Mechanisms Underlying Hepatocellular Carcinoma Progression in Patients with Type 2 Diabetes

Hepatocellular carcinoma (HCC) ranks third in cancer-related deaths from solid tumors worldwide. The incidence of type 2 diabetes mellitus (T2DM) has increased worldwide in conjunction with the expansion of the Western lifestyle. Furthermore, patients with T2DM have been documented to have an increased risk of HCC, as well as bile tract cancer. Growing evidence shows that T2DM is a strong additive metabolic risk factor for HCC, but how diabetes affects the incidence of HCC requires additional investigation. In this review, we discuss the underlying mechanisms of HCC in patients with T2DM. Topics covered include abnormal glucose and lipid metabolism, hyperinsulinemia, and insulin resistance; the effect of activated platelets; hub gene expression associated with HCC; inflammation and signaling pathways; miRNAs; altered gut microbiota and immunomodulation. The evidence suggests that reducing obesity, diabetes, and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis through efficient measures of prevention may lead to decreased rates of T2DM-related HCC.