Islet Cell Antibodies as Predictive Markers for IDDM in Children With High Background Incidence of Disease

To determine the prevalence and predictive value of islet cell antibodies (ICAs) for the development of insulin-dependent diabetes mellitus (IDDM) in 1212 Finnish children aged 3–18 yr, samples for ICA determination were taken in 1980, and subsequent analyses were performed in originally ICA⁺ children and in 296 initially ICA⁻ children in 1983 and 1986. All 1212 subjects were followed for 8 yr for the development of IDDM. Fifty children (4.1%) were positive for conventional ICAs (IF-ICAs) in 1980 (range 3–80 Juvenile Diabetes Foundation units [JDF U]; median 30 JDF U), of which 12 (1.0%) had complementfixing ICAs (CF-ICAs) in their serums (range 3–30 JDF U; median 8 JDF U). None were exclusively CF-ICA⁺ Boys were CF-ICA⁺ more often than girls (9 of 563 [1.6%] vs. 3 of 649 [0.5%], respectively; P < 0.05). Over the next 6 yr, 4 of 39 subjects lost their IF-ICAs, and 4 of 12 lost their CF-ICAs without progressing to diabetes. The initial IF-ICA levels in these subjects were lower (range 3–8 JDF U; median 7 JDF U; P < 0.05) than those in the persistent cases. In the initially ICA⁻ subgroup (n = 296), 7 subjects (2.4%) later became IF-ICA⁺, and 4 (1.4%) became CF-ICA⁺. The levels of ICA in these subjects were lower than in the originally ICA⁺ ones (P < 0.05), and 3 IF-ICA⁺ and 2 CF-ICA⁺ subjects again became ICA⁻ before 1986. Three initially IF-ICA⁺ subjects (2 also with CF-ICA) presented with IDDM after 3 yr, compared to no cases among IF-ICA⁻ children. High persistent ICA levels (≥18 JDF U) had the highest positive predictive value for the development of IDDM. The results reveal a high ICA prevalence in unaffected Finnish children. However, only high and persistent levels, especially when they are complement fixing, seem to predict the development of IDDM in healthy children.