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DOI: 10.1160/TH11-03-0179
Association of vitronectin and plasminogen activator inhibitor-1 levels with the risk of metabolic syndrome and type 2 diabetes mellitus
Results from the D.E.S.I.R. prospective cohort Financial support: This work was supported in part by ANR grants ANR-07-PHYSIO-019–01 Obepi project and by the Fondation pour la recherché Médicale DEQ20071210508 (to MCA). The D.E.S.I.R. study has been supported by INSERM contracts with CNAMTS, Lilly, Novartis Pharma and Sanofi-Aventis; by INSERM (Réseaux en Santé Publique, Interactions entre les déterminants de la santé), Cohortes Santé TGIR, the Association Diabète Risque Vasculaire, the Fédération Française de Cardiologie, La Fondation de France, ALFEDIAM, ONIVINS, Ardix Medical, Bayer Diagnostics, Becton Dickinson, Cardionics, Merck Santé, Novo Nordisk, Pierre Fabre, Roche, Topcon.Publication History
Received: 15 March 2011
Accepted after major revision: 26 May 2011
Publication Date:
24 November 2017 (online)


Summary
It was the objective of this study to investigate the relation between vitronectin and plasminogen activator inhibitor (PAI)-1 plasma levels with nine-year incidences of the metabolic syndrome (MetS) and of type 2 diabetes mellitus (T2DM). Baseline plasma concentrations of vitronectin and PAI-1 were measured in 627 healthy participants from the prospective D.E.S.I.R. cohort who subsequently developed MetS (n=487) and T2DM (n=182) over a nine-year follow-up (42 presented both) and who were matched with two healthy control subjects each by use of a nested case-control design. Parameters composing the MetS explained about 20% of plasma vitronectin levels. An increase of one standard deviation of vitronectin was associated with increased risks of both the MetS (odds ratio [OR] = 1.21 [1.07 – 1.37], p = 0.003) and T2DM (OR = 1.24 [1.01 – 1.53], p = 0.045). Corresponding ORs for PAI-1 levels were 1.46 [1.27 – 1.68] (p < 10−4) and 1.40 [1.14 – 1.72] (p = 0.0012). However, the effects of vitronectin and PAI-1 levels on outcomes were not independent. The vitronectin–MetS association was restricted to individuals with low to modest PAI-1 levels (OR = 1.33 [1.14 – 1.54], p = 0.0003) while no association was observed in individuals with high PAI-1 levels (OR = 0.87 [0.68 – 1.10], p = 0.24), the test for interaction being highly significant (p = 0.0009). In conclusion, baseline plasma vitronectin is a marker of incident MetS at nine years. Its predictive ability for MetS and T2DM should not be assessed independently of PAI-1 levels.