Impact of initial severity and progression pattern of new-onset diabetes on pancreatic cancer risk: a 15-year longitudinal nationwide cohort study

BACKGROUND: New-onset diabetes (NOD) increases the risk of pancreatic cancer. Previous studies have mainly focused on the presence or absence of diabetes, with limited attention to NOD severity at diagnosis and its clinical course. OBJECTIVE: This 15-year longitudinal nationwide cohort study aimed to analyse the pancreatic cancer risk based on the initial severity and progression pattern of NOD. DESIGN: We included 402 663 individuals with or without NOD from the Korean National Health Insurance Service (2005-2019). Initial NOD severity was defined by baseline antidiabetic treatment intensity: no antidiabetics, oral antidiabetics and insulin. RESULTS: Pancreatic cancer risk increased stepwise with higher initial treatment intensity in NOD compared with individuals without diabetes (adjusted HRs (aHRs) 3.01, 4.32 and 5.60 for no antidiabetics, oral antidiabetics and insulin, respectively). Within the same baseline treatment-intensity category, individuals with rapid escalation within 6 months had a higher risk of pancreatic cancer than those with stable or decreased treatment intensity. In some comparisons between groups with different baseline treatment intensities, the risk of pancreatic cancer was higher with less intensive baseline therapy but subsequent intensification than with more intensive baseline therapy without progression. Notably, drug-naïve individuals who initiated antidiabetic treatment within 6 months had a greater risk even than those who were initially on oral medication without worsening (aHR 6.50 vs 3.67). These patterns were more prominent in pancreatic cancer cases diagnosed within 3 years after NOD. CONCLUSION: Greater initial severity of NOD and rapid early aggravation were both associated with an increased risk of pancreatic cancer.