title: 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.
abstract: 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.
authors.affiliation: U626, Inserm, Marseille, France.
authors.forename: Marie-Christine
authors.initials: MC
authors.lastname: Alessi
authors.forename: Viviane
authors.initials: V
authors.lastname: Nicaud
authors.forename: Ilse
authors.initials: I
authors.lastname: Scroyen
authors.forename: Celine
authors.initials: C
authors.lastname: Lange
authors.forename: Noemie
authors.initials: N
authors.lastname: Saut
authors.forename: Frederic
authors.initials: F
authors.lastname: Fumeron
authors.forename: Michel
authors.initials: M
authors.lastname: Marre
authors.forename: Olivier
authors.initials: O
authors.lastname: Lantieri
authors.forename: Benedicte
authors.initials: B
authors.lastname: Fontaine-Bisson
authors.forename: Iréne
authors.initials: I
authors.lastname: Juhan-Vague
authors.forename: Beverley
authors.initials: B
authors.lastname: Balkau
authors.forename: David-Alexandre
authors.initials: DA
authors.lastname: Tregouet
authors.forename: Pierre-Emmanuel
authors.initials: PE
authors.lastname: Morange
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D015331:Cohort Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000175:diagnosis* / Q000235:genetics; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012306:Risk; D013997:Time Factors; D019096:Vitronectin / Q000096:biosynthesis / Q000097:blood* / Q000235:genetics
chemical_list: D015415:Biomarkers; D017395:Plasminogen Activator Inhibitor 1; C051321:SERPINE1 protein, human; D019096:Vitronectin