Metabolic syndrome accompanied by hypercholesterolemia is strongly associated with proinflammatory state and impairment of fibrinolysis in patients with type 2 diabetes - Synergistic effects of plasminogen activator inhibitor-1 and thrombin-activatable fibrinolysis inhibitor

OBJECTIVE- To determine whether plasma concentrations of thrombin-activatable fibrinolysis inhibitor (TAFI) in patients with type 2 diabetes were associated with components of metabolic syndrome (MS), including high-sensitivity C-reactive protein (hs-CRP), plasminogen activator inhibitor (PAI)-1, and LDL cholesterol. RESEARCH DESIGN AND METHODS- We studied 136 consecutive patients with type 2 diabetes. Diagnosis of MS was diagnosed by current criteria. Hypercholesterolemia (HC) was defined as serum LDL cholesterol > 140 mg/dl (3.6 mmol/l) or treatment with a statin. For comparisons, diabetic patients were divided into four groups: those with no MS and no HC (n = 38), with MS but not HC (n = 39), with no MS but with HC (n = 26), and with both MS and HC (n = 33). RESULTS- Considering all patients with type 2 diabetes, plasma PAI-1 was strongly associated with MS components such as BMI, triglyceride, alanine aminotransferase, a homeostasis model assessment of insulin resistance, and hs-CRP. Plasma TAFI only correlated positively an l independently with LDL cholesterol. Plasma concentrations of plasmin-alpha 2-antip (PAP), a measure of fibrinolytic activity in blood, showed a significant negative correlation with plasma PAI-1 but not TAFI. Diabetic patients with both MS and HC had the highest serum hs-CRP concentrations and the lowest plasma PAP concentrations. CONCLUSIONS - LDL cholesterol is a main determinant of plasma TAFI in patients with type 2 diabetes. Coexistence of MS and HC synergistically accelerates inflammation and impairment of fibrinolysis via elevated concentrations of both TAFI and PAI-1, which inhibit fibrinolysis.