Models for Predicting Type 1 Diabetes in Siblings of Affected Children
OBJECTIVE -To generate predictive models for the assessment of risk of type 1 diabetes and age at diagnosis in siblings of children with newly diagnosed type 1 diabetes. RESEARCH DESIGN AND METHODS -Cox regression analysis was used to assess the risk of progression to type 1 diabetes, and multiple regression analysis was used to estimate the age at disease presentation in 701 siblings of affected children. Sociodemographic, genetic, and immunological variables were included in the analyses.
... n the analyses. Subanalyses were performed in a group of 77 autoantibody-positive siblings with additional metabolic data. RESULTS -A total of 47 siblings (6.7%) presented with type 1 diabetes during the 15-year observation period. Young age, an increasing number of detectable diabetes-associated autoantibodies at initial sampling and of affected first-degree relatives, and HLA DR-conferred disease susceptibility predicted progression to type 1 diabetes. In the subgroup of 77 autoantibodypositive siblings, young age, HLA DR-conferred susceptibility, an increasing number of autoantibodies, a reduced first-phase insulin response, and decreased insulin sensitivity in relation to first-phase insulin response were associated with increased risk of progression to type 1 diabetes. Age at diagnosis was predicted by age, insulinoma-associated protein 2 antibody levels, and number of autoantibodies at initial sampling (R 2 ϭ 0.76; P Ͻ 0.001). In the smaller cohort of autoantibody-positive subjects, first-phase insulin response and HLA DR-conferred susceptibility were additional predictors of age at diagnosis. CONCLUSIONS -Information on autoantibody status and levels, HLA-conferred disease susceptibility, and insulin secretion and sensitivity seems to be useful in addition to age and family history of type 1 diabetes when assessing risk of progression to type 1 diabetes and time to diagnosis in siblings of children with newly diagnosed type 1 diabetes. Abbreviations: FPIR, first-phase insulin response; GADA, GAD antibody; HOMA-IR, homeostasis model assessment of insulin resistance; IA-2, insulinoma-associated protein 2; IA-2A, IA-2 antibody; IAA, insulin autoantibody; ICA, islet cell antibody; IVGTT, intravenous glucose tolerance test; ROC, receiver operating characteristic. A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.