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Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort



Tenascin-C (TN-C) is an extracellular matrix glycoprotein highly expressed in inflammatory and cardiovascular (CV) diseases. Serum TN-C has not yet been specifically studied in individuals with type 2 diabetes, a condition associated with chronic low-grade inflammation and increased CV disease risk. In this study, we hypothesised that elevated serum TN-C at enrolment in participants with type 2 diabetes would be associated with increased risk of death and major adverse CV events (MACE) during follow-up.


We used a prospective, monocentric cohort of consecutive type 2 diabetes participants (the SURDIAGENE [SUivi Rénal, DIAbète de type 2 et GENEtique] cohort) with all-cause death as a primary endpoint and MACE (CV death, non-fatal myocardial infarction or stroke) as a secondary endpoint. We used a proportional hazard model after adjustment for traditional risk factors and the relative integrated discrimination improvement (rIDI) to assess the incremental predictive value of TN-C for these risk factors.


We monitored 1321 individuals (58% men, mean age 64 ± 11 years) for a median of 89 months. During follow-up, 442 individuals died and 497 had MACE. Multivariate Cox analysis showed that serum TN-C concentrations were associated with an increased risk of death (HR per 1 SD: 1.27 [95% CI 1.17, 1.38]; p < 0.0001) and MACE (HR per 1 SD: 1.23 [95% CI 1.13, 1.34]; p < 0.0001). Using TN-C concentrations on top of traditional risk factors, prediction of the risk of all-cause death (rIDI: 8.2%; p = 0.0006) and MACE (rIDI: 6.7%; p = 0.0014) improved significantly, but modestly.


In individuals with type 2 diabetes, increased serum TN-C concentrations were independently associated with death and MACE. Therefore, including TN-C as a prognostic biomarker could improve risk stratification in these individuals.

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Fig. 1

Data availability

The datasets generated during and/or analysed during the current study are available from the corresponding author on reasonable request.



Angiopoietin-like 2


Coronary artery disease


Chronic kidney disease


C-reactive protein




Extracellular matrix


Left ventricular


Major adverse cardiovascular events


Myocardial infarction


N-terminal pro-B-type natriuretic peptide


Relative integrated discrimination improvement


Systolic BP


SUivi Rénal, DIAbète de type 2 et GENEtique




TNF receptor 1


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All participants included and followed in the cohort study are warmly thanked for their kind participation in this research. Their general practitioners (GPs) are acknowledged for their help in collecting clinical information. E. Migault (Inserm CIC1402, Poitiers, France) and the staff of the Diabetes Department at Poitiers hospital are acknowledged for their help with data collection and monitoring. We thank A. Pavy, M.-C. Pasquier (Information Technology Department, CHU de Poitiers, Poitiers, France) and A. Neveu and J. Guignet (Medical Information Department, CHU de Poitiers, Poitiers, France). J. Arsham (CHU de Poitiers, Poitiers, France) carried out English language editing of the manuscript. A list of centres and staff involved in SURDIAGENE recruitment and adjudication is given as electronic supplementary material (ESM). Some of the data were presented as an abstract at the 30th European Meeting of the French Society of Cardiology (Journées européennes de la Société française de cardiologie, JESFC) meeting in 2020.


The SURDIAGENE cohort was supported by grants from the French Ministry of Health (PHRC-Poitiers 2004; PHRC-IR 2008), the Association Française des Diabétiques (Research Grant 2003) and the Groupement pour l’Etude des Maladies Métaboliques et Systémiques (GEMMS Poitiers, France). TN-C measurements were supported by a research grant from ELSAN, France (2016).

Author information

BG conceived the work, obtained the grant for the measurement of TN-C and wrote the manuscript. NT-T conceived the work and wrote the manuscript. ET was involved with data analysis and interpretation and edited the manuscript. EG performed statistical analysis, contributed to drafting and revision of the manuscript. PS was involved in the study design, collected data, adjudicated clinical endpoints, and revised the manuscript. SB performed the assay for TN-C and contributed to the drafting of the manuscript. SH conceived and constituted the SURDIAGENE cohort, collected data, was involved with data analysis and interpretation, and revised the manuscript. VR, DM, VJ, YP and PG adjudicated clinical endpoints, interpreted data and contributed to the drafting and revision of the manuscript. XP collected data and contributed to the drafting and revision of the manuscript. P-JS collected data, was involved with data analysis and interpretation and wrote the manuscript. All authors critically revised the article. BG and PJS are the guarantors of this work and take full responsibility for the contents of the article.

Correspondence to Barnabas Gellen.

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Gellen, B., Thorin-Trescases, N., Thorin, E. et al. Serum tenascin-C is independently associated with increased major adverse cardiovascular events and death in individuals with type 2 diabetes: a French prospective cohort. Diabetologia (2020). https://doi.org/10.1007/s00125-020-05108-5

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  • Cardiovascular risk
  • MACE
  • Tenascin-C
  • Type 2 diabetes