Brief Article
Copyright ©2010 Baishideng. All rights reserved
World J Gastroenterol. Jun 28, 2010; 16(24): 3025-3032
Published online Jun 28, 2010. doi: 10.3748/wjg.v16.i24.3025
Glycated hemoglobin and antidiabetic strategies as risk factors for hepatocellular carcinoma
Valter Donadon, Massimiliano Balbi, Francesca Valent, Angelo Avogaro
Valter Donadon, Massimiliano Balbi, Department of Medicine, Internal Medicine 3rd, Pordenone Hospital, Via Montereale 24, Pordenone 33170, Italy
Francesca Valent, Institute of Hygiene and Epidemiology, Udine University Hospital, Udine 33100, Italy
Angelo Avogaro, Department of Clinical and Experimental Medicine, Padova University, Padova 35100, Italy
Author contributions: Donadon V designed the research; Balbi M and Donadon V performed the research; Valent F analyzed the data; Donadon V, Balbi M and Avogaro A wrote the paper.
Correspondence to: Dr. Valter Donadon, Department of Medicine, Internal Medicine 3rd, Pordenone Hospital, Via Montereale 24, Pordenone 33170, Italy.
Telephone: +39-434-399330 Fax: +39-434-399559
Received: March 12, 2010
Revised: April 17, 2010
Accepted: April 24, 2010
Published online: June 28, 2010

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.

Keywords: Hepatocellular carcinoma, Type 2 diabetes mellitus, Glycemic control, Metformin therapy, HbA1c level