Background: Screening for presymptomatic type 1 diabetes (T1D) reduces the risk of diabetic ketoacidosis (DKA) and allows for early intervention with disease-modifying therapies. Despite the rising incidence of T1D in Bulgaria, screening initiatives remain limited. This pilot study aims to evaluate the feasibility of selective T1D screening in high-risk children and identify potential clinical associations with islet autoimmunity. Methods: The study targeted a recruitment of 250 children aged 0–18 years (200 with a relative with T1D and 50 without). Screening for islet autoantibodies (AABs), including glutamic acid decarboxylase (GADA), insulin (IAA), insulinoma-associated-2 (IA-2A), zinc transporter-8 (ZnT8A), and islet cell cytoplasmic autoantibodies (ICAs), was performed via chemiluminescence immunoassay (CLIA). Participants testing positive for one or more AABs were scheduled for longitudinal immunological and metabolic follow-up to evaluate the persistence of autoimmunity and disease progression. Results: Between October 2024 and February 2026, the pilot study recruited 210 participants (84% of the 250 target), including 160 children with a relative (target 200) and 50 without a family history of T1D (target 50). Within the high-risk group, seven children (4.4%) tested positive for a single autoantibody (3 GADA, 2 ZnT8A, 1 IA-2A, and 1 IAA), while no autoantibodies were detected in the group without a relative. No cases of multiple autoantibody positivity or stage 3 T1D were identified in either group. Furthermore, no statistically significant associations were observed between autoantibody positivity and secondary factors, including breastfeeding, allergic status, a high-glycemic diet, frequent illness, and personal history of autoimmune disease. Conclusions: The findings validate the feasibility of selective T1D screening in Bulgaria, driven by high public interest and successful recruitment across both high-risk and general population cohorts. While this exploratory study found no significant clinical correlations, it establishes a vital roadmap for larger, longitudinal research. Ultimately, this pilot framework provides a scalable model for implementing standardized early detection to reduce the burden of T1D on the national healthcare system.

Background: Type 1 diabetes (T1D) incidence is rising at 3–5% per year. Autoantibody (AAB) screening identifies at-risk children pre-symptomatically, yet the clinical significance of single AAB positivity and its short-term trajectory remain incompletely characterized. Methods: Five T1D-associated AABs (anti-GAD65, anti-IA2, anti-ZnT8, ICA, IAA) were measured in 210 Bulgarian children (160 with first-degree T1D relatives, 50 controls). Seven single-AAB-positive children received lifestyle counseling (low-glycemic-index diet, physical activity ≥ 60 min/day) and were reassessed at 3 or 6 months with repeat AAB panels, HbA_1c, blood glucose and C-peptide. Results: Anti-GAD65 was the most frequent single AAB (n = 3), followed by anti-ZnT8 (n = 2), anti-IA2 (n = 1) and IAA (n = 1). None developed a second AAB or metabolic abnormalities. Titer dynamics were heterogeneous: two children showed apparent seroreversion (in one, substantially confounded by concurrent immunosuppressive therapy for an unrelated condition), one showed a ~15-fold titer reduction while remaining seropositive, one showed a minimal titer decrease, and three displayed mildly increasing titers. None progressed to multiple autoantibody positivity, and all maintained normal metabolic profiles. Conclusions: Favorable short-term outcomes were observed during follow-up of children with single autoantibody positivity. These findings suggest that single AAB positivity may follow a non-progressive course in some children. However, this study design cannot distinguish the contribution of lifestyle counseling from natural variability. Prospective controlled studies with larger cohorts, HLA stratification and longer follow-up are needed to determine whether lifestyle interventions can independently alter autoantibody dynamics and delay T1D progression.