Metabolic factors, adipose tissue, and plasminogen activator inhibitor-1 levels in type 2 diabetes: findings from the look AHEAD study

Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1689-95. doi: 10.1161/ATVBAHA.111.224386. Epub 2011 Apr 21.


Objective: 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.

Methods and results: 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.

Conclusions: 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.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / metabolism*
  • Adipose Tissue / physiopathology
  • Adiposity
  • Biomarkers / blood
  • Blood Glucose / metabolism
  • Cholesterol, HDL / blood
  • Diabetes Mellitus, Type 2 / blood*
  • Diabetes Mellitus, Type 2 / physiopathology
  • Diet
  • Exercise
  • Female
  • Fibrin Fibrinogen Degradation Products / metabolism
  • Fibrinogen / metabolism
  • Humans
  • Male
  • Middle Aged
  • Obesity / blood
  • Obesity / physiopathology
  • Obesity / therapy*
  • Physical Fitness
  • Plasminogen Activator Inhibitor 1 / blood*
  • Regression Analysis
  • Risk Reduction Behavior*
  • Time Factors
  • Treatment Outcome
  • United States
  • Weight Loss


  • Biomarkers
  • Blood Glucose
  • Cholesterol, HDL
  • Fibrin Fibrinogen Degradation Products
  • Plasminogen Activator Inhibitor 1
  • SERPINE1 protein, human
  • fibrin fragment D
  • Fibrinogen

Associated data