scholarly journals Evidence for human diabetic cardiomyopathy

2021 ◽  
Author(s):  
Raffaele Marfella ◽  
Celestino Sardu ◽  
Gelsomina Mansueto ◽  
Claudio Napoli ◽  
Giuseppe Paolisso
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Epidemiological Data ◽  
Diabetic Patients ◽  
Preclinical Models ◽  
Unique Data ◽  
High Incidence ◽  
Definition Of ◽  
End Stage ◽  
Heart Specimen

AbstractGrowing interest has been accumulated in the definition of worsening effects of diabetes in the cardiovascular system. This is associated with epidemiological data regarding the high incidence of heart failure (HF) in diabetic patients. To investigate the detrimental effects both of hyperglycemia and insulin resistance, a lot of preclinical models were developed. However, the evidence of pathogenic and histological alterations of the so-called diabetic cardiomyopathy (DCM) is still poorly understood in humans. Here, we provide a stringent literature analysis to investigate unique data regarding human DCM. This approach established that lipotoxic-related events might play a central role in the initiation and progression of human DCM. The major limitation in the acquisition of human data is due to the fact of heart specimen availability. Postmortem analysis revealed the end stage of the disease; thus, we need to gain knowledge on the pathogenic events from the early stages until cardiac fibrosis underlying the end-stage HF.

Metformin impairs homing ability and efficacy of mesenchymal stem cells for cardiac repair in streptozotocin-induced diabetic cardiomyopathy in rats

2021 ◽  
Author(s):  
Hania Ibrahim Ammar ◽  
Asmaa Mohammed Shamseldeen ◽  
Heba Samy Shoukry ◽  
Hend Ashour ◽  
Samaa Samir Kamar ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Diabetic Patients ◽  
World Population ◽  
Metformin Treatment ◽  
Poor Survival ◽  
Male Wistar Rats ◽  
Multiple Drugs

Bone marrow derived mesenchymal stem cells (BM-MSCs) have demonstrated potential in treating diabetic cardiomyopathy. However, diabetic patients are on multiple drugs and there is lack of understanding on how transplanted stem cells would respond in presence of such drugs. Metformin is an AMP Kinase (AMPK) activator, the widest used anti-diabetic drug. In this study, we investigated the effect of metformin on the efficacy of stem cell therapy in a diabetic cardiomyopathy animal model using streptozotocin (STZ) in male Wistar rats. To comprehend the effect of metformin on the efficacy of BM-MSCs, we transplanted BM-MSCs (1 million cells/rat) with or without metformin. Our data demonstrate that transplantation of BM-MSCs prevented cardiac fibrosis and promoted angiogenesis in diabetic hearts. However, metformin supplementation downregulated BM-MSCs mediated cardioprotection. Interestingly, both BM-MSCs and metformin treatment individually, improved cardiac function with no synergistic effect of metformin supplementation along with BM-MSCs. Investigating the mechanisms of loss of efficacy of BM-MSCs in the presence of metformin, we found that metformin treatment impairs homing of implanted BM-MSCs in the heart and leads to poor survival of transplanted cells. Furthermore, our data demonstrate that metformin mediated activation of AMPK is responsible for poor homing and survival of BM-MSCs in the diabetic heart. Hence, current study confirms that a conflict arises between metformin and BM-MSCs for treating diabetic cardiomyopathy. Approximately 10% of the world population is diabetic to which metformin is prescribed very commonly. Hence, future cell replacement therapies in combination with AMPK inhibitors may be more effective for diabetic patients.

scholarly journals Current Status and Potential Therapeutic Strategies for Using Non-coding RNA to Treat Diabetic Cardiomyopathy

2021 ◽  
Vol 11 ◽  
Author(s):  
Amit K. Rai ◽  
Brooke Lee ◽  
Ramesh Gomez ◽  
Deepu Rajendran ◽  
Mahmood Khan ◽  
...  
Keyword(s):  
Diabetic Cardiomyopathy ◽  
Cardiac Fibrosis ◽  
Systolic Dysfunction ◽  
Therapeutic Strategies ◽  
Current Status ◽  
Circular Rnas ◽  
Diabetic Patients ◽  
Mortality And Morbidity ◽  
Micro Rnas ◽  
Non Coding Rnas

Diabetic cardiomyopathy (DMCM) is the leading cause of mortality and morbidity among diabetic patients. DMCM is characterized by an increase in oxidative stress with systemic inflammation that leads to cardiac fibrosis, ultimately causing diastolic and systolic dysfunction. Even though DMCM pathophysiology is well studied, the approach to limit this condition is not met with success. This highlights the need for more knowledge of underlying mechanisms and innovative therapies. In this regard, emerging evidence suggests a potential role of non-coding RNAs (ncRNAs), including micro-RNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) as novel diagnostics, mechanisms, and therapeutics in the context of DMCM. However, our understanding of ncRNAs’ role in diabetic heart disease is still in its infancy. This review provides a comprehensive update on pre-clinical and clinical studies that might develop therapeutic strategies to limit/prevent DMCM.

scholarly journals Nutraceuticals as a New Approach in Management of Diabetic Nephropathy

2021 ◽  
Vol 23 (08) ◽  
pp. 720-737
Author(s):  
Rajni ◽  
◽  
Rashmi ◽  
Richa ◽  
Riya ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Epidemiological Data ◽  
Diabetic Complication ◽  
Omega 3 ◽  
New Approach ◽  
Clinical Endpoints ◽  
Definition Of ◽  
Stage Renal Disease ◽  
End Stage ◽  
And Control

Diabetic nephropathy (DN), a fatal diabetic complication, is a prime reason of end-stage renal disease (ESRD), which is pathologically identified by thickened tubular basal and glomerular membranes, amassed extracellular matrix (ECM), and developing meningeal hypertrophy. Various deformities in the signaling pathway can interact to give rise to these pathologic activities in DN. In spite of the accessibility of numerous approaches to prevent these metabolic changes which include proper diet, exercising regularly, control of weight and control of drugs, epidemiological data are observing the growing tendency of the complication, indicating both the multifactorial nature of these disorders as well as the scarce conformance of patients to begin strategies. A number of Nutraceuticals utilized in clinical practice were shown to aim the pathophysiology of diabetes mellitus, metabolic disorder and their complications and to favorably modify numerous biochemical and clinical endpoints. These compounds comprise of antioxidants, vitamins like vitamin C, E, D; Omega 3 fatty acids, alpha lipoic acid (ALA), dietary fibers, flavonoids, phytoestrogens and minerals like chromium, magnesium. Various areas of concern prevail with regard of the use of nutraceuticals and dietary supplements in this setting, inclusive of standardization of products, potential side effects, definition of dosing regimen, interaction of drugs and need for evidence based interactions.

scholarly journals Comprehensive Analysis of Cardiac Xeno-Graft Unveils Rejection Mechanisms

2021 ◽  
Vol 22 (2) ◽  
pp. 751
Author(s):  
Min Young Park ◽  
Bala Murali Krishna Vasamsetti ◽  
Wan Seop Kim ◽  
Hee Jung Kang ◽  
Do-Young Kim ◽  
...  
Keyword(s):  
Graft Rejection ◽  
Molecular Mechanisms ◽  
Cardiac Fibrosis ◽  
Cardiac Tissue ◽  
Inflammatory Responses ◽  
Blood Parameters ◽  
Quantitative Real Time Pcr ◽  
Porcine Heart ◽  
End Stage Heart Failure ◽  
End Stage

Porcine heart xenotransplantation is a potential treatment for patients with end-stage heart failure. To understand molecular mechanisms of graft rejection after heart transplantation, we transplanted a 31-day-old alpha-1,3-galactosyltransferase knockout (GTKO) porcine heart to a five-year-old cynomolgus monkey. Histological and transcriptome analyses were conducted on xenografted cardiac tissue at rejection (nine days after transplantation). The recipient monkey’s blood parameters were analyzed on days −7, −3, 1, 4, and 7. Validation was conducted by quantitative real-time PCR (qPCR) with selected genes. A non-transplanted GTKO porcine heart from an age-matched litter was used as a control. The recipient monkey showed systemic inflammatory responses, and the rejected cardiac graft indicated myocardial infarction and cardiac fibrosis. The transplanted heart exhibited a total of 3748 differentially expressed genes compared to the non-transplanted heart transcriptome, with 2443 upregulated and 1305 downregulated genes. Key biological pathways involved at the terminal stage of graft rejection were cardiomyopathies, extracellular interactions, and ion channel activities. The results of qPCR evaluation were in agreement with the transcriptome data. Transcriptome analysis of porcine cardiac tissue at graft rejection reveals dysregulation of the key molecules and signaling pathways, which play relevant roles on structural and functional integrities of the heart.

scholarly journals Serum Amyloid Beta42 Is Not Eliminated by the Cirrhotic Liver: A Pilot Study

2021 ◽  
Vol 10 (12) ◽  
pp. 2669
Author(s):  
Reiner Wiest ◽  
Thomas S. Weiss ◽  
Lusine Danielyan ◽  
Christa Buechler
Keyword(s):  
Liver Cirrhosis ◽  
Hepatic Clearance ◽  
Protective Role ◽  
Tissue Growth ◽  
Cirrhotic Liver ◽  
Diabetic Patients ◽  
Peripheral Clearance ◽  
End Stage ◽  
The Brain

Amyloid-beta (Aβ) deposition in the brain is the main pathological hallmark of Alzheimer disease. Peripheral clearance of Aβ may possibly also lower brain levels. Recent evidence suggested that hepatic clearance of Aβ42 is impaired in liver cirrhosis. To further test this hypothesis, serum Aβ42 was measured by ELISA in portal venous serum (PVS), systemic venous serum (SVS), and hepatic venous serum (HVS) of 20 patients with liver cirrhosis. Mean Aβ42 level was 24.7 ± 20.4 pg/mL in PVS, 21.2 ± 16.7 pg/mL in HVS, and 19.2 ± 11.7 pg/mL in SVS. Similar levels in the three blood compartments suggested that the cirrhotic liver does not clear Aβ42. Aβ42 was neither associated with the model of end-stage liver disease score nor the Child–Pugh score. Patients with abnormal creatinine or bilirubin levels or prolonged prothrombin time did not display higher Aβ42 levels. Patients with massive ascites and patients with large varices had serum Aβ42 levels similar to patients without these complications. Serum Aβ42 was negatively associated with connective tissue growth factor levels (r = −0.580, p = 0.007) and a protective role of Aβ42 in fibrogenesis was already described. Diabetic patients with liver cirrhosis had higher Aβ42 levels (p = 0.069 for PVS, p = 0.047 for HVS and p = 0.181 for SVS), which is in accordance with previous reports. Present analysis showed that the cirrhotic liver does not eliminate Aβ42. Further studies are needed to explore the association of liver cirrhosis, Aβ42 levels, and cognitive dysfunction.

scholarly journals Identification of Novel Biomarker for Early Detection of Diabetic Nephropathy

Biomedicines ◽  
2021 ◽  
Vol 9 (5) ◽  
pp. 457
Author(s):  
Kyeong-Seok Kim ◽  
Jin-Sol Lee ◽  
Jae-Hyeon Park ◽  
Eun-Young Lee ◽  
Jong-Seok Moon ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Early Stage ◽  
Kidney Injury ◽  
Diabetic Patients ◽  
High Morbidity ◽  
Neutrophil Gelatinase Associated Lipocalin ◽  
Zucker Diabetic Fatty Rats ◽  
Kidney Injury Molecule 1 ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is one of the most common complications of diabetes mellitus. After development of DN, patients will progress to end-stage renal disease, which is associated with high morbidity and mortality. Here, we developed early-stage diagnostic biomarkers to detect DN as a strategy for DN intervention. For the DN model, Zucker diabetic fatty rats were used for DN phenotyping. The results revealed that DN rats showed significantly increased blood glucose, blood urea nitrogen (BUN), and serum creatinine levels, accompanied by severe kidney injury, fibrosis and microstructural changes. In addition, DN rats showed significantly increased urinary excretion of kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-associated lipocalin (NGAL). Transcriptome analysis revealed that new DN biomarkers, such as complementary component 4b (C4b), complementary factor D (CFD), C-X-C motif chemokine receptor 6 (CXCR6), and leukemia inhibitory factor (LIF) were identified. Furthermore, they were found in the urine of patients with DN. Since these biomarkers were detected in the urine and kidney of DN rats and urine of diabetic patients, the selected markers could be used as early diagnosis biomarkers for chronic diabetic nephropathy.

scholarly journals Renoprotective Effects of the Dipeptidyl Peptidase-4 Inhibitor Sitagliptin: A Review in Type 2 Diabetes

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Cristina Mega ◽  
Edite Teixeira-de-Lemos ◽  
Rosa Fernandes ◽  
Flávio Reis
Keyword(s):  
Type 2 Diabetes ◽  
Current Knowledge ◽  
Diabetic Patients ◽  
Dipeptidyl Peptidase 4 ◽  
Dipeptidyl Peptidase 4 Inhibitor ◽  
Increased Risk ◽  
Long Time ◽  
Stage Renal Disease ◽  
End Stage

Diabetic nephropathy (DN) is now the single commonest cause of end-stage renal disease (ESRD) worldwide and one of the main causes of death in diabetic patients. It is also acknowledged as an independent risk factor for cardiovascular disease (CVD). Since sitagliptin was approved, many studies have been carried out revealing its ability to not only improve metabolic control but also ameliorate dysfunction in various diabetes-targeted organs, especially the kidney, due to putative underlying cytoprotective properties, namely, its antiapoptotic, antioxidant, anti-inflammatory, and antifibrotic properties. Despite overall recommendations, many patients spend a long time well outside the recommended glycaemic range and, therefore, have an increased risk for developing micro- and macrovascular complications. Currently, it is becoming clearer that type 2 diabetes mellitus (T2DM) management must envision not only the improvement in glycaemic control but also, and particularly, the prevention of pancreatic deterioration and the evolution of complications, such as DN. This review aims to provide an overview of the current knowledge in the field of renoprotective actions of sitagliptin, namely, improvement in diabetic dysmetabolism, hemodynamic factors, renal function, diabetic kidney lesions, and cytoprotective properties.

scholarly journals Clinical and laboratorial features of visceral toxocariasis in infancy

1994 ◽  
Vol 36 (1) ◽  
pp. 19-26 ◽  
Author(s):  
Cristina M. A. Jacob ◽  
Antonio C. Pastorino ◽  
Benedito A. Peres ◽  
Elizabete O. Mello ◽  
Yassuhiko Okay ◽  
...  
Keyword(s):  
Significant Relationship ◽  
Epidemiological Data ◽  
Toxocara Canis ◽  
Clinical Findings ◽  
Pulmonary Manifestations ◽  
High Incidence ◽  
Diagnostic Support

Forty children with a diagnosis of Visceral Toxocariasis were evaluated prospectively from February 1982 to June 1989. Diagnosis was established by clinical, laboratorial and serological (ELISA - ES Toxocara canis antigen) evaluations. A great clinical polymorphism was found in our patients, ranging from unspecific or absent manifestations to an exhuberant symptomatology. The laboratorial findings were: leukocytosis,eosinophilia and elevation of serum gammaglobulin and isohemagglutinin levels. No significant relationship between clinical findings and laboratorial parameters was found. Serology (ELISA) was a method of great diagnostic support but did not show a correlation with clinical and laboratorial findings in this study. There was a significant relationship between pulmonary manifestations and the presence of signs and/or symptoms, when the patients were sent to us. Our findings, especially the high incidence of pulmonary manifestations, suggest that Visceral Toxocariasis has to be included in the differential diagnostic of children with pulmonary manifestations, characteristic epidemiological data and associated eosinophilia.

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