Pharmacol Res. 2026 Aug 15:108388. doi: 10.1016/j.phrs.2026.108388. Online ahead of print.
ABSTRACT
Diabetic vascular complications are a major determinant of poor prognosis in diabetic patients, with their development closely linked to persistent low-grade inflammation. Macrophages, as key regulatory cells in the immune system, undergo significant metabolic reprogramming in the diabetic hyperglycemic microenvironment. This reprogramming involves a coordinated remodeling of key metabolic pathways, including carbohydrate metabolism, lipid metabolism, and amino acid metabolism. This review systematically discusses the classical theories of macrophage polarization and provides an in-depth analysis of how key molecules drive the M1/M2 imbalance. Additionally, it explores the intricate regulatory interactions between the three major metabolic pathways. The metabolic reprogramming-polarization axis is further examined in the context of four typical diabetic vascular complications-diabetic atherosclerosis, diabetic kidney disease, diabetic retinopathy, and diabetic cardiomyopathy-highlighting their specific pathological roles. This work aims to elucidate the theoretical value of this regulatory axis as a central mechanism in diabetic vascular complications and explores its clinical translational potential as a precise therapeutic target. It provides a systematic theoretical foundation and proposes new directions for future research.
PMID:42603577 | DOI:10.1016/j.phrs.2026.108388