Combined Positivity for GAD and IA-2 Autoantibodies Has Similar Positive Predictive Value for Type 1 Diabetes among Siblings of Affected Children and in the General Population
Abstract Number: 1007-P
Authors: MIKAEL KNIP, RIITTA VEIJOLA, ANTTI REUNANEN, SUVI M. VIRTANEN, HANS K. AKERBLOM
Institutions: Helsinki, Finland; Oulu, Finland
Results: To compare the characteristics of GAD and IA-2 antibodies (GADA and IA-2A) in the prediction of type 1 diabetes (T1D) between siblings of affected children and the general population (GP) we studied 755 siblings (349 males) with a mean age of 9.9 years at first screening in the Childhood Diabetes in Finland (DiMe) Study and 3475 subjects (1713 males) with an initial mean age of 10.5 years from a population-based study on cardiovascular risk in young Finns. All participants were tested for GADA and IA-2A with specific radiobinding assays. Data on subjects who had presented with T1D within 15 years were obtained from the National Social Insurance Institute. Fifty-three siblings (7.0%) tested positive for GADA and 40 (5.3%) for IA-2A. Thirty siblings (4.0%) had both antibodies. Thirty-four subjects (1.0%) had GADA and 22 (0.6%) IA-2A in the GP cohort. Only seven individuals (0.2%) were positive for both antibodies. Fifty-one siblings (6.8%) and 15 subjects in the GP cohort (0.4%) progressed to T1D during the observation period. GADA had a sensitivity of 65%, a specificity of 97% and a positive predictive value (PPV) of 62% among the siblings, while the corresponding characteristics in the GP were 53%, 99% (difference 2.1%, 95% confidence interval [CI] 0.8-3.4%) and 24% (difference 38.7%, CI 19.4-58.1%). IA-2A had a sensitivity of 55%, a specificity of 98% and a PPV of 70% among siblings compared to figures of 47%, 100% (difference 1.3%, CI 0.3-2.2%) and 32% (difference 38.2%, CI 14.1-62.3%) in the GP. Combined positivity for GADA and IA-2A had a sensitivity of 47%, a specificity of 99% and a PPV of 80%, the corresponding figures being 40%, 100% (difference 0.8%, CI 0.1-1.5%) and 87% among the GP. These data imply that single GADA or IA-2A positivity is characterized by a higher PPV but lower specificity for development of T1D among siblings when compared to young subjects from the GP, whereas double positivity for GADA and IA-2A has similar PPV in both groups.