Diabetes Mellitus Impairs the Response to Intra-arterial Chemotherapy in Hepatocellular Carcinoma

Diabetes mellitus is associated with a poorer outcome in patients with hepatocellular carcinoma. The impact of diabetes mellitus on the treatment of hepatocellular carcinoma, especially chemotherapy, is uncertain. Intra-arterial chemotherapy is one of the therapeutic options of unrespectable hepatocellular carcinoma. To clarify this point, we analyze the therapeutic effect of intra-arterial chemotherapy in unrespectable hepatocellular carcinoma patients with or without diabetes mellitus. Fifty-two patients with advanced hepatocellular carcinoma underwent intra-arterial chemotherapy with cisplatin and fluorouracil. Tumor response was assessed by computed tomography. An in vitro hepatocellular carcinoma cell line, Hep G2, was evaluated for the cytotoxic effect of cisplatin and fluorouracil in different concentrations of insulin and glucose mimicking diabetic conditions. Fifty-two patients were included, 14 had diabetes and 38 were non-diabetics. Non-diabetic patients had a lower rate of progressive disease (16% vs. 43%, P=0.039). The median time to progression was significantly longer in non-diabetics compared with the diabetic counterpart (a median of 206 days vs. 88 days, P=0.02). In the hepatocellular carcinoma cell line, Hep G2, insulin rather than glucose was more important for promoting cell proliferation and enhancing the drug resistance of cisplatin or fluorouracil. Our study showed that intra-arterial chemotherapy for unrespectable hepatocellular carcinoma was less effective in diabetic patients than the non-diabetic counterpart in terms of the progression-free rate and time to disease progression survival.