**2.2 Bone Marrow and megakaryocytes in T1DM**

Changes in platelet indices in DM correlate with mekaryocyte DNA content or ploidy [11] reflecting direct influence on bone marrow function even prior to systemic circulation observations. The thrombopoiesis associated with T1DM releases an enormous amount of hyperactive platelets from the bone marrow into circulation [12]. Moreover, the newly released large but immature platelets from bone marrow have increased synthetic capacity for thromboxane and thrombospondin, have enhanced membrane surface expression of receptors such as GPIIbIIIa, CD61, and CD63, [13, 14], and have enhanced aggregation [14, 15]. In DM, the hyperglycemia acts through neutrophils to stimulate thrombopoietin (TPO) production in the liver and enhance megakaryocyte thrombopoiesis [16]. In T1DM, increased circulating TPO has been shown to be linked to elevated blood sugar levels and HbA1c HbA1C [17] providing evidence linking bone marrow megakaryopoiesis and metabolic state.
