MEGAKARYOCYTE PLOIDY AND PLATELET CHANGES IN HUMAN DIABETES AND ATHEROSCLEROSIS

Altered platelet morphology and function have been reported in patient s with diabetes. They are likely to be associated with the pathologica l processes and increased risk of vascular disease seen in these patie nts. Mean platelet volume (MPV), platelet count, and megakaryocyte (MK ) ploidy (DNA content) were measured in (1) nondiabetics with normal c oronary arteries, (2) nondiabetics with coronary artery atherosclerosi s, (3) diabetics without evidence of vascular complications, and (4) d iabetics with vascular disease. The platelet count (+/-SD) was increas ed in all groups but only significantly in the diabetics with vascular disease (236+/-65 versus 250+/-54 versus 257+/-64 versus 295+/-90 [P less than or equal to.05]x10(9)/L, for groups I, II, II, and IV, respe ctively). The MPV was significantly increased in patients with atheros clerosis (7.0+/-0.4 versus 8.0+/-1.2 [P less than or equal to.05] vers us 7.2+/-0.9 versus 8.1+/-0.9 [P less than or equal to.05] fL). Geomet ric mean MK ploidy was significantly increased in all groups compared with controls (16+/-1.5 versus 18.7+/-1.8 [P less than or equal to.05] versus 19.8+/-1.6 [P less than or equal to.05] versus 20.1+/-2.7 [P l ess than or equal to.05]). Furthermore, some patients with vascular di sease and/or diabetes had a modal ploidy shift from 16 (the normal mam malian modal ploidy) to 32, with a concomitant reduction of MKs in the 8 and 16 ploidy classes. This shift was seen particularly in the diab etics with vascular disease (P=.007). Interleukin-6 (IL-6) levels were measured and were elevated in patients with atherosclerosis; the high est levels were found in the diabetic patients (0.7+/-0.9 versus 5.3+/ -5.5 [P less than or equal to.05] versus 2.5+/-2.8 versus 6.7+/-5.5 [P less than or equal to.05] ng/L). In the diabetic patients with athero sclerosis, 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 less than or equal to.05] g/L). Furthermore, IL-6 levels correlated with MK ploidy (r=.4 5, P=.009) and fibrinogen levels (r=.5, P=.0001). This study demonstra tes that patients with vascular disease, particularly diabetics, have an altered MK ploidy distribution, showing a shift toward higher ploid y in association with an increased platelet mass (countxvolume). Chang es in platelets in diabetes probably reflect MK changes, which themsel ves are a response to systemic change.