PREDICTION OF INSULIN-DEPENDENT DIABETES-MELLITUS IN SIBLINGS OF CHILDREN WITH DIABETES - A POPULATION-BASED STUDY

An unselected population of 755 siblings of children with insulin-depe ndent diabetes mellitus (IDDM) was studied to evaluate the predictive characteristics of islet cell antibodies (ICA), antibodies to the IA-2 protein (IA-2A), antibodies to the 65-kD isoform of glutamic acid dec arboxylase (GADA), insulin autoantibodies (IAA), and combinations of t hese markers. We also evaluated whether the histochemical ICA test cou ld be replaced by the combined detection of other markers. 32 siblings progressed to IDDM within 7.7 yr of the initial sample taken at or cl ose to the diagnosis of the index case (median follow-up, 9.1 yr). The positive predictive values of ICA, IA-2A, GADA, and IAA were 43, 55, 42, and 29%, and their sensitivities 81, 69, 69, and 25%, respectively . In contrast to the other three antibody specificities, GADA levels w ere not related to the risk for IDDM, The risk for IDDM in siblings wi th four, three, two, one, or no antibodies was 40, 70, 25, 2, and 0.8% , respectively. Combined screening for IA-2A and GADA identified 70% o f all ICA-positive siblings, and all of the ICA-positive progressors w ere also positive for at least one of the three other markers. The sen sitivity of the combined analysis of IA-2A and GADA was 81%, and the p ositive predictive value was 41%. In conclusion, combined screening fo r IA-2A and GADA may replace the ICA assay, giving comparable sensitiv ity, specificity, and positive predictive value. Accurate assessment o f the risk for IDDM in siblings is complicated, as not even all those with four antibody specificities contract the disease, and some with o nly one or no antibodies initially will progress to IDDM.