There is a consensus that both type 1 and type 2 diabetes are associated with a spectrum of cancers but the underlying mechanisms are largely unknown. On the other hand, there are ongoing debates about the risk association of insulin use with cancer. We have briefly reviewed recent related research on exploration of risk factors for cancer and pharmacoepidemiological investigations into drug use in diabetes on the risk of cancer, as well as the current understanding of metabolic pathways implicated in intermediary metabolism and cellular growth. Based on the novel findings from the Hong Kong Diabetes Registry and consistent experimental evidence, we argue that use of insulin to control hyperglycemia is unlikely to contribute to increased cancer risk and that dysregulations in the AMP-activated protein kinase pathway due to reduced insulin action and insulin resistance, the insulin-like growth factor-1 (IGF-1)-cholesterol synthesis pathway and renin-angiotensin system, presumably due to reduced insulin secretion and hyperglycemia, may play causal roles in the increased risk of cancer in diabetes. Further exploration into the possible causal relationships between abnormalities of these pathways and the risk of cancer in diabetes is warranted.
Keywords: Diabetes, Insulin, Cancer, Hyperglycemia, Cholesterol synthesis pathway, Renin-angiotensin system, adenosine 5′-monophosphate -activated protein kinase pathway