Reduced adiposity decreases PAI-1 levels in obese diabetic patients
MedWire News: Sustained weight loss over a 1-year period significantly decreases plasminogen activator inhibitor-1 (PAI-1) levels in obese patients with Type 2 diabetes, researchers report.
The authors found that a behavioral lifestyle intervention, designed to reduce adiposity, helps to normalize PAI-1 levels in obese diabetic patients. But interestingly, their study also showed that factors known to affect adipose tissue function such as fitness, fasting glucose levels (HbA1c), and high-density lipoprotein (HDL) cholesterol levels, contribute to the change in PAI-1 levels independently of weight loss.
As reported in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, L Maria Belalcazar (University of Texas, Galveston, USA) and team performed a post hoc analysis of 1817 obese diabetic patients who participated in the Look AHEAD (Action for Health in Diabetes) trial, to explore the impact of intensive lifestyle intervention (ILI) for weight loss on PAI-1 levels.
Patients partaking in the lifestyle change were encouraged to perform 175 weekly minutes of moderate-intensity exercise, reduce their caloric and saturated fat intake, and change macronutrient composition of their diet to improve glycemic control. These individuals were compared with a group receiving usual care including diabetes support and education (DSE).
The authors found that moderate weight loss with ILI sustained over a 1-year period was sufficient to achieve significant reductions in PAI-1 levels (29% from baseline) compared with usual care (2.5% reduction).
Although reduced adiposity was a factor associated with the fall in PAI-1, improvements in fitness (19% increase on graded exercise stress test), glucose control (0.7% reduction in HbA1c), and HDL cholesterol levels (increase of 4.4 mg/dl), contributed to the lowering of PAI-1 levels independently of adiposity change.
The authors say that previous studies have suggested that oxidative stress accumulates in adipose tissue in obese individuals, leading to the increased production of proinflammatory adipokines and of PAI-1.
"The beneficial effects of fitness on PAI-1 levels in our participants may be associated with those of regular moderate physical activity on adipose tissue function, including the promotion of antioxidant mechanisms and an improvement in insulin sensitivity," they propose.
They also found no association between the reductions in PAI-1 levels and changes in fibrinogen and D-dimer, which "may reflect an improvement in adipose tissue health that could affect cardiovascular risk without changing fibrinogen or D-dimer levels," write Belalcazar and co-authors.
The team adds that "these results support expanding the role of PAI-1 to that of a marker of adipose tissue health."
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By Sally Robertson