Glycaemic control is a modifiable risk factor for pancreatic cancer development in patients with diabetes: a population-based cohort study

Background Effect of glycaemic control on pancreatic cancer (PC) development in patients with long-standing type 2 diabetes (T2D) remains unclear. Objective To investigate effects of glycaemic control on PC development in patients with T2D. Design Retrospective cohort study. Methods Adults from a territory-wide healthcare registry were followed from T2D diagnosis until PC, death, pancreatectomy or end of study (December 2020). Exclusions were PC within 3 years after T2D diagnosis (addressing reverse causality), prior PC, immunoglobulin G 4 disease and pancreatectomy. The primary outcome was PC and secondary outcomes included PC-related and all-cause mortality. Optimal glycaemic control throughout follow-up was defined as time-weighted mean haemoglobin A1c (A1c)<7%; with time-weighted mean fasting glucose (FG)≤7 mmol/L as secondary analysis. Adjusted HR (aHR) was estimated using Cox models with propensity score adjustment for covariates including demographics, diabetes complications, comorbidities and medications. Results Among 458 331 patients (median age: 59.8 (P25–P75: 51.8–68.5) years; 51.2% male), there were 1382 (0.3%; 2.8 per 10 000 person-years) PC, 922 (0.2%; 1.9 per 10 000 person-years) PC-related deaths, and 70 936 (15.5%; 142.9 per 10 000 person-years) deaths over a median follow-up of 9.9 (P25–P75: 7.4–14.1) years. Optimal glycaemic control was associated with lower PC risk—A1c<7%(aHR: 0.43; 95% CI: 0.37 to 0.48) and FG≤7 mmol/L (aHR: 0.71; 95% CI: 0.63 to 0.80). Optimal control of both A1c and FG conferred lowest PC risk (aHR: 0.39; 95% CI: 0.33 to 0.46). PC risk increased stepwise with A1c (P trend <0.001), with aHRs from 1.85 (A1c 7.0–7.5%) to 4.61 (A1c≥9.0%). Every 1% rise in A1c and 1 mmol/L rise in FG increased PC risk by 46% and 14%, respectively. Optimal control is also associated with lower PC-related mortality (aHR: 0.35; 95% CI: 0.30 to 0.41) and all-cause mortality (aHR: 0.83; 95% CI: 0.82 to 0.85). Conclusion Optimal glycaemic control was associated with lower PC risk in T2D. Further multicentre cohort studies are warranted to confirm its oncopreventive strategy.