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.


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-alpha2-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.
Aso
Yoshimasa
Y
Department of Internal Medicine, Koshigaya Hospital, Dokkyo University School of Medicine, 2-1-50 Minami-Koshigaya, Koshiagya, Saitama 343-8555, Japan. yaso@dokkyomed.ac.jp
Wakabayashi
Sadao
S
Yamamoto
Ruriko
R
Matsutomo
Rika
R
Takebayashi
Kohzo
K
Inukai
Toshihiko
T
D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D015992:Body Mass Index; D002097:C-Reactive Protein / Q000378:metabolism; D025901:Carboxypeptidase B2 / Q000097:blood*; D008078:Cholesterol, LDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000150:complications / Q000503:physiopathology* / Q000628:therapy; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications* / Q000628:therapy; D007249:Inflammation / Q000097:blood / Q000150:complications* / Q000628:therapy; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000628:therapy; D008875:Middle Aged; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood* / Q000627:therapeutic use; D015912:Thrombolytic Therapy; D014280:Triglycerides / Q000097:blood
D008078:Cholesterol, LDL; D007328:Insulin; D017395:Plasminogen Activator Inhibitor 1; D014280:Triglycerides; D002097:C-Reactive Protein; D000410:Alanine Transaminase; D025901:Carboxypeptidase B2