Tumor Markers and Pancreatic Enzymes Reflect Early Pancreatic Dysfunction in Type 2 Diabetes

Objective: To evaluate whether pancreatic enzymes and tumor markers reflect early pancreatic dysfunction in patients with type 2 diabetes mellitus (T2DM). Methods: In this cross-sectional study conducted between January 2023 and January 2024, 300 Saudi adults with T2DM were assessed for serum CA19-9, CA125, amylase, and lipase. Associations with glycemic control, insulin resistance (homeostatic model assessment for insulin resistance HOMA-IR), and metabolic parameters were examined using multivariable linear and logistic regression adjusted for age, sex, body mass index, diabetes duration, lipid profile, and medication use. Receiver-operating characteristic analyses evaluated biomarker performance for identifying poor glycemic control (HbA1c >8.5%). Exploratory analyses assessed associations with recent acute pancreatitis. Results: Patients with poor glycemic control had significantly higher CA19-9 and CA125 levels and lower amylase and lipase levels (all p < 0.05). HbA1c and HOMA-IR remained independent predictors of tumor marker elevation and enzyme reduction after adjustment. Adjusted area under the curve values for detecting poor glycemic control were 0.81 for CA125, 0.79 for CA19-9, 0.75 for lipase, and 0.73 for amylase. A high-risk biomarker profile, defined as elevated CA19-9 or CA125 combined with low amylase or lipase, was associated with recent acute pancreatitis (adjusted odds ratio 2.3; 95% confidence interval 1.3–4.2). Conclusion: In T2DM, elevated tumor markers and reduced pancreatic enzyme activity are associated with poor glycemic control and insulin resistance and may indicate early pancreatic dysfunction. These biomarkers may aid risk stratification and warrant evaluation in prospective studies.