{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T15:30:13Z","timestamp":1789659013109,"version":"4.0.1"},"reference-count":157,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T00:00:00Z","timestamp":1789603200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the National Institute of General Medical Sciences of the National Institutes of Health","award":["R16GM165339"],"award-info":[{"award-number":["R16GM165339"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"crossref"}]},{"award":["R16GM165339"],"award-info":[{"award-number":["R16GM165339"]}],"id":[{"id":"https:\/\/ror.org\/04q48ey07","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/cells15181680","type":"journal-article","created":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T08:03:17Z","timestamp":1789632197000},"page":"1680","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-Specific Mechanisms of Perivascular Adipose Tissue (PVAT) Dysfunction in Prediabetes and Diabetes: From Metabolic Crosstalk to Vascular Outcomes"],"prefix":"10.3390","volume":"15","author":[{"given":"Khadizatul","family":"Kobra","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-4133-4829","authenticated-orcid":false,"given":"Md Arafat","family":"Hossain","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Audreen","family":"Bandegan","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Moshiur","family":"Rahman","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4060-7328","authenticated-orcid":false,"given":"Atefeh","family":"Rabiee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9803-0619","authenticated-orcid":false,"given":"Roshanak","family":"Rahimian","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,17]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/S2213-8587(25)00299-2","article-title":"11th edition of the IDF Diabetes Atlas: Global, regional, and national diabetes prevalence estimates for 2024 and projections for 2050","volume":"14","author":"Genitsaridi","year":"2026","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1038\/s41591-025-03944-9","article-title":"Prevention of type 2 diabetes through prediabetes remission without weight loss","volume":"31","author":"Sandforth","year":"2025","journal-title":"Nat. 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