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

Diabetes Care. 2005 Sep;28(9):2211-6. doi: 10.2337/diacare.28.9.2211.

Abstract

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-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.

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Body Mass Index
  • C-Reactive Protein / metabolism
  • Carboxypeptidase B2 / blood*
  • Cholesterol, LDL / blood
  • Diabetes Mellitus, Type 2 / blood
  • Diabetes Mellitus, Type 2 / complications
  • Diabetes Mellitus, Type 2 / physiopathology*
  • Diabetes Mellitus, Type 2 / therapy
  • Female
  • Humans
  • Hypercholesterolemia / blood
  • Hypercholesterolemia / complications*
  • Hypercholesterolemia / therapy
  • Inflammation / blood
  • Inflammation / complications*
  • Inflammation / therapy
  • Insulin / blood
  • Insulin Resistance
  • Male
  • Metabolic Syndrome / blood
  • Metabolic Syndrome / complications*
  • Metabolic Syndrome / therapy
  • Middle Aged
  • Plasminogen Activator Inhibitor 1 / blood*
  • Plasminogen Activator Inhibitor 1 / therapeutic use
  • Thrombolytic Therapy*
  • Triglycerides / blood

Substances

  • Cholesterol, LDL
  • Insulin
  • Plasminogen Activator Inhibitor 1
  • Triglycerides
  • C-Reactive Protein
  • Alanine Transaminase
  • Carboxypeptidase B2