Fatty Pancreas Disease and the Risk of Future Diseases of the Exocrine Pancreas: A US Matched Cohort Study

INTRODUCTION: Fatty pancreas disease (FPD), marked by excess fat within the pancreas, is often incidentally detected on imaging. Despite recognized metabolic links, its clinical significance remains unclear. More granular data from large, well-characterized US cohorts are needed to clarify its relevance. This study quantified intrapancreatic fat deposition and assess its natural history and related outcomes. METHODS: Adults 18 years and older with radiologically confirmed FPD between 2004 and 2024 were identified from institutional databases. Controls without FPD were matched 1:2 by age, sex, body mass index, and smoking status. Patients with excessive alcohol intake, previous pancreatitis, pancreatic cancer, surgery, cystic fibrosis, or prolonged steroid/antiviral use were excluded. Fat content in the pancreas and liver, as well as subcutaneous and visceral fat areas, were measured using iNtuition software on noncontrast computed tomography scans. RESULTS: We included 82 FPD patients and 164 matched controls (median age 65 years; 55% women; median body mass index 32). Subcutaneous and hepatic fat were similar between groups, but intrapancreatic fat deposition was markedly higher in FPD patients (26.8% vs 4.9%, P < 0.001). Over a mean 4-year follow-up, FPD patients had significantly higher rates of acute pancreatitis (12% vs 1.2%, P < 0.001), chronic pancreatitis (6.1% vs 0.6%, P = 0.017), pancreatic cysts (34.1% vs 4.9%, P < 0.001), and pancreatic cancer (1.6% vs 0%, P = 0.012). Extrapancreatic cancer incidence did not differ. DISCUSSION: FPD is associated with an increased risk of pancreatic cancer, acute pancreatitis, chronic pancreatitis, and incidental pancreatic cysts, independent of obesity or hepatic steatosis, suggesting a potentially causative role of FPD in the pathogenesis of exocrine pancreatic diseases.