Diabetes and Risk of Cancer

Abstract

Diabetes and cancer represent two complex, diverse, chronic, and potentially fatal diseases. Cancer is the second leading cause of death, while diabetes is the seventh leading cause of death with the latter still likely underreported. There is a growing body of evidence published in recent years that suggest substantial increase in cancer incidence in diabetic patients. The worldwide prevalence of diabetes was estimated to rise from 171 million in 2000 to 366 million in 2030. About 26.9% of all people over 65 have diabetes and 60% have cancer. Overall, 8–18% of cancer patients have diabetes. In the context of epidemiology, the burden of both diseases, small association between diabetes and cancer will be clinically relevant and should translate into significant consequences for future health care solutions. This paper summarizes most of the epidemiological association studies between diabetes and cancer including studies relating to the general all-site increase of malignancies in diabetes and elevated organ-specific cancer rate in diabetes as comorbidity. Additionally, we have discussed the possible pathophysiological mechanisms that likely may be involved in promoting carcinogenesis in diabetes and the potential of different antidiabetic therapies to influence cancer incidence.

Effects of Sulfonylureas on Tumor Growth: A Review of the Literature

“…Higher relative risks of liver, pancreatic, or endometrial cancer have been reported in diabetic patients, whereas the increase of relative risks of breast, bladder, colorectal, kidney, and biliary neoplasms is less evident; moreover, the relative risk of prostate cancer seems even lower in diabetic patients [2,76].…”

Diabetes and cancer: A critical appraisal of the pathogenetic and therapeutic links

“…According to several meta-analyses, an increased frequency of malignancies in diabetic patients has been attributed to various general and local mechanisms (1,3,4,10,12).…”

“…The hepatocellular carcinoma (HCC) incidence is higher in those with T2DM in the two genders, with a greater risk in males and in those with concomitant hepatitis C virus (HCV) infection: As the majority of epidemiological studies indicate a 2-3-fold increase in liver cancer in diabetic patients, it is feasible that diabetes may also act synergistically with other well-established risk factors for HCC, including hepatitis B virus and HCV infection, non-alcoholic fatty liver disease (also considered as hepatic manifestation of diabetes and metabolic syndrome), non-alcoholic steatohepatitis and chronic alcohol consumption leading to steatosis and cirrhosis (1,3,16). In particular, the mitogenic pathway of insulin is unlikely to be involved considering that healthy liver cells, due to insulin secretion bursts in the portal circulatory system, are physiologically exposed to higher insulin concentrations compared to other peripheral tissues (10), above all in the insulin-resistant hyperinsulinemic type 2 states (whereas in insulin-deficient T1DM individuals treated with exogenous insulin, the liver is exposed to the same insulin levels as the other organs).…”

“…Several cohort studies and meta-analyses have strongly demonstrated that the T2DM and insulin-resistant states (such as in metabolic syndrome) are independent risk factors for the development of several types of cancer (1,(3)(4)(5). There is also increasing evidence confirming that these two high-impact diseases share factors that influence their development and progression, significantly modifying the outcome of the other.…”

“…In addition, it is currently believed that diabetes is a marker of elevated cancer risk due to changes in underlying metabolic conditions, such as insulin resistance or hyperinsulinemia. Alternatively, the multidrug therapy required for the treatment of diabetes and cancer may complicate this association (3).…”