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1.
Metabolism ; 131: 155196, 2022 06.
Article in English | MEDLINE | ID: covidwho-1768409

ABSTRACT

BACKGROUND: Diabetes is an independent predictor of poor outcomes in patients with COVID-19. We compared the effects of the preadmission use of antidiabetic medications on the in-hospital mortality of patients with COVID-19 having type 2 diabetes. METHODS: A systematic search of PubMed, EMBASE, Scopus and Web of Science databases was performed to include studies (except case reports and review articles) published until November 30, 2021. We excluded papers regarding in-hospital use of antidiabetic medications. We used a random-effects meta-analysis to calculate the pooled OR (95% CI) and performed a sensitivity analysis to confirm the robustness of the meta-analyses. MAIN FINDINGS: We included 61 studies (3,061,584 individuals), which were rated as having low risk of bias. The OR (95% CI) indicated some medications protective against COVID-related death, including metformin [0.54 (0.47-0.62), I2 86%], glucagon-like peptide-1 receptor agonist (GLP-1RA) [0.51 (0.37-0.69), I2 85%], and sodium-glucose transporter-2 inhibitor (SGLT-2i) [0.60 (0.40-0.88), I2 91%]. Dipeptidyl peptidase-4 inhibitor (DPP-4i) [1.23 (1.07-1.42), I2 82%] and insulin [1.70 (1.33-2.19), I2 97%] users were more likely to die during hospitalization. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitor were mortality neutral [0.92 (95% CI 0.83-1.01, I2 44%), 0.90 (95% CI 0.71-1.14, I2 46%), and 0.61 (95% CI 0.26-1.45, I2 77%), respectively]. The sensitivity analysis indicated that our findings were robust. CONCLUSIONS: Metformin, GLP-1RA, and SGLT-2i were associated with lower mortality rate in patients with COVID-19 having type 2 diabetes. DPP-4i and insulin were linked to increased mortality. Sulfonylurea, thiazolidinedione, and alpha-glucosidase inhibitors were mortality neutral. These findings can have a large impact on the clinicians' decisions amid the COVID-19 pandemic.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , Insulins , Metformin , Sodium-Glucose Transporter 2 Inhibitors , Thiazolidinediones , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Hypoglycemic Agents/pharmacology , Insulins/therapeutic use , Metformin/therapeutic use , Pandemics , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sulfonylurea Compounds/therapeutic use , Thiazolidinediones/therapeutic use
2.
Life Sci ; 291: 120267, 2022 Feb 15.
Article in English | MEDLINE | ID: covidwho-1587054

ABSTRACT

Tauopathy is a term that has been used to represent a pathological condition in which hyperphosphorylated tau protein aggregates in neurons and glia which results in neurodegeneration, synapse loss and dysfunction and cognitive impairments. Recently, drug repositioning strategy (DRS) becomes a promising field and an alternative approach to advancing new treatments from actually developed and FDA approved drugs for an indication other than the indication it was originally intended for. This paradigm provides an advantage because the safety of the candidate compound has already been established, which abolishes the need for further preclinical safety testing and thus substantially reduces the time and cost involved in progressing of clinical trials. In the present review, we focused on correlation between tauopathy and common diseases as type 2 diabetes mellitus and the global virus COVID-19 and how tau pathology can aggravate development of these diseases in addition to how these diseases can be a risk factor for development of tauopathy. Moreover, correlation between COVID-19 and type 2 diabetes mellitus was also discussed. Therefore, repositioning of a drug in the daily clinical practice of patients to manage or prevent two or more diseases at the same time with lower side effects and drug-drug interactions is a promising idea. This review concluded the results of pre-clinical and clinical studies applied on antidiabetics, COVID-19 medications, antihypertensives, antidepressants and cholesterol lowering drugs for possible drug repositioning for management of tauopathy.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/physiopathology , Drug Repositioning , Hypoglycemic Agents/pharmacology , Tauopathies/drug therapy , Antidepressive Agents/pharmacology , Antihypertensive Agents/pharmacology , Apoptosis/drug effects , COVID-19/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Glycogen Synthase Kinase 3 beta/antagonists & inhibitors , Humans , Molecular Targeted Therapy/methods , Proto-Oncogene Proteins c-akt/metabolism , Tauopathies/physiopathology
3.
Diabetes ; 70(12): 2745-2755, 2021 12.
Article in English | MEDLINE | ID: covidwho-1556100

ABSTRACT

Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium-glucose cotransporter 2 inhibitor, or ß3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.


Subject(s)
COVID-19/complications , COVID-19/pathology , Diabetes Mellitus , Obesity/complications , SARS-CoV-2 , Adipose Tissue/metabolism , Adrenergic beta-3 Receptor Agonists/pharmacology , Aged , Aging , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Line , Humans , Hyperinsulinism/complications , Hyperinsulinism/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/therapeutic use , Mice , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Up-Regulation , Virus Internalization
4.
Biomed Pharmacother ; 144: 112230, 2021 Dec.
Article in English | MEDLINE | ID: covidwho-1517059

ABSTRACT

The COVID-19 pandemic caused by the coronavirus SARS-CoV-2 has become a serious challenge for medicine and science. Analysis of the molecular mechanisms associated with the clinical manifestations and severity of COVID-19 has identified several key points of immune dysregulation observed in SARS-CoV-2 infection. For diabetic patients, factors including higher binding affinity and virus penetration, decreased virus clearance and decreased T cell function, increased susceptibility to hyperinflammation, and cytokine storm may make these patients susceptible to a more severe course of COVID-19 disease. Metabolic changes induced by diabetes, especially hyperglycemia, can directly affect the immunometabolism of lymphocytes in part by affecting the activity of the mTOR protein kinase signaling pathway. High mTOR activity can enhance the progression of diabetes due to the activation of effector proinflammatory subpopulations of lymphocytes and, conversely, low activity promotes the differentiation of T-regulatory cells. Interestingly, metformin, an extensively used antidiabetic drug, inhibits mTOR by affecting the activity of AMPK. Therefore, activation of AMPK and/or inhibition of the mTOR-mediated signaling pathway may be an important new target for drug therapy in COVID-19 cases mostly by reducing the level of pro-inflammatory signaling and cytokine storm. These suggestions have been partially confirmed by several retrospective analyzes of patients with diabetes mellitus hospitalized for severe COVID-19.


Subject(s)
COVID-19/drug therapy , Diabetes Mellitus/drug therapy , Hypoglycemic Agents/therapeutic use , Immunity, Cellular/drug effects , Metformin/therapeutic use , Severity of Illness Index , COVID-19/epidemiology , COVID-19/immunology , COVID-19/metabolism , Diabetes Mellitus/epidemiology , Diabetes Mellitus/immunology , Diabetes Mellitus/metabolism , Humans , Hypoglycemic Agents/pharmacology , Immunity, Cellular/physiology , Lymphocytes/drug effects , Lymphocytes/immunology , Lymphocytes/metabolism , Metformin/pharmacology , Mortality/trends , T-Lymphocytes, Regulatory/drug effects , T-Lymphocytes, Regulatory/immunology , T-Lymphocytes, Regulatory/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/immunology , TOR Serine-Threonine Kinases/metabolism
5.
J Trace Elem Med Biol ; 69: 126887, 2022 Jan.
Article in English | MEDLINE | ID: covidwho-1487875

ABSTRACT

An increasing evidence suggests that vanadium compounds are novel potential drugs in the treatment of diabetes, atherosclerosis, and cancer. Vanadium has also demonstrated activities against RNA viruses and is a promising candidate for treating acute respiratory diseases. The antidiabetic, antihypertensive, lipid-lowering, cardioprotective, antineoplastic, antiviral, and other potential effects of vanadium are summarized here. Given the beneficial antihyperglycemic and antiinflammatory effects as well as the potential mechanistic link between the COVID-19 and diabetes, vanadium compounds could be considered as a complement to the prescribed treatment of COVID-19. Thus, further clinical trials are warranted to confirm these favorable effects of vanadium treatment in COVID-19 patients, which appear not to be studied yet.


Subject(s)
Antiviral Agents/pharmacology , COVID-19 , Vanadium/pharmacology , Anti-Inflammatory Agents/pharmacology , COVID-19/drug therapy , Diabetes Mellitus/drug therapy , Humans , Hypoglycemic Agents/pharmacology , SARS-CoV-2 , Vanadium Compounds/pharmacology
6.
Front Endocrinol (Lausanne) ; 12: 731974, 2021.
Article in English | MEDLINE | ID: covidwho-1485049

ABSTRACT

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is causing a worldwide epidemic. It spreads very fast and hits people of all ages, especially patients with underlying diseases such as diabetes. In this review, we focus on the influences of diabetes on the outcome of SARS-CoV-2 infection and the involved mechanisms including lung dysfunction, immune disorder, abnormal expression of angiotensin-converting enzyme 2 (ACE2), overactivation of mechanistic target of rapamycin (mTOR) signaling pathway, and increased furin level. On the other hand, SARS-CoV-2 may trigger the development of diabetes. It causes the damage of pancreatic ß cells, which is probably mediated by ACE2 protein in the islets. Furthermore, SARS-CoV-2 may aggravate insulin resistance through attacking other metabolic organs. Of note, certain anti-diabetic drugs (OADs), such as peroxisome proliferator-activated receptor γ (PPARγ) activator and glucagon-like peptide 1 receptor (GLP-1R) agonist, have been shown to upregulate ACE2 in animal models, which may increase the risk of SARS-CoV-2 infection. However, Metformin, as a first-line medicine for the treatment of type 2 diabetes mellitus (T2DM), may be a potential drug benefiting diabetic patients with SARS-CoV-2 infection, probably via a suppression of mTOR signaling together with its anti-inflammatory and anti-fibrosis function in lung. Remarkably, another kind of OADs, dipeptidyl Peptidase 4 (DPP4) inhibitor, may also exert beneficial effects in this respect, probably via a prevention of SARS-CoV-2 binding to cells. Thus, it is of significant to identify appropriate OADs for the treatment of diabetes in the context of SARS-CoV-2 infections.


Subject(s)
COVID-19/epidemiology , COVID-19/metabolism , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Lung/drug effects , Lung/metabolism , T-Lymphocytes/drug effects , T-Lymphocytes/metabolism , TOR Serine-Threonine Kinases/antagonists & inhibitors , TOR Serine-Threonine Kinases/metabolism
7.
Diabetes ; 70(12): 2745-2755, 2021 12.
Article in English | MEDLINE | ID: covidwho-1456233

ABSTRACT

Aging, obesity, and diabetes are major risk factors for the severe progression and outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection (coronavirus disease 2019 [COVID-19]), but the underlying mechanism is not yet fully understood. In this study, we found that the SARS-CoV-2 spike protein physically interacts with cell surface GRP78, which promotes the binding to and accumulation in ACE2-expressing cells. GRP78 was highly expressed in adipose tissue and increased in humans and mice with older age, obesity, and diabetes. The overexpression of GRP78 was attributed to hyperinsulinemia in adipocytes, which was in part mediated by the stress-responsive transcription factor XBP-1s. Management of hyperinsulinemia by pharmacological approaches, including metformin, sodium-glucose cotransporter 2 inhibitor, or ß3-adrenergic receptor agonist, decreased GRP78 gene expression in adipose tissue. Environmental interventions, including exercise, calorie restriction, fasting, or cold exposure, reduced the gene expression of GRP78 in adipose tissue. This study provides scientific evidence for the role of GRP78 as a binding partner of the SARS-CoV-2 spike protein and ACE2, which might be related to the severe progression and outcome of COVID-19 in patients with older age, obesity, and diabetes. The management of hyperinsulinemia and the related GRP78 expression could be a therapeutic or preventative target.


Subject(s)
COVID-19/complications , COVID-19/pathology , Diabetes Mellitus , Obesity/complications , SARS-CoV-2 , Adipose Tissue/metabolism , Adrenergic beta-3 Receptor Agonists/pharmacology , Aged , Aging , Angiotensin-Converting Enzyme 2/metabolism , Animals , Cell Line , Humans , Hyperinsulinism/complications , Hyperinsulinism/drug therapy , Hypoglycemic Agents/pharmacology , Metformin/therapeutic use , Mice , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Spike Glycoprotein, Coronavirus/metabolism , Up-Regulation , Virus Internalization
8.
Molecules ; 26(6)2021 Mar 23.
Article in English | MEDLINE | ID: covidwho-1389468

ABSTRACT

Natural products are gaining more interest recently, much of which focuses on those derived from medicinal plants. The common chicory (Cichorium intybus L.), of the Astraceae family, is a prime example of this trend. It has been proven to be a feasible source of biologically relevant elements (K, Fe, Ca), vitamins (A, B1, B2, C) as well as bioactive compounds (inulin, sesquiterpene lactones, coumarin derivatives, cichoric acid, phenolic acids), which exert potent pro-health effects on the human organism. It displays choleretic and digestion-promoting, as well as appetite-increasing, anti-inflammatory and antibacterial action, all owing to its varied phytochemical composition. Hence, chicory is used most often to treat gastrointestinal disorders. Chicory was among the plants with potential against SARS-CoV-2, too. To this and other ends, roots, herb, flowers and leaves are used. Apart from its phytochemical applications, chicory is also used in gastronomy as a coffee substitute, food or drink additive. The aim of this paper is to present, in the light of the recent literature, the chemical composition and properties of chicory.


Subject(s)
Chicory/chemistry , Plant Extracts/chemistry , Plant Extracts/pharmacology , Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antineoplastic Agents, Phytogenic/chemistry , Antineoplastic Agents, Phytogenic/pharmacology , Antiparasitic Agents/chemistry , Antiparasitic Agents/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Chicory/physiology , Cooking , Food Hypersensitivity/etiology , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Plants, Medicinal/chemistry
9.
Int J Mol Sci ; 22(16)2021 Aug 20.
Article in English | MEDLINE | ID: covidwho-1374421

ABSTRACT

Polyphenols, such as flavonoids and phenolic acids, are a group of specialized metabolites in plants that largely aid in plant defense by deterring biotic stressors and alleviating abiotic stress. Polyphenols offer a wide range of medical applications, acting as preventative and active treatments for diseases such as cancers and diabetes. Recently, researchers have proposed that polyphenols may contribute to certain applications aimed at tackling challenges related to the COVID-19 pandemic. Understanding the beneficial impacts of phytochemicals, such as polyphenols, could potentially help prepare society for future pandemics. Thus far, most reviews have focused on polyphenols in cancer prevention and treatment. This review aims to provide a comprehensive discussion on the critical roles that polyphenols play in both plant chemical defense and human health based on the most recent studies while highlighting prospective avenues for future research, as well as the implications for phytochemical-based applications in both agricultural and medical fields.


Subject(s)
Plants/metabolism , Polyphenols/pharmacology , Polyphenols/therapeutic use , Animals , Anti-Inflammatory Agents/pharmacology , Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , Biological Availability , COVID-19/drug therapy , COVID-19/prevention & control , Flavonoids/pharmacology , Flavonoids/therapeutic use , Humans , Hydroxybenzoates/pharmacology , Hypoglycemic Agents/pharmacology , Neoplasms/drug therapy , Phytochemicals , Plants/chemistry , Polyphenols/metabolism , Prospective Studies , SARS-CoV-2/drug effects
10.
Arch Med Res ; 53(2): 186-195, 2022 02.
Article in English | MEDLINE | ID: covidwho-1347493

ABSTRACT

BACKGROUND AND AIMS: During the current Coronavirus Disease 2019 (COVID-19) pandemic, patients with diabetes face disproportionately more. This study was performed to clarify anti-inflammatory effects of anti-diabetic agents on COVID-19 in patients with diabetes. METHODS AND RESULTS: Relevant literature was searched on 15 databases up to November 14, 2020 and was updated on April 13, 2021. The pooled ORs along with 95% CIs were calculated to evaluate combined effects. 31 studies with 66,914 patients were included in qualitative and quantitative synthesis. Meta-analysis showed that metformin was associated with a statistically significant lower mortality (pooled OR = 0.62, 95% CI, 0.50-0.76, p = 0.000) and poor composite outcomes (pooled OR = 0.83, 95% CI, 0.71-0.97, p = 0.022) in diabetic patients with COVID-19. Significance of slight lower mortality remained in sulfonylurea/glinides (pooled OR = 0.93, 95% CI, 0.89-0.98, p = 0.004), but of poor composite outcomes was not (pooled OR = 1.48, 95% CI, 0.61-3.60, p = 0.384). Dipeptidyl peptidase-4 inhibitors (DPP-4 inhibitors) were associated with statistically non-significant lower mortality (pooled OR = 0.95, 95% CI, 0.72-1.26, p = 0.739) or poor composite outcomes (pooled OR = 1.27, 95% CI, 0.91-1.77, p = 0.162) of COVID-19 in diabetic patients. CONCLUSION: Metformin might be beneficial in decreasing mortality and poor composite outcomes in diabetic patients infected with SARS-CoV-2. DPP-4 inhibitors, sulfonylurea/glinides, SGLT-2 inhibitors, and GLP-1RA would not seem to be adverse. There was insufficient evidence to conclude effects of other anti-diabetic agents. Limited by retrospective characteristics, with relative weak capability to verify causality, more prospective studies, especially RCTs are needed. REGISTRATION NUMBER: PROSPERO-CRD42020221951.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Dipeptidyl-Peptidase IV Inhibitors , COVID-19/drug therapy , Diabetes Mellitus, Type 2/complications , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Prospective Studies , Retrospective Studies , SARS-CoV-2
11.
Endocrinol Metab (Seoul) ; 36(4): 904-908, 2021 08.
Article in English | MEDLINE | ID: covidwho-1328154

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic remains an unbeaten enemy. Unfortunately, no targeted treatment option is available. Patients with type 2 diabetes mellitus (T2DM) have increased odds for severe or fatal disease, as demonstrated in recent observational studies. There is an ongoing discussion regarding the impact of different antidiabetic drug classes on outcomes of interest among affected subjects. Dipeptidyl peptidase-4 (DPP-4) inhibitors have been placed at the epicenter, since the DPP-4 enzyme seems to be implicated in the disease pathogenesis. Herein we present an updated meta-analysis of observational studies addressing the risk of COVID-19 death among patients with T2DM on prior DPP-4 inhibitor treatment. We pooled data from 10 observational studies, showing that DPP-4 inhibitors produce a non-significant decrease in the risk for COVID-19-related death. However, when administered in the inpatient setting, DPP-4 inhibitors decrease the risk for COVID-19-related death by 50%. Ongoing randomized controlled trials will shed further light.


Subject(s)
COVID-19/drug therapy , COVID-19/mortality , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/mortality , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Observational Studies as Topic/methods , COVID-19/blood , Diabetes Mellitus, Type 2/blood , Dipeptidyl Peptidase 4/blood , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , Mortality/trends
12.
Cardiovasc Diabetol ; 20(1): 90, 2021 04 27.
Article in English | MEDLINE | ID: covidwho-1204077

ABSTRACT

BACKGROUND: Diabetic and obese patients are at higher risk of severe disease and cardiac injury in corona virus 2 (SARS-CoV-2) infections. Cellular entry of SARS-CoV-2 is mainly via the angiotensin-converting enzyme 2 (ACE2) receptor, which is highly expressed in normal hearts. There is a disagreement regarding the effect of factors such as obesity and diabetes on ACE2 expression in the human heart and whether treatment with renin-angiotensin system inhibitors or anti-diabetic medications increases ACE2 expression and subsequently the susceptibility to infection. We designed this study to elucidate factors that control ACE2 expression in human serum, human heart biopsies, and mice. METHODS: Right atrial appendage biopsies were collected from 79 patients that underwent coronary artery bypass graft (CABG) surgery. We investigated the alteration in ACE2 mRNA and protein expression in heart tissue and serum. ACE2 expression was compared with clinical risk factors: diabetes, obesity and different anti-hypertensive or anti-diabetic therapies. WT or db/db mice were infused with Angiotensin II (ATII), treated with different anti-diabetic drugs (Metformin, GLP1A and SGLT2i) were also tested. RESULTS: ACE2 gene expression was increased in diabetic hearts compared to non-diabetic hearts and was positively correlated with glycosylated hemoglobin (HbA1c), body mass index (BMI), and activation of the renin angiotensin system (RAS), and negatively correlated with ejection fraction. ACE2 was not differentially expressed in patients who were on angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARBs) prior to the operation. We found no correlation between plasma free ACE2 and cardiac tissue ACE2 expression. Transmembrane serine protease 2 (TMPRSS2), metalloprotease ADAM10 and ADAM17 that facilitate viral-ACE2 complex entry and degradation were increased in diabetic hearts. ACE2 expression in mice was increased with ATII infusion and attenuated following anti-diabetic drugs treatment. CONCLUSION: Patients with uncontrolled diabetes or obesity with RAS activation have higher ACE2 expressions therefore are at higher risk for severe infection. Since ACEi or ARBs show no effect on ACE2 expression in the heart further support their safety.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , COVID-19/virology , Diabetes Mellitus, Type 2/enzymology , Diabetic Cardiomyopathies/enzymology , Myocardium/enzymology , Obesity/enzymology , Receptors, Virus/metabolism , Renin-Angiotensin System , SARS-CoV-2/pathogenicity , Aged , Angiotensin-Converting Enzyme 2/genetics , Animals , COVID-19/enzymology , Case-Control Studies , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/physiopathology , Diabetic Cardiomyopathies/etiology , Diabetic Cardiomyopathies/physiopathology , Disease Models, Animal , Female , Host-Pathogen Interactions , Humans , Hypoglycemic Agents/pharmacology , Male , Mice , Middle Aged , Obesity/complications , Obesity/physiopathology , Renin-Angiotensin System/drug effects , Risk Factors , SARS-CoV-2/metabolism , Up-Regulation
13.
Future Med Chem ; 13(8): 691-700, 2021 04.
Article in English | MEDLINE | ID: covidwho-1190567

ABSTRACT

Aim: To identify virtual bioisosteric replacements of two GPR40 agonists. Materials & methods: Bioinformatic docking of candidate molecules featuring a wide range of carboxylic acid bioisosteres into complex with GPR40 was performed using TAK-875 and GW9508 templates. Results: This study suggests that 2,6-difluorophenol and squaric acid motifs are the preferred bioisosteric groups for conferring GPR40 affinity. Conclusion: This study suggests that compounds 10 and 20 are worthy synthetic targets.


Subject(s)
Benzofurans/pharmacology , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/chemistry , Methylamines/pharmacology , Propionates/pharmacology , Receptors, G-Protein-Coupled/agonists , Sulfones/pharmacology , Animals , Benzofurans/metabolism , Cyclobutanes/chemistry , Humans , Hypoglycemic Agents/pharmacology , Methylamines/metabolism , Molecular Docking Simulation , Phenols/chemistry , Propionates/metabolism , Protein Binding , Protein Conformation , Sulfones/metabolism
14.
Molecules ; 25(22)2020 Nov 11.
Article in English | MEDLINE | ID: covidwho-917015

ABSTRACT

Flavonoids are phytochemical compounds present in many plants, fruits, vegetables, and leaves, with potential applications in medicinal chemistry. Flavonoids possess a number of medicinal benefits, including anticancer, antioxidant, anti-inflammatory, and antiviral properties. They also have neuroprotective and cardio-protective effects. These biological activities depend upon the type of flavonoid, its (possible) mode of action, and its bioavailability. These cost-effective medicinal components have significant biological activities, and their effectiveness has been proved for a variety of diseases. The most recent work is focused on their isolation, synthesis of their analogs, and their effects on human health using a variety of techniques and animal models. Thousands of flavonoids have been successfully isolated, and this number increases steadily. We have therefore made an effort to summarize the isolated flavonoids with useful activities in order to gain a better understanding of their effects on human health.


Subject(s)
Flavonoids/chemistry , Flavonoids/pharmacology , Alzheimer Disease/drug therapy , Alzheimer Disease/prevention & control , Animals , Anti-Inflammatory Agents/chemistry , Anti-Inflammatory Agents/pharmacology , Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antimalarials/chemistry , Antimalarials/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Antioxidants/chemistry , Antioxidants/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , Cardiovascular System/drug effects , Flavonoids/economics , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Mice , Nervous System/drug effects , Neurons/drug effects , Neuroprotective Agents/chemistry , Neuroprotective Agents/pharmacology , Plant Extracts/pharmacology , Plant Leaves/chemistry , Plants/chemistry , Polyphenols/chemistry , Polyphenols/pharmacology , Quercetin/chemistry , Quercetin/pharmacology , Rats , Rats, Sprague-Dawley , Rats, Wistar , Stroke/drug therapy , Stroke/prevention & control
15.
Int J Biol Macromol ; 179: 239-258, 2021 May 15.
Article in English | MEDLINE | ID: covidwho-1115898

ABSTRACT

For thousands of years, fungi have been a valuable and promising source of therapeutic agents for treatment of various diseases. Mushroom is a macrofungus which has been cultivated worldwide for its nutritional value and medicinal applications. Several bioactive molecules were extracted from mushroom such as polysaccharides, lectins and terpenoids. Lectins are carbohydrate-binding proteins with non-immunologic origin. Lectins were classified according to their structure, origin and sugar specificity. This protein has different binding specificity with surface glycan moiety which determines its activity and therapeutic applications. A wide range of medicinal activities such as antitumor, antiviral, antimicrobial, immunomodulatory and antidiabetic were reported from sugar-binding proteins. However, glycan-binding protein from mushroom is not well explored as antiviral agent. The discovery of novel antiviral agents is a public health emergency to overcome the current pandemic and be ready for the upcoming viral pandemics. The mechanism of action of lectin against viruses targets numerous steps in viral life cycle such as viral attachment, entry and replication. This review described the history, classification, purification techniques, structure-function relationship and different therapeutic applications of mushroom lectin. In addition, we focus on the antiviral activity, purification and physicochemical characteristics of some mushroom lectins.


Subject(s)
Agaricales/chemistry , Antioxidants/pharmacology , Antiviral Agents/pharmacology , Hypoglycemic Agents/pharmacology , Lectins , Lectins/classification , Lectins/pharmacology
16.
Diabetes Metab Syndr ; 15(1): 55-62, 2021.
Article in English | MEDLINE | ID: covidwho-1065018

ABSTRACT

BACKGROUND AND AIMS: The ongoing pandemic of coronavirus disease 2019 (COVID-19) is rapidly evolving, thereby posing a profound challenge to the global healthcare system. Cardiometabolic disorders are associated with poor clinical outcomes in persons with COVID-19. Healthcare challenges during the COVID-19 pandemic are linked to resource constraints including shortage of Personal Protective Equipment's (PPE), laboratory tests and medication. In this context, a group of clinical experts discussed the endocrine and cardiology vigilance required in times of COVID-19. Further, the group proposed certain resource husbandry recommendations to be followed during the pandemic to overcome the constraints. METHOD: The clinical experts discussed and provided their inputs virtually. The expert panel included clinical experts comprising endocrinologists, Consultant Physicians and cardiologists from India. The panel thoroughly reviewed existing literature on the subject and proposed expert opinion. RESULTS: The expert panel put forward clinical practice-based opinion for the management of cardiometabolic conditions including diabetes mellitus and hypertension. As these conditions are associated with poor clinical outcomes, the expert panel recommends that these persons be extra-cautious and take necessary precautions during the ongoing pandemic. Further, experts also provided appropriate, affordable, available and accessible solution to the resource constraint situations in times of COVID-19 pandemic. CONCLUSION: The clinical expert opinion put forward in this article will serve as a reference for clinicians treating diabetes and cardiovascular disease during the COVID-19 pandemic.


Subject(s)
COVID-19/epidemiology , Cardiovascular Diseases/epidemiology , Expert Testimony/trends , Health Resources/trends , Metabolic Diseases/epidemiology , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19/diagnosis , COVID-19/prevention & control , Cardiotonic Agents/therapeutic use , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/drug therapy , Humans , Hypertension/diagnosis , Hypertension/drug therapy , Hypertension/epidemiology , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , India/epidemiology , Metabolic Diseases/diagnosis , Metabolic Diseases/drug therapy
17.
Diabetes Metab Syndr ; 15(1): 407-413, 2021.
Article in English | MEDLINE | ID: covidwho-1062312

ABSTRACT

BACKGROUND AND AIMS: Diabetes and coronavirus disease 2019 (COVID-19) share a bidirectional relationship. Hyperglycemia occurring in the setting of either previously diagnosed or undiagnosed diabetes is known to be associated with poor outcomes. Here, we aim to provide a simple and practical guidance on the diagnosis and management of hyperglycemia in admitted patients with COVID-19. METHODS: The guidance is formulated based on experience of authors and relevant literature on the subject searched using Pubmed. RESULTS: Every patient admitted to a COVID care facility should be investigated for hyperglycemia using a combination of tests including capillary blood glucose, fasting plasma glucose and HbA1c. Oral glucose lowering drugs can be considered in patients with mild COVID illness who have mild hyperglycemia [pre-meal blood glucose of <180 mg/dl (10 mmol/L) and post-meal blood glucose of <250 mg/dl (13.9 mmol/L)] and no contraindication to the use of these agents.. All patients with moderate-severe disease and/or hyperglycemia of greater severity should be initiated on insulin therapy. Hyperglycemia should be aggressively screened for and managed in patients receiving systemic glucocorticoids. CONCLUSION: This document provides a broad overview on the diagnosis and management of hyperglycemia at COVID care facilities and should be useful to a wide range of healthcare personnel involved in care of patients with COVID-19.


Subject(s)
COVID-19/diagnosis , COVID-19/epidemiology , Hospitalization/trends , Hyperglycemia/diagnosis , Hyperglycemia/epidemiology , Mass Screening/trends , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19/therapy , Disease Management , Humans , Hyperglycemia/therapy , Hypoglycemic Agents/pharmacology , Hypoglycemic Agents/therapeutic use , India/epidemiology , Mass Screening/standards
18.
Clin Obes ; 11(2): e12439, 2021 Apr.
Article in English | MEDLINE | ID: covidwho-1015529

ABSTRACT

The aim of the present manuscript is to discuss on potential pros and cons of glucagon-like peptide-1 receptor agonists (GLP-1RAs) as glucose-lowering agents during COVID-19 pandemic, and what is more to evaluate them as potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without diabetes mellitus type 2. Besides being important glucose-lowering agents, GLP-1RAs pose promising anti-inflammatory and anti-obesogenic properties, pulmonary protective effects, as well as beneficial impact on gut microbiome composition. Hence, taking everything previously mentioned into consideration, GLP-1RAs seem to be potential candidates for the treatment of patients, affected by COVID-19 infection, with or even without type 2 diabetes mellitus, as well as excellent antidiabetic (glucose-lowering) agents during COVID-19 pandemic times.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Glucagon-Like Peptide-1 Receptor/agonists , Hypoglycemic Agents/pharmacology , Obesity , COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Drug Repositioning/methods , Humans , Obesity/drug therapy , Obesity/metabolism , Protective Agents/pharmacology , SARS-CoV-2
19.
Therapie ; 75(4): 327-333, 2020.
Article in English | MEDLINE | ID: covidwho-1005621

ABSTRACT

According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.


Subject(s)
Coronavirus Infections/epidemiology , Diabetes Mellitus/epidemiology , Hypoglycemic Agents/administration & dosage , Pneumonia, Viral/epidemiology , Animals , COVID-19 , Coronavirus Infections/physiopathology , Diabetes Mellitus/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/pharmacology , Insulin/administration & dosage , Pandemics , Pneumonia, Viral/physiopathology , Risk Factors , Severity of Illness Index
20.
Diabetes Metab Syndr ; 15(1): 159-167, 2021.
Article in English | MEDLINE | ID: covidwho-987529

ABSTRACT

BACKGROUND & AIMS: Several observational studies have recently reported the outcomes of non-insulin anti-diabetic agents (ADA) in patients with T2DM and coronavirus disease 2019 (COVID-19). We sought to review the literature to appraise the clinicians on these outcomes. METHODS: A literature search using the specific keywords was carried out in the database of PubMed, MedRxiv and Google Scholar up till December 11, 2020 applying Boolean method. Full text of all the relevant articles that reported the outcomes of ADA in patients with T2DM and COVID-19 were retrieved. Subsequently, an appraisal of literature report was narratively presented. RESULTS: Available studies that reported the outcomes of ADA are either case series or retrospective cohorts or prospective observational studies, in absence of the randomized controlled trials (RCTs). Results from these observational studies suggest that amongst all the non-insulin ADA, metformin users prior to the hospitalization had improved outcomes compared to the non-users. Data for dipeptidyl-peptidase-4 inhibitors (DPP-4i) are encouraging although inconsistent. No documentation of any harm or benefit has been observed for sulfonylureas (SUs), sodium glucose co-transporter-2 inhibitors (SGLT-2i) and glucagon-like peptide receptor agonists (GLP-1RAs). No data is yet available for pioglitazone. CONCLUSION: Metformin and DPP-4i should be continued in patients with T2DM until hospitalization or unless contraindicated. No evidence of harm suggests that SUs, SGLT-2i or GLP-1RAs may not be stopped unless very sick, hospitalized or contraindicated. The results from RCTs are needed to claim any meaningful benefit with either metformin or DPP-4i in patients with T2DM and COVID-19.


Subject(s)
COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Hypoglycemic Agents/therapeutic use , Blood Glucose/drug effects , Blood Glucose/metabolism , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Humans , Hypoglycemic Agents/pharmacology , Metformin/pharmacology , Metformin/therapeutic use , Prospective Studies , Retrospective Studies , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use
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