Effect of glucose tolerance status on PAI-1 plasma levels in overweight and obese subjects

Objective: The aim of our study was to examine whether plasminogen activator inhibitor-1 (PAI-1) plasma levels varied as a function of differences in glucose tolerance status independently of body fatness, body-fat distribution, and insulin sensitivity. Research Methods and Procedures: Plasma PAI-1 antigen levels, along with insulin resistance [measured by homeostatic model assessment (HOMA(IR))], central fat accumulation, body composition, blood pressure, and fasting concentrations of glucose, insulin, and lipids, were measured in 229 overweight and obese [body mass index (BMI) greater than or equal to25 kg/m(2)) subjects with normal glucose tolerance (NGT) and in 44 age- and BMI-matched subjects with impaired glucose tolerance (IGT). Results: Plasma PAI-1 antigen levels were significantly higher in IGT than in NGT subjects. Log PAI-1 was positively correlated with BMI, HOMA(IR), and log insulin, and inversely associated with high-density lipoprotein-cholesterol both in IGT and in NGT individuals. On the other hand, log PAI-1 was positively correlated with waist circumference, fat mass (FM), fat-free mass, systolic and diastolic blood pressure, and log triglycerides only in the NGT group. After multivariate analyses, the strongest determinants of PAI-1 levels were BMI, FM, waist circumference, and high-density lipoprotein cholesterol in the NGT group and only HOMAIR in the IGT cohort. Discussion: This study demonstrates that PAI-1 concentrations are higher in IGT than in NGT subjects. Furthermore, we suggest that the influences of total adiposity, central fat, and insulin resistance, main determinants of PAI-1 concentrations, are different according to the degree of glucose tolerance.