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Review
. 2019 Nov 27;8(12):2075.
doi: 10.3390/jcm8122075.

Biomarkers of Vascular Injury and Type 2 Diabetes: A Prospective Study, Systematic Review and Meta-Analysis

Laura Pletsch-Borba  1   2 , Cora Watzinger  1 , Renée Turzanski Fortner  1 , Verena Katzke  1 , Lukas Schwingshackl  3   4 , Solomon A Sowah  1   2 , Anika Hüsing  1 , Theron Johnson  1 , Marie-Luise Groß  5 , Sandra González Maldonado  1 , Michael Hoffmeister  6 , Peter Bugert  7   8 , Rudolf Kaaks  1 , Mirja Grafetstätter  1   2 , Tilman Kühn  1
Affiliations
Review

Biomarkers of Vascular Injury and Type 2 Diabetes: A Prospective Study, Systematic Review and Meta-Analysis

Laura Pletsch-Borba et al. J Clin Med. .

Abstract

Data on biomarkers of vascular injury and type 2 diabetes (T2D) risk from prospective studies are lacking. We evaluated seven biomarkers of vascular injury in relation to T2D. Additionally, a meta-analysis was performed. From the EPIC-Heidelberg cohort, 2224 participants were followed-up from baseline for 16 (median) years. E-Selectin, P-Selectin, intercellular adhesion molecule 3 (ICAM3), thrombomodulin, thrombopoietin, glycoprotein IIb/IIIa and fibrinogen levels were measured in baseline blood samples. The systematic review and meta-analysis included prospective studies identified through MEDLINE and Web of Science that investigated the association between mentioned biomarkers and T2D. The study population included 55% women, median age was 50 years, and 163 developed T2D. ICAM3 was associated with lower T2D risk (fully adjusted HRhighest vs. lowest tertile 0.62 (95% CI: 0.43, 0.91)), but no other studies on ICAM3 were identified. Overall, fifteen studies were included in the systematic review and meta-analysis (6,171 cases). E-Selectin was associated with higher T2D risk HRper SD: 1.34 (95% CI: 1.16, 1.54; I2 = 63%, n = 9 studies), while thrombomodulin was associated with lower risk HRper SD: 0.82 (95% CI: 0.71, 0.95; I2 = 0%, n = 2 studies). In the EPIC-Heidelberg, ICAM3 was associated with lower T2D risk. The meta-analysis showed a consistent positive association between E-Selectin and T2D. It was also suggestive of an inverse association between thrombomodulin and T2D, although further studies are needed to corroborate this finding.

Keywords: E-Selectin; Epidemiology; ICAM3; P-Selectin; Type 2 Diabetes; thrombomodulin; vascular injury biomarkers.

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Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

Figures

Figure 1
Figure 1
Flowchart illustrating selection of studies for the systematic review and meta-analysis. The present study using EPIC–Heidelberg data is not included.
Figure 2
Figure 2
Meta-analysis on biomarkers of vascular injury and type 2 diabetes risk. Random effects meta-analysis on E-Selectin, P-Selectin, Thrombomodulin, and Fibrinogen and type 2 diabetes risk. All effect estimates and confidence intervals derived from the multivariable-adjusted models, as described in Table 4. * Data derived from transformation of quantiles analyses into “per SD”, † No log-transformation of the original circulating biomarker concentration performed, except for standardization (mean = 0, SD = 1).
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