Sex-Specific Mechanisms of Perivascular Adipose Tissue (PVAT) Dysfunction in Prediabetes and Diabetes: From Metabolic Crosstalk to Vascular Outcomes

Perivascular adipose tissue (PVAT) is a metabolically active adipose depot surrounding most blood vessels and contributes to vascular homeostasis through local regulation of vascular tone, inflammation, and metabolic signaling. In prediabetes and diabetes, PVAT may shift from a predominantly vasoprotective phenotype toward a pro-inflammatory and pro-contractile state characterized by reduced release of protective mediators and increased cytokine, reactive oxygen species, and vasoconstrictor signaling. Vascular injury may, in turn, further alter the PVAT phenotype, creating bidirectional adipose-vascular crosstalk that may contribute to disease progression. Biological sex, reproductive aging, and sex-hormone signaling appear to influence PVAT morphology, cellular composition, secretory function, and vascular effects, but the strength of this evidence varies substantially across species, vascular beds, and disease models. Unlike recent broad reviews of PVAT biology, this review examines PVAT across the prediabetes-to-diabetes continuum while recognizing that direct longitudinal evidence tracking PVAT between these metabolic states remains scarce. We critically evaluate the direct, indirect, and still-limited evidence for sex-specific PVAT mechanisms and integrate findings on immune-cell activity, adipokine and redox signaling, and vascular function across prediabetes, established diabetes, and related metabolic conditions. Defining these mechanisms may support the development of appropriately tested, sex-informed strategies for preventing and treating diabetes-associated vascular complications.