Immunogenetic Determinants and Prediction of IDDM in French Schoolchildren

Abstract

Islet cell antibodies (ICAs) are predictive markers of the disease in first-degree relatives of patients with insulin-dependent diabetes mellitus (IDDM). The large majority of newly diagnosed cases, however, will develop in children with no family history of diabetes. In France, the risk for development of IDDM up to the age of 20 years is 60 times higher in first-degree relatives than in the general population. The aim of this study was to test whether data collected in the first-degree relatives of IDDM patients could be transferred to children for the prediction of overt diabetes. A large population-based cohort of French school-aged children (n = 13,380; ages 6–17 years) were screened for ICAs, and results were compared with those of 1,185 first-degree relatives of IDDM patients. ICA prevalence rates were significantly different in the two populations (5.5% vs. 1.5%; P < 0.0001), with a significantly higher proportion of high ICA titers in first-degree relatives (37%) than in schoolchildren (14%) (P = 0.0005). ICA titers remained remarkably stable in children over 4 years. Insulin autoantibodies (IAAs) were found in 3.4 and 15.4% of ICA⁺ children and first-degree relatives, respectively. Susceptibility alleles at the human leukocyte antigen (HLA)-DQB1 locus were observed significantly more frequently in children in whom ICA titers ≥20 Juvenile Diabetes Foundation units (JDF U) were found on two separate occasions (67%) than in ICA⁻ children (52%) (P = 0.05). Five subjects developed overt diabetes during follow-up. ICA titers of > 20 JDF U were found in all of them on the first sample and at follow-up. Four of them were siblings; two of them were also IAA⁺. One was a child from the group. He was IAA⁻ and had HLA typing of *0201/*0302 at the DQB1 locus. Our results do not strongly support the hypothesis that data derived from family studies can be transferred to the general population for IDDM prediction in children.