Inflammation in diabetic women with cardiovascular disease

Abstract

Diabetics have a much greater morbidity and mortality due to coronary heart disease (CHD) than non-diabetics. Furthermore, diabetic women have a 3.8 fold greater risk for CHD compared to diabetic men. Inflammation is now considered a risk factor for cardiovascular disease and also plays a role in diabetes. It is possible that diabetic women with cardiovascular disease (CVD) have a greater inflammatory response and increased interaction between white cells and platelets than diabetic men with CVD or non-diabetic women with CVD. This study tested the hypothesis that platelet-neutrophil conjugates, platelet activation, neutrophil activation, and cytokine production (interleukin-6 (IL-6), tumor necrosis factor (TNF-α), and interleukin-1 (IL-1β) are increased in diabetic women with CVD compared to diabetic men with CVD and non-diabetic women with CVD. Neutrophil activation was assessed by measuring the expression of neutrophil CD11b and the production of Reactive Oxygen Species (ROS). We found that the baseline expression of CD11b and ROS was not statistically different among any of the groups. Platelet activation was quantified by the expression of GPIIb/IIIa and P-selectin. We found that the baseline expression of GPIIb/IIIa was not significantly different among any of the groups. Diabetic women with CVD had a 2 fold greater expression of platelet P-selectin compared to diabetic women without CVD. We also found the platelet-neutrophil conjugate reactivity to platelet activating factor (PAF) was significantly increased by 60% in diabetic and non-diabetic women with CVD in comparison to diabetic men with CVD. Finally, we found that IL-6 was increased over fourfold in diabetic women with CVD compared to non-diabetic women. These results indicate that platelets are chronically activated and IL-6 is chronically elevated in diabetic women with CVD compared to diabetic women without CVD and may contribute to thrombosis and the greater severity of coronary heart disease observed in diabetic women. The platelet-neutrophil conjugates may contribute to thrombosis/inflammation and the greater severity of coronary heart disease observed in diabetic women as compared to diabetic men. These aspects of inflammation may indicate one of the processes that exacerbate cardiovascular disease in diabetic women.