Intersections and Clinical Translations of Diabetes Mellitus with Cancer Promotion, Progression and Prognosis

ABSTRACT

The association between cancer and dysglycemia has been well documented. It is underappreciated, however, that sustained dysglycemia could potentially be a catalyst toward a pro-cancer physiologic milieu and/or increase the burden of cancer. Hyperglycemia, hyperinsulinemia and energy metabolism at large impact a cascade of growth pathways, epi/genetic modifications, and mitochondrial changes that could feasibly link to tumor processes. Oxidative stress is a recurring motif in cell dysfunction: in diabetes, oxidative stress and reactive oxygen species (ROS) feature prominently in the damage and demise of pancreatic beta cells, as well as cell damage contributing to diabetes-related complications. Oxidative stress may be one intersection at which metabolic and oncogenic processes cross paths with deleterious results in the development of precancer, cancer, and cancer progression. This would augur for tight glucose control. Regrettably, some medical societies have recently relaxed hemoglobin A1c targets. A framework for the hyperglycemic state is presented that helps account and translate the full scope of effects of dysglycemia to ultimately improve clinical best practices.

KEYWORDS:

• Type 2 diabetes
• cancer
• hyperglycemia
• egregious eleven
• beta-cell–centric model
• common origins of diabetes and its complications construct

Author contributions

S.S.S. conceived the model described. S.F.A.G. and M.E.H. critically reviewed, provided incisive input, edited, and approved, the final version of the manuscript. M.E.H. also contributed moderately to synthesis of the larger construct, and substantially to the writing of the manuscript. S.S.S. is the guarantor of this work and as such, takes responsibility for the genesis and general framing of the models described.

Declaration of interest

S.S.S. is a speaker and advisor to Merck, Takeda, Johnson and Johnson, Boehringer Ingelheim/Eli Lilly and Company, and, a speaker for GlaxoSmithKline. S.F.A.G. and M.E.H. have no conflicts. No potential conflicts of interest relevant to this article were reported. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

S.S.S. and S.G., NIH grant R01 DK085212; S.G., Daniel B. Burke Endowed Chair for Diabetes Research. No funding was received by any of authors for this manuscript.