Prevention of Macrovascular Disease in Type 2 Diabetic Patients: Blockade of the Renin-Angiotensin-Aldosterone System

Abstract

Type 2 diabetes is reaching epidemic proportions throughout the world, which has major health implications as such patients have considerably increased risk of coronary heart disease (CHD). The renin-angiotensin-aldosterone system (RAAS) is involved in a wide range of adverse effects that contribute to the pathogenesis of CHD in diabetic patients, including vascular haemodynamic regulation, oxidative stress and hypertrophy of vascular cells. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) are widely used in clinical practice. In diabetic patients ACE inhibitors and ARBs both effectively lower blood pressure, particularly in combination with low-dose thiazide diuretics, and may be considered first line therapies in the treatment of diabetic hypertension. Additionally they have important renoprotective actions independent of their blood pressure-lowering action, which is of particular benefit in diabetic patients, who are at increased risk of developing nephropathy. ARBs are generally well tolerated, but ACE inhibitor therapy is associated with some side effects such as cough and both may result in hyperkalaemia. Blockade of the RAAS with these agents appears to play an important role not only in protecting from renal disease, but it may also help to reduce morbidity and mortality from certain vascular diseases in diabetic patients.

Effect of Comorbidities and Medications on Left Ventricular Mass Regression After Bariatric Surgery

“…17,19 ACE inhibitors and ARBs are clearly preferred agents for treatment of HTN and ⁄ or congestive heart failure in diabetic patients. 21 Our study offers new insights into this important problem. We observed that, despite similar baseline BP control, b-blocker-treated obese patients have significantly increased pre-weight loss LVM.…”

“…The choice of BP medication may also be an important predictor of LVM reduction. 5,7,[16][17][18][19][20][21] Interaction between comorbidities and cardiovascular medications and LVH regression in patients after substantial weight loss has not been well studied. Although, the average baseline LVM in all subgroups was >215 g, which can be defined as LVH, [11][12][13][14][15] this cannot be generalized for all of our study patients.…”

Renin–angiotensin–aldosterone system genotypes and haplotypes affect the susceptibility to nephropathy in type 2 diabetes patients

“…Diabetic nephropathy (DN) is a leading cause of morbidity and mortality in type 2 diabetes (T2DM) patients, 1,2 and is multifactorial, with both modifiable (hypertension, smoking, hyperlipidaemia) and non-modifiable (race, genetic background) factors influencing its susceptibility. 3,4 DN is characterised by progressive deterioration of renal function and hypertension, and is aggravated by hyperglycemia.…”

“…17 Blockade of RAAS by ACE-I and ARBs prevented structural and functional changes in the diabetic kidney, further establishing a role for RAAS in DN. 2,18 Several studies investigated the possible associations between RAAS gene polymorphisms, including renin (C-4063T) and angiotensinogen (AGT; T174M, M235T and A-6G) and DN susceptibility, with inconsistencies. M235T variant associated with higher levels of circulating AGT, 19,20 was associated with hypertension 21,22 and faster progression to end-stage renal disease (ESRD) in glomerulonephritis patients, 23 and increased susceptibility to nephropathy in type 1 diabetes (T1D) patients; 24 others failed to establish a role for this variant in DN.…”

Genetic Predisposition to Diabetic Nephropathy: Evidence for a Role of ACE (I/D) Gene Polymorphism in Type 2 Diabetic Population from Kutch Region

“…This has occurred based on the findings that angiotensin II induces progressive renal injury in DN, in part by increasing cellular growth and proliferation and matrix synthesis, leading to glomerular sclerosis [15], as well as by bringing changes in renal hemodynamics, such as an increase in intra-glomerular pressure [16,17]. Blockade of RAAS by ACE-Inhibitors and angiotensin receptor blockers (ARBs) in clinical and experimental studies prevented structural and functional changes in the diabetic kidney, further establishing its role in DN [18][19][20].…”