Abstract
Objective. Increased coagulation activation may contribute to the high incidence of cardiovascular complications observed in obese and type 2 diabetes (T2D) subjects. Although tissue factor (TF), the primary initiator of coagulation is increased in obesity, its expression in adipose tissues and its association with metabolic parameters are unclear. We sought to compare TF expression in plasma and adipose tissues of obese subjects with and without T2D, its correlation with metabolic parameters, and regulation in response to antidiabetic drugs. Methods Subjects were recruited from diabetes clinics and adipose tissue was obtained by needle biopsy of lower subcutaneous abdominal depot. For the intervention study, subjects were randomized into treatment groups with rosiglitazone or metformin for 4 months. Results. Plasma TF antigen, activity, and adipose TF mRNA were greater in obese T2D subjects compared with obese nondiabetics. Plasma TF activity correlated with fasting insulin, glucose, and free fatty acids, (FFAs), and adipose TF mRNA correlated with plasma FFA. Plasma TF activity was reduced by metformin and increased with rosiglitazone treatment. Conclusions. Specific diabetes-related metabolic parameters, but not obesity per se, are correlated with TF expression. Regulation of TF activity by different classes of antidiabetic drugs may relate to protective or adverse cardiovascular outcomes.
Highlights
Obesity is a major risk factor for the development of type 2 diabetes (T2D), and clinical studies have established an increased incidence of thrombosis and cardiovascular disease as a primary cause of mortality in diabetic patients [1, 2]
Whereas plasma tissue factor (TF) activity and antigen levels have been shown to be increased in obese subjects as well as in patients with T2D, whether its expression is higher in obese diabetics compared with obese nondiabetics is unclear
We examined TF expression in plasma and adipose tissues of obese subjects with and without diabetes, how its expression correlates with a number of metabolic parameters, and how its activity is regulated in response to the antidiabetic drugs, metformin, and rosiglitazone
Summary
Increased coagulation activation may contribute to the high incidence of cardiovascular complications observed in obese and type 2 diabetes (T2D) subjects. Tissue factor (TF), the primary initiator of coagulation is increased in obesity, its expression in adipose tissues and its association with metabolic parameters are unclear. We sought to compare TF expression in plasma and adipose tissues of obese subjects with and without T2D, its correlation with metabolic parameters, and regulation in response to antidiabetic drugs
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