Extended family history of type 1 diabetes in HLA‐predisposed children with and without islet autoantibodies

Abstract

<div lang="en" class="abs"><p class="abs_header">Abstract</p><p><em>Objective:</em> The aim of this study was to explore the extended family history of type 1 diabetes in children at genetic risk and define the impact of a positive family history on the development of islet autoimmunity and type 1 diabetes.</p><p><em>Methods:</em> The subjects were participants in The Finnish Type 1 Diabetes Prediction and Prevention (DIPP) study and carried increased HLA‐conferred risk for type 1 diabetes. The case children (N = 343) were positive for at least one islet autoantibody, and the control children (N = 343) matched by age, gender and class II HLA genotype were negative for islet autoantibodies at the time of data collection. Extended family history of type 1 diabetes was obtained by using a structured questionnaire.</p><p><em>Results:</em> Among children who were autoantibody positive and progressed to type 1 diabetes 62.2% (28/45) had at least one relative with type 1 diabetes. Interestingly, 57.8% of these children (26/45) had such a relative outside the nuclear family compared to 30.7% of children with no autoantibodies (<em>P</em> = .001), 35.2% of those with only classical islet cell antibodies (<em>P</em> = .006), and 35.2% of non‐progressors with biochemical autoantibodies (<em>P</em> = 0.011). A positive history of type 1 diabetes in the paternal extended family was more common in children with multiple biochemical autoantibodies compared to those with only one biochemical autoantibody (<em>P</em> = .010). No association between the specificity of the first appearing autoantibody and family history of the disease was found.</p><p><em>Conclusions:</em> Type 1 diabetes in relatives outside the nuclear family is a significant risk factor for islet autoimmunity and progression to clinical disease in HLA susceptible children.</p></div>