Integrating the metabolic and molecular circuits in diabetes, obesity and cancer: a comprehensive review

The progressive globalization of sedentary lifestyles and diets rich in lipids and processed foods has caused two major public health hazards-diabetes and obesity. The strong interlink between obesity and type 2 diabetes mellitus and their combined burden encompass them into a single term 'Diabesity'. They have also been tagged as the drivers for the onset of cancer. The clinical association between diabetes, obesity, and several types of human cancer demands an assessment of vital junctions correlating the three. This review focuses on revisiting the molecular axis linking diabetes and obesity to cancer through pathways that get imbalanced owing to metabolic upheaval. We also attempt to describe the functional disruptions of DNA repair mechanisms due to overwhelming oxidative DNA damage caused by diabesity. Genomic instability, a known cancer hallmark results when DNA repair does not work optimally, and as will be inferred from this review the obtruded metabolic homeostasis in diabetes and obesity creates a favorable microenvironment supporting metabolic reprogramming and enabling malignancies. Altered molecular and hormonal landscapes in these two morbidities provide a novel connection between metabolomics and oncogenesis. Understanding various aspects of the tumorigenic process in diabesity-induced cancers might help in the discovery of new biomarkers and prompt targeted therapeutic interventions.