Exocrine Pancreatic Dysfunction Increases the Risk of New-Onset Diabetes Mellitus: Results of a Nationwide Cohort Study

Abstract

It is well established that individuals with diabetes mellitus (DM) may develop exocrine pancreatic dysfunction (EPD) requiring pancreatic enzyme replacement therapy, whereas the converse relationship has been poorly studied. Pancreatitis is a disease that is well suited to investigate the latter as it is often characterized by the development of EPD and/or new-onset DM. The aim was to investigate the association between EPD and the risk of new-onset DM in individuals after the first attack of pancreatitis. Using nationwide pharmaceutical dispensing data and hospital discharge data, this cohort study included a total of 9,124 post-pancreatitis individuals. EPD was defined as having two or more dispensing records of pancreatic enzymes. Considering EPD as a time-dependent variable, multivariable Cox regression analysis was conducted. A 1-year lag period between EPD and DM was introduced to minimize reverse causality. Age, sex, ethnicity, alcohol consumption, tobacco smoking, social deprivation index, Charlson comorbidity index, and use of proton pump inhibitors were adjusted for. In the overall cohort, EPD was associated with a significantly higher risk for new-onset DM (adjusted hazard ratio, 3.83; 95% confidence interval, 2.37–6.18). The association remained statistically significant when a 1-year lag period was applied (adjusted hazard ratio, 2.51; 95% confidence interval, 1.38–4.58), as well as when the analysis was constrained to mild acute pancreatitis (4.65; 2.18–9.93). The findings suggest that individuals with EPD, even those without extensive mechanistic destruction of the pancreas, are at an increased risk for new-onset DM. Purposely designed studies are warranted to investigate mechanisms behind the association and if the mechanisms could be targeted therapeutically.