Our study shows that DM2 is an independent risk factor for HCC and pre-exists to HCC occurrence. In DM2 patients with HCC, metformin therapy is associated with a reduced HCC risk and seems to have a protective effect on HCC development.

Our study confirms that type 2 diabetes mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC patients. Moreover, in male patients with type 2 diabetes mellitus, our data shows a direct association of HCC with insulin and sulphanylureas treatment and an inverse relationship with metformin therapy.

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

AIM:To investigate the relationships between Type 2 diabetes mellitus (DM2) and the risk of hepatocellular carcinoma (HCC). METHODS:We studied the association between DM2 and HCC in a large case-control study that enrolled 465 consecutive Caucasian patients with HCC (78.3% males, mean age 68.5 ± 8.9 years) compared with an age and sex matched control group of 490 subjects. RESULTS: Prevalence of DM2 was significantly higher in HCC patients (31.2% vs 12.7%; OR = 3.12, 95% CI: 2.22-4.43) and in HCC cases with alcohol abuse. DM2 has been diagnosed before the appearance of HCC in 84.1% of diabetic HCC subjects with mean duration of 141.5 mo, higher in cases treated with insulin than in those with oral antidiabetic agents (171.5 vs 118.7 mo). Compared to controls, males DM2 with HCC were more frequently treated with insulin (38.1% vs 17.6%, P = 0.009) and with sulfonylurea with or without metformin than with diet with or without metformin (84% vs 68.3%, P = 0.049).CONCLUSION: DM2 in our patients is associated with a 3-fold increase risk of HCC. In most of our cases DM2 pre-existed to HCC. Patients with DM2 and chronic liver disease, particularly insulin treated males, should be considered for HCC close surveillance programs.

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