The relationship among TAFI, t-PA, PAI-1 and F1 + 2 in type 2 diabetic patients with normoalbuminuria and microalbuminuria

Abstract

Disturbances of coagulation and fibrinolysis in type 2 diabetes mellitus (DM2) contribute to increased rates of macrovascular complications such as myocardial infarction and ischemic stroke. The aim of the study was to investigate the relationship among plasminogen activator inhibitor 1 (PAI-1), thrombin-activable fibrinolysis inhibitor (TAFI), tissue plasminogen activator (t-PA), prothrombin fragments 1+2 (F1+2), glycemic control, hypertension, sex and body mass index (BMI) in DM2 patients with normoalbuminuria and microalbuminuria. Forty-two normoalbuminuric (NAU), 42 microalbuminuric (MAU) patients with DM2 and 42 blood donors as control group were enrolled. TAFI, PAI-1, t-PA and F1+2 were assessed by enzyme-linked immunosorbent assay (ELISA) in all patients. TAFI was significantly increased in the MAU group, PAI-1 and F1+2 were increased in both groups and t-PA was not elevated in either group compared to controls. We found positive correlations in the NAU: TAFI and fibrinogen (r=0.65, P=0.02), PAI-1 and triglycerides (r=0.67, P=0.01), in the MAU: TAFI and F1+2 (r=0.48, P=0.02), TAFI and systolic blood pressure (r=0.53, P=0.01), PAI-1 and BMI (r=0.43, P<0.05). We found decreased fibrinolysis in DM2 patients presented with increased PAI-1 in both NAU and MAU. Hypofibrinolysis in MAU is further accented by the elevation of TAFI. TAFI-mediated inhibition of fibrinolysis in DM2 is regulated independently from PAI-1. Patient[Combining Acute Accent]s sex does not affect diabetes-related changes in hemostasis and fibrinolysis.

Type 2 Diabetes and Fibrinolysis

“…While PAI-1 is up-regulated mainly in obesity and in endothelial dysfunction, TAFI is activated in conditions of enhanced coagulation activation, which was also proved by positive correlation between TAFI and F1+2 in our MAU group as well as TAFI and fibrinogen in the NAU group. TAFI may be up-regulated by arterial hypertension, which is supported by the significantly positive correlation found between TAFI and systolic blood pressure in our MAU subjects, while dyslipidemia defined by elevated total cholesterol seems to down-regulate TAFI, which is supported by significant inverse correlation between TAFI and total cholesterol in our MAU subjects (Chudý et al, 2011). This finding is in agreement with previous study in subjects with essential hypertension where diastolic blood pressure significantly correlated with TAFI concentrations in untreated subjects, and in betablocker-treated subjects (Malyszko & Tymcio, 2008).…”

“…We suggest decreased fibrinolysis in DM2 subjects presenting with increased levels of PAI-1 in both normoalbuminuric (NAU) and microalbuminuric (MAU) diabetics. We found a positive correlation between PAI-1 levels and BMI in the MAU group and between PAI-1 and triglycerids in our NAU subjects, which proves that obesity, dyslipidemia and hypofibrinolysis are closely linked together (Chudý et al, 2011;Soares et al, 2007;Umpaichitra et al, 2005;Sobel et al, 2005).…”

“…Yener et al observed in normotensive DM2 subjects without diabetes-related complications that PAI-1 level was significantly elevated, but level of TAFI antigen did not differ from healthy controls (Yener et al, 2009). Our results in DM2 subjects (Chudý et al, 2011) showed that TAFI was significantly increased only in the MAU group compared to the controls (table 4). Neither the difference in TAFI levels between NAU and controls, nor the difference between diabetic subgroups MAU and NAU were statistically significant.…”

“…Neither the difference in TAFI levels between NAU and controls, nor the difference between diabetic subgroups MAU and NAU were statistically significant. These results indicate that the disease progression in DM2 subjects leads to more profound TAFI mediated inhibition of fibrinolysis (Chudý et al, 2011). Table 4.…”

A new fructose-free, resistant-starch type IV-enriched enteral formula improves glycaemic control and cardiovascular risk biomarkers when administered for six weeks to elderly diabetic patients

“…On the other hand, inhibition of fibrinolysis, which is attributable to elevated concentrations of the acute-phase response protein PAI-1, is associated with insulin resistance and type 2 diabetes, and predicts myocardial infarction and stroke (37). Indeed, subjects with type 2 diabetes have shown elevated levels of PAI-1 (38).…”