Overlapping roles of dysregulated glycolysis in the pathophysiology of diabetes and cancer

Abstract

Emerging evidence highlights a strong association between type 2 diabetes (T2D) and increased cancer risk, with partially overlapping metabolic disruptions potentially driving both diseases. Chronic hyperglycemia, a hallmark of T2D, disrupts glycolytic flux and contributes to the accumulation of toxic intermediates, driving cellular damage and diabetic complications. Specifically, dysregulation of glycolytic enzymes diverts metabolites into harmful pathways, promoting oxidative and glycative stress across multiple cell types. Similar metabolic disturbances support cancer development and progression by fueling rapid tumor cell proliferation. This review explores the role of abnormal glycolysis as a potential mechanistic link between T2D and cancer, detailing shared enzymatic alterations and metabolic pathway shifts. Additionally, it discusses pharmacological therapeutic strategies targeting glycolysis-related abnormalities common to both diseases, emphasizing the need for balanced metabolic modulation.