Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma.

Aim: To evaluate the relationship between glycemic control [assessed by glycated hemoglobin (HbA1c)], antidiabetic therapies and the risk of hepatocellular carcinoma (HCC).

Methods: We recruited 465 patients with HCC, 618 cases with liver cirrhosis and 490 controls with no liver disease. Among subjects with type 2 diabetes mellitus (DM2), the associations between the antidiabetic strategies and HbA1c level with HCC were determined through 2 series of multivariate logistic regression models using cirrhotic patients and controls as comparison groups.

Results: DM2 prevalence was 31.2% in patients with HCC, 23.2% in cirrhotic patients and 12.6% in controls (P < 0.0001). In 86% of study subjects, DM2 had been diagnosed for more than 1 year before the HCC diagnosis. HCC patients with DM2 had a 1.5-2.5-fold increased risk of liver cancer. The HbA1c mean levels were significantly higher in DM2 patients with HCC than in cirrhotic and control DM2 patients. Antidiabetic treatment with metformin was more common among cirrhotic and control DM2 subjects than among cases with HCC. In both series of multivariate analyses, treatment with metformin significantly reduced the risk of HCC by more than 80% compared with sulphonylureas and insulin therapy. No significant differences were seen between sulphonylureas and insulin treatment. Elevated HbA1c levels were positively related to the risk for HCC in diabetic patients, with a 26%-50% increase in risk for each 1% increase in HbA1c values.

Conclusion: In patients with preexisting DM2, the risk of HCC is positively associated with poor chronic glycemic control and significantly decreased by metformin therapy.