The diabetes-cancer link.

Abstract

Type 2 diabetes is associated with increased risks for several cancers, including colon,1 postmenopausal breast,2 pancreatic,3 liver,4 endometrial,5 and bladder6 cancers and non-Hodgkins lymphoma.7 Type 2 diabetes is also linked to a modest decrease in the risk for prostate cancer.8 However, diabetes does not reduce aggressive forms, and prostate cancer mortality rates are higher among men with diabetes.9,10 Overall, increased cancer mortality associated with diabetes reflects both increased cancer incidence and decreased survival among people with diabetes who develop cancer.11–13 Research is underway examining how antihyperglycemic medications may affect cancer risk and progression. Some evidence suggests that metformin may decrease risk, and researchers are exploring whether it might even play a role in the treatment of some cancers.14,15 Normal cells develop into malignant cancer cells through a complex process, including initiation (DNA damage from a carcinogen or reactive molecule), promotion (stimulation of initiated cells' growth), and progression (more aggressive growth with angiogenesis and metastasis). Most cancers develop over at least 10–20 years. Numerous factors, including some related to metabolic states in overweight, obesity, and type 2 diabetes, as well as dietary intake and physical activity, appear to promote or inhibit cancer development.16–18 In epidemiological studies, elevated levels of insulin or C-peptide (a biomarker of insulin production) predict increased risk for colorectal, postmenopausal breast, pancreatic, bladder, and endometrial cancers.14,19 Insulin binding to its receptor activates the metabolic pathway, which stimulates glucose uptake and glycogenesis and suppresses lipolysis and liver gluconeogenesis. Although insulin resistance blocks signaling in the metabolic pathway, it does not inhibit activation of the cell-signaling pathway involving mitogen-activated protein kinase that promotes cell proliferation. Increased insulin production to overcome blockade of the metabolic pathway exaggerates activation …