Pharmacological Management of Diabetic Nephropathy

2020 ◽  
Vol 18 (2) ◽  
pp. 139-147 ◽  
Author(s):  
Vasilios Papademetriou ◽  
Sofia Alataki ◽  
Konstantinos Stavropoulos ◽  
Christodoulos Papadopoulos ◽  
Kostas Bakogiannis ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Renin Angiotensin System ◽  
Lipid Lowering ◽  
Pharmacological Management ◽  
Drug Classes ◽  
Sodium Glucose Cotransporter ◽  
Glucagon Like Peptide 1 ◽  
Lipid Lowering Agents ◽  
The Impact ◽  
Ras Inhibitors

Introduction:Diabetes mellitus (DM) is one of the most common diseases worldwide. Its adverse effects on several body organs, have made treatment of DM a priority. One of the most serious complications of DM is diabetic nephropathy (DN).Objective:The aim of this review is to critically discuss available data on the pharmacological management of DN.Objective:A comprehensive review of the literature was performed to identify studies assessing the impact of several drug classes on DN.Results:Several studies have been conducted in order to find a novel and effective treatment of DN. So far, the cornerstone therapy of DN consists of renin-angiotensin system (RAS) inhibitors, agents that decrease the synthesis of intrarenal angiotensin II or block its receptors. Their antiproteinuric and antihypertensive effects can not only decelerate the progress of DN but prevent its onset as well. Novel antidiabetic drugs, such as sodium-glucose cotransporter 2 inhibitors (SGLT-2i) and glucagon-like peptide- 1 receptor agonists (GLP-1 RA), are promising agents in the therapy of DN, due to their positive effect on renal and cardiovascular adverse events. From lipid-lowering agents, atorvastatin improves DN up to stage 3 and substantially reduces CVD.Conclusion:RAS inhibitors, SGLT-2i and GLP-1 agonists were found to be beneficial for the treatment of DN. Larger renal trials are needed in order to incorporate these drugs into the first line treatment of DN.

scholarly journals Renin Angiotensin System Inhibition and Susceptibility and Outcomes from COVID-19: A Systematic Review and Meta-analysis of 69,200 COVID-19 Patients

2020 ◽  
Author(s):  
Yi Zhang ◽  
Shikai Yu ◽  
Yawei Xu ◽  
Bryan Williams
Keyword(s):  
Systematic Review ◽  
Observational Studies ◽  
Meta Analysis ◽  
Renin Angiotensin System ◽  
Risk Of Infection ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Significant Difference ◽  
The Impact ◽  
Ras Inhibitors

ABSTRACTBackgroundEarly observational studies suggested that the use of the renin angiotensin system (RAS) inhibitors, specifically angiotensin converting enzyme inhibitors or angiotensin receptor blockers, may increase the risk of infection with SARS-CoV-2 and adversely affect the prognosis or survival of infected patients. To explore the impact of RAS inhibitor use on the risk of SARS-CoV-2 infection and the prognosis of SARS-CoV-2 infected patients, from all published studies.Methods and FindingsA systematic review and meta-analysis of the use of RAS inhibitors in relation to infection with SARS-CoV-2 and/or the severity and mortality associated with COVID-19 was conducted. English language bibliographic databases PubMed, Web of Science, OVID Embase, Scopus, MedRxiv, BioRxiv, searched from Jan 1st, 2020 to July 20th, 2020. 58 observational studies (69,200 COVID-19 patients and 3,103,335 controls) were included. There was no difference in the susceptibility to SARS-CoV-2 infection between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.90 to 1.21), (adjusted OR 0.93, 95% CI 0.85 to 1.02), (adjusted HR 1.07, 95% CI 0.87 to 1.31). There was no significant difference in the severe Covid-19 case rate between RAS inhibitor users and non-users (unadjusted OR 1.05, 95% CI 0.81 to 1.36), (adjusted OR 0.76, 95% CI 0.52 to 1.12), or in mortality due to COVID-19 between RAS inhibitor users and non-users (unadjusted OR 1.12, 95% CI 0.88 to 1.44), (adjusted OR 0.97, 95% CI 0.77 to 1.23), (adjusted HR 0.62, 95% CI 0.34 to 1.14).ConclusionsIn the most comprehensive analysis of all available data to date, treatment with RAS inhibitors was not associated with increased risk of infection, severity of disease, or mortality due to COVID-19. The best available evidence suggests that these treatments should not be discontinued on the basis of concern about risk associated with COVID-19.

scholarly journals Treatments for NAFLD: State of Art

2021 ◽  
Vol 22 (5) ◽  
pp. 2350
Author(s):  
Alessandro Mantovani ◽  
Andrea Dalbeni
Keyword(s):  
Risk Factors ◽  
Liver Disease ◽  
Current Knowledge ◽  
Lipid Lowering ◽  
Major Health Problem ◽  
Alcoholic Fatty Liver ◽  
History Of ◽  
Glucagon Like Peptide 1 ◽  
Lipid Lowering Agents

Non-alcoholic fatty liver disease (NAFLD) is to date the most common chronic liver disease in clinical practice and, consequently, a major health problem worldwide. It affects approximately 30% of adults in the general population and up to 70% of patients with type 2 diabetes (T2DM). Despite the current knowledge of the epidemiology, pathogenesis, and natural history of NAFLD, no specific pharmacological therapies are until now approved for this disease and, consequently, general strategies have been proposed to manage it. They include: (a) lifestyle change in order to promote weight loss by diet and physical activity, (b) control of the main cardiometabolic risk factors, (c) correction of all modifiable risk factors leading the development and progression of advanced forms of NAFLD, and (d) prevention of hepatic and extra-hepatic complications. In the last decade, several potential agents have been widely investigated for the treatment of NAFLD and its advanced forms—shedding some light but casting a few shadows. They include some glucose-lowering drugs (such as pioglitazone, glucagon-like peptide-1 (GLP-1) receptor agonists, sodium-glucose co-transporter-2 (SGLT-2) inhibitors), antioxidants (such as vitamin E), statins or other lipid lowering agents, bile and non-bile acid farnesoid X activated receptor (FXR) agonists, and others. This narrative review discusses in detail the different available approaches with the potential to prevent and treat NAFLD and its advanced forms.

scholarly journals Crosstalk of Magnesium and Serum Lipids in Dyslipidemia and Associated Disorders: A Systematic Review

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1411
Author(s):  
Mihnea-Alexandru Găman ◽  
Elena-Codruța Dobrică ◽  
Matei-Alexandru Cozma ◽  
Ninel-Iacobus Antonie ◽  
Ana Maria Alexandra Stănescu ◽  
...  
Keyword(s):  
Lipid Profile ◽  
Serum Lipids ◽  
The Body ◽  
Lipid Lowering ◽  
Cochrane Library ◽  
The Metabolic Syndrome ◽  
The Cochrane Library ◽  
Lipid Lowering Agents ◽  
Lipid Abnormalities ◽  
The Impact

Dyslipidemia is a significant threat to public health worldwide and the identification of its pathogenic mechanisms, as well as novel lipid-lowering agents, are warranted. Magnesium (Mg) is a key element to human health and its deficiency has been linked to the development of lipid abnormalities and related disorders, such as the metabolic syndrome, type 2 diabetes mellitus, or cardiovascular disease. In this review, we explored the associations of Mg (dietary intake, Mg concentrations in the body) and the lipid profile, as well as the impact of Mg supplementation on serum lipids. A systematic search was computed in PubMed/MEDLINE and the Cochrane Library and 3649 potentially relevant papers were detected and screened (n = 3364 following the removal of duplicates). After the removal of irrelevant manuscripts based on the screening of their titles and abstracts (n = 3037), we examined the full-texts of 327 original papers. Finally, after we applied the exclusion and inclusion criteria, a number of 124 original articles were included in this review. Overall, the data analyzed in this review point out an association of Mg concentrations in the body with serum lipids in dyslipidemia and related disorders. However, further research is warranted to clarify whether a higher intake of Mg from the diet or via supplements can influence the lipid profile and exert lipid-lowering actions.

scholarly journals The Role of cAMP in Beta Cell Stimulus–Secretion and Intercellular Coupling

Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1658
Author(s):  
Andraž Stožer ◽  
Eva Paradiž Leitgeb ◽  
Viljem Pohorec ◽  
Jurij Dolenšek ◽  
Lidija Križančić Bombek ◽  
...  
Keyword(s):  
Insulin Secretion ◽  
Pancreatic Beta Cells ◽  
Molecular Mechanisms ◽  
Gastric Inhibitory Polypeptide ◽  
Nucleotide Exchange ◽  
Intercellular Coupling ◽  
Pharmacological Management ◽  
Secondary Messenger ◽  
Glucagon Like Peptide 1 ◽  
The Impact

Pancreatic beta cells secrete insulin in response to stimulation with glucose and other nutrients, and impaired insulin secretion plays a central role in development of diabetes mellitus. Pharmacological management of diabetes includes various antidiabetic drugs, including incretins. The incretin hormones, glucagon-like peptide-1 and gastric inhibitory polypeptide, potentiate glucose-stimulated insulin secretion by binding to G protein-coupled receptors, resulting in stimulation of adenylate cyclase and production of the secondary messenger cAMP, which exerts its intracellular effects through activation of protein kinase A or the guanine nucleotide exchange protein 2A. The molecular mechanisms behind these two downstream signaling arms are still not fully elucidated and involve many steps in the stimulus–secretion coupling cascade, ranging from the proximal regulation of ion channel activity to the central Ca2+ signal and the most distal exocytosis. In addition to modifying intracellular coupling, the effect of cAMP on insulin secretion could also be at least partly explained by the impact on intercellular coupling. In this review, we systematically describe the possible roles of cAMP at these intra- and inter-cellular signaling nodes, keeping in mind the relevance for the whole organism and translation to humans.

scholarly journals Novel multidisciplinary cardiometabolic clinic in a UK tertiary cardiology centre: early activity, interventions and potential for cardiovascular risk optimisation

2021 ◽  
Vol 42 (Supplement_1) ◽  
Author(s):  
R Narain ◽  
L Bijman ◽  
H Joshi ◽  
M Chen
Keyword(s):  
Beta Blockers ◽  
Lipid Lowering ◽  
Current Evidence ◽  
Pharmacological Management ◽  
Funding Sources ◽  
Increased Risk ◽  
Related Hospitalisation ◽  
Cardiac Centre ◽  
Risk Patients ◽  
Glucagon Like Peptide 1

Abstract Introduction Diabetes mellitus (DM) is associated with increased risk of adverse cardiovascular (CV) outcomes and a 2.5x risk of heart failure (HF). The potential to improve clinical outcomes in patients with DM and cardiovascular diseases (CVD) have been augmented by evidence from CV outcome trials of sodium-glucose co-transporter 2 inhibitors (SGLT2) and glucagon-like peptide 1 receptor agonists (GLP-1) demonstrating significant reduction in major adverse CV events (MACE) and reduction in HF-related hospitalisation. Purpose To review the initial activity and clinical interventions resulting from an innovative cardiometabolic clinic (CMC) service within an NHS tertiary cardiac centre, incorporating a consultant diabetologist and cardiologist, in which high risk patients' are addressed simultaneously. Methods Patient data (biochemistry, radiology results and observations including weight, symptoms, blood pressure, blood glucose) and clinic activity (consultation notes and GP correspondence) were reviewed retrospectively over a 6 month period from 29/09/2020 to 29/03/2021. Results A total of 144 patients were referred to CMC, of which 64 were seen during the study period, 6 did not attend, and 74 await an appointment. Of the 64 seen, 13 were discharged back to the referrer and/or to a more appropriate clinician. Referrals to other specialists have been made for 26 patients to augment their care. Initiation of SGLT2 and GLP-1 was recommended for 31 and 9 patients, respectively. Up-titrationof existing SGLT2i and GLP-1 was carried out for two patients already on each of these agents. Additionally, 28 other medications were initiated or optimised (5 diuretics, 3 antihypertensives, 3 lipid-lowering therapies, 2 beta blockers, 1 angiotensin-receptor blocker, 1 anticoagulant, 2 orlistat, 8 metformin and 3 other anti-diabetic). Medications for 12 patients were stopped due to intolerance. Each consultation included lifestyle interventions as per latest ESC guidelines. Among the 32 patients in whom antidiabetic drugs (including SGLT2, GLP-1) have been initiated or titrated, reduction in HbA1c has been observed in 11 patients (mean reduction 17.7 mmol/mol), while 3 have noted an increase (mean 4.7 mmol/mol) and results are pending for 18 patients. Collection of outcomes including hospitalisations for HF, CV events, ejection fraction, and is ongoing. The above has been achieved despite limitations imposed by the remote nature of the clinic due to the COVID-19 pandemic, which limits blood tests, echocardiograms and observations. This limitation is expected to be ameliorated by conducting in-person clinics in future. Conclusions Running of CMC in a MDT setting facilitates optimisation of the pharmacological management of risk factors in patients with cardiac and metabolic disease, particularly incorporation of current evidence-based therapies. Emerging outcomes indicate the potential impact of this service on patients' long term CV outcomes. FUNDunding Acknowledgement Type of funding sources: None.

P5448Enzymatic regulation of the myocardial tissue renin-angiotensin-system of the failing heart

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
H Arfsten ◽  
N Pavo ◽  
R Wurm ◽  
S Prausmueller ◽  
G Spinka ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Failing Heart ◽  
Conversion Rates ◽  
Neprilysin Inhibitor ◽  
Metabolic Activities ◽  
End Stage ◽  
The Impact ◽  
Ras Inhibitors

Abstract Background In heart failure with reduced ejection fraction (HFrEF) the renin-angiotensin-system (RAS) is dysregulated and serves as therapeutic target. Research has been focusing on plasma RAS. Information on tissue RAS is scarce although assumedly more crucial for myocardial function. Among known angiotensins, only AngII and AngIII are detectable in the failing heart. Plasma samples in HFrEF show high AngI and AngII levels with clearly distinguishable AngI/AngII ratios for different RAS-inhibitors. AngII and AngIII levels in the myocardium were comparable for different RAS-inhibitors, i.e. no RAS-blocker, ACE-inhibitor, ARB or angiotensin-receptor neprilysin-inhibitor (ARNI). Here we aimed to elucidate the metabolic regulation of tissue RAS enzymes for these four different modalities of RAS-inhibition. Methods Enzyme regulation and metabolic activities were investigated in myocardial samples of end-stage HFrEF patients undergoing heart transplantation with a mass-spectrometry based method. Concentrations of respective angiotensin metabolites AngI, AngII, Ang1–7, AngIII, Ang1–5 and AngIV (RAS-fingerprints) were investigated after adding AngI or AngII and incubation to display metabolic patterns of the main plasma angiotensins. Metabolic activities of distinct enzymes have been assessed for the no therapy and ACE-I subgroups. Patients were stratified according to background therapy with RAS-inhibitors. Results A total of 30 patients were included (n=6 without RAS-blockade, n=16 with ACE-I, n=6 with ARB, n=2 with ARNI). Median age was 55 (IQR 45–63) years, 87%were male. Etiology of HF was ischemic in 40%, median NT-proBNP levels were 3498pg/ml (IQR 1761–8400). Patterns for tissue RAS metabolism of AngI and AngII was visually similar for all groups, indicating comparable regulation of tissue RAS enzymes independent from therapy (Figure 1). The formation of AngII from AngI was mainly chymase dependent with conversion rates of 99.4 (IQR 77.0–254.1) (pg/μg protein)/h for ACE-I and 141.8 (IQR 67.9–369.2) (pg/μg protein)/h for no RAS-blockade, whereas ACE-related generation of AngII was under the detection limit. The formation of Ang1–7 from AngI was mediated by NEP and PEP. The contribution of NEP was significantly higher [5022 (IQR 5002–5286) (pg/μg)/h vs 3555 (IQR 3351–3849) (pg/μg)/h, p=0.005 for the ACE-I group and 4729 (IQR 4438–6135) (pg/μg)/h vs 3601 (IQR 3052–4182) (pg/μg)/h, p=0.012 for no RAS-blockade]. No differences in tissue enzymatic activities between ACE-I and no therapy, as already indicated by the metabolization patterns occurred. Figure 1 Conclusions Enzymatic tissue RAS regulation in end-stage HF seems to be independent from the mode of established RAS-inhibitor therapy.In contrast to plasma, AngII formation of the tissue is mainly chymase dependent, whereas ACE seems to play an unsignificant role. NEP has a substantial role in generating beneficial Ang1–7 from AngI. The impact of NEP inhibition by ARNI on tissue RAS and mechanism of action have to be further investigated.

scholarly journals Impact of renin-angiotensin system inhibitors and beta-blockers on dental implant stability

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Babak Saravi ◽  
Andreas Vollmer ◽  
Gernot Lang ◽  
Nicholai Adolphs ◽  
Zhen Li ◽  
...  
Keyword(s):  
Bone Remodeling ◽  
Dental Implant ◽  
Antihypertensive Medication ◽  
Beta Blockers ◽  
Renin Angiotensin System ◽  
Implant Stability ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Impact ◽  
Ras Inhibitors

Abstract Background Current experimental research suggests antihypertensive medication reduces the failure risk of dental implants due to enhanced bone remodeling. However, evidence from clinical studies evaluating the impact of antihypertensive medication on implant stability is lacking. Methods We retrospectively analyzed 377 implants in 196 patients (46 implants inserted in antihypertensive drug users (AH) and 331 implants in non-users (NAH)) for implant stability measured by radiofrequency analysis, and we determined the implant stability quotient (ISQ). AH subgroups were stratified by the use of beta-blockers, renin-angiotensin system (RAS) inhibitors, and both of the aforementioned. The impact of antihypertensive medication on ISQ values at implant insertion (primary stability) and implant exposure (secondary stability) was analyzed by a linear regression model with a regression coefficient and its 95% confidence interval (95% CI), adjusted for potential confounders. Results Time between implant insertion and implant exposure was 117.1 ± 56.6 days. ISQ values at insertion were 71.8 ± 8.7 for NAH and 74.1 ± 5.6 for AH, respectively. ISQ at exposure was 73.7 ± 8.1 for NAH and 75.7 ± 5.9 for AH. Regression analysis revealed that none of the AH subgroups were significantly related to ISQ at implant insertion. However, renin-angiotensin system inhibitors (RAS) were significantly associated with higher ISQ values at exposure (reg. coeff. 3.59, 95% CI 0.46–6.71 (p=0.025)). Conclusions Outcome of the present study indicates enhanced bone remodeling and osseointegration following dental implant insertion in patients taking RAS inhibitors than in non-users. Future randomized prospective studies must confirm these indicative results.

scholarly journals Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Targets

2020 ◽  
Vol 11 ◽  
Author(s):  
Carlamaria Zoja ◽  
Christodoulos Xinaris ◽  
Daniela Macconi
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Therapeutic Targets ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Experimental Models ◽  
Lipid Lowering ◽  
Diabetic Patients ◽  
Functional Changes

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes mellitus and the leading cause of end-stage kidney disease. The standard treatments for diabetic patients are glucose and blood pressure control, lipid lowering, and renin-angiotensin system blockade; however, these therapeutic approaches can provide only partial renoprotection if started late in the course of the disease. One major limitation in developing efficient therapies for DN is the complex pathobiology of the diabetic kidney, which undergoes a set of profound structural, metabolic and functional changes. Despite these difficulties, experimental models of diabetes have revealed promising therapeutic targets by identifying pathways that modulate key functions of podocytes and glomerular endothelial cells. In this review we will describe recent advances in the field, analyze key molecular pathways that contribute to the pathogenesis of the disease, and discuss how they could be modulated to prevent or reverse DN.

scholarly journals Targeting Metabolic Dysfunction for the Treatment of Mood Disorders: Review of the Evidence

Life ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 819
Author(s):  
Brett D. M. Jones ◽  
Salman Farooqui ◽  
Stefan Kloiber ◽  
Muhammad Omair Husain ◽  
Benoit H. Mulsant ◽  
...  
Keyword(s):  
Mood Disorders ◽  
Structural Changes ◽  
Current Knowledge ◽  
Lipid Lowering ◽  
Current Evidence ◽  
Metabolic Dysfunction ◽  
Specific Symptom ◽  
Novel Treatments ◽  
Lipid Lowering Agents ◽  
The Impact

Major depressive disorder (MDD) and bipolar disorder (BD) are often chronic with many patients not responding to available treatments. As these mood disorders are frequently associated with metabolic dysfunction, there has been increased interest in novel treatments that would target metabolic pathways. The objectives of this scoping review were to synthesize evidence on the impact on mood symptoms of lipid lowering agents and anti-diabetics drugs, while also reviewing current knowledge on the association between mood disorders and dyslipidemia or hyperglycemia. We propose that metabolic dysfunction is prevalent in both MDD and BD and it may contribute to the development of these disorders through a variety of pathophysiological processes including inflammation, brain structural changes, hormonal alterations, neurotransmitter disruptions, alteration on brain cholesterol, central insulin resistance, and changes in gut microbiota. Current evidence is conflicting on the use of statins, polyunsaturated fatty acids, thiazolidinediones, glucagon-like peptide agonists, metformin, or insulin for the treatment of MDD and BD. Given the paucity of high-quality randomized controlled trials, additional studies are needed before any of these medications can be repurposed in routine clinical practice. Future trials need to enrich patient recruitment, include evaluations of mechanism of action, and explore differential effects on specific symptom domains such as anhedonia, suicidality, and cognition.

scholarly journals Pharmacogenetics of new classes of antidiabetic drugs

2021 ◽  
Author(s):  
Selma Imamovic Kadric ◽  
Aida Kulo Cesic ◽  
Tanja Dujic
Keyword(s):  
Drug Targets ◽  
Antidiabetic Drugs ◽  
Atherosclerotic Cardiovascular Disease ◽  
Protective Effects ◽  
Metabolizing Enzymes ◽  
Dipeptidyl Peptidase 4 ◽  
Drug Classes ◽  
Sodium Glucose Cotransporter ◽  
Dipeptidyl Peptidase 4 Inhibitors ◽  
Glucagon Like Peptide 1

Type 2 diabetes (T2D) has a continuously rising prevalence worldwide. Pharmacogenetics has been recognized as a promising concept for pharmacological treatment of T2D, as antidiabetic drugs are not equally effective and safe for all patients, and the costs of diabetes treatment are increasing. The latest published guidelines on T2D treatment firmly endorse the use of newer antidiabetic drugs, sodium-glucose cotransporter-2 inhibitors (SGLT2i), dipeptidyl peptidase-4 inhibitors (DPP-IVi), and glucagon-like peptide-1 receptor agonists (GLP-1RA), considering their satisfactory pharmacological effect and good safety profile. Furthermore, SGLT2i and GLP-1RA show protective effects in patients with established atherosclerotic cardiovascular disease and chronic kidney disease. However, there has been growing evidence that the effectiveness and safety of these drug classes could depend on genetic variability. Here we summarized the results of the published studies on the pharmacogenetic biomarkers for the three drug classes. A number of genetic variations have been investigated so far. The explored candidate genes mostly encode drug targets, drug-metabolizing enzymes, and genes linked to T2D risk. Although many of the results are promising, it is still necessary to obtain more information from larger controlled studies to confirm their clinical significance. This approach may lead towards more personalized treatment for patients with T2D.

Sign in / Sign up

Export Citation Format

Share Document