The Role of Chronic Inflammation in the Obesity-Diabetes-Cancer Axis

The global rise in obesity and type 2 diabetes mellitus (T2DM) has triggered increased scientific attention toward their shared pathophysiological mechanisms and their connection with cancer. A growing body of evidence highlights chronic low-grade systemic inflammation as a central link in the obesity-diabetes-cancer axis. In obesity, hypertrophic adipocytes and immune cell infiltration contribute to the release of pro-inflammatory cytokines such as TNF-α, IL-6, and MCP-1, which not only perpetuate insulin resistance but also create a pro-tumorigenic microenvironment. In parallel, hyperinsulinemia and increased levels of insulin-like growth factor-1 (IGF-1) promote cellular proliferation and inhibit apoptosis, providing fertile ground for malignant transformation. This review explores the molecular and cellular mechanisms by which chronic inflammation serves as a bridge between obesity, diabetes, and cancer. It discusses the role of adipose tissue dysfunction, inflammatory signaling pathways, and metabolic reprogramming in cancer development and progression. Furthermore, it examines potential therapeutic interventions targeting inflammation to disrupt this triad and mitigate cancer risk in obese and diabetic individuals. Understanding the inflammatory underpinnings of this disease continuum offers valuable insights for the development of novel preventive and therapeutic strategies in the era of precision medicine. Keywords: Chronic inflammation, Obesity, Type 2 diabetes, Cancer, Insulin resistance