P-123: Proteomic evidence of exocrine pancreatic involvement in type 1 diabetes

Abstract

Circulating biomarkers are increasingly explored to monitor disease progression and support personalized care in type 1 diabetes (T1D). Most biomarker studies have focused on β-cell pathways, however, other pancreatic compartments may also contribute to systemic molecular signatures. Integrating proteomics with longitudinal clinical data offers an opportunity to identify protein profiles associated with T1D. To compare circulating proteomic profiles in adolescents with long-duration T1D and healthy controls. Fortyfour adolescents with T1D (duration ≥8 years) were matched by age and sex to 44 healthy controls. Plasma proteins were analyzed using the Olink Explore 384 cardiometabolic panel. Differential protein expression between groups was assessed using linear regression models, with effect sizes reported as log2-fold changes and P-values adjusted for multiple testing. Results were visualized using volcano plots. Mean HbA1c (SD) since diabetes diagnosis was 56 (6) mmol/mol; 7.3 (0.6) % NGSP. Ninety-eight percent of adolescents with T1D used glucose sensors, and 84% used insulin pumps. Forty proteins were differentially expressed between individuals with T1D and controls. Six pancreas-derived digestive enzymes (Phospholipase A2 group 1B (PLA2G1B), Trypsin-2 (PRSS2), Carboxypeptidase A1 (CPA1), Carboxypeptidase B1 (CPB1), Chymotrypsin-like elastase 3A (CELA3A), and Pancreatic alpha-amylase (AMY2B)) were significantly downregulated in T1D, whereas four immune related proteins (Plexin-B2 (PLXNB2), Semaphorin-7A (SEMA7A), Neuronal cell adhesion molecule (NRCAM), and Leptin receptor (LEPR)) were upregulated. Persistent downregulation of pancreatic digestive enzymes supports exocrine pancreatic involvement as a durable feature of T1D, remaining evident in adolescents more than a decade after diagnosis despite good metabolic control and widespread use of advanced diabetes technologies.