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Diabetes Care 28:2211-2216, 2005
© 2005 by the American Diabetes Association, Inc.

Metabolic Syndrome/Insulin Resistance Syndrome/Pre-Diabetes
Original Article

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

Yoshimasa Aso, MD, Sadao Wakabayashi, MD, Ruriko Yamamoto, MD, Rika Matsutomo, MD, Kohzo Takebayashi, MD and Toshihiko Inukai, MD

Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, Saitama, Japan

Address correspondence and reprint requests to Yoshimasa Aso MD, Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minami-Koshigaya, Koshiagya, Saitama 343-8555, Japan. E-mail: yaso{at}dokkyomed.ac.jp

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 and independently with LDL cholesterol. Plasma concentrations of plasmin-{alpha}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.

Abbreviations: CVD, cardiovascular disease • hs-CRP, high-sensitivity CRP • HC, hypercholesterolemia • MS, metabolic syndrome • PAI, plasminogen activator inhibitor • PAP, plasmin-{alpha}2-antiplasmin complex • TAFI, thrombin-activatable fibrinolysis inhibitor


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