Diabetes mellitus as a prothrombotic condition.

Area of Science:

• Cardiovascular Medicine
• Endocrinology
• Hematology

Background:

• Diabetes mellitus (DM) is linked to a 3-5 fold higher risk of myocardial infarction (MI) and increased vascular mortality.
• Vascular risk factors like hyperinsulinaemia, dysglycaemia, dyslipidaemia, and hypertension cluster around insulin resistance (IR).
• This risk clustering, including thrombotic factors, is also observed in individuals with IR, impaired glucose tolerance (IGT), and long-standing Type 1 DM with renal disease.

Purpose of the Study:

• To elucidate the mechanisms linking insulin resistance (IR) to the heightened atherothrombotic and thrombotic risk in diabetes mellitus (DM).
• To explore the role of IR in the clustering of vascular and prothrombotic factors contributing to cardiovascular disease (CVD).

Main Methods:

• Review of evidence linking IR to vascular risk factors (hyperinsulinaemia, dysglycaemia, dyslipidaemia, hypertension).
• Analysis of studies on thrombotic risk factors associated with IR, including PAI-1, coagulation factors, and endothelial dysfunction.
• Examination of the impact of hyperglycaemia and glycation on fibrin structure and function.

Main Results:

• Insulin resistance (IR) is associated with clustering of vascular risk factors and prothrombotic factors, including elevated PAI-1 and coagulation factors.
• Endothelial cell dysfunction, impaired nitric oxide and prostacyclin synthesis, and platelet resistance to anti-aggregatory effects contribute to thrombotic risk.
• Hyperglycaemia and glycation alter fibrin structure, creating denser clots resistant to fibrinolysis.

Conclusions:

• The clustering of increased coagulation, inhibited fibrinolysis, altered fibrin structure, and heightened platelet reactivity driven by IR underpins the development of cardiovascular disease in DM.
• Understanding these mechanisms is crucial for managing cardiovascular risk in diabetic and insulin-resistant populations.