Megakaryocyte Ploidy and Platelet Changes in Human Diabetes and Atherosclerosis

Abstract

Abstract Altered platelet morphology and function have been reported in patients with diabetes. They are likely to be associated with the pathological processes and increased risk of vascular disease seen in these patients. Mean platelet volume (MPV), platelet count, and megakaryocyte (MK) ploidy (DNA content) were measured in (1) nondiabetics with normal coronary arteries, (2) nondiabetics with coronary artery atherosclerosis, (3) diabetics without evidence of vascular complications, and (4) diabetics with vascular disease. The platelet count (±SD) was increased in all groups but only significantly in the diabetics with vascular disease (236±65 versus 250±54 versus 257±64 versus 295±90 [ P ≤.05]×10 9 /L, for groups I, II, III, and IV, respectively). The MPV was significantly increased in patients with atherosclerosis (7.0±0.4 versus 8.0±1.2 [ P ≤.05] versus 7.2±0.9 versus 8.1±0.9 [ P ≤.05] fL). Geometric mean MK ploidy was significantly increased in all groups compared with controls (16±1.5 versus 18.7±1.8 [ P ≤.05] versus 19.8±1.6 [ P ≤.05] versus 20.1±2.7 [ P ≤.05]). Furthermore, some patients with vascular disease and/or diabetes had a modal ploidy shift from 16 (the normal mammalian modal ploidy) to 32, with a concomitant reduction of MKs in the 8 and 16 ploidy classes. This shift was seen particularly in the diabetics with vascular disease ( P =.007). Interleukin-6 (IL-6) levels were measured and were elevated in patients with atherosclerosis; the highest levels were found in the diabetic patients (0.7±0.9 versus 5.3±5.5 [ P ≤.05] versus 2.5±2.8 versus 6.7±5.5 [ P ≤.05] ng/L). In the diabetic patients with atherosclerosis, fibrinogen levels were also increased (2.85±0.76 versus 3.34±1.32 versus 2.43±1.50 versus 5.59±1.72 [ P ≤.05] g/L). Furthermore, IL-6 levels correlated with MK ploidy ( r =.45, P =.009) and fibrinogen levels ( r =.5, P =.0001). This study demonstrates that patients with vascular disease, particularly diabetics, have an altered MK ploidy distribution, showing a shift toward higher ploidy in association with an increased platelet mass (count×volume). Changes in platelets in diabetes probably reflect MK changes, which themselves are a response to systemic change.