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

Abstract

Background: 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. Methods: 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-α), 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. Results: 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-α (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). Conclusion: 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.