Our results show that FDTV produces a greater reduction of VCAM-1 circulating levels than trandolapril alone. This may explain some of the beneficial effects of this fixed dosed combination that are non-related to its antihypertensive effects.
Endothelial dysfunction is a common feature in type-2 diabetic patients and in hypertension, and is associated with inflammation, increased levels of circulating soluble adhesion molecules, and atherosclerosis. The aim of this study was to evaluate the relationship between the levels of circulating soluble adhesion molecules and the degree of atherosclerosis in hypertensive type-2 diabetic patients. We studied 30 hypertensive type-2 diabetic patients in whom VCAM-1, ICAM-1, and E-selectin were measured by ELISA. Additionally, the intimal-medial thickness of both the common and internal carotid arteries was measured (B-mode ultrasound). The levels of circulating adhesion molecules and maximal carotid artery intimal-medial thicknesses were correlated using the Spearman correlation coefficient test. Statistical analysis was performed with ANOVA. We found significant correlations between ICAM-1 (r = 0.5) levels and maximal carotid artery intimal-medial thickness these patients. No correlation was observed with E-selectin and VCAM-1. Our results suggest that ICAM-1 is associated and correlated with the degree of atherosclerosis in type-2 diabetic hypertensive patients.
OBJECTIVE -To compare the effect of fixed-dose trandolapril-verapamil (FDTV) with that of trandolapril on proteinuria in normotensive, type 2 diabetic patients.
RESEARCH DESIGN AND METHODS-A total of 60 normotensive, type 2 diabetic patients with 24-h proteinuria Ͼ300 mg were randomly assigned to two groups for open-label treatment. One group received 2 mg trandolapril/180 mg verapamil FDTV once daily; the other group received 2 mg trandolapril once daily. Study drugs were administered for 6 months in both groups. Creatinine clearance and 24-h urinary protein excretion were measured at the beginning and the end of the study. Patients were evaluated monthly for blood pressure, fasting blood glucose level, heart rate, and adverse events. Statistical analysis was performed using ANOVA.RESULTS -Both groups experienced a statistically significant (P Ͻ 0.005) mean decrease in mean proteinuria from baseline: FDTV ([mean Ϯ SD] 1,200 Ϯ 200 to 540 Ϯ 79 mg; P Ͻ 0.001) and trandolapril (1,105 Ϯ 212 to 750.9 Ϯ 134 mg; P Ͻ 0.005). A significantly greater reduction from baseline in proteinuria was observed in the FDTV group compared with the trandolapril group. Patients who received trandolapril experienced a statistically significant (P Ͻ 0.05) decrease in mean creatinine clearance (91.1 Ϯ 3.4 to 75.3 Ϯ 3 ml/min; P Ͻ 0.05) compared with patients who received FDTV (88.3 Ϯ 3.6 to 82.9 Ϯ 3.5 ml/min; P Ͼ 0.05). Final fasting blood glucose was significantly lower in the FDTV group (139 Ϯ 19) compared with the trandolapril group (154 Ϯ 22; P Ͻ 0.001). No significant differences were observed between the two groups in mean baseline or final measurements of blood pressure, mean heart rate, or frequency of adverse events.CONCLUSIONS -Our results suggest that FDTV is more effective than trandolapril in reducing proteinuria in normotensive, type 2 diabetic patients. This effect on proteinuria is not related with blood pressure reduction.
Diabetes Care 27:1688 -1691, 2004T he prevalence of diabetic nephropathy is ϳ30% in patients with type 2 diabetes after 20 -30 years. It is the most common cause of end-stage renal disease and increases the mortality rate in those patients (1,2). In diabetic patients, proteinuria levels are related not only to the progression of nephropathy but also to cardiovascular mortality, and in Mexico, proteinuria has a prevalence of 9.3% in type 2 diabetic normotensive patients (3). In turn, reduction of proteinuria or delay in its progression may delay the onset of end-stage renal disease.Recent clinical studies have shown that several therapeutic strategies are available to delay the progression of diabetic nephropathy: rigorous glycemic control, aggressive antihypertensive control to achieve blood pressure values Ͻ130/80 mmHg, and blockade of the renin-angiotensin system (1).To decrease morbidity and mortality due to diabetic nephropathy, early detection of patients at risk is critical, as is the application of all necessary therapeutic measures. The 2003 European Society of Hypertension-European Society of C...
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