**6. Conclusions**

Some studies have suggested that the link between prostate cancer and diabetes is mediated by the effect of hyperinsulinemia on testosterone levels [89]. Other studies have shown a negative association between hyperglycemia, hyperinsulinemia and prostate cancer. For example, Stocks and colleagues [90] in their prospective study reported that increased insulin resistance and low glycemic control is associated with low risk for prostate cancer in diabetic patients.

Despite the fact that prostate cancer risk may be low in diabetic patients, they may have higher

Prostate cancer is an important example of the complexity of carcinogenesis associated with diabetes. On the one hand, an association between diabetes, IGF-1, hyperinsulinemia and insulin resistance appears plausible, but on the other, these features can be somewhat counterbalanced as well and can reduce the risk for the development of one of the leading cancer entities

Hepatocellular carcinoma (HCC) represents the most common form of primary liver cancer. The association between HCC and type 2 diabetes was reported first 30 years ago, when Lawson documented that type 2 diabetes is more prevalent in patients with HCC, irrespective

Since then, multiple studies have shown an association between type 2 diabetes and HCC, and documented the increased risk for HCC in diabetic patients, independent of age, sex, obesity,

The exact pathophysiological mechanisms linking type 2 diabetes and HCC are not completely understood, but the understanding of HCC pathophysiology has improved in recent years.

It is well known that type 2 diabetes is associated with increased hepatic and peripheral insulin resistance, lipotoxicity, increased oxidative stress and chronic low-grade inflammatory state, and several studies suggest that all these factors may contribute to the development of HCC by promoting hepatic cellular growth/proliferation and by inhibiting cellular apoptosis. In addition, in the presence of insulin resistance, insulin levels rise in blood, resulting in increased insulin-like growth factor-1 (IGF-1) production that is capable to stimulate hepatic cellular growth and proliferation and inhibit cellular apoptosis in the liver. Hyperinsulinemia also stimulates insulin receptor substrate-1 (IRS-1), which plays an important role in the activation of some intracellular cytokine signaling pathways implicated in hepatic carcinogenesis [95, 96].

There are ongoing studies trying to improve our knowledge about the pathophysiology of HCC. Recently, we have evidence that suggest that gut microbiota alteration may play a role in pathogenesis of type 2 diabetes [98], other studies reported some epigenetic alterations that might be also important for HCC development, for example, the hypermethylation of the E-cadherin-1

*(*CDH-1*)* gene has been related to increased incidence of NAFLD-related HCC [95–97].

risk for cancer related mortality than non-diabetic patients.

of viral hepatitis, alcoholic cirrhosis or hemochromatosis [91].

smoking, hypertension, presence of cirrhosis and hepatic steatosis [92–94].

worldwide.

128 Diabetes and Its Complications

**5.6. Diabetes and hepatic cancer**

Diabetes and cancer are common and serious global health problems, and incidence of both diseases is increasing all over the world. Many studies have suggested the relationship between diabetes and cancer and the fact that diabetes, may affect the risk of developing a variety of cancers, and this association is also biological plausible.

It is important as a clinician to take in consideration all aspects when treating a cancer patient who has diabetes. It is important to consider all complications, cardiac, neurologic and renal complications that are commonly associated with diabetes. Continued improvement of cancer outcomes may be dependent also by the control of diabetes. Taking in consideration the results of numerous epidemiologic and clinical studies involving diabetes and cancer, clinicians must also pay attention to the increased risk of new or longstanding diabetics for some tumor entities by regularly screening diabetic patients for early development of cancer.

The association between diabetes and cancer is complex and need further studies.

It is an important health problem worldwide, and scientists, clinicians and politicians have to develop national policies for early diagnosis and prevention of diabetes and cancer more effectively, otherwise both diseases with their biologic and sociologic relationships could overwhelm health systems.
