The increase in plasma PAI-1 associated with insulin resistance may be mediated by the presence of hepatic steatosis.
OBJECTIVE
Recent evidence suggests that plasminogen-activator inhibitor-1 (PAI-1) is abundantly produced by the fatty liver, but it is unclear whether hepatic steatosis (HS) can mediate the increase in plasma PAI-1 induced by insulin resistance/compensatory hyperinsulinemia (IR/CH).


RESULTS
To address this issue, we cross-sectionally evaluated IR/CH as area under the curve of plasma insulin (AUC-PI) concentrations during OGTT, metabolic profile, and ultrasound degree of HS in 235 healthy volunteers (132M, age: 60+/-7 years) with normal transaminase concentrations. Circulating PAI-1 was increased in subjects with classical features of IR/CH (overweight, high fasting and post-OGTT insulin and glucose, high triglycerides (TG), and low HDL-cholesterol), and significantly correlated to prevalence and degree of HS, but not to alcohol intake. In a multivariate model, AUC-PI, TG and degree of HS were independent predictors of plasma PAI-1 (R(2)=0.32). However, AUC-PI was significantly correlated to PAI-1 only in subjects with HS, suggesting an interaction between AUC-PI and HS. In addition, in the presence of HS and IR/CH, PAI-1 concentrations were increased to a similar extent both in heavy and moderate drinkers, suggesting that metabolic and alcoholic steatosis have a similar effect on the relationship between IR/CH and PAI-1.


CONCLUSIONS
These results support the hypothesis that HS has a major impact on the relationship between IR/CH and plasma PAI-1 concentrations, and this effect seems to be unaffected by the etiology of the HS.
Ardigò
Diego
D
Department of Internal Medicine and Biomedical Sciences, Parma University, Via Gramsci 14, Parma, PR, Italy.
Franzini
Laura
L
Valtueña
Silvia
S
Numeroso
Filippo
F
Piatti
Pier Marco
PM
Monti
Lucilla
L
Reaven
Gerald M
GM
Zavaroni
Ivana
I
D003430:Cross-Sectional Studies; D005234:Fatty Liver / Q000097:blood / Q000378:metabolism*; D005260:Female; D006801:Humans; D007333:Insulin Resistance; D008297:Male; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood*
D017395:Plasminogen Activator Inhibitor 1