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

Laura Pletsch-Borba,Marie-Luise Groß,Rudolf Kaaks,Renée Turzanski Fortner,Tilman Kühn,Cora Watzinger,Lukas Schwingshackl,Sandra González Maldonado,Solomon A Sowah,Anika Hüsing,Verena Katzke,Mirja Grafetstätter,Michael Hoffmeister,Theron Johnson,Peter Bugert

doi:10.3390/jcm8122075

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.

Highlights

An estimated 8% of the world’s adult population live with type 2 diabetes mellitus (T2D), with the global prevalence predicted to increase in the coming years [1]
E-Selectin was associated with higher T2D risk HRper SD: 1.34, while thrombomodulin was associated with lower risk HRper SD: 0.82
E-Selectin was associated with increased T2D risk among study participants in the second, but not the third tertile of E-Selectin concentrations, with hazard ratios (HRs) of 2.13 (95%confidence intervals (CI) 1.38, 3.29) and 1.44 (0.93, 2.22), respectively

Summary

Introduction

An estimated 8% of the world’s adult population live with type 2 diabetes mellitus (T2D), with the global prevalence predicted to increase in the coming years [1]. According to the Global Burden of Disease study, diabetes was the 12th leading cause of death, and total deaths from T2D increased from 2007 to 2017 by nearly 50% [2]. Microvascular dysfunction has been suggested to be one mechanistic pathway linking obesity to increased insulin resistance and, subsequently, T2D [3,4,5,6]. Endothelial dysfunction can diminish insulin’s delivery to the interstitium and could thereby limit insulin action [7]. In this context, vascular injury could be a risk factor for T2D

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Discussion

Conclusion