Abstract

Type 1 diabetes (T1D) is a chronic autoimmune disorder characterized by the progressive destruction of pancreatic beta cells, preceded by a prolonged asymptomatic phase marked by the presence of circulating islet autoantibodies (IAb). The predictive value of IAb screening for identifying individuals at risk and recognizing the early, pre-symptomatic phase of the disease has been well established in several longitudinal studies involving relatives of individuals with T1D. These findings have provided the basis for pre-clinical staging (Stage 1 and Stage 2) and have enabled an accurate assessment of the progression to clinical diabetes (Stage 3). However, since more than 90% of new T1D cases occur in individuals without a family history of the disease, effective strategies to reduce the overall societal burden of the disease require screening programmes targeting the general population. Early detection offers several potential benefits, including increased disease awareness, timely initiation of insulin therapy, and prevention of complications associated with delayed diagnosis, including life-threatening diabetic ketoacidosis.

Individuals identified as at risk or in the early stages of T1D may also benefit from emerging diseasemodifying therapies such as teplizumab. Consequently, population-based T1D screening programmes have recently expanded worldwide. In 2023, Italy became the first country to mandate population screening for both type 1 diabetes and coeliac disease by law (Law 130/2023). The D1Ce (Diabete tipo 1 e Celiachia) national pilot study assessed operational and feasibility aspects (involvement of primary care paediatricians, blood sample collection accuracy, acceptability for families) and investigated the prevalence of islet and transglutaminase autoantibodies in the general paediatric population. D1Ce enrolled children aged 2–2.9, 6–6.9, and 10–10.9 years through primary care paediatricians in four Italian regions (Lombardy, Marche, Campania and Sardinia). 5,535 children were enrolled and tested with a two-step autoantibody screening procedure for T1D and coeliac disease, using an ELISA assay followed by a LIPS for confirmation in the same sample, in order to reduce the burden of false positive. The findings from D1Ce support the feasibility of combined screening for T1D and coeliac disease in the general paediatric population at a national scale.