Platelet dysfunction in type 2 diabetes.
Insulin resistance is a uniform finding in type 2 diabetes, as are abnormalities in the microvascular and macrovascular circulations. These complications are associated with dysfunction of platelets and the neurovascular unit. Platelets are essential for hemostasis, and knowledge of their function is basic to understanding the pathophysiology of vascular disease in diabetes. Intact healthy vascular endothelium is central to the normal functioning of smooth muscle contractility as well as its normal interaction with platelets. What is not clear is the role of hyperglycemia in the functional and organic microvascular deficiencies and platelet hyperactivity in individuals with diabetes. The entire coagulation cascade is dysfunctional in diabetes. Increased levels of fibrinogen and plasminogen activator inhibitor 1 favor both thrombosis and defective dissolution of clots once formed. Platelets in type 2 diabetic individuals adhere to vascular endothelium and aggregate more readily than those in healthy people. Loss of sensitivity to the normal restraints exercised by prostacyclin (PGI(2)) and nitric oxide (NO) generated by the vascular endothelium presents as the major defect in platelet function. Insulin is a natural antagonist of platelet hyperactivity. It sensitizes the platelet to PGI(2) and enhances endothelial generation of PGI(2) and NO. Thus, the defects in insulin action in diabetes create a milieu of disordered platelet activity conducive to macrovascular and microvascular events.
Vinik
A I
AI
Department of Medicine and Pathology/Anatomy/Neurobiology, the Strelitz Diabetes Research Institutes, Eastern Virginia Medical School, Norfolk, Virginia, USA. vinikai@evms.edu
Erbas
T
T
Park
T S
TS
Nolan
R
R
Pittenger
G L
GL
D000818:Animals; D001161:Arteriosclerosis / Q000097:blood / Q000503:physiopathology; D001792:Blood Platelets / Q000502:physiology*; D003924:Diabetes Mellitus, Type 2 / Q000097:blood* / Q000503:physiopathology; D003925:Diabetic Angiopathies / Q000097:blood / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000502:physiology / Q000503:physiopathology; D006801:Humans; D007328:Insulin / Q000502:physiology; D007333:Insulin Resistance / Q000502:physiology
D007328:Insulin