1889-P: Acute Proteomic Inflammatory Signatures from Infusion Cannulas Associated with CSII Therapy at Insulin Infusion Sites

Introduction and Objective: Lipohypertrophy (LH) is a frequent complication of continuous subcutaneous insulin infusion (CSII), marked by localized adipose hypertrophy at infusion sites. Despite affecting over half of individuals with type 1 diabetes, its molecular basis is unclear. This pilot study uses proteomic profiling of matched infusion cannulas to identify inflammatory, extracellular matrix, and adipose pathways implicated in LH. Methods: Infusion cannulas were collected from adults with T1D after 72 hours of CSII. In one participant, insulin-infused cannulas were compared with matched control cannulas placed without insulin. In a second participant, “early” (active infusion) and “delayed” (8-80 hours post-discontinuation) samples assessed temporal effects. Proteins adherent to cannula tips were extracted, digested, and analyzed by LC-MS/MS. Normalized data were compared using unpaired t-tests with Benjamini-Hochberg correction, and pathway enrichment was performed using Gene Ontology and Ingenuity Pathway Analysis. Results: An average of 373 proteins were identified per sample. Insulin-infused cannulas exhibited 68 differentially abundant proteins (p < 0.05), including upregulation of inflammatory and phagocytic markers (CAMP, PGLYRP1, S100A8, CORO1A, PLG) and downregulation of immunoglobulin-related proteins (A2M, IGKC, IGHA1, IGLC3). Pathway enrichment revealed activation of innate immune, antimicrobial, lipid metabolic, and actin/ECM remodeling processes. Temporal analyses showed evolving expression of cytoskeletal and adipogenic regulators (ACTB, FLNA, LUM, DEFA3), with conserved insulin-related proteomic signatures across patients (r = 0.50, p = 0.0037). Conclusion: As a first-of-its-kind feasibility study, this work demonstrates that insulin infusion induces localized immune activation, metabolic remodeling, and structural reorganization within subcutaneous tissue. Disclosure S. Rajeev: None. J. Blanchard: None. D. Subramani: None. R. Sharma: None. B.M. Thompson: None. P. Pirrotte: None. S. Rangasamy: None. Funding Flinn Foundation