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

Ligia Belalcazar, Christie M. Ballantyne, Wei Lang, Steven M. Haffner, Julia Rushing, Dawn C. Schwenke, F. Xavier Pi-Sunyer, Russell P. Tracy

Research output: Contribution to journalArticle

39 Scopus citations


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. Conclusion-: 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.

Original languageEnglish (US)
Pages (from-to)1689-1695
Number of pages7
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Issue number7
StatePublished - Jul 2011



  • adipokines
  • diabetes mellitus
  • fibrinolysis
  • fitness
  • obesity

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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