Abstract
Background: The relationship between Mediterranean diet (MedDiet) adherence and acute pancreatitis (AP) risk is largely unknown. Objectives: To investigate the associations between MedDiet adherence and AP risk and joint associations of genetic risk and MedDiet adherence with AP risk. Design: A prospective cohort study using data from UK Biobank, a large population-based prospective study that recruited over 500,000 participants aged 40-69 between 2006 and 2010 across the United Kingdom. Methods: We included 103,449 participants free of AP with typical dietary intake from 24-h dietary recalls. MedDiet adherence was measured via the Mediterranean Diet Adherence Screener (MEDAS) continuous score. Genetic predisposition to AP was estimated by polygenic risk score (PRS). Incident AP cases were identified via electronic medical records. Hazard ratios (HRs) with 95% confidence intervals (CIs) were estimated by Cox proportional hazards models. Mediation analyses were further applied to explore the mediating effects of the low-grade inflammation (INFLA) score and metabolic status. Results: Over a mean follow-up period of 10.4 years, 371 AP cases were documented. Higher MedDiet adherence defined by MEDAS continuous score was inversely associated with lower AP risk (highest vs lowest tertiles: HR 0.60, 95% CI 0.46-0.79, p < 0.001), with the INFLA score and metabolic status mediating 10% and 7.1% of the association, respectively. Although no interaction was observed between PRS and MedDiet adherence, participants with combined low genetic risk and the highest MedDiet adherence had the lowest risk of AP (HR 0.54, 95% CI 0.36-0.80, p = 0.002). Conclusion: The study suggests that higher adherence to the MedDiet is associated with a decreased risk of AP, which is partially mediated by inflammation and metabolic status, and may attenuate the deleterious impact of genetics on AP risk. </p>