The Impact of Hyperinsulinemia and Hyperglycemia on Cancer Risk and Progression in Obese Diabetics

Obesity and type 2 diabetes mellitus (T2DM) are metabolic disorders that are increasingly prevalent worldwide and frequently co-exist, forming a syndemic with cancer. Central to the pathological link between these conditions are persistent hyperinsulinemia and hyperglycemia hallmarks of insulin resistance. Chronic hyperinsulinemia stimulates mitogenic signaling pathways, reduces apoptosis, and increases bioavailability of insulin-like growth factors (IGFs), all of which contribute to tumor initiation and progression. Concurrently, hyperglycemia fosters a pro-tumorigenic environment through oxidative stress, inflammation, and enhanced glucose availability to cancer cells, which depend heavily on glycolysis. Together, these metabolic disturbances synergistically promote oncogenesis, particularly in tissues sensitive to insulin and glucose, including the breast, colon, pancreas, and liver. This review explores the mechanistic underpinnings and epidemiological evidence linking hyperinsulinemia and hyperglycemia to cancer risk and progression in obese diabetic individuals. It also highlights emerging therapeutic interventions aimed at modulating insulin and glucose levels as a strategy to mitigate cancer burden in this high-risk population. Keywords: Hyperinsulinemia, Hyperglycemia, Obesity, Type 2 Diabetes Mellitus, Cancer Risk, Tumor Progression, Insulin Resistance, IGF-1, Metabolic Reprogramming, Inflammation