IntroductionCardiovascular disease (CVD) and chronic kidney disease (CKD) closely parallel the epidemic of obesity and insulin resistance. Current estimates in the United States predict 70 million adults are obese and an additional 70 million have hypertension and/or type II diabetes (28, 42, 45). Even more, the National Health and Nutrition Examination Survey (NHANES) suggests that there is a graded and continuous relationship between widespread hypertension and increased body mass index (BMI); a measure that is closely associated with insulin resistance and self-identified type II diabetes (8, 34). Latent vascular complications of diabetes are a hallmark of the disease and are known to significantly affect the cardiovascular and renal systems. Atherosclerosis is the main reason for decreased life expectancy in diabetic patients, while diabetic nephropathy and retinopathy are the largest contributors to end-stage renal disease and blindness, respectively (37, 56). . Current treatment aims to manage blood glucose concentrations and increase insulin resistance. Thus, mitigation of vascular complications includes: monitoring and lowering blood sugar levels, which reduces the risk of nephropathy and retinopathy. Antihypertensive medications are also used to decrease the risk of cardiovascular disease, kidney disease, and retinopathy (15, 26). Additionally, hypertension is closely associated with stroke and pulmonary edema. Despite these advances, diabetes complications and their treatments aim to alleviate symptoms with the goal of improving physiological function. Atherosclerosis in Diabetes Atherosclerotic lesions in diabetic patients cannot be distinguished from lesions in patients in whom another feature, such as hypercholesterolemia or smoking, is the primary one. ..... middle of paper ......insulin resistance in skeletal muscle (11, 32, 43). It should not be overlooked, however, that the MR also has a strong affinity for aldosterone and 11β-hydroxy-glucocorticoids, which exist at lower levels in non-epithelial tissues that allow glucocorticoids to signal via the MR in the cardiovascular and metabolic tissues such as skeletal tissues. muscles, liver and fat (72). This is not a marginal point because insulin-resistant populations have plasma concentrations of glucocorticoids higher than those of aldosterone, which may favor activation of MR by glucocorticoids. Potentiation of oxidative stress in cardio-renal metabolic syndrome (71). Regardless of the indirect/direct mechanism, evidence of RAAS blockade or inactivation may attenuate oxidative stress, improve endothelial function, and contribute to the reduction of hypertension in the cardio-renal metabolic phenotype...