Independent of Cirrhosis, Hepatocellular Carcinoma Risk Is Increased with Diabetes and Metabolic Syndrome

Abstract

In the absence of cirrhosis, type II diabetes and hypertension were independent risk factors for hepatocellular carcinoma. Hyperlipidemia and medical management of type II diabetes with metformin and cholesterol medication appeared to reduce the incidence of hepatocellular carcinoma. In contrast, insulin was associated with a higher risk of hepatocellular carcinoma.

Reptin regulates insulin‐stimulated Akt phosphorylation in hepatocellular carcinoma via the regulation of SHP‐1/PTPN6

“…Indeed, Reptin silencing resulted in a striking enhancement of Akt phosphorylation in response to insulin. This indicates that Reptin silencing increases the sensitivity of HCC cells to insulin, and conversely that the high level of Reptin found in HCC cells likely participates to insulin resistance, a known promoting factor for HCC development . To our knowledge, the regulation of insulin signalling by Reptin in mammalian cells has been so far addressed only in a single study, performed in murine adipocytes, which showed that Reptin silencing reduced the phosphorylation of the Akt substrate AS160, although Akt phosphorylation itself was not examined .…”

“…As mentioned, the metabolic syndrome is emerging as a major cause of HCC, and of many other cancers as well . Metabolic syndrome is associated with insulin resistance that has itself been repeatedly linked to an increased risk of HCC . Although the mechanisms involved are far from being understood, these data raise the hypothesis that factors modulating insulin resistance may have a critical impact on HCC development.…”

Letter: metformin treatment and hepatocellular carcinoma risk in non‐alcoholic fatty liver disease

“…Hence, hyperinsulinaemia and IGF-1 may have a hepatocarcinogenic effect and metformin treatment appeared to reduce the incidence of HCC in subjects with T2DM. 2,3 However, insulin resistance is significantly associated with liver fibrosis that predicts liver-related adversed outcomes (cirrhosis and mortality) in NAFLD. 4,5 Second, as shown in Table 1, the percentage of patients using pioglitazone was significantly greater in metformin users than nonusers.…”

“…However, other mechanisms involving oncogenic signalling pathways, down-regulating pro-inflammatory cytokines, attenuating levels of reactive oxygen species and even modifying gut microbiota could also support its beneficial effects. 3,4 Dogru et al further suggested that other insulin sensitiser drugs such as pioglitazone might exert positive effects on study outcomes. Unfortunately, only 9% of patients were taking pioglitazone during the study period; therefore, sensitivity analyses exploring its relationship with transplant-free survival and HCC were not conducted.…”

Inverse Association of Fibrates and Liver Cancer: A Population‐Based Case‐Control Study in Taiwan

“…It commonly occurs in men and patients aged over 40 years and contributes to approximately 745,000 deaths annually . Many risk factors, including demographics, hepatitis B, hepatitis C, metabolic syndrome, chronic renal failure, diet habits (such as alcohol abuse and tobacco use disorder), and other factors, may play important roles in liver cancer progression . In general, liver cancer is typically diagnosed at a late stage because its symptoms are frequently ambiguous in its early stages.…”