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.

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.

• Authors: Yoshimasa Aso, Sadao Wakabayashi, Ruriko Yamamoto, Rika Matsutomo, Kohzo Takebayashi, Toshihiko Inukai
• Journal: Diabetes care (Diabetes Care) Vol. 28 Issue 9 Pg. 2211-6 (Sep 2005) ISSN: 0149-5992 [Print] United States
• PMID: 16123492 (Publication Type: Journal Article)

Chemical References

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

Topics

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