Association of prediabetes, diabetes, and diabetes duration with biliary tract cancer risk: A nationwide cohort study

Population-based evidence of the association between diabetes and biliary tract cancer (BTC) risk is lacking. We aimed to evaluate the association of prediabetes, diabetes, and diabetes duration with subsequent risk of BTC, including cholangiocarcinoma (CCA) and gallbladder cancer (GBC), in the Korean general population.This nationwide cohort study included 9,697,773 adults aged ≥20 years without cancer who underwent national health screening between January and December 2009. Subjects' glycemic status was categorized as normoglycemic, impaired fasting glucose (IFG), newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years. Incident BTC was identified using claims data. Follow-up continued until December 2017. Cox proportional hazard models were used to estimate multivariable-adjusted hazard ratios and 95% CIs of BTC.During a median follow-up of 7.2 years, 13,022 patients were newly diagnosed with BTC. Compared with the normoglycemic group, the IFG, newly-diagnosed diabetes, diabetes duration <5 years, and diabetes duration ≥5 years groups showed the following adjusted hazard ratios (95% CIs) for BTC: 1.08 (1.04-1.12), 1.31 (1.22-1.41), 1.35 (1.27-1.43), and 1.47 (1.39-1.55), respectively. BTC risk significantly increased with deteriorating glycemic status (P for trend <0.001). These results were consistent with those of CCA and GBC analyses.Both IFG and diabetes were independently associated with an increased risk of BTC, including CCA and GBC. A longer diabetes duration was associated with a further increase in BTC risk. Diabetes and even IFG may be modifiable risk factors for BTC.