Obesity But not Hypertension Is the Major Determinant of Endothelial Activation in Type II Diabetes.
In order to evaluate the independent role of hypertension and other risk factors in promoting endothelial activation in type II diabetes, several markers of endothelial damage were studied in 43 type II diabetic patients (24 F,30-65 ys), before and after the random assignment to a 20-week period of either aggressive (AC, n=20) or usual (UC, n=22) metabolic control. Compared to matched controls (n=15) type II diabetic patients showed a significant (p<0.05 or less) elevation of circulating P-selectin, E-selectin, ICAM-1, VCAM-1 and Endothelin-1 (ET-1) levels and a simultaneos decrement of total nitric oxide(NO). Multivariate analysis showed that only BMI not dependently influenced (p=0.01 or less) E-selectin, ICAM-1 and total NO, with a trend for P-selectin levels (p=0.06). Accordingly, basal BMI correlated with ICAM-1 (r=0.45, p=0.003), E-selectin (r=0.41, p=0.007) and P-selectin (r=0.34, p=0.02). In addition, P-selectin and E-selectin resulted higher(p<0.03), while total NO lower (p=0.0001), in the 26 patients with a BMI >28 kg/m2(33.4±0.7 kg/m2) than in the non-obese ones (BMI=24.8±0.6 kg/m2). These latter showed similar endothelial adhesin, ET-1 and NO levels than controls. Age, race, gender, blood pressure, albumin excretion and all metabolic variables with the exclusion of BMI did not predict endothelial factor levels. Hypertensive (i.e. blood pressure >140/90 mmHg) and normotensive diabetic patients had similar levels of circulating adhesins, ET-1 and NO. AC was followed by a significant reduction of plasma E-selectin (p=0.04) and HbA1c levels (-2.2%, 95% CI 1.5 to 2.9%, p=0.0001). E-selectin decrements correlated with HbA1cchanges after 20 weeks in AC (r=0.42, p=0.01). In conclusion,E-selectin reduction after AC suggests metabolic control may influence endothelial activation in type II diabetics. However, multivariate analysis showed that only obesity influenced the whole endothelium. Surprisingly, neither blood pressure nor other well-recognized cardiovascular risk factors influenced endothelial adhesins, ET-1 and NO production. Thus, central obesity is the main determinant of endothelial activation in type II diabetics.