A risk factor in the development of hepatocellular carcinoma: Insulin analogues

Abstract

Aim: The most important mechanisms in the pathogenesis of the relationship between diabetes mellitus and cancer; hyperglycemia, insulin resistance and the inflammation resulting from the activation of insulin receptors. Apart from insulin resistance, hyperinsulinemia may also occur with the use of exogenous insulin. We aimed to investigate the effect of diabetes mellitus and insulin use as a risk factor for hepatocellular carcinoma development in a large patient population with chronic hepatitis B cirrhosis.

Materials and Methods: 493 chronic hepatitis B-associated cirrhotic patients were included in the study. The patients were evaluated at 3–6-month intervals during follow-up for hepatocellular carcinoma screening. Demographic and laboratory variables, presence of diabetes mellitus, insulin usage, and hepatocellular carcinoma occurrence were recorded.

Results: The mean age of patients was 53.5±13.9 years, and 66.2% were male. 18.7% of the patients had a diagnosis of diabetes mellitus and 12% of the patients had insulin use. 68 patients (13.8%) were decompensated cirrhotic. The mean follow-up period was 50.6±33.6 months, during which 43 patients (8.7%) developed hepatocellular carcinoma. In the multivariable analysis, older age, male gender, presence of decompensation, use of exogenous insulin were associated with HCC occurrence (all p<0.05).

Conclusion: Diabetes mellitus and insulin resistance have been associated with many cancers due to insulins’ mitogenic effects. We showed that insulin use is a risk factor for hepatocellular carcinoma development in our chronic hepatitis B-associated cirrhotic patients. Further studies including antidiabetic treatment subgroups are needed.