Leukocyte count and vascular function in Type 2 diabetic subjects with treated hypertension

Traditional cardiovascular risk factors may only partially explain abnormal vascular function in Type 2 diabetic patients. This study examined the associations between vascular function and markers of inflammation in Type 2 diabetic subjects with treated hypertension.

Flow-mediated dilatation (FMD) and glyceryl-trinitrate mediated dilatation (GTNMD) of the brachial artery were used to assess endothelium-dependent and -independent function, respectively, in 29 hypertensive Type 2 diabetic subjects (HbA1c <9%), and 17 healthy control subjects. Plasma C-reactive protein (CRP), fibrinogen, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and leukocyte count were used as markers of inflammation. Soluble L-selectin, P-selectin, and von Willebrand factor (vWf) were measured to assess leukocyte, platelet and endothelial cell activation, respectively.

Compared with controls, diabetic subjects had impaired FMD (3.9+/-3.0 vs. 5.5+/-2.4%, P=0.07) and GTNMD (11.4+/-4.8% vs. 15.4+/-7.1%, P=0.04). They also had higher levels of CRP (2.7+/-2.6 vs. 1.4+/-1.1 mg/l, P=0.03), fibrinogen (3.4+/-0.7 vs. 2.7+/-0.3 g/l, P<0.001) and TNF-alpha (20.9+/-13.4 vs. 2.5+/-1.7 pg/l, P<0.001). In diabetic subjects, after adjustment for age and gender, leukocyte count was an independent predictor of FMD (P=0.02), accounting for 17% of total variance. Similarly, leukocyte count (P<0.001) accounted for 23% and IL-6 (P=0.03) for 12% of the variance in GTNMD. vWf was correlated with leukocyte count (r=0.38, P=0.04), FMD (r=-0.35, P=0.06) and GTNMD (r=-0.47, P=0.009), whilst P-selectin correlated with fibrinogen (r=0.58, P=0.001).

These cross-sectional observations are consistent with the hypothesis that reduced FMD and GTNMD in Type 2 diabetes is at least in part secondary to increased inflammation, with associated endothelial and platelet activation.