Introduction: Type 1 diabetes (T1D) progresses through stages, from islet autoantibodies (AAbs) with dysglycaemia (Stage-1 and Stage-2) to overt hyperglycaemia (Stage-3). AAbs are pivotal but limited in predicting stage-3 onset timing. This study aims to identify a combined biomarker signature based on biochemical parameters and circulating miRNAs across pre-Stage-1, Stage-1 and Stage-2 individuals for Stage-3 onset prediction. Methods: Aab-positive Unaffected Family Members (UFM) with T1D family history were monitored for Stage-3 T1D progression with programmed visits every 3/6 months. We selected 65 subjects: 21 T1D Progressors (T1D-P) (Age: 13.9±10.4y; median follow-up: 15.0±8.4mo) and 44 Non Progressors (NP) (Age: 15,9±11,5y; median follow-up: 20,1±10,6mo) matched 1:2 for age and number of AAbs. Small RNA-seq was carried out on plasma samples collected at baseline visit. Differentially expressed small RNAs between T1D-P and NP were evaluated using DESeq2. A LASSO model was used to integrate circulating miRNAs and clinical parameters. Cells/tissues miRNA expression specificity analysis was performed using isomiRdb database. Results: 19 miRNAs were differentially expressed: 18 upregulated and 1 downregulated in T1D-P vs NP (Padj<0.05). The predictive LASSO combined signature included IA-2A AAb titers, HbA1c, OGTT C-Peptide AUC, Glucose AUC and circulating miRNAs miR-1294, miR-628-3p, miR-425-3p and miR-328-3p. Adding miRNAs, increased ROC AUC of logistic regression, from 0.81 to 0.91. miR-628-3p, miR-425-3p, miR-328-3p were validated by ddPCR and showed significant increase in T1D-P plasma. Cells/tissues specificity analysis revealed expression enrichment of these miRNAs in neutrophils. Conclusion: A combined miRNA-based signature measured in at-risk individuals, predicts progression to Stage-3 T1D onset within 15 months, enhancing prediction accuracy based on AAb positivity. Enriched miRNAs neutrophil expression suggests their potential involvement in early disease stages.