COVID-19 and diabetes mellitus: potential metabolic associations

2021 ◽  
Vol 21 ◽  
Author(s):  
Pedro Henrique Abreu da Silva ◽  
Andressa Santos Garcia ◽  
Fábio Aguiar Alves ◽  
André Luis Souza dos Santos ◽  
Cátia Lacerda Sodré
Keyword(s):  
Diabetes Mellitus ◽  
Viral Entry ◽  
Molecular Mechanisms ◽  
Renin Angiotensin System ◽  
Cell Receptor ◽  
Protective Role ◽  
Infection Process ◽  
Point Of View ◽  
Diabetic Patients ◽  
Viral Binding

: The COVID-19 pandemic turned the SARS-CoV-2 into the main target of scientific research all around the world. Many advances have already been made, but there is still a long way to go to solve the molecular mechanisms related to the process of the SARS-CoV-2 infection, as well as the particularities of the disease, its course and the complex host-pathogen relationships. However, a lot has been theorized and associated with COVID-19, like the worst prognosis of the disease among individuals with some comorbidities, like diabetes mellitus. In this perspective, diabetic patients are repeatedly associated with more severe cases of COVID-19 when compared to non-diabetic patients. Even though ACE2 (angiotensin-converting enzyme 2) was recognized as the host cell receptor for both binding and entering of SARS-CoV-2 particles, it was also pointed out that this enzyme plays an important protective role against pulmonary damage. Therefore, paradoxically as it may seem, the low baseline level of this receptor in people with diabetes is directly linked to a more expressive loss of ACE2 protective effect, which could be one of the possible factors for the worst prognosis of COVID-19. Still, COVID-19 may also have a diabetogenic effect. From this point of view, the main topics that will be highlighted are (i) the mechanism of the viral entry, with special attention to the cellular receptor (ACE2) and the viral binding protein (spike), (ii) the relationship among the renin-angiotensin system, the infection process and the patients' prognosis, (iii) the glucose control and the medicines used in this event, and (iv) a brief analysis on diabetes triggered by COVID-19.

Hyperglycemic memory in metabolism and cancer

2016 ◽  
Vol 26 (2) ◽  
Author(s):  
Changhu Lee ◽  
Dohyeon An ◽  
Jiyoung Park
Keyword(s):  
Diabetes Mellitus ◽  
Molecular Mechanisms ◽  
Prolonged Exposure ◽  
Expression Profiles ◽  
Strong Association ◽  
Gene Expression Profiles ◽  
Metabolic Memory ◽  
Target Cells ◽  
Diabetic Patients

AbstractHyperglycemia is a hallmark of both type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM). Recent evidence strongly suggests that prolonged exposure to hyperglycemia can epigenetically modify gene expression profiles in human cells and that this effect is sustained even after hyperglycemic control is therapeutically achieved; this phenomenon is called hyperglycemic memory. This metabolic memory effect contributes substantially to the pathology of various diabetic complications, such as diabetic retinopathy, hypertension, and diabetic nephropathy. Due to the metabolic memory in cells, diabetic patients suffer from various complications, even after hyperglycemia is controlled. With regard to this strong association between diabetes and cancer risk, cancer cells have emerged as key target cells of hyperglycemic memory in diabetic cancer patients. In this review, we will discuss the recent understandings of the molecular mechanisms underlying hyperglycemic memory in metabolism and cancer.

scholarly journals Stress-Induced Hyperglycaemia in Non-Diabetic Patients with Acute Coronary Syndrome: From Molecular Mechanisms to New Therapeutic Perspectives

2021 ◽  
Vol 22 (2) ◽  
pp. 775
Author(s):  
Alessandro Bellis ◽  
Ciro Mauro ◽  
Emanuele Barbato ◽  
Antonio Ceriello ◽  
Antonio Cittadini ◽  
...  
Keyword(s):  
Acute Coronary Syndrome ◽  
Insulin Therapy ◽  
Molecular Mechanisms ◽  
Pancreatic Beta Cell ◽  
Renin Angiotensin System ◽  
Organ Damage ◽  
Diabetic Patients ◽  
Coronary Syndrome ◽  
Improved Outcomes ◽  
Reduction Of Mortality

Stress-induced hyperglycaemia (SIH) at hospital admission for acute coronary syndrome is associated with poor outcome, especially in patients without known diabetes. Nevertheless, insulin treatment in these subjects was not correlated with the reduction of mortality. This is likely due to the fact that SIH in the context of an acute coronary syndrome, compared to that in known diabetes, represents an epiphenomenon of other pathological conditions, such as adrenergic and renin-angiotensin system over-activity, hyperglucagonaemia, increase of circulating free fatty acids and pancreatic beta-cell dysfunction, which are not completely reversed by insulin therapy and so worsen the prognosis. Thus, SIH may be considered not only as a biomarker of organ damage, but also as an indicator of a more complex therapeutic strategy in these subjects. The aim of this review is to analyse the molecular mechanisms by which SIH may favour a worse prognosis in non-diabetic patients with acute coronary syndrome and identify new therapeutic strategies, in addition to insulin therapy, for a more appropriate treatment and improved outcomes.

scholarly journals Circulating Soluble ACE2 and Upstream microRNA Expressions in Serum of Type 2 Diabetes Mellitus Patients

2021 ◽  
Vol 22 (10) ◽  
pp. 5263
Author(s):  
Noha Mousaad Elemam ◽  
Hind Hasswan ◽  
Hayat Aljaibeji ◽  
Nabil Sulaiman
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Viral Entry ◽  
In Silico Analysis ◽  
Serum Levels ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Patients ◽  
Serum Samples

The global coronavirus disease 2019 (COVID-19) pandemic was associated with multiple organ failure and comorbidities, such as type 2 diabetes mellitus (T2DM). Risk factors, such as age, gender, and obesity, were associated with COVID-19 infection. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is known to use several host receptors for viral entry, such as angiotensin-converting enzyme 2 (ACE2) and transmembrane protease serine 2 (TMPRSS2) in the lung and other organs. However, ACE2 could be shed from the surface to be soluble ACE2 (sACE2) in the circulation. The epigenetic factors affecting ACE2 expression include a type of small non-coding RNAs called microRNAs (miRNAs). In this study, we aimed at exploring the status of the sACE2 as well as serum levels of several upstream novel miRNAs as non-invasive biomarkers that might have a potential role in T2DM patients. Serum samples were collected from 50 T2DM patients and 50 healthy controls, and sACE2 levels were quantified using enzyme-linked immunosorbent assay (ELISA). Also, RNA was extracted, and TaqMan miRNA reverse transcription quantitative PCR (RT-qPCR) was performed to measure serum miRNA levels. Our results revealed that sACE2 is decreased in the T2DM patients and is affected by age, gender, and obesity level. Additionally, 4 miRNAs, which are revealed by in silico analysis to be potentially upstream of ACE2 were detectable in the serum. Among them, miR-421 level was found to be decreased in the serum of diabetic patients, regardless of the presence or absence of diabetic complications, as well as being differential in various body mass index (BMI) groups. The other 3 miRNAs (miR-3909, miR-212-5p, and miR-4677-3p) showed associations with multiple factors including age, gender, BMI, and serum markers, in addition to being correlated to each other. In conclusion, our study reveals a decline in the circulating serum levels of sACE2 in T2DM patients and identified 4 novel miRNAs that were associated with T2DM, which are influenced by different clinical and demographic factors.

scholarly journals Biologia Futura: is ADAM 17 the reason for COVID-19 susceptibility in hyperglycemic and diabetic patients?

2021 ◽  
Author(s):  
Ganna Stepanova
Keyword(s):  
Glycemic Control ◽  
Viral Entry ◽  
Combined Therapy ◽  
Renin Angiotensin System ◽  
Antioxidant Response ◽  
Diabetic Patients ◽  
Angiotensin System ◽  
Point Of Entry ◽  
Current Controversy ◽  
Ras Blockers

AbstractCOVID-19 is a disease-causing current pandemic. It prevails in patients with pre-existing conditions such as diabetes and hypertension. Renin–angiotensin system was identified as a center of COVID-19 pathophysiology. There is a current controversy concerning the usage of ACE inhibitors and AR blockers in patients with COVID-19. Multiple clinical trials are on the way to determine the effect of RAS blockers in patients with COVID-19. ACE2 receptor is thought to be the point of entry utilized by a coronavirus. However, other factors have been identified which potentially facilitate SARS-CoV-2 entry into the cell. ADAM17 could facilitate viral entry in hyperglycemic and diabetic patients. Insulin is an ADAM17 inhibitor. Heme oxygenase (HO)-1 level is reduced in diabetic patients, contributing to the worst outcome for patients with poor glycemic control. The combined therapy of glycemic control and antioxidant response to oxidative stress could be explored in patients with COVID-19.

scholarly journals Proteomics Analysis of Gastric Cancer Patients with Diabetes Mellitus

2021 ◽  
Vol 10 (3) ◽  
pp. 407
Author(s):  
Hugo Osório ◽  
Cátia Silva ◽  
Marta Ferreira ◽  
Irene Gullo ◽  
Valdemar Máximo ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Gastric Cancer ◽  
Molecular Mechanisms ◽  
Solid Phase ◽  
Receptor Protein ◽  
Cell Junction ◽  
Control Group ◽  
Diabetic Patients ◽  
Proteomics Analysis ◽  
Patients With Diabetes

Proteomics is a powerful approach to study the molecular mechanisms of cancer. In this study, we aim to characterize the proteomic profile of gastric cancer (GC) in patients with diabetes mellitus (DM) type 2. Forty GC tissue samples including 19 cases from diabetic patients and 21 cases from individuals without diabetes (control group) were selected for the proteomics analysis. Gastric tissues were processed following the single-pot, solid-phase-enhanced sample preparation approach—SP3 and enzymatic digestion with trypsin. The resulting peptides were analyzed by LC-MS Liquid Chromatography—Mass Spectrometry (LC-MS). The comparison of protein expression levels between GC samples from diabetic and non-diabetic patients was performed by label-free quantification (LFQ). A total of 6599 protein groups were identified in the 40 samples. Thirty-seven proteins were differentially expressed among the two groups, with 16 upregulated and 21 downregulated in the diabetic cohort. Statistical overrepresentation tests were considered for different annotation sets including the Gene Ontology(GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), Reactome, and Disease functional databases. Upregulated proteins in the GC samples from diabetic patients were particularly enriched in respiratory electron transport and alcohol metabolic biological processes, while downregulated proteins were associated with epithelial cancers, intestinal diseases, and cell–cell junction cellular components. Taken together, these results support the data already obtained by previous studies that associate diabetes with metabolic disorders and diabetes-associated diseases, such as Alzheimer’s and Parkinson’s, and also provide valuable insights into seven GC-associated protein targets, claudin-3, polymeric immunoglobulin receptor protein, cadherin-17, villin-1, transglutaminase-2, desmoglein-2, and mucin-13, which warrant further investigation.

scholarly journals The level of physical activity for hypertensive and diabetic patients and the damage caused by the physical exercise requirement / O nível de actividade física para doentes hipertensos e diabéticos e os danos causados pela necessidade de exercício físico

2021 ◽  
Vol 4 (3) ◽  
pp. 12636-12647
Author(s):  
Grace Fernanda Nunes ◽  
José Alberto R. Duarte ◽  
Maurilio Tiradentes Dutra ◽  
Antonio Bovolini ◽  
Michelle Matos Duarte ◽  
...  
Keyword(s):  
Physical Activity ◽  
Physical Exercise ◽  
Good Health ◽  
Protective Role ◽  
Point Of View ◽  
Diabetic Patients ◽  
Activity Levels ◽  
Cardiac Damage ◽  
Damage Process ◽  
To Come

Physical exercise has been identified as a major non-pharmacological agent, assuming a protective role in the treatment of chronic non-communicable diseases, especially in hypertension and diabetes mellitus. The levels of physical activity as well as its intensity are of great impact for the full benefits to come of this practice. We know that the level of physical activity is a relevant factor for maintaining good health, however, little attention has been paid to what is established in relation to high-intensity daily exercise adjusted to cardiac damage or adaptation. The objective was to reflect on the prescription of physical activity in the treatment of hypertensive and diabetic patients and how eccentric exercise is related to the cardiomyocyte tissue in the damage process. We observed that the highest level of physical activity was associated with better quality of life, and that active patients have an 80% chance of survival when compared to sedentary ones. Thus, despite the potential benefits from the metabolic point of view, public health efforts should also focus on maintaining and protocols of physical activity levels since our study showed that intense eccentric physical activity had harmful effects at the cardiac level.

scholarly journals Coronavirus Disease (COVID)-19 and Diabetic Kidney Disease

2021 ◽  
Vol 14 (8) ◽  
pp. 751
Author(s):  
Swayam Prakash Srivastava ◽  
Rohit Srivastava ◽  
Subhash Chand ◽  
Julie E. Goodwin
Keyword(s):  
Kidney Disease ◽  
Viral Entry ◽  
Diabetic Kidney Disease ◽  
Thrombus Formation ◽  
Renin Angiotensin System ◽  
Cell Types ◽  
Protective Role ◽  
Kidney Cells ◽  
Diabetic Kidney

The present review describes COVID-19 severity in diabetes and diabetic kidney disease. We discuss the crucial effect of COVID-19-associated cytokine storm and linked injuries and associated severe mesenchymal activation in tubular epithelial cells, endothelial cells, and macrophages that influence neighboring cell homeostasis, resulting in severe proteinuria and organ fibrosis in diabetes. Altered microRNA expression disrupts cellular homeostasis and the renin-angiotensin-system, targets reno-protective signaling proteins, such as angiotensin-converting enzyme 2 (ACE2) and MAS1 receptor (MAS), and facilitates viral entry and replication in kidney cells. COVID-19-associated endotheliopathy that interacts with other cell types, such as neutrophils, platelets, and macrophages, is one factor that accelerates prethrombotic reactions and thrombus formation, resulting in organ failures in diabetes. Apart from targeting vital signaling through ACE2 and MAS, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections are also associated with higher profibrotic dipeptidyl transferase-4 (DPP-4)-mediated mechanisms and suppression of AMP-activated protein kinase (AMPK) activation in kidney cells. Lowered DPP-4 levels and restoration of AMPK levels are organ-protective, suggesting a pathogenic role of DPP-4 and a protective role of AMPK in diabetic COVID-19 patients. In addition to standard care provided to COVID-19 patients, we urgently need novel drug therapies that support the stability and function of both organs and cell types in diabetes.

scholarly journals DIABETIC NEUROPATHY: MOLECULAR MECHANISMS OF DEVELOPMENT AND POSSIBILITIES FOR PATHOGENETIC THERAPY

2019 ◽  
pp. 8-12
Author(s):  
N.V. Hudiakova ◽  
N.V. Ivanov ◽  
I. Yu. Pchelin ◽  
A.N. Shishkin ◽  
N.V. Vorokhobina ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Neuropathy ◽  
Molecular Mechanisms ◽  
Nitrosative Stress ◽  
Treatment Options ◽  
Neurological Complications ◽  
Diabetic Patients ◽  
Oxidative And Nitrosative Stress ◽  
Pathogenetic Therapy ◽  
Mechanisms Of Development

The present review summarizes the results of global studies and assesses contribution of hyperglycemia towards formation of neurologic complications in diabetic patients. Hyperglycemia is believed to play a leading role in the formation of neurological complications in diabetes mellitus. However, the achievement of normalization of glycemia level does not ensure the cessation of their development and progression, which indicates a lack of knowledge about the pathogenetic relationships in diabetic neuropathy. Limited understanding of these issues entails the absence of treatment options that effectively affect the course of this complication. Based on the analysis of experimental and clinical studies of recent years, data on the molecular-biological relationships of hyperglycemia with the formation of neurological complications in diabetes mellitus are summarized. The influence of the oxidative and nitrosative stress, advanced glycation end products, the activation of the polyol and hexosamine pathways on the state of the nerve fiber is analyzed. The data on molecular mechanisms of development of diabetic neuropathy are contradictory. On the basis of recent experimental and clinical data we review possibilities for pathogenetic therapy. The problem of oppositely directed effects of treatment is discussed. Clinical rationale is given for declared direction of further studies.

scholarly journals Diabetes mellitus augments the complications of patients with COVID-19: a review

2020 ◽  
Vol 8 (7) ◽  
pp. 2716
Author(s):  
Parthiba Pramanik ◽  
Purushottam Pramanik
Keyword(s):  
Diabetes Mellitus ◽  
Severe Acute Respiratory Syndrome ◽  
Virus Disease ◽  
Rna Virus ◽  
Renin Angiotensin System ◽  
Acute Effect ◽  
Host Cells ◽  
Diabetic Patients ◽  
Angiotensin Converting Enzyme 2 ◽  
Appropriate Therapy

Corona virus disease 2019 (COVID-19) is current pandemic infection caused by RNA virus named severe acute respiratory syndrome coronavirus-2 (SARS Cov-2). The lungs are the organs most affected by COVID-19 and people were died due to severe acute respiratory s syndrome, pneumonia and multi-organs failure. Fatality rate was more, those who suffer in chronic diseases including diabetes mellitus (DM). As COVID-19 pandemic is accelerating , it is important to understand the molecular mechanism through which DM increases the severity related to COVID-19 to able to design more appropriate therapy. The aims of this study was to identify mechanisms through re-analysis of publicly available data by which DM increases susceptibility for COVID-19 infection and/or increase complication for SARS-Cov-2 infection. SARS Cov-2 accesses host cells via membrane bound enzyme, angiotensin converting enzyme-2 (ACE2). This leads to imbalance of vasoprotective and vasodeletorious arms of renin angiotensin system (RAS) with over activity of vasodeletorious arms. Such imbalance of RAS induces alveolar damage, flooding the alveoli and difficulty in breathing. DM augmented the chance of pulmonary infection by impairment of innate immunity and down regulation of ACE2. Hence, diabetic patients of COVID-19 die from multi-organ failure, shock, heart failure, arrhythmias and renal failure along with severe acute respiratory syndrome. Thus it is concluded that DM augments the complications from COVID-19 by enhancing development of RAS imbalance. From view point of public health it is suggested to keep the lung healthy, maintain blood glucose level properly, and intake foods rich in antioxidant and anti-inflammatory agents to prevent and ameliorate the acute effect of COVID-19 in diabetic patients.

scholarly journals Molecular Mechanisms Lead to Sex-Specific COVID-19 Prognosis and Targeted Therapies

2020 ◽  
Vol 7 ◽  
Author(s):  
Thushara Galbadage ◽  
Brent M. Peterson ◽  
Jeffrey S. Wang ◽  
Avishka Jayasekara ◽  
Danny A. Ramirez ◽  
...  
Keyword(s):  
Risk Factor ◽  
Viral Entry ◽  
Targeted Therapies ◽  
Molecular Mechanisms ◽  
Severe Disease ◽  
Renin Angiotensin System ◽  
Epidemiological Studies ◽  
Endocrine Regulation ◽  
Regulatory Systems ◽  
Males And Females

Clinical and epidemiological studies have identified male sex as an important risk factor for COVID-19 clinical outcomes and mortality. This raises the question as to how this risk factor can be addressed in the prognosis, clinical management, and the treatment of patients with Coronavirus disease 2019 (COVID-19). Currently, there are no guidelines or protocols to help alter the course of sex-specific COVID-19 prognosis, especially in severe disease presentations. This is partly due to the lack of research studies characterizing the differences in male vs. female host response to the severe acute respiratory syndrome Coronavirus-2 (SARS-CoV-2) infection and a lack of a well-rounded understanding of the molecular mechanisms involved. Here, we discuss three distinct but interconnected molecular-level differences in males and females that likely play an essential role in the COVID-19 prognosis. We review interactions of SARS-CoV-2 with host cell angiotensin-converting enzyme 2 (ACE2) in the viral entry between males vs. females and discuss the differential regulation of the renin-angiotensin system (RAS) between the two sexes. Next, we present immune response disparities and how immune function and endocrine regulation may render males increasingly vulnerable to severe COVID-19. We describe the interconnected roles of these three regulatory systems in males and females in response to SARS-CoV-2 infection. Finally, we highlight the clinical implications of these mechanisms to patients with COVID-19 and propose putative targeted therapies that can help reduce COVID-19 severity in those critically ill.

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