Adiponectin (Acrp30), an adipocyte-derived protein, exists in serum as a trimer, a hexamer, and a high-molecular weight (HMW) form, including 12-18 subunits. Because HMW adiponectin may be biologically active, we measured it in serum using a novel enzyme-linked immunosorbent assay (ELISA) confirmed by gel filtration chromatography that the ELISA detected mainly adiponectin with 12-18 subunits, and we compared HMW with total adiponectin concentration in patients with type 2 diabetes. We next investigated the relationship between serum HMW and coronary artery disease (CAD) in 280 consecutive type 2 diabetic patients, including 59 patients with angiographically confirmed CAD. Total adiponectin was measured in serum by a commercially available ELISA. Like serum total adiponectin, HMW adiponectin correlated positively with HDL cholesterol and negatively with triglyceride, insulin sensitivity, creatinine clearance, and circulating inflammatory markers. Total and HMW adiponectin were significantly higher in women than in men, as was the HMW-tototal adiponectin ratio. Serum HMW and the HMW-to-total adiponectin ratio were significantly lower in men with than without CAD (P < 0.05, respectively). In women, the ratio, but neither total nor HMW adiponectin, tended to be lower when CAD was present. In conclusion, determination of HMW adiponectin, especially relative to total serum adiponectin, is useful for evaluating CAD in type 2 diabetic patients. Diabetes

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 Ͼ140 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 ϭ 38), with MS but not HC (n ϭ 39), with no MS but with HC (n ϭ 26), and with both MS and HC (n ϭ 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 and independently with LDL cholesterol. Plasma concentrations of plasmin-␣2-antiplasmin complex (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. Diabetes Care 28:2211-2216, 2005M etabolic syndrome (MS), also known as insulin resistance syndrome, is defined by the clustering of several cardiovascular risk factors in an individual patient, including impaired glucose tolerance (diabetes), hypertension, dyslipidemia, and visceral obesity (1,2). Several studies have demonstrated that this syndrome strongly predicts cardiovascular disease (CVD), especially coronary heart disease (3,4), independently of LDL cholesterol. Recently, a close association of MS with hemostatic abnormalities has been reported. Among hemostatic abnormalities, an increase in plasma plasminogen activator inhibitor (PAI)-1, a strong inhibitor of fibrinolysis, is considered a core feature of MS (5). High plasma PAI-1 concentrations may be associated with thrombus formation, causing cardiovascular events (6).A new inhibitor of fibrinolysis has been recently identified in plasma. As this protein is activated by thrombin and then downregulates fibrinolysis, it has been named thrombin-activatable fibrinolysis inhibitor (TAFI) (7). TAFI proved to be identical with plasma procarboxypeptidase B, U, or R (8). TAFI removes COOHterminal lysine or arginine residues from partially degraded fibrin, decreasing plasminogen binding to the fibrin surface (9). Since TAFI is associated with coagulation/ fibrinolysis and inflammation, plasma TAFI may participate in arterial thromb...

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Increased serum HMW adiponectin may contribute to the improvement in glycaemic control after pioglitazone treatment. Plasma PAI-1 and TAFI were unchanged by either drug.