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We used a targeted proteomic approach (Olink Cardiovascular panel III, targeting 92 proteins) to characterize the proteomic profile of cardiovascular resilience in T1D by comparing 92 patients with long-standing T1D (age 59.8 [53.2, 69.1], duration 40.0 [35.0, 45.2] years) free from macrovascular complications or nephropathy against a reference group of 57 T1D patients with accelerated vascular pathology (age 42.0 [32.0, 56.0], duration 22.0 [18.0, 27.0] years), proliferative retinopathy and\/or nephropathy in relation to diabetes duration, termed Rapid Progressors (RP). Twenty proteins differed significantly between RP and Escapers (False Discovery Rate [FDR]\u2009&lt;\u20090.05) after adjustment for age, sex, HbA1c, and eGFR: Caspase-3 was significantly higher in RP (Adjusted difference: +\u00a02.12 Normalized Protein eXpression [NPX],\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). Proteins associated with platelet activation and leukocyte adhesion with increased levels in RP included Junctional Adhesion Molecule A (+\u20091.40 NPX), Glycoprotein VI (GP6: + 1.29 NPX), and P-Selectin (+\u20090.82 NPX) (all\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001). PECAM-1 (+\u20090.55 NPX) and TNFRSF14 (+\u20090.43 NPX), were also elevated. RP also showed higher levels of metabolic and tissue-remodelling proteins; Transferrin Receptor (+\u20090.53 NPX) and Fatty Acid Binding Protein 4 (+\u20090.52 NPX), as well as higher Bleomycin Hydrolase, Trefoil Factor 3, GDF-15, U-PAR, and Cystatin B. Conversely, von Willebrand Factor (vWF) levels (\u2212\u00a01.35 NPX,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009&lt;\u20090.001) and Paraoxonase 3 (PON3) was lower in RP (\u2212\u00a00.34 NPX,\n                    <jats:italic>p<\/jats:italic>\n                    \u2009=\u20090.003). In conclusion, escaping complications in long-term T1D appears to be associated with active molecular mechanisms. Progression is marked by apoptosis (Caspase-3), fibrosis (CHI3L1) and platelet activation (GP6), whereas resilience is associated with a distinct signature involving higher vWF and PON3. These findings highlight a profound biological divergence between extreme T1D phenotypes and provide a foundation for further research into vascular resilience.\n                  <\/jats:p>","DOI":"10.1186\/s12933-026-03261-6","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T09:14:17Z","timestamp":1781946857000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Targeted proteomics of extreme vascular phenotypes in type 1 diabetes: the ESCAPER study"],"prefix":"10.1186","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4857-0892","authenticated-orcid":false,"given":"Ola","family":"Ekstr\u00f6m","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cecilia","family":"Kennb\u00e4ck","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeriya","family":"Lyssenko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Magnus","family":"L\u00f6ndahl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Christensson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter M.","family":"Nilsson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anders","family":"Gotts\u00e4ter","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the ESCAPER Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"issue":"15","key":"3261_CR1","doi-asserted-by":"publisher","first-page":"1407","DOI":"10.1056\/NEJMoa1608664","volume":"376","author":"A Rawshani","year":"2017","unstructured":"Rawshani A, Rawshani A, Franz\u00e9n S, Eliasson B, Svensson AM, Miftaraj M, et al. 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