Macrophage polarization in diabetic vascular complications: mechanistic insights and therapeutic targets.

Abstract

Diabetes mellitus, particularly type 2 diabetes mellitus, is a widespread chronic metabolic disorder characterized by persistent hyperglycemia and low-grade chronic inflammation. This sustained inflammatory state is a major driver of both macrovascular and microvascular complications. Among immune cells, macrophages play a central role as effectors and regulators of chronic inflammation. In the diabetic milieu, they respond to diverse microenvironmental cues and polarize into distinct functional phenotypes, thereby contributing to both the progression and potential resolution of diabetes-associated vascular damage. This review examines the mechanisms of macrophage polarization in diabetic vascular complications, elucidates key signaling pathways and their interactions with metabolic dysfunction, and summarizes current regulatory strategies and emerging therapeutic targets. Particular emphasis is placed on recent pharmacological approaches that modulate macrophage polarization, highlighting their potential as novel strategies to delay or prevent the onset and progression of vascular complications in diabetes.