplasmic antibodies together wit h a test for GAD(65) antibodies to predict the subsequent development of diabetes over a period of 11.5 years was assessed in an open childh ood population comprising 2,805 individuals. A single serum sample was obtained from each individual between 1975 and 1977 and screened for islet cell cytoplasmic antibodies for which eight individuals were pos itive (0.29 %). During the average follow-up period of 11.5 years, fou r of eight islet cell antibody positive and three islet cell antibody negative individuals developed clinical diabetes. Sera from all indivi duals, who were islet cell antibody positive and/or developed diabetes (total of 11) and from 100 randomly selected control subjects were an alysed for GAD(65) antibodies. Six of eight islet cell antibody positi ve individuals were GAD(65) antibody positive including all four who s ubsequently developed IDDM. Furthermore, one of the three islet cell a ntibody negative individuals who developed IDDM was GAD(65) antibody p ositive both in 1976 and in 1989. Thus, a positive test for GAD(65) an tibodies alone correctly predicted diabetes in five of seven children, who developed the disease. Only one of the children, who developed di abetes was positive for insulin autoantibodies and this individual was also positive for islet cell cytoplasmic antibodies and GAD(65) antib odies. One of the 100 control subjects was positive for GAD(65) antibo dies (1%). The results suggest that a single GAD(65) antibody test may have a higher sensitivity for predicting IDDM than a test for islet c ell cytoplasmic antibodies, but that a combined positive test for both antibodies increases the specificity for predicting IDDM over a perio d of 11.5 years.