**3.3 Membrane surface receptor expression and platelet-leukocyte aggregates (PLA)**

Evaluation of platelets from T1DM patients has shown increased membrane surface expression of activation markers such as P-selectin, platelet-leukocyte aggregates (PLA)(platelet-monocyte, platelet-granulocytes) [17, 40, 41]. Importantly, it has been demonstrated that first relatives of T1DM patients at risk of T1DM have increased expression of P-selectin, CD63, and thrombospondin compared with at-no-risk controls [42]. Given that these changes are also observed in megakayryocytes, and peripherally, there is ongoing debate whether the changes are predetermined and intrinsic to disease process or epigenetic secondary to the altered metabolic milieu, are yet to be resolved.
