Type 2 diabetes mellitus (T2D) affects roughly 589 million adults worldwide, with cardiovascular disease as the leading cause of mortality. Endothelial dysfunction, marked by impaired vasodilation, increased permeability, and leukocyte adhesion, is a central, early driver of diabetic cardiovascular complications, yet its transcriptional basis in adipose endothelium remains poorly defined. We hypothesized that genes driving adipose endothelial cell (EC) dysfunction in diabetes could be identified, prioritized by relevance to human disease, and functionally validated. Single-nucleus RNA sequencing (snRNA-seq) was performed on nuclei from gonadal adipose tissue of streptozotocin-western diet (STZ-WD) diabetic mice and chow-fed controls, with endothelial nuclei analyzed as a pooled population to define a diabetic EC transcriptional signature. Differentially expressed genes in mouse adipose EC were compared against human diabetic visceral adipose endothelial data, generated in-house by other members of the research team, to identify genes dysregulated in the same direction in both species. ASPH, PLVAP, STAT1, and F8 were concordantly upregulated, while EXT1 and CDH13 were concordantly downregulated. PLVAP was upregulated in mouse adipose EC (log2FC +1.98, padj 0.0018) and human diabetic endothelium (log2FC +0.50, padj 9.1e-12), and is a leading-edge gene in four significant GO-BP pathways governing leukocyte extravasation and cytokine signaling (NES 1.55-1.92, padj <0.05), supporting its prioritization for functional validation. Immunofluorescence in human adipose tissue will be used to confirm protein-level upregulation of PLVAP in the diabetic vasculature, and siRNA-mediated knockdown in endothelial cells under diabetic stimulation (high glucose and palmitate) will be used to test its causal contribution to barrier integrity, inflammatory activation, and immune cell transmigration. This work identifies genes driving adipose EC dysfunction in diabetes, prioritizes those with relevance to human disease, and functionally validates their causal role in promoting dysfunction, using PLVAP as proof of concept, with direct implications for therapeutic targeting of diabetic vascular complications.