RESUMO
BACKGROUND: Endothelial dysfunction is an important contributor to micro and macrovascular complications of type 2 diabetes (T2D) and is reflected by increased systemic oxidative stress. Endothelial cell selective adhesion molecule (ESAM) influences endothelial function. We aimed to assess, for the first time to our knowledge, the relationship of soluble ESAM to markers of systemic oxidative stress. MATERIALS AND METHODS: ESAM, malondialdehyde (MDA) level and catalase activity were determined in 54 T2D patients and 43 controls. RESULTS: T2D patients had significantly higher ESAM when compared to controls (16.07 ± 5.77 µg/L versus 8.57 ± 5.28 µg/L, p < 0.0001), they also had higher MDA level (3.88 ± 1.50 µmol/L vs. 1.58 ± 0.72 µmol/L, p < 0.0001) and lower catalase activity (3.07 (2.63-3.44) U/mg vs. 8.72 (4.55-10.46) U/mg, p < 0.0001). In T2D patients ESAM was inversely related to catalase activity (r = -0.27, p = 0.04), relationship to MDA level was direct but not significant (r = 0.16, p = 0.24). MDA concentration correlated inversely to catalase activity (r = -0.28, p = 0.04). In multiple regression catalase activity remained significantly correlated to ESAM (p = 0.02) and MDA level was significantly related to glycated hemoglobin (p = 0.01); there was trend towards a positive correlation of MDA level to ESAM (p = 0.08). When patients were divided according to oxidative stress, those with increased oxidative stress (defined as MDA concentration > 2.98 µmol/L and catalase activity < 3.38 U/mg) had higher ESAM than the rest of the patients (17.99 ± 5.02 µg/L vs. 14.29 ± 5.94 µg/L p = 0.01). CONCLUSION: ESAM is higher in T2D than in controls and parallels oxidative stress: ESAM is inversely related to catalase activity and higher ESAM is found in T2D patients with increased oxidative stress.
Assuntos
Moléculas de Adesão Celular/sangue , Diabetes Mellitus Tipo 2/sangue , Células Endoteliais/metabolismo , Endotélio Vascular/metabolismo , Estresse Oxidativo , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Catalase/sangue , Estudos Transversais , Diabetes Mellitus Tipo 2/patologia , Células Endoteliais/patologia , Endotélio Vascular/patologia , Feminino , Humanos , Masculino , Malondialdeído/sangue , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
BACKGROUND: Endothelial cell-selective adhesion molecule (ESAM) contributes to the integrity of tight junctions and modulates endothelial function. ESAM has been linked to experimental diabetic nephropathy; its soluble fraction is related to atherosclerosis in humans. In this cross-sectional observational study, we describe for the first time serum ESAM in type 2 diabetic patients with different stages of chronic kidney disease (CKD) and its relationship to vascular endothelial growth factor-A (VEGF-A). Materials and methods We included diabetic patients with different stages of CKD and controls. History, laboratory evaluation, serum ESAM and VEGF-A and urinary albumin/creatinine ratio were obtained. RESULTS: Endothelial cell-selective adhesion molecule was higher in non-CKD diabetic patients 13.80 (6.15-18.70) ng/mL (n=45) than controls 7.30 (4.60-9.40) ng/mL (n=48), P=0.001. VEGF-A had a similar pattern: 71.3 (54.75-120.70) vs. 43.20 (30.1-65.90) pg/mL, P<0.0001. ESAM was 10.4 (5.6-17.4) ng/mL in predialysis CKD patients (n=59) and 22.35 (8.55-29.95) ng/mL in dialysis patients (n=36), P<0.001. Patients with glomerular filtration rate (GFR)<15 mL/min had the highest ESAM (P=0.003). ESAM was similar in normoalbuminuric, microalbuminuric and proteinuric patients. ESAM was directly correlated with the duration of diabetes (r(2)=0.048, P=0.009), C-reactive protein (r(2)=0.028, P=0.05), VEGF-A (r(2)=0.040, P=0.01) and inversely with HbA1C (r(2)=0.036, P=0.03), haemoglobin (r(2)=0.062, P=0.005) and albumin (r(2)=0.0·40, P=0.026). In multiple regression diabetes duration, HbA1C and VEGF-A were significant predictors of ESAM. In controls, ESAM was inversely related to VEGF (r(2)=037, P=0.01). CONCLUSION: Endothelial cell-selective adhesion molecule and VEGF-A are higher in patients with diabetes than in controls. The highest ESAM is found in dialysis patients. ESAM correlates with diabetes duration and control, inflammation and VEGF-A in patients with diabetes, but not in controls.