Megakaryocytes and Platelets in Diabetes Mellitus

Summary

In patients with diabetes mellitus vascular diseases and related complications still represent the main cause of death. Neuropathy, nephropathy, retinopathy and disturbed nutritive tissue perfusion result from reduced capillary microcirculation. Macroangiopathic mechanisms lead to accelerated cerebral, coronary and peripheral artery disease precipitating life terminating thrombotic events superimposed to those vascular lesions. Thus morbidity and mortality depend mainly on vascular complications. The functional thromboresistance is reduced in the diabetic state with hyperactive platelets operating by three mechanisms: 1) microembol-isation of the capillaries; 2) local progression of preexisting vascular lesions by secretion of constrictive, mitogenic and oxidative substances; 3) trigger of the prognosis limiting arterial thrombotic event. The increased functional properties of di-abetic platelets result from the primary release of larger platelets with enhanced thromboxane formation capacity and increased numbers of functional glycoprotein receptors GPIb and GPIIb-llla which are synthesized in the megakaryocytes. It could be demonstrated with the Düsseldorf III method of flowcytometric activation marker testing (CD62, CD63, thrombospondin) that predominantly large platelets circulate in an activated state even in very early (pre)diabetic stages sug-gesting that the megakaryocyte-platelet system might be systemically affected. Based on these observation a "stem cell hypothesis" is developed which suggests that bone marrow derived platelets may be systemically involved in the pathogenesis of the vascular complications and eventually of type-l diabetes. The idea of antiplatelet agents as an useful early adjunct to metabolic therapy is promoted.

Keywords

Platelets - megakaryocytes - flowcytometry - diabetes

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