Association Between Impaired Vascular Endothelial Function and High Sensitivity C-reactive Protein, a Chronic Inflammatory Marker, in Patients with Type 2 Diabetes Mellitus

Shin, Jang Yel; Lee, Mi Young; Koh, Jang Hyun; Kim, Jang Young; Shin, Young Goo; Chung, Choon Hee

Abstract

BACKGOUND: Eighty percents of diabetes-related mortalities are due to atherosclerotic vascular complications. The accelerated atherosclerosis in type 2 diabetic patients is partly due to the increased incidences of cardiovascular risk factors, such as hypertension, obesity, dyslipidemia, insulin resistance and oxidative stress. Endothelial dysfunction is known as an early marker of cardiovascular disease and a predictor of cardiovascular events. The flow mediated dilation (FMD) of the brachial artery has been documented as being reduced in type 2 diabetic patients. Inflammatory markers, such as C-reactive protein(CRP) and interleukin-6(IL-6), are associated with the risk of cardiovascular disease. Endothelial dysfunction has a direct correlation with the levels of CRP, which are elevated in patients with diabetes compared with non-diabetic subjects. In this study, the FMD in diabetic and non-diabetic subjects were compared, and the association of cardiovascular risk factors and endothelial function examined in type 2 diabetic patients.
METHODS
57 consecutive diabetic subjects and 29 non-diabetic subjects, aged 35 to 69(54.0+/-1.0 years), without proven macrovascular complications, were enrolled in this study. Cardiovascular risk factors, such as body weight, height, waist and hip circumference, fasting plasma glucose and insulin levels, lipid profiles, inflammatory and coagulation markers were measured. The FMD of the brachial artery and the intima-media thickness(IMT) of the carotid artery were determined using high-resolution B-mode ultrasound.
RESULTS
The FMD values were significantly lower in the diabetic compared with the non-diabetic subjects(7.6+/-0.2% vs. 8.9+/-0.4%, P=0.004). The homocysteine levels were significantly higher in the diabetic than non-diabetic subjects(12.4+/-0.4micromol/L vs. 9.5+/-0.6micromol/L, P<0.0001). In diabetic subjects, the FMD was shown to be significantly negatively correlated with high sensitivity C-reactive protein(hsCRP)(P=0.006), fibrinogen(P=0.024) and homocysteine (P=0.038). A multiple regression analysis, after adjusted for age, sex, body mass index(BMI), hypertension, and smoking, showed that hsCRP(beta=-0.424, P=0.002) and fibrinogen(beta=-0.324, P=0.025) had significant inverse association with the FMD in diabetic subjects.
CONCLUSION
Diabetic subjects have an impaired endothelial function compared with the non-diabetic subjects, and the vascular endothelial function has a significant negative correlation with hsCRP and fibrinogen. These findings suggest that hsCRP might be an independent predictor of endothelial dysfunction and atherosclerosis, and chronic inflammation might play a pivotal role in the impairment of the endothelial function in diabetic patients.