Diabetes mellitus and the risk of cancer

Although diabetes has been known to increase the risk of cancer for over a century, it was not until recently when this area gained momentum and generated a lot of interest. That is in- part because of the rising global diabetes epidemic and the wide spread use of insulin analogues, metformin and other anti-diabetic agents, providing hypothesis generating data on the cancer risk in the diabetic population. Type 2 diabetes is associated with increased risk of breast, colon, pancreatic and other types of cancer, while type 1 diabetes is associated with increase in stomach, pancreatic, endometrial and cervical cancer. Mechanisms postulated for increased cancer risk in diabetes include hyperglycemia, hyperinsulinemia with stimulation of IGF-1 axis, obesity that serves as a common soil hypothesis for both cancer and diabetes as well as other factors such as increased cytokine production. More recently some antidiabetic agents have been thought to increase cancer risk such as insulin glargine, while metformin appears to lower cancer risk. In this review, we present the evidence for the link between diabetes and cancer highlighting the general mechanisms proposed for such a link as well as specific hypotheses for individual cancer. We will also discuss the role of insulin, metformin and other antidiabetic agents in cancer risk.