Increased plasma levels of endothelin 1 and von Willebrand factor in patients with type 2 diabetes and dyslipidemia.

Abstract

OBJECTIVE -Endothelial markers endothelin 1 (ET-1) and von Willebrand factor (vWF) were assessed in patients with type 2 diabetes and dyslipidemia and in patients with hypercholesterolemia.RESEARCH DESIGN AND METHODS -In this case-control study, plasma ET-1 and vWF levels were measured by enzyme-linked immunosorbent assay in 35 normoalbuminuric type 2 diabetic patients with dyslipidemia (56 ± 5 years), in 21 nondiabetic patients with hypercholesterolemia (52 ± 7 years), and in 19 healthy control subjects (45 ± 4 years).All of the individuals were normotensive and nonsmokers. Urinary albumin was measured by immunoturbidimetry.RESULTS -ET-1 levels were higher (P Ͻ 0.0001) in type 2 diabetic dyslipidemic patients (1.62 ± 0.73 pg/ml) than in both nondiabetic hypercholesterolemic patients (0.91 ± 0.73 pg/ml) and control subjects (0.69 ± 0.25 pg/ml). vWF levels were significantly increased (P = 0.02) in type 2 diabetic (185.49 ± 72.1%) and hypercholesterolemic (163.29 ± 50.7%) patients compared with control subjects (129.70 ± 35.2%). In the multiple linear regression analysis, ET-1 was significantly associated (adjusted r 2 = 0.42) with serum triglyceride levels (P Ͻ 0.001), age (P Ͻ 0.01), insulin sensitivity index (P Ͻ 0.02), and albuminuria levels (P Ͻ 0.04). vWF levels were associated (adjusted r 2 = 0.22) with albuminuria (P Ͻ 0.001), fibrinogen levels (P Ͻ 0.02), and BMI (P Ͻ 0.03).CONCLUSIONS -Compared with hypercholesterolemic patients, type 2 diabetic patients with dyslipidemia have increased levels of ET-1 and vWF, which may indicate more pronounced endothelial injury. These findings appear to be related to components of the insulin resistance syndrome.

Insulin resistance, haemostatic and inflammatory markers and coronary heart disease risk factors in Type 2 diabetic men with and without coronary heart disease

“…These differences in haemostatic and inflammatory markers were not explained by potential confounders such as smoking, physical activity, alcohol intake and abdominal obesity, although the relationship with CRP was weakened after adjustment for abdominal adiposity. The increased levels of endothelial markers (t-PA antigen, vWF antigen), clotting factors (fibrinogen, factors VII and VIII), inflammatory markers (CRP, white cell count) and plasma viscosity in subjects with diabetes have also been reported in other studies [6,7,8,13,29], and these factors are also related to CHD risk [27,30,31,32,33,34]. In addition we showed that men with diabetes also had markedly increased levels of factor IX and shortened APPT.…”

Oxidative stress could precede endothelial dysfunction and insulin resistance in Indian Mauritians with impaired glucose metabolism

“…Furthermore, a relatively small amount of 8-epi-PGF 2a could be formed using a cyclooxygenase-dependent pathway [30]. 8-epi-PGF 2a is a potent vasoconstrictor and is involved in the activation of intracellular signalling, suggesting that it could act as an important mediator in the manifestation of endotheliopathy in the early stages of Type II diabetes, either directly, or through the stimulated synthesis of other vasoconstrictor agents such as endothelin-1 [31,32]. The absence of significant changes in plasma TAOS and vitamin E between the groups in our study is in agreement with a recent report [33], where no significant differences were found in plasma total antioxidant activity and vitamin E in both Caucasian and Indo-Asian subjects with Type II diabetes, compared to corresponding control subjects matched for age.…”

Different role of endothelin ETA and ETB receptors and endothelial modulators in diabetes-induced hyperreactivity of the rabbit carotid artery to endothelin-1

“…The activity of endogenous endothelin-1 in the regulation of the vascular tone of resistance vessels of patients with type II diabetes mellitus is enhanced (Cardillo , 2002); nevertheless, these vessels exhibit a reduced response to exogenous endothelin-1 (Cardillo et al, 2002). The vascular hyperreactivity to endothelin-1, together with the increased plasma levels of this peptide in diabetic individuals (Sarman et al, 2000;Seligman et al, 2000;Kalogeropoulou et al, 2002;Schneider et al, 2002), could play a role in the pathogenesis of cerebral ischaemia in diabetic patients. The absence of changes in the maximal contraction of the carotid artery from diabetic rabbits in response to depolarising solutions (50 mM KCl) and 5-HT (Miranda et al, 2000b) shows the selectivity of the altered response to endothelin-1 reported in the present study.…”

“…The endothelin system is altered in both vascular and neuronal components of the retina in early diabetic retinopathy (De Juan et al, 2000). The increased plasma levels of endothelin-1 in diabetic patients (Sarman et al, 2000;Seligman et al, 2000;Schneider et al, 2002), together with increased free radical levels and a deficiency of prostacyclin, have been related to carotid atherosclerosis in diabetic patients (Kalogeropoulou et al, 2002). Finally, current experimental evidence suggests that endothelin antagonism may potentially represent an adjuvant therapeutic tool in the treatment of chronic diabetic complications (Chakrabarti et al, 2000;Mather et al, 2002).…”