Diabetes and Colorectal Cancer Risk: A New Look at Molecular Mechanisms and Potential Role of Novel Antidiabetic Agents

Abstract

Epidemiological data have demonstrated a significant association between the presence of type 2 diabetes mellitus (T2DM) and the development of colorectal cancer (CRC). Chronic hyperglycemia, insulin resistance, oxidative stress, and inflammation, the processes inherent to T2DM, also play active roles in the onset and progression of CRC. Recently, small dense low-density lipoprotein (LDL) particles, a typical characteristic of diabetic dyslipidemia, emerged as another possible underlying link between T2DM and CRC. Growing evidence suggests that antidiabetic medications may have beneficial effects in CRC prevention. According to findings from a limited number of preclinical and clinical studies, glucagon-like peptide-1 receptor agonists (GLP-1RAs) could be a promising strategy in reducing the incidence of CRC in patients with diabetes. However, available findings are inconclusive, and further studies are required. In this review, novel evidence on molecular mechanisms linking T2DM with CRC development, progression, and survival will be discussed. In addition, the potential role of GLP-1RAs therapies in CRC prevention will also be evaluated.

Keywords: glucagon-like peptide-1 receptor agonists; hyperglycemia; inflammation; insulin resistance; oxidative stress; small dense LDL.

Figure 1

The role of insulin resistance in pathogenesis of CRC.

Figure 2

The role of hyperglycemia in pathogenesis of CRC (The figure was composed using Servier Medical Art templates, licensed under a Creative Common Attribution 3.0 https://smart.servier.com (accessed on 12 November 2021)).

Figure 3

Major sources of free radicals and main antioxidants.

Figure 4

Glucagon-like peptide-1 receptor agonist (GLP-1RAs) pleiotropic effects.