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

ABSTRACT: 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: http://clinicaltrials.gov/ct2/show/NCT00017953. Unique identifier: NCT00017953.

SUBMITTER: Belalcazar LM

PROVIDER: S-EPMC3130500 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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

Belalcazar L Maria LM Ballantyne Christie M CM Lang Wei W Haffner Steven M SM Rushing Julia J Schwenke Dawn C DC Pi-Sunyer F Xavier FX Tracy Russell P RP

Arteriosclerosis, thrombosis, and vascular biology 20110421 7

<h4>Objective</h4>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 c ...[more]

PMID: 21512162

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Project description:Background Metabolic dyslipidemia (high triglyceride) and low high-density lipoprotein cholesterol (HDL-C) is highly prevalent in type 2 diabetes mellitus (T2DM). The extent to which diabetes mellitus-related abnormalities in the triglyceride-HDL-C profile associates with cardiovascular disease (CVD) risk is incompletely understood. We evaluated the associations of triglyceride and HDL-C status with CVD outcomes in individuals with T2DM. Methods and Results We analyzed data from 4199 overweight/obese adults with T2DM free of CVD with available data on triglyceride and HDL-C at baseline (2001-2004) in the Look AHEAD (Action for Health in Diabetes) study. We used Cox proportional models to estimate hazard ratios (HRs) and 95% CIs of: (1) composite CVD outcome (myocardial infarction, stroke, hospitalization for angina, and/or death from cardiovascular causes); (2) coronary artery disease events; and (3) cerebrovascular accidents (stroke). Of the 4199 participants, 62% (n=2600) were women, with a mean age of 58 years (SD, 7), and 40% (n=1659) had metabolic dyslipidemia at baseline. Over a median follow-up of 9.5 years (interquartile range, 8.7-10.3), 500 participants experienced the composite CVD outcome, 396 experienced coronary artery disease events, and 100 experienced stroke. Low HDL-C was associated with higher hazards of the composite CVD outcome (HR, 1.36; 95% CI, 1.12-1.64 [P=0.002]) and coronary artery disease events (HR, 1.46; 95% CI, 1.18-1.81 [P=0.001]) but not stroke (HR, 1.38; 95% CI, 0.90-2.11 [P=0.140]). Compared with patients with normal triglyceride and normal HDL, participants with metabolic dyslipidemia had higher risks of the composite CVD outcome (HR, 1.30; 95% CI, 1.03-1.63 [P=0.025]) and coronary artery disease events (HR, 1.48; 95% CI, 1.14-1.93 [P=0.003]) but not stroke (HR, 1.23; 95% CI, 0.74-2.05 [P=0.420]). Conclusions In a large sample of overweight/obese individuals with T2DM, metabolic dyslipidemia was associated with higher risks of CVD outcomes. Our findings highlight the necessity to account for metabolic dyslipidemia in CVD risk stratification among patients with T2DM. Registration URL: https://www.lookaheadtrial.org; Unique identifier: NCT00017953.

Dataset Information

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

Publications

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

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