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: http://clinicaltrials.gov/ct2/show/NCT00017953. Unique identifier: NCT00017953.
RCT Entities:
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-1increases cardiovascular risk by favoring clot stability, interfering with vascular remodeling, or both. We investigated in obese diabeticpersons 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 diabeticpersons. 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: http://clinicaltrials.gov/ct2/show/NCT00017953. Unique identifier: NCT00017953.
Authors: A Pandolfi; A Giaccari; C Cilli; M M Alberta; L Morviducci; E A De Filippis; A Buongiorno; G Pellegrini; F Capani; A Consoli Journal: Acta Diabetol Date: 2001 Impact factor: 4.280
Authors: L Maria Belalcazar; Andrea M Anderson; Wei Lang; Dawn C Schwenke; Steven M Haffner; Hiroshi Yatsuya; Julia Rushing; Mara Z Vitolins; Rebecca Reeves; F Xavier Pi-Sunyer; Russell P Tracy; Christie M Ballantyne Journal: J Acad Nutr Diet Date: 2014-08-15 Impact factor: 4.910
Authors: Brian R Kupchak; Amy L McKenzie; Hui-Ying Luk; Cathy Saenz; Laura J Kunces; Lindsay A Ellis; Jakob L Vingren; Elaine C Lee; Kevin D Ballard; Evan C Johnson; Stavros A Kavouras; Matthew S Ganio; Jonathon E Wingo; Keith H Williamson; Lawrence E Armstrong Journal: Eur J Appl Physiol Date: 2015-01-22 Impact factor: 3.078
Authors: João Tomé-Carneiro; Manuel Gonzálvez; Mar Larrosa; María J Yáñez-Gascón; Francisco J García-Almagro; José A Ruiz-Ros; Francisco A Tomás-Barberán; María T García-Conesa; Juan Carlos Espín Journal: Cardiovasc Drugs Ther Date: 2013-02 Impact factor: 3.727