scholarly journals Possible Mechanisms of Local Tissue Renin-Angiotensin System Activation in the Cardiorenal Metabolic Syndrome and Type 2 Diabetes Mellitus

2011 ◽  
Vol 1 (3) ◽  
pp. 193-210 ◽  
Author(s):  
Melvin R. Hayden ◽  
Kurt M. Sowers ◽  
Lakshmi Pulakat ◽  
Tejaswini Joginpally ◽  
Bennett Krueger ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Type 2 Diabetes Mellitus ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Local Tissue ◽  
System Activation

scholarly journals Efficacy and Safety of Esaxerenone (CS-3150) for the Treatment of Type 2 Diabetes with Microalbuminuria

2019 ◽  
Vol 14 (8) ◽  
pp. 1161-1172 ◽  
Author(s):  
Sadayoshi Ito ◽  
Kenichi Shikata ◽  
Masaomi Nangaku ◽  
Yasuyuki Okuda ◽  
Tomoko Sawanobori
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Adverse Events ◽  
Renin Angiotensin System ◽  
Urinary Albumin ◽  
Creatinine Ratio ◽  
Angiotensin System ◽  
Renin Angiotensin

Background and objectivesThe progression of kidney disease in some patients with type 2 diabetes mellitus may not be adequately suppressed by renin-angiotensin system inhibitors. Esaxerenone (CS-3150) is a nonsteroidal mineralocorticoid receptor blocker that has shown kidney protective effects in preclinical studies, and it is a potential add-on therapy to treat diabetic kidney disease. This phase 2 study evaluated the efficacy and safety of esaxerenone in Japanese patients with type 2 diabetes mellitus and microalbuminuria.Design, setting, participants, & measurementsThis multicenter, randomized, double-blind, placebo-controlled trial enrolled 365 hypertensive or normotensive patients with type 2 diabetes mellitus and microalbuminuria (urinary albumin-to-creatinine ratio ≥45 to <300 mg/g creatinine) treated with renin-angiotensin system inhibitor who had eGFR≥30 ml/min per 1.73 m2. Participants were randomized to receive 0.625, 1.25, 2.5, or 5 mg/d esaxerenone or placebo for 12 weeks. The primary end point was the change in urinary albumin-to-creatinine ratio from baseline to week 12 (with last observation carried forward).ResultsEsaxerenone treatment at 1.25, 2.5, and 5 mg/d significantly reduced urinary albumin-to-creatinine ratio by the end of treatment (38%, 50%, and 56%, respectively) compared with placebo (7%; all P<0.001). The urinary albumin-to-creatinine ratio remission rate (defined as urinary albumin-to-creatinine ratio <30 mg/g creatinine at the end of treatment and ≥30% decrease from baseline) was 21% in the 2.5- and 5-mg/d groups versus 3% for placebo (both P<0.05). Adverse events occurred slightly more frequently with esaxerenone versus placebo, but the frequencies of drug-related adverse events and discontinuation rates were similar in the placebo and the 0.625-, 1.25-, and 2.5-mg/d groups. Drug-related adverse events and treatment discontinuations were marginally higher in the 5-mg/d group. The most common drug-related adverse event was hyperkalemia, which was dose proportional.ConclusionsAdding esaxerenone at 1.25, 2.5, and 5 mg/d for 12 weeks to an ongoing renin-angiotensin system inhibitor significantly reduces urinary albumin-to-creatinine ratio in patients with type 2 diabetes mellitus and microalbuminuria.

scholarly journals Family history and renin-angiotensin system gene polymorphisms in Chinese patients with type 2 diabetes mellitus

Medicine ◽  
2017 ◽  
Vol 96 (51) ◽  
pp. e9148 ◽  
Author(s):  
Yan-Hong Pan ◽  
Yan-Mei Huang ◽  
Yong-Chao Qiao ◽  
Wei Ling ◽  
Li-Jun Geng ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Family History ◽  
Gene Polymorphisms ◽  
Renin Angiotensin System ◽  
Chinese Patients ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals Renin-Angiotensin System Gene Variants and Type 2 Diabetes Mellitus: Influence of Angiotensinogen

2016 ◽  
Vol 2016 ◽  
pp. 1-7 ◽  
Author(s):  
Siew Mei Joyce-Tan ◽  
Shamsul Mohd Zain ◽  
Munavvar Zubaid Abdul Sattar ◽  
Nor Azizan Abdullah
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Renin Angiotensin System ◽  
Gene Interactions ◽  
Candidate Gene Approach ◽  
Genome Wide Association Studies ◽  
Angiotensin System ◽  
Renin Angiotensin

Genome-wide association studies (GWAS) have been successfully used to call for variants associated with diseases including type 2 diabetes mellitus (T2DM). However, some variants are not included in the GWAS to avoid penalty in multiple hypothetic testing. Thus, candidate gene approach is still useful even at GWAS era. This study attempted to assess whether genetic variations in the renin-angiotensin system (RAS) and their gene interactions are associated with T2DM risk. We genotyped 290 T2DM patients and 267 controls using three genes of the RAS, namely, angiotensin converting enzyme (ACE), angiotensinogen (AGT), and angiotensin II type 1 receptor (AGTR1). There were significant differences in allele frequencies between cases and controls forAGTvariants (P=0.05) but not forACEandAGTR1. Haplotype TCG of theAGTwas associated with increased risk of T2DM (OR 1.92, 95% CI 1.15–3.20, permutedP=0.012); however, no evidence of significant gene-gene interactions was seen. Nonetheless, our analysis revealed that the associations of theAGTvariants with T2DM were independently associated. Thus, this study suggests that genetic variants of the RAS can modestly influence the T2DM risk.

scholarly journals The role of the renin-angiotensin system gene polymorphisms in the development of carbohydrate disorders in patients with arterial hypertension

2019 ◽  
Vol 34 (3) ◽  
pp. 33-39
Author(s):  
L. V. Zhuravlyova ◽  
M. V. Kulikova
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Arterial Hypertension ◽  
Gene Polymorphisms ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

Arterial hypertension and type 2 diabetes mellitus are the most widespread comorbid pathologies. The coexistence of these disorders accelerates the development of micro- and macrovascular complications, considerably increases the cardiovascular risk, as well as the risk of stroke and end stage renal disease. The synergism of these two pathologies is caused by the unity of pathogenetic mechanisms. Genetic predisposition also contributes to the development of both pathologies. It is well known that blockade of the renin-angiotensin system slows down the development of type 2 diabetes mellitus and also reduces the frequency of cardiovascular or kidney events in patients with these disorders. Gene polymorphisms of the reninangiotensin system are thoughtfully studied in the context of cardiovascular disease development. Currently, the role of gene polymorphisms in the development of carbohydrate disorders is not established, however, there is a high probability of their influence and importance. The purpose of review is to analyze the accumulated data on the effects of the renin-angiotensin system gene polymorphisms on the development of arterial hypertension and type 2 diabetes mellitus.

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