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Published on: April 1, 2015
Interrelations between carbohydrates, lipids, and the hemostatic system in relation to the risk of thrombotic and
1Laboratoire d'Hématologie, CHU Timone, Marseille, France.
Insights
Metabolic diseases increase atherothrombosis risk via hemostatic abnormalities. Hyperinsulinemia strongly correlates with elevated plasminogen activator inhibitor-1, promoting hypofibrinolysis and fibrin deposition.
Area of Science:
- Cardiovascular Medicine
- Metabolic Disorders
- Hemostasis Research
Background:
- Metabolic diseases like obesity and diabetes are key risk factors for atherothrombosis.
- These conditions are associated with hemostatic system abnormalities, including platelet hyperaggregability, hypercoagulability, and hypofibrinolysis.
- Evaluating individual disease effects on hemostasis is challenging due to frequent co-occurrence.
Purpose of the Study:
- To investigate a potential common abnormality linking metabolic diseases to cardiovascular impact.
- To explore the role of hyperinsulinemia in the hemostatic system's response.
- To determine the independent correlation between insulin levels and fibrinolytic system components.
Main Methods:
- Assessed correlations between plasma insulin, body mass index, triglyceride levels, and plasminogen activator inhibitor-1 (PAI-1).
- Utilized partial correlation analysis to identify independent relationships.
- Examined the link between hyperinsulinemia and hypofibrinolysis.
Main Results:
- A strong correlation was found between plasma insulin, BMI, triglyceride levels, and PAI-1.
- Partial correlation analysis revealed an independent correlation solely between insulin and PAI-1.
- Elevated insulin levels may lead to increased PAI-1, causing hypofibrinolysis.
Conclusions:
- Hyperinsulinemia is independently linked to elevated PAI-1 levels.
- Increased PAI-1 contributes to hypofibrinolysis, potentially playing a role in atherothrombosis development.
- While specific disease effects exist, hyperinsulinemia-induced hypofibrinolysis is a significant factor in metabolic disease-related atherothrombosis.
Abstract:
Metabolic diseases, such as obesity, impaired glucose tolerance, type I and type II diabetes, hypercholesterolemia, and hypertriglyceridemia, are among the main risk factors for the development of atherothrombosis. Various abnormalities of the hemostatic system (platelet hyperaggregability, hypercoagulability, and hypofibrinolysis) have been described in all these situations. The individual effect of each of these disease on the hemostatic system is difficult to evaluate because these states are often associated in the same patient and the treatment of one can benefit the others. Therefore it may be queried if a common abnormality of these pathologic states might explain their impact on the cardiovascular system. We have been interested by hyperinsulinemia, which is observed in obesity, impaired glucose tolerance, type II diabetes, and hypertriglyceridemia, and we have shown a very strong correlation between plasma insulin, body mass index, triglyceride levels, and one of the main inhibitors of the fibrinolytic system, plasminogen activator inhibitor-1. Partial correlation analysis showed that only the correlation between insulin and plasminogen activator inhibitor-1 was independent. Therefore a high plasma insulin level could be responsible for elevated levels of plasminogen activator inhibitor-1, which by inducing an hypofibrinolysis, could play a role in the deposition of fibrin and the development of atherothrombosis. The description of some interrelations between metabolic diseases and hemostasis is satisfactory but does not exclude specific effects of these diseases on hemostasis, such as glycation of the coagulation and fibrinolytic factors in diabetes or toxic action of lipoprotein on endothelial cells in hyperlipoproteinemia.
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