OBJECTIVE: To examine the relationship of obesity, body fat distribution, and fasting plasma insulin concentrations with the plasma levels of both pro-thrombotic and anti-thrombotic factors in premenopausal women. SUBJECTS: 32 obese women with BMI b 28 and 33 age-matched non-obese women with BMI`25. MEASUREMENTS: (i) plasma concentrations of plasminogen activator inhibitor-1 antigen (PAI-1 Ag), plasminogen activator inhibitor-1 activity (PAI-1 activity), ®brinogen, von Willebrand factor antigen (vWF Ag), von Willebrand factor activity (vWF activity), and factor VII activity as pro-thrombotic factors; (ii) plasma concentrations of tissue plasminogen activator antigen (t-PA Ag), protein C, and antithrombin III as anti-thrombotic factors; (iii) fasting plasma insulin and glucose concentrations, and the lipid pattern (triglycerides, total and HDL-cholesterol) as metabolic parameters. The body fat distribution was evaluated by measuring the waist circumference and the waist-to-hip ratio (WHR). RESULTS: Obese subjects had higher plasma concentrations of all pro-thrombotic factors as compared to non-obese controls (PAI-1 Ag, P`0.001; PAI-1 activity, P`0.05; ®brinogen, P`0.001; vWF Ag, P`0.001; vWF activity, P`0.05; factor VII, P`0.05). The plasma concentrations of PAI-1 Ag and vWF Ag were directly correlated with the waist circumference independently of other metabolic and non-metabolic variables (P`0.05). Obese women were also characterized by higher plasma concentrations of anti-thrombotic factors such as t-PA Ag and protein C as compared to non-obese controls (P`0.001 and P`0.001, respectively), although these factors were not independently correlated with the waist circumference or the WHR. CONCLUSION: Plasma concentrations of the pro-thrombotic factors are increased in obese women as compared to non-obese controls, and plasma levels of PAI-1 Ag and vWF Ag correlate with central fat accumulation speci®cally. Plasma concentrations of anti-thrombotic factors (namely protein C and t-PA Ag) are also raised in obese women, but they are not correlated with parameters of body fat distribution. The increase in protein C levels may represent a protective response partly counteracting the increase in pro-thrombotic factors in these individuals.

No abstract

PANNACCIULLI, NICOLA, VITO DE MITRIO, RENATO MARINO, RICCARDO GIORGINO, AND GIOVANNI DE PERGOLA. Effect of glucose tolerance status on PAI-1 plasma levels in overweight and obese subjects. Obes Res. 2002;10:717-725. 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) Ն25 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 HOMA IR 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.

No abstract