Targeted proteomics of extreme vascular phenotypes in type 1 diabetes : the ESCAPER study
Ekström, Ola LU ; Kennbäck, Cecilia LU ; Lyssenko, Valeriya LU ; Löndahl, Magnus LU ; Christensson, Anders LU ; Nilsson, Peter M. LU and Gottsäter, Anders LU
(2026)
In Cardiovascular Diabetology
25(1).
- Abstract
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia and a significant risk factor burden. 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... (More)
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia and a significant risk factor burden. 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] < 0.05) after adjustment for age, sex, HbA1c, and eGFR: Caspase-3 was significantly higher in RP (Adjusted difference: + 2.12 Normalized Protein eXpression [NPX], p < 0.001). Proteins associated with platelet activation and leukocyte adhesion with increased levels in RP included Junctional Adhesion Molecule A (+ 1.40 NPX), Glycoprotein VI (GP6: + 1.29 NPX), and P-Selectin (+ 0.82 NPX) (all p < 0.001). PECAM-1 (+ 0.55 NPX) and TNFRSF14 (+ 0.43 NPX), were also elevated. RP also showed higher levels of metabolic and tissue-remodelling proteins; Transferrin Receptor (+ 0.53 NPX) and Fatty Acid Binding Protein 4 (+ 0.52 NPX), as well as higher Bleomycin Hydrolase, Trefoil Factor 3, GDF-15, U-PAR, and Cystatin B. Conversely, von Willebrand Factor (vWF) levels (− 1.35 NPX, p < 0.001) and Paraoxonase 3 (PON3) was lower in RP (− 0.34 NPX, p = 0.003). 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.
(Less)
- author
- Ekström, Ola
LU
; Kennbäck, Cecilia
LU
; Lyssenko, Valeriya
LU
; Löndahl, Magnus
LU
; Christensson, Anders
LU
; Nilsson, Peter M.
LU
and Gottsäter, Anders
LU
- author collaboration
- organization
- publishing date
- 2026-12
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Type 1 diabetes, Cardiovascular disease, Proteomics, Extreme phenotype, Vascular resilience, Biomarkers, von Willebrand factor, Endothelial function
- in
- Cardiovascular Diabetology
- volume
- 25
- issue
- 1
- article number
- 183
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:105042403764
- pmid:42323624
- ISSN
- 1475-2840
- DOI
- 10.1186/s12933-026-03261-6
- language
- English
- LU publication?
- yes
- id
- d48ffee0-9357-4da1-8921-e8775da17bd4
- date added to LUP
- 2026-07-03 09:40:32
- date last changed
- 2026-07-31 12:14:11
@article{d48ffee0-9357-4da1-8921-e8775da17bd4,
abstract = {{<p>Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia and a significant risk factor burden. 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] < 0.05) after adjustment for age, sex, HbA1c, and eGFR: Caspase-3 was significantly higher in RP (Adjusted difference: + 2.12 Normalized Protein eXpression [NPX], p < 0.001). Proteins associated with platelet activation and leukocyte adhesion with increased levels in RP included Junctional Adhesion Molecule A (+ 1.40 NPX), Glycoprotein VI (GP6: + 1.29 NPX), and P-Selectin (+ 0.82 NPX) (all p < 0.001). PECAM-1 (+ 0.55 NPX) and TNFRSF14 (+ 0.43 NPX), were also elevated. RP also showed higher levels of metabolic and tissue-remodelling proteins; Transferrin Receptor (+ 0.53 NPX) and Fatty Acid Binding Protein 4 (+ 0.52 NPX), as well as higher Bleomycin Hydrolase, Trefoil Factor 3, GDF-15, U-PAR, and Cystatin B. Conversely, von Willebrand Factor (vWF) levels (− 1.35 NPX, p < 0.001) and Paraoxonase 3 (PON3) was lower in RP (− 0.34 NPX, p = 0.003). 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.</p>}},
author = {{Ekström, Ola and Kennbäck, Cecilia and Lyssenko, Valeriya and Löndahl, Magnus and Christensson, Anders and Nilsson, Peter M. and Gottsäter, Anders}},
issn = {{1475-2840}},
keywords = {{Type 1 diabetes, Cardiovascular disease, Proteomics, Extreme phenotype, Vascular resilience, Biomarkers, von Willebrand factor, Endothelial function}},
language = {{eng}},
number = {{1}},
publisher = {{BioMed Central (BMC)}},
series = {{Cardiovascular Diabetology}},
title = {{Targeted proteomics of extreme vascular phenotypes in type 1 diabetes : the ESCAPER study}},
url = {{http://dx.doi.org/10.1186/s12933-026-03261-6}},
doi = {{10.1186/s12933-026-03261-6}},
volume = {{25}},
year = {{2026}},
}