Increased PAI-1 and tPA Antigen Levels Are Reduced with Metformin Therapy in HIV-Infected Patients with Fat Redistribution and Insulin Resistance

• DOI: 10.1210/jcem.86.2.7410
• Publication Date: 2014-01-08T17:06:55Z
• Authors: C. Hadigan; J. B. Meigs; J. Rabe; R. B. D’Agostino; P. W. F. Wilson; I. Lipinska; G. H. Tofler; S. Grinspoon
• Keywords: Hyperinsulinemia

Cardiovascular disease (CVD) risk associated with fat redistribution seen among HIV-infected individuals remains unknown, but may be increased due to hyperlipidemia, hyperinsulinemia, visceral adiposity, and a prothrombotic state these metabolic abnormalities. In this study we characterized plasminogen activator inhibitor-1 (PAI-1) tissue-type (tPA) antigen levels, markers of fibrinolysis CVD risk, in HIV lipodystrophic patients compared controls. Furthermore, investigated the effect treatment metformin on PAI-1 tPA levels HIV-associated redistribution. Eighty-six (age 43 ± 1 yr, BMI 26.1 0.5 kg/m2) were 258 age- BMI-matched subjects from Framingham Offspring study. addition, 25 fasting insulin> 15 μU/mL [104 pmol/L] or impaired glucose tolerance, without diabetes mellitus enrolled placebo-controlled 500 mg twice daily. significantly related control (46.1 4 vs 18.9 0.9μ g/L PAI-1, 16.6 0.8 vs. 8.0 0.3 μg/L tPA, P = 0.0001). Among infection, multivariate regression analysis including age, sex, waist-to-hip ratio, BMI, smoking status, protease inhibitor use insulin area under curve (AUC), found gender AUC significant predictors antigen. Twelve weeks resulted decreased (−1.9 1.4 +1.4 1.0 placebo-treated group 0.02). Similarly, improvement (−8.7 2.3 +1.7 2.9 μg/L, 0.03). Change correlated change (r 0.43, antigen, are association hyperinsulinemia Metformin reduces concentrations ultimately improve risk.