Diabetes, antihyperglycemic medications and cancer risk: smoke or fire?

ObjectiveThe aim of this review article is to discuss the epidemiological links between diabetes and cancer; the potential biological mechanisms linking diabetes, obesity and cancer; the risk of cancer associated with antidiabetic medications.MethodsThe data discussed in this review were obtained from the American Association of Clinical Endocrinologists Consensus Conference on Diabetes and Cancer, held in New York, NY, USA, September 2012.ResultsThe results of these studies demonstrate a significant association between diabetes and the risk of multiple cancers, including hepatocellular, pancreatic, endometrial, colorectal, breast, kidney, bladder, gastric, and ovarian cancer, non-Hodgkin lymphoma, T cell lymphoma and leukemia. There are multiple potential biological mechanisms that may link type 2 diabetes, obesity and cancer. Insulin resistance and hyperinsulinemia may lead to direct activation of the insulin receptors on tumor cells and promote tumor growth. Other potential mechanisms include increased circulating, local or bioavailable insulin-like growth factor 1, hyperglycemia, dyslipidemia, increased circulating or local estrogen, adipokines and direct and indirect effects of inflammatory cytokines. Epidemiological studies have had conflicting results regarding the associations between various classes of antidiabetic medication and cancer development. Animal studies have demonstrated increased tumor growth with certain medications, but their relevance to humans is uncertain. Metformin may, however, have protective effects on cancer development and may improve survival in patients with cancer.ConclusionWe describe the current understanding of the links among diabetes, antidiabetic medication and cancer risk. We highlight some of the issues that should be addressed in the future to prevent cancer development and death in those with diabetes.