Metabolic syndrome and risk of incident chronic pancreatitis: a prospective cohort study.

Background and aim: The association between metabolic syndrome (MetS) and chronic pancreatitis (CP) remains unclear. This study aimed to examine whether MetS is independently associated with an increased risk of CP. Methods: We analyzed data from 349,995 participants in the UK Biobank who were free of CP at baseline. MetS was defined according to NCEP-ATP III criteria. Incident CP cases were identified via hospital admissions and death registries using ICD codes. Cox proportional hazards models were used to estimate hazard ratios (HRs) with sequential adjustment for demographic, lifestyle, clinical, and inflammatory factors. Subgroup, nonlinear, mediation, and sensitivity analyses were performed to assess robustness. Results: Over a median follow-up of 18 years, 623 incident CP cases occurred. MetS was significantly associated with increased CP risk after full adjustment (HR 2.02, 95% CI 1.64-2.49). A clear dose-response relationship was observed between the number of MetS components and CP risk. Among individual components, hyperglycemia (HR 2.59) and elevated waist-to-hip ratio (Q4 vs. Q1 HR 2.78) were the strongest predictors. Subgroup analyses showed stronger associations in younger individuals, females, never smokers, and current drinkers. Systemic inflammation, particularly via neutrophils and CRP, mediated approximately 8 and 3% of the association, respectively. Sensitivity analyses confirmed the robustness of these findings. Conclusion: MetS is an independent risk factor for CP, with risk rising as the number of MetS components increases. Hyperglycemia and central adiposity are key drivers. Managing metabolic health may help reduce CP risk.