Single Autoantibody Positivity in Pediatric Type 1 Diabetes: Serological Profiles, Clinical Trajectories and Implications for Early Disease Monitoring—A Case Series of Seven Patients

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, HbA1c, 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.