Risk Associations of Glycemic Burden and Obesity With Liver Cancer—A 10‐Year Analysis of 15,280 Patients With Type 2 Diabetes

Liver is a major site for glucose metabolism. Patients with type 2 diabetes (T2D) and obesity have increased risk of liver cancer. We explored the association of glycemic burden (GB) and obesity with liver cancer in T2D in the prospective Hong Kong Diabetes Register (1995‐2019). We calculated GB using the area under the curve above hemoglobin A1c (HbA1c) of 5.7% and defined obesity as body mass index (BMI) ≥ 25 kg/m(2). We used Cox proportional hazards models to evaluate the association between GB and liver cancer. We included 15,280 patients with at least 10 years of disease duration before liver cancer occurred or censor date, ≥3 years of observation, and ≥5 HbA1c measurements (64% male, age: 58.23 ± 12.47 years, HbA1c: 7.60 ± 1.65%, BMI: 25.58 ± 4.10 kg/m(2)). We excluded 3 years of HbA1c values before liver cancer to avoid reverse causality. Every 1‐SD increase in GB was associated with an adjusted hazard ratio (aHR) of liver cancer of 1.22 (95% confidence interval [CI]: 1.01‐1.47). The top GB quartile group (range: >2.41) had aHR of 1.78 (1.01‐3.13) versus the lowest quartile group (0‐1.19). The aHRs for each SD increase in GB were 1.34 (1.05, 1.70) in the obese group and 1.12 (0.81‐1.53) in the nonobese group, but no interaction (P (interaction) = 0.120). When stratified by GB median (1.69 [1.13, 2.43]) and obesity, obese patients with high GB had the highest aHR of 2.51 (1.44‐4.37) for liver cancer versus the nonobese group with low GB, but no interaction (P (interaction) = 0.071). Subgroup analysis of patients with available hepatitis B surface antigen status (n = 9,248) yielded similar results. Conclusion: Our results emphasized the importance of glycemic and weight control for reducing the risk of liver cancer in T2D.