Background & Aims
Metabolic syndrome (MetS) is reversible; however, the effect of changes in MetS status on pancreatic cancer risk is unknown. We aimed to investigate the effects of changes and persistence in MetS status on pancreatic cancer risk.

Methods
This nationwide cohort study included 8,203,492 adults without cancer who underwent two consecutive biennial health screenings provided by the Korean National Health Insurance System between 2009 and 2012 and were followed up until 2017. MetS was defined as the presence of three of its five components, which were evaluated at two consecutive biennial health screenings. Participants were categorized into the MetS-free, MetS-recovered, MetS-developed, or MetS-persistent group. Multivariable Cox proportional hazards regression models were used.

Results
During the 40,464,586 person-years of follow-up (median, 5.1 years), 8,010 individuals developed pancreatic cancer. Compared to the MetS-free group, the MetS-persistent group had the highest risk of pancreatic cancer (hazard ratio [HR] 1.30, 95% CI 1.23–1.37), followed by the MetS-developed group (HR 1.17, 95% CI 1.09–1.25) and the MetS-recovered group (HR 1.12, 95% CI 1.04–1.21) after adjusting for potential confounders (P for trend < 0.001).

The MetS-recovered group was associated with a lower risk of pancreatic cancer than that in the MetS-persistent group (P<0.001). The association between changes in MetS status and pancreatic cancer risk did not differ according to sex or obesity (all P for interactions > 0.05).

Conclusions

In this study, recovering from MetS was associated with a reduced risk of pancreatic cancer compared to persistent MetS, suggesting that pancreatic cancer risk can be altered by changes in MetS.

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