Worldwide deaths from diabetes mellitus (DM) and colorectal cancer increased by 90% and 57%, respectively, over the past 20 years. The risk of colorectal cancer was estimated to be 27% higher in patients with type 2 DM than in non-diabetic controls. However, there are potential confounders, information from lower income countries is scarce, across the globe there is no correlation between DM prevalence and colorectal cancer incidence and the association has evolved over time, suggesting the impact of additional environmental factors. The clinical relevance of these associations depends on understanding the mechanism involved. Although evidence is limited, insulin use has been associated with increased and metformin with decreased incidence of colorectal cancer. In addition, colorectal cancer shares some cellular and molecular pathways with diabetes target organ damage, exemplified by diabetic kidney disease. These include epithelial cell injury, activation of inflammation and Wnt/β-catenin pathways and iron homeostasis defects, among others. Indeed, some drugs have undergone clinical trials for both cancer and diabetic kidney disease. Genome-wide association studies have identified diabetes-associated genes (e.g. TCF7L2) that may also contribute to colorectal cancer. We review the epidemiological evidence, potential pathophysiological mechanisms and therapeutic implications of the association between DM and colorectal cancer. Further studies should clarify the worldwide association between DM and colorectal cancer, strengthen the biological plausibility of a cause-and-effect relationship through characterization of the molecular pathways involved, search for specific molecular signatures of colorectal cancer under diabetic conditions, and eventually explore DM-specific strategies to prevent or treat colorectal cancer.

Thirteen years after the isolation of adrenomedullin (AM) from a human pheochromocytoma, the literature is awash with reports describing its implication in countless physiological and disease mechanisms ranging from vasodilatation to cancer promotion. A growing body of evidence illustrates AM as a pivotal component in normal physiology and disease with marked beneficial effects in the host defense mechanism. Exogenous administration of AM as well as its ectopic overexpression and the use of drugs, which potentiates its activity, are promising strategies for treatment of septic shock and several other pathogen-related disorders. Although major progress toward this end has been achieved over the past few years, our further understanding of the pleiotropic mechanisms involved with AM as a protective peptide is paramount to maximize its clinical application.