Cancer and diabetes are two major health problems worldwide, and incidence is increasing globally for both diseases. Type 2 diabetes is characterized by hyperinsulinemia and insulin resistance and the effect of insulin and insulin growth factor I on cancer development and progression have been demonstrated in animal and human studies. The relationship between diabetes and cancer was reported for more than 60 years. Many epidemiological studies conducted over time suggested the association between diabetes and cancer. Epidemiological studies show an increased risk in type 2 diabetic patients for colon, breast, liver, pancreas, bladder cancers and non-Hodgkin’s lymphoma, and a decrease risk for prostate cancer. Lung cancer does not appear to be related to diabetes and for renal cancer data are inconclusive. Diabetes, beside the fact that it is an independent risk factor for different type of cancer, can also have an impact on prognosis of cancer, and studies shown an increased cancer mortality in patients with diabetes.
Part of the book: Diabetes and Its Complications
Advanced liver cirrhosis requiring hospitalization is frequently associated with electrolytic disturbances, the most common finding being serum hyponatremia. The goal of treatment in patients with decompensated liver cirrhosis complicated with severe hyponatremia is to normalize the increased amount of water in the body and to improve the sodium concentration. Fluid restriction is recommended at 1.5 L/day to prevent sodium depletion in the serum, but the lack of efficacy is probably due to a poor patient compliance. Discontinuation or adjustments of diuretic dosages are sometimes required. Albumin associated with vasoconstrictors as midodrine can increase the effective arterial blood volume and seems to improve the serum sodium concentration. A promising therapeutic option targeting the pathophysiological mechanism of hyponatremia consists of improving solute-free water excretion, which is markedly impaired in these patients. The use of agents such as k opioid agonists has been attempted, but has been dropped due to the severe side effects. Recently, a new therapeutic class called vaptans has taken an important place in the treatment of hypervolemic hyponatremia. The main side effects during the administration of these drugs in patients with liver cirrhosis are reversible after discontinuing therapy. Therefore, it is recommended to use vaptans for short periods of time.
Part of the book: Management of Chronic Liver Diseases
Hepatocellular carcinoma (HCC) is the most frequent primary malignancy of the liver and it is one of the leading causes of cancer-related deaths worldwide. The global burden of hepatocellular carcinoma is growing nowadays. Most cases of hepatocellular carcinoma develop in the background of chronic hepatitis C and B and liver cirrhosis‑well-known risk factor. But despite the reducing incidence of chronic hepatitis infections, an increase in the incidence of hepatocellular carcinoma was observed in the last decades. This could be explained by the increasing prevalence of obesity, type 2 diabetes mellitus, nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH), which are becoming important risk factors in hepatocellular carcinoma. Regular surveillance, as performed for patients with viral hepatitis, is required for patients with metabolic risk factors.
Part of the book: Liver Cancer
Metformin has been used for almost half a century as the first line of treatment for type 2 diabetes. Mechanisms of action are still incompletely known, recent studies have shown that metformin exerts its effects through several mechanisms, including the stimulation of AMP-activated protein kinase, decreasing production of cyclic AMP, inhibition of mitochondrial complex I of the electron transport chain, targeting glycerophosphate dehydrogenase and altering gut microbiota. In recent years, studies have shown that patients with type 2 diabetes mellitus have a lower risk of developing cancer, and patients with cancer and type 2 diabetes have a lower mortality. Experimental studies have demonstrated that metformin has anti-tumor activity by inhibiting mTORC1 signaling pathway and mitochondrial complex, inhibiting tumor growth and proliferation, and inducing cellular apoptosis. There are multiple studies showing that combination of metformin with different types of anti-cancer therapies may reduce toxicities and tumor resistance. This chapter is focused on the progress made in understanding the anti-tumor effect of metformin and its association with cancer therapy.
Part of the book: Metformin