Altered myosin light-chain phosphorylation in resting platelets from premenopausal women with diabetes

Gender-related differences in the rate of coronary heart disease (CHD) betw een premenopausal women and men are greatly diminished in women with diabet es mellitus (DM). This may be related, in part, to altered platelet functio n in premenopausal diabetic women. Hyperglycemia may contribute to increase platelet aggregation through enhancement of oxidative stress, increased ni tric oxide (NO) destruction, and increased myosin light-chain (MLC) phospho rylation (MLC-P). Accordingly, we investigated functional acid biochemical parameters of platelet function in 32 women (14 premenopausal and postmenop ausal controls and 18 age-matched patients with DM); platelet MLC-P and cyc lic guanosine monophosphate ([cGMP] reflecting NO) were assessed. Other par ameters including age, body mass index (BMI), waist to hip ratio, total cho lesterol, and platelet count were not different in the control and diabetic groups. In the premenopausal women, baseline MLC-P was lower in women with DM versus the control group (P = .02). GMP levels were similar in the two groups at baseline (22.7 +/- 3 fmol/ml in controls v 23.1 +/- 3 fmol/ml in diabetic subjects) and 3 minutes after insulin exposure. The platelet conte nt of ascorbic acid (AA), an endogenous antioxidant compound, was elevated in premenopausal women with DM (P = .02) compared with the controls. Despit e similar estradiol (BE,) levels, platelets of premenopausal women with DM exhibited reduced MLC-P. This paradoxic difference may be accounted for by an increase in platelet AA, as this suggests decreased platelet oxidative s tress in this patient population. These observations indicate that an alter ed redox state and associated MLC-P of platelets does not contribute to enh anced platelet aggregation and CHD in premenopausal women with DM. Copyrigh t (C) 2001 by W.B. Saunders Company.