The Coexistence of Diabetes Mellitus and Low Fecal Elastase is associated with Increased Pancreatic Cancer Risk: A Retrospective, Real-world Cohort Study

Objectives: Diabetes mellitus and chronic pancreatitis are established risk factors for pancreatic ductal adenocarcinoma (PDAC). The co-occurence of exocrine and endocrine pancreatic dysfunction may increase the risk of progression to PDAC and could play a role in early detection. We sought to explore this hypothesis by comparing PDAC risk among patients with diabetes mellitus (DM) and low fecal elastase (FE) in a real-world cohort of patients. Materials and Methods: A retrospective cohort study was conducted using the TriNetX research network including adults with continuous follow-up from 2016 to 2023. The cohort was stratified into four groups based on the prescene or absence of DM, and normal FE (>200 µg/g) or low FE (<200 µg/g). The four groups included: (1) low FE and DM, (2) low FE without DM, (3) normal FE and DM, (4) normal FE without DM. Propensity score matching was performed to balance covariates including age, sex, race, comorbidities to allow for a six-way comparison of PDAC risk between groups. Time-to-event analyses were conducted with Kaplan-Meier curves and Cox proportional hazards models to estimate hazard ratios (HR) and 95% confidence intervals (95% CI) for the primary outcome of PDAC incidence. Results: Of the study cohort, 29,207 had fecal elastase levels. Low FE (<200 µg/g) was observed in 33% (n=9,585) of these patients. After six-way comparisons, we observed a higher PDAC risk among individuals with both DM and low FE compared to other groups. The highest PDAC risk was observed in patients with both a low FE (<200 µg/g) and DM compared to those with a normal FE and without a history of DM (HR 3.68; 95% CI, 2.07–6.53; P <0.001). Sensitivity analysis using a stricter fecal elastase cutoff of <100 µg/g showed a similar finding, with the highest hazard ratio for PDAC among patients with both DM and very low FE levels [HR 3.07, 95% CI, 1.37-6.91; P =0.004]. Conclusions: The coexistence of low fecal elastase and DM amplifies the risk of pancreatic ductal adenocarcinoma in our cohort of patients. These results suggest that fecal elastase values may be used to enrich the diabetic population for future PDAC risk stratification, though more studies are needed to validate these findings.