Diabetes and the risk of cirrhosis and HCC: An analysis of the UK Biobank

BACKGROUND: Diabetes increases the risk of cirrhosis and HCC. We aimed to assess such associations given different diabetes statuses. METHODS: We included 449,497 participants in the UK Biobank cohort (mean age 56.7±8.0 y; 45.5% male) and assessed the association between preclinical diabetes (prediabetes, having a high risk of diabetes), clinical diabetes (presence, duration, or glycemic control of type 2 diabetes), and incident liver cirrhosis and HCC by the Cox regression. Liver diseases were ascertained through inpatient records and national death registration. Gene-environment interaction was examined using the polygenic risk scores of cirrhosis and HCC. RESULTS: Compared with normoglycemia, having <5 years,≥5 years of diabetes showed adjusted HRs (aHRs) of cirrhosis as 2.85 (2.45–3.32) and 3.43 (2.92–4.02), respectively, which was similarly observed in HCC. In diabetes, a level of hemoglobin A1c ≥ 7.5% showed aHRs of 1.37 (1.07–1.76) and 1.89 (1.10–3.25) for cirrhosis and HCC, respectively, compared with hemoglobin A1c < 6.5%. In non-diabetes, prediabetes presented aHRs of 1.41 (1.14–1.73) and 1.80 (1.06–3.04) of cirrhosis and HCC, respectively. Participants with a high risk of diabetes at baseline showed an aHR of 3.31 (2.65–4.13) for cirrhosis and 2.09 (1.15–3.80) for HCC. In those with a high genetic risk of HCC, having an increased risk of diabetes posed a significantly higher risk of HCC (aHR: 1.93, 1.45–2.58, P (interaction)=0.005), compared with those without a high genetic risk of HCC. CONCLUSIONS: Not only diabetes but preclinical diabetes, longer diabetes duration, and higher baseline hemoglobin A1c were associated with an increased risk of incident cirrhosis and HCC in the general population.