Abstract Body: Heart failure is a significant co-morbidity amongst diabetic individuals, especially individuals with type 1 diabetes (T1D). The development of heart failure in T1D is due to, in part, diastolic dysfunction which is contributed by cardiac fibrosis. Currently, there are no specific therapies for the underlying fibrosis in T1D, warranting investigation into novel therapeutic approaches. This predicament is confounded by limited studies characterizing and understanding the heterogeneity of fibrogenic cardiac fibroblast subpopulations. With the full support from the Cardiovascular Repository for Type 1 Diabetes (CaRe-T1D) Consortium, combined with spatial transcriptomic technology, we aimed to assess cardiac fibroblast transcriptomic profile and subpopulations in the left ventricle (LV) from T1D individuals. We hypothesized that distinctive fibrogenic cardiac fibroblast subpopulations will correlate with overall cardiac fibrosis in T1D individuals. Posterior LV sections from non-diabetic (ND) and T1D individuals were assessed for fibrosis by picrosirius red staining. Posterior LV sections from T1D individuals (n=4) were also processed for spatial transcriptomic analysis. T1D hearts were more fibrotic compared to ND hearts (4.8±0.5% vs 3.5±0.3%, p=0.04, n=22/group). For spatial transcriptomic analysis, cardiac fibroblasts were identified as clusters being COL1A1⁺, COL3A1⁺, DCN⁺, and PDGFRA1⁺. Within this cluster, distinct CILP, FAP, POST and FN1 genes were amongst the most highly differentially expressed genes with Log2FC values of 3.22, 2.99, 2.83 and 2.72, respectively. Interestingly, the T1D individual that did not develop cardiac fibrosis (2.4%) and had the lowest COL1A1 Log2FC value (3.87 vs the mean Log2FC of 4.91) showed a lack of POST gene enrichment in the overall fibroblast population. However, the three other T1D individuals showed POST Log2FC value of 2.83. Spatially, CILP+ and FAP+ fibroblasts were mainly located on the edge of fibrotic region but within areas containing cardiomyocytes. Conversely, POST+ fibroblasts were mainly located on the edge of fibrotic region but within the fibrotic scar. In conclusion, distinct CILP+, FAP+, POST+ fibroblasts are associated with fibrosis in the T1D heart.