Metabolic Factors, Adipose Tissue, and Plasminogen Activator Inhibitor-1 Levels in Type 2 Diabetes Findings From the Look AHEAD Study

Department of Medicine, University of Texas Medical Branch, Galveston, TX 77555-1060, USA.
Arteriosclerosis Thrombosis and Vascular Biology (Impact Factor: 6). 07/2011; 31(7):1689-95. DOI: 10.1161/ATVBAHA.111.224386
Source: PubMed


Plasminogen activator inhibitor-1 (PAI-1) production by adipose tissue is increased in obesity, and its circulating levels are high in type 2 diabetes. PAI-1 increases cardiovascular risk by favoring clot stability, interfering with vascular remodeling, or both. We investigated in obese diabetic persons whether an intensive lifestyle intervention for weight loss (ILI) would decrease PAI-1 levels independently of weight loss and whether PAI-1 reduction would be associated with changes in fibrinogen, an acute phase reactant, or fibrin fragment D-dimer (D-dimer), a marker of ambient coagulation balance.
We examined 1-year changes in PAI-1, D-dimer, and fibrinogen levels; adiposity; fitness; glucose; and lipid control with ILI in 1817 participants from Look AHEAD, a randomized trial investigating the effects of ILI, compared with usual care, on cardiovascular events in overweight or obese diabetic persons. Median PAI-1 levels decreased 29% with ILI and 2.5% with usual care (P < 0.0001). Improvements in fitness, glucose control, and high-density lipoprotein cholesterol were associated with decreased PAI-1, independently of weight loss (P = 0.03 for fitness, P < 0.0001 for others). Fibrinogen and D-dimer remained unchanged.
Reductions in PAI-1 levels with ILI in obese diabetic individuals may reflect an improvement in adipose tissue health that could affect cardiovascular risk without changing fibrinogen or d-dimer levels. Clinical Trial Registration- URL: Unique identifier: NCT00017953.

5 Reads
  • Source
    • "In this regard, methods for increasing adiponectin have been suggested as a promising therapy for the prevention and treatment of CAD [27]. Unlike adiponectin, PAI-1 is higher in CAD patients [28] and its reduction can decrease CVD risk because the impairment of fibrinolysis, due to high circulating PAI-1 levels, is associated with the development of AMI [29]. The inverse relation between adiponectin and PAI-1 has also been described in obese [30] and stable angina patients [31]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Purpose: The grape and wine polyphenol resveratrol exerts cardiovascular benefits but evidence from randomized human clinical trials is very limited. We investigated dose-depending effects of a resveratrol-containing grape supplement on stable patients with coronary artery disease (CAD) treated according to currently accepted guidelines for secondary prevention of cardiovascular disease. Methods: In a triple-blind, randomized, placebo-controlled, one-year follow-up, 3-arm pilot clinical trial, 75 stable-CAD patients received 350 mg/day of placebo, resveratrol-containing grape extract (grape phenolics plus 8 mg resveratrol) or conventional grape extract lacking resveratrol during 6 months, and a double dose for the following 6 months. Changes in circulating inflammatory and fibrinolytic biomarkers were analyzed. Moreover, the transcriptional profiling of inflammatory genes in peripheral blood mononuclear cells (PBMCs) was explored using microarrays and functional gene expression analysis. Results: After 1 year, in contrast to the placebo and conventional grape extract groups, the resveratrol-containing grape extract group showed an increase of the anti-inflammatory serum adiponectin (9.6 %, p = 0.01) and a decrease of the thrombogenic plasminogen activator inhibitor type 1 (PAI-1) (-18.6 %, p = 0.05). In addition, 6 key inflammation-related transcription factors were predicted to be significantly activated or inhibited, with 27 extracellular-space acting genes involved in inflammation, cell migration and T-cell interaction signals presenting downregulation (p < 0.05) in PBMCs. No adverse effects were detected in relation to the study products. Conclusions: Chronic daily consumption of a resveratrol-containing grape nutraceutical could exert cardiovascular benefits in stable-CAD patients treated according to current evidence-based standards, by increasing serum adiponectin, preventing PAI-1 increase and inhibiting atherothrombotic signals in PBMCs.
    Cardiovascular Drugs and Therapy 12/2012; 27(1). DOI:10.1007/s10557-012-6427-8 · 3.19 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: Obesity is an independent risk factor for the development of coronary heart disease and chronic heart failure. It is associated with hypertension, dyslipidemia, and insulin resistance, in addition to vascular endothelial cell dysfunction and a proinflammatory prothrombotic state. Obesity furthermore, is associated with left ventricular remodeling leading to hypertrophy and diastolic and systolic dysfunction. Intentional weight loss of as little at 5% to 10% body weight improves cardiac and vascular function, blood pressure control, lipid profile, insulin resistance, diabetes control, and prevents or delays the onset of type 2 diabetes mellitus. These reductions in cardiovascular risk factors and improvements in cardiovascular function are seen with intentional weight loss achieved by any combination of exercise, calorie-restriction, behavioral weight loss programs, pharmacologic-induced, and surgical procedures. This review focuses on the cardiovascular effects of intentional weight loss achieved through intensive lifestyle modifications.
    Current Cardiovascular Risk Reports 02/2011; 6(1). DOI:10.1007/s12170-011-0211-3

  • Current opinion in lipidology 12/2011; 22(6):503-4. DOI:10.1097/MOL.0b013e32834d1716 · 5.66 Impact Factor
Show more

Similar Publications


5 Reads
Available from