scholarly journals Diabetes and coronavirus (SARS-CoV-2): Molecular mechanism of Metformin intervention and the scientific basis of drug repurposing

2021 ◽  
Vol 17 (6) ◽  
pp. e1009634
Author(s):  
Elizabeth Varghese ◽  
Samson Mathews Samuel ◽  
Alena Liskova ◽  
Peter Kubatka ◽  
Dietrich Büsselberg
Keyword(s):  
Molecular Mechanisms ◽  
Drug Repurposing ◽  
Scientific Basis ◽  
Adverse Outcomes ◽  
Oral Antidiabetic Drugs ◽  
Vascular Protection ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Increased Risk

Coronavirus Disease 2019 (COVID-19), caused by a new strain of coronavirus called Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), was declared a pandemic by WHO on March 11, 2020. Soon after its emergence in late December 2019, it was noticed that diabetic individuals were at an increased risk of COVID-19–associated complications, ICU admissions, and mortality. Maintaining proper blood glucose levels using insulin and/or other oral antidiabetic drugs (such as Metformin) reduced the detrimental effects of COVID-19. Interestingly, in diabetic COVID-19 patients, while insulin administration was associated with adverse outcomes, Metformin treatment was correlated with a significant reduction in disease severity and mortality rates among affected individuals. Metformin was extensively studied for its antioxidant, anti-inflammatory, immunomodulatory, and antiviral capabilities that would explain its ability to confer cardiopulmonary and vascular protection in COVID-19. Here, we describe the various possible molecular mechanisms that contribute to Metformin therapy’s beneficial effects and lay out the scientific basis of repurposing Metformin for use in COVID-19 patients.

Diabetes and Heart Failure: Is it Hyperglycemia or Hyperinsulinemia?

2020 ◽  
Vol 18 (2) ◽  
pp. 148-157 ◽  
Author(s):  
Triantafyllos Didangelos ◽  
Konstantinos Kantartzis
Keyword(s):  
Heart Failure ◽  
Insulin Treatment ◽  
Close Association ◽  
Adverse Outcomes ◽  
Negative Effects ◽  
Beneficial Effects ◽  
Appropriate Treatment ◽  
Increased Risk ◽  
Treatment Of Diabetes

The cardiac effects of exogenously administered insulin for the treatment of diabetes (DM) have recently attracted much attention. In particular, it has been questioned whether insulin is the appropriate treatment for patients with type 2 diabetes mellitus and heart failure. While several old and some new studies suggested that insulin treatment has beneficial effects on the heart, recent observational studies indicate associations of insulin treatment with an increased risk of developing or worsening of pre-existing heart failure and higher mortality rates. However, there is actually little evidence that the associations of insulin administration with any adverse outcomes are causal. On the other hand, insulin clearly causes weight gain and may also cause serious episodes of hypoglycemia. Moreover, excess of insulin (hyperinsulinemia), as often seen with the use of injected insulin, seems to predispose to inflammation, hypertension, dyslipidemia, atherosclerosis, heart failure, and arrhythmias. Nevertheless, it should be stressed that most of the data concerning the effects of insulin on cardiac function derive from in vitro studies with isolated animal hearts. Therefore, the relevance of the findings of such studies for humans should be considered with caution. In the present review, we summarize the existing data about the potential positive and negative effects of insulin on the heart and attempt to answer the question whether any adverse effects of insulin or the consequences of hyperglycemia are more important and may provide a better explanation of the close association of DM with heart failure.

scholarly journals Effects of Apocynin on Heart Muscle Oxidative Stress of Rats with Experimental Diabetes: Implications for Mitochondria

Antioxidants ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 335
Author(s):  
Estefanía Bravo-Sánchez ◽  
Donovan Peña-Montes ◽  
Sarai Sánchez-Duarte ◽  
Alfredo Saavedra-Molina ◽  
Elizabeth Sánchez-Duarte ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Sensitivity ◽  
Cardiac Tissue ◽  
Diabetic Rats ◽  
Oxidase Inhibitor ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Transport Chain ◽  
Male Wistar Rats

Diabetes mellitus (DM) constitutes one of the public health problems today. It is characterized by hyperglycemia through a defect in the β-cells function and/or decreased insulin sensitivity. Apocynin has been tasted acting directly as an NADPH oxidase inhibitor and reactive oxygen species (ROS) scavenger, exhibiting beneficial effects against diabetic complications. Hence, the present study’s goal was to dissect the possible mechanisms by which apocynin could mediate its cardioprotective effect against DM-induced oxidative stress. Male Wistar rats were assigned into 4 groups: Control (C), control + apocynin (C+A), diabetes (D), diabetes + apocynin (D+A). DM was induced with streptozotocin. Apocynin treatment (3 mg/kg/day) was applied for 5 weeks. Treatment significantly decreased blood glucose levels and insulin resistance in diabetic rats. In cardiac tissue, ROS levels were higher, and catalase enzyme activity was reduced in the D group compared to the C group; the apocynin treatment significantly attenuated these responses. In heart mitochondria, Complexes I and II of the electron transport chain (ETC) were significantly enhanced in the D+A group. Total glutathione, the level of reduced glutathione (GSH) and the GSH/ oxidized glutathione (GSSG) ratio were increased in the D+A group. Superoxide dismutase (SOD) and the glutathione peroxidase (GSH-Px) activities were without change. Apocynin enhances glucose uptake and insulin sensitivity, preserving the antioxidant defense and mitochondrial function.

Association of Acrochordons with Diabetes Mellitus - A Hospital based Case Control Study

2021 ◽  
Vol 4 (1) ◽  
pp. 51-60
Author(s):  
Sunita Karki ◽  
Anjan Rai ◽  
Manish Pradhan
Keyword(s):  
Diabetes Mellitus ◽  
Blood Glucose ◽  
Postprandial Glucose ◽  
Early Screening ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Increased Risk ◽  
Skin Tags ◽  
And Gender ◽  
Control Study

Introduction Acrochordons or skin tags are common benign cutaneous tumors that occur especially over the neck and major flexures. A possible association between diabetes mellitus and dyslipidemia is observed in numerous past studies with varying results. We aim to find out the association of diabetes mellitus with acrochordons Methods: One hundred patients were enrolled in our study. Among them, 50 (27 males and 23 females) with skin tags were selected as cases and 50 with other dermatologic diseases after matching age and gender were taken as controls. Blood glucose levels including both fasting and postprandial glucose levels were determined for both cases and controls and compared. Results: There was a higher frequency of Diabetes Mellitus and impaired glucose tolerance in patients with skin tags in comparison to controls (p<0.001). Moreover, there were higher odds of acquiring skin tags in patient with abnormal blood glucose levels. Conclusions: There is an increased risk of developing DM in patients with skin tags. It is highly recommended that suspicion for Diabetes Mellitus is to be done in patients with skin tags for early screening and diagnosis of Diabetes.

scholarly journals POLYCYSTIC OVARIAN SYNDROME;

2012 ◽  
Vol 19 (06) ◽  
pp. 786-788
Author(s):  
KIRAN BUTT ◽  
FARAH DEEBA ◽  
HAVAIDA ATTIQUE
Keyword(s):  
Blood Glucose ◽  
Lipid Profile ◽  
Glucose Level ◽  
Fasting Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Increased Risk ◽  
Commercial Kits ◽  
The University ◽  
Ovarian Syndrome

Objective: The objective of the present study was to determine the changes in the glucose level and lipid profile in patients withpolycystic ovarian syndrome (PCOS). Study Design: Descriptive study. Place and Duration of the study: This study was conducted atInstitute of Molecular Biology and Biotechnology, The University of Lahore from June 2009 to June 2010. Patients and Methods: Total 50patients with PCOS were included and 50 age-matched control subjects were also selected for comparison. Their glucose levels and lipidprofile were assessed using commercial kits. The data thus obtained was subjected to statistical analysis. Results: Significant differences(P<0.05) in fasting blood glucose level and individual parameters of lipid profile were observed in women with PCOS. A higher prevalence ofhypertriglyceridemia, hypercholesterolemia, higher LDL, lower HDL and higher fasting blood glucose levels was explored in PCOS womenthan controls. Conclusions: Abnormal glucose level and lipid profile in PCOS women showed that these women are at an increased risk ofdeveloping diabetes and subsequently cardiovascular diseases.

scholarly journals Increased Inflammation in Atherosclerotic Lesions of DiabeticAkita-LDLr−/−Mice Compared to NondiabeticLDLr−/−Mice

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Daniel Engelbertsen ◽  
Fong To ◽  
Pontus Dunér ◽  
Olga Kotova ◽  
Ingrid Söderberg ◽  
...  
Keyword(s):  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Plasma Cholesterol ◽  
Microvascular Complications ◽  
Fold Increase ◽  
Inflammatory Cells ◽  
Glucose Levels ◽  
Atherosclerotic Lesions ◽  
Blood Glucose Levels ◽  
Plaque Inflammation

Background. Diabetes is associated with increased cardiovascular disease, but the underlying cellular and molecular mechanisms are poorly understood. One proposed mechanism is that diabetes aggravates atherosclerosis by enhancing plaque inflammation. TheAkitamouse has recently been adopted as a relevant model for microvascular complications of diabetes. Here we investigate the development of atherosclerosis and inflammation in vessels ofAkitamice onLDLr−/−background.Methods and Results.Akita-LDLr−/−andLDLr−/−mice were fed high-fat diet from 6 to 24 weeks of age. Blood glucose levels were higher in both male and femaleAkita-LDLr−/−mice (137% and 70%, resp.). MaleAkita-LDLr−/−mice had markedly increased plasma cholesterol and triglyceride levels, a three-fold increase in atherosclerosis, and enhanced accumulation of macrophages and T-cells in plaques. In contrast, femaleAkita-LDLr−/−mice demonstrated a modest 29% increase in plasma cholesterol and no significant increase in triglycerides, atherosclerosis, or inflammatory cells in lesions. MaleAkita-LDLr−/−mice had increased levels of plasma IL-1βcompared to nondiabetic mice, whereas no such difference was seen between female diabetic and nondiabetic mice.Conclusion.Akita-LDLr−/−mice display considerable gender differences in the development of diabetic atherosclerosis. In addition, the increased atherosclerosis in maleAkita-LDLr−/−mice is associated with an increase in inflammatory cells in lesions.

Influence of glucose levels on clinical outcome after mechanical thrombectomy for large-vessel occlusion: a systematic review and meta-analysis

2021 ◽  
pp. neurintsurg-2021-017771
Author(s):  
Carlos Perez-Vega ◽  
Ricardo A Domingo ◽  
Shashwat Tripathi ◽  
Andres Ramos-Fresnedo ◽  
Samir Kashyap ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Clinical Outcome ◽  
Mechanical Thrombectomy ◽  
Meta Analysis ◽  
Large Vessel Occlusion ◽  
Vessel Occlusion ◽  
High Blood Glucose ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Increased Risk

Mechanical thrombectomy (MT) represents the mainstay of treatment for patients with acute ischemic stroke due to large-vessel occlusion (LVO). Intravenous thrombolysis has been associated with worse clinical outcome in patients presenting with high blood glucose levels at admission; to date the true effect of hyperglycemia in the setting of MT has not been fully elucidated. In this meta-analysis, we analyzed the influence of high blood glucose levels at admission on clinical outcome after MT. Ovid EMBASE, PubMed, Scopus, and Cochrane Library databases were searched from their dates of inception up to March 2021. An initial search identified 2118 articles representing 1235 unique studies. After applying selection criteria, three prospective and five retrospective studies were analyzed, yielding a pooled cohort of 5861 patients (2041 who presented with hyperglycemia, and 3820 who presented with normal blood glucose levels). Patients in the hyperglycemia group were less likely to have a modified Ranking Scale (mRS) score <3 (risk ratio (RR): 0.65; 95% CI 0.59 to 0.72; p<0.0001; I2=13%), and had an increased risk of symptomatic intracranial hemorrhage (sICH) (RR: 2.07; 95% CI 1.65 to 2.60; p<0.0001; I2=0%) and mortality (RR: 1.73; 95% CI 1.57 to 1.91; p<0.0001; I2=0%). Patients who present with hyperglycemia and undergo MT for treatment of LVO have an increased risk of unfavorable clinical outcome, sICH, and mortality. Glucose levels at admission appear to be a prognostic factor in this subset of patients. Further studies should focus on evaluating control of the glucose level at admission as a modifiable risk factor in patients undergoing MT for LVO.

scholarly journals Leptin contributes to the beneficial effects of insulin treatment in streptozotocin-diabetic male mice

2018 ◽  
Vol 315 (6) ◽  
pp. E1264-E1273
Author(s):  
Ursula H. Neumann ◽  
Michelle M. Kwon ◽  
Robert K. Baker ◽  
Timothy J. Kieffer
Keyword(s):  
Blood Glucose ◽  
Insulin Therapy ◽  
Daily Injection ◽  
Diabetic Mice ◽  
Glucose Lowering ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Lowering Effect ◽  
Blood Glucose Levels ◽  
Glucose Lowering Effect

It was long thought that the only hormone capable of reversing the catabolic consequences of diabetes was insulin. However, various studies have demonstrated that the adipocyte-derived hormone leptin can robustly lower blood glucose levels in rodent models of insulin-deficient diabetes. In addition, it has been suggested that some of the metabolic manifestations of insulin-deficient diabetes are due to hypoleptinemia as opposed to hypoinsulinemia. Because insulin therapy increases leptin levels, we sought to investigate the contribution of leptin to the beneficial effects of insulin therapy. To do this, we tested insulin therapy in streptozotocin (STZ) diabetic mice that were either on an ob/ ob background or that were given a leptin antagonist to determine if blocking leptin action would blunt the glucose-lowering effects of insulin therapy. We found that STZ diabetic ob/ ob mice have a diminished blood glucose-lowering effect in response to insulin therapy compared with STZ diabetic controls and exhibited more severe weight loss post-STZ injection. In addition, STZ diabetic mice administered a leptin antagonist through daily injection or plasmid expression respond less robustly to insulin therapy as assessed by both fasting blood glucose levels and blood glucose levels during an oral glucose tolerance test. However, leptin antagonism did not prevent the insulin-induced reduction in β-hydroxybutyrate and triglyceride levels. Therefore, we conclude that elevated leptin levels can contribute to the glucose-lowering effect of insulin therapy in insulin-deficient diabetes.

scholarly journals Glycemic Variability in Diabetes Increases the Severity of Influenza

mBio ◽  
2020 ◽  
Vol 11 (2) ◽  
Author(s):  
Rebecca J. Marshall ◽  
Pornthida Armart ◽  
Katina D. Hulme ◽  
Keng Yih Chew ◽  
Alexandra C. Brown ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Glycemic Variability ◽  
Endothelial Barrier ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Severe Influenza ◽  
Increased Risk ◽  
History Of

ABSTRACT People with diabetes are two times more likely to die from influenza than people with no underlying medical condition. The mechanisms underlying this susceptibility are poorly understood. In healthy individuals, small and short-lived postprandial peaks in blood glucose levels occur. In diabetes mellitus, these fluctuations become greater and more frequent. This glycemic variability is associated with oxidative stress and hyperinflammation. However, the contribution of glycemic variability to the pathogenesis of influenza A virus (IAV) has not been explored. Here, we used an in vitro model of the pulmonary epithelial-endothelial barrier and novel murine models to investigate the role of glycemic variability in influenza severity. In vitro, a history of glycemic variability significantly increased influenza-driven cell death and destruction of the epithelial-endothelial barrier. In vivo, influenza virus-infected mice with a history of glycemic variability lost significantly more body weight than mice with constant blood glucose levels. This increased disease severity was associated with markers of oxidative stress and hyperinflammation both in vitro and in vivo. Together, these results provide the first indication that glycemic variability may help drive the increased risk of severe influenza in people with diabetes mellitus. IMPORTANCE Every winter, people with diabetes are at increased risk of severe influenza. At present, the mechanisms that cause this increased susceptibility are unclear. Here, we show that the fluctuations in blood glucose levels common in people with diabetes are associated with severe influenza. These data suggest that glycemic stability could become a greater clinical priority for patients with diabetes during outbreaks of influenza.

scholarly journals Preventive Effect of Salicylate and Pyridoxamine on Diabetic Nephropathy

2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Tarek Kamal Abouzed ◽  
Seiichi Munesue ◽  
Ai Harashima ◽  
Yusuke Masuo ◽  
Yukio Kato ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Blood Glucose ◽  
Macrophage Infiltration ◽  
Gene Expressions ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Developmental Factors ◽  
Blood Glucose Levels ◽  
Patients With Diabetes ◽  
Long Acting

Objective. Diabetic nephropathy is a life-threatening complication in patients with long-standing diabetes. Hemodynamic, inflammatory, and metabolic factors are considered as developmental factors for diabetic nephropathy. In this study, we evaluated whether pharmacological interventions with salicylate, compared to pyridoxamine, could prevent diabetic nephropathy in mice. Methods. Male mice overexpressing inducible nitric oxide synthase in pancreatic β-cells were employed as a diabetic model. Salicylate (3 g/kg diet) or pyridoxamine (1 g/L drinking water; ~200 mg/kg/day) was given for 16 weeks to assess the development of diabetic nephropathy. Treatment with long-acting insulin (Levemir 2 units/kg twice a day) was used as a control. Results. Although higher blood glucose levels were not significantly affected by pyridoxamine, early to late stage indices of nephropathy were attenuated, including kidney enlargement, albuminuria, and increased serum creatinine, glomerulosclerosis, and inflammatory and profibrotic gene expressions. Salicylate showed beneficial effects on diabetic nephropathy similar to those of pyridoxamine, which include lowering blood glucose levels and inhibiting macrophage infiltration into the kidneys. Attenuation of macrophage infiltration into the kidneys and upregulation of antiglycating enzyme glyoxalase 1 gene expression were found only in the salicylate treatment group. Conclusions. Treatment with salicylate and pyridoxamine could prevent the development of diabetic nephropathy in mice and, therefore, would be a potentially useful therapeutic strategy against kidney problems in patients with diabetes.

scholarly journals The Beneficial Effects of SesaVitaTM on Lipid Profiles and Blood Glucose Levels in Subjects With Prediabetes and Mild-To-Moderate Hyperlipidemia in India

2013 ◽  
Vol 2 (5) ◽  
pp. 104 ◽  
Author(s):  
H. N. Shivaprasad ◽  
M. Bhanumathy ◽  
Ceyhun Tamer ◽  
G. Sushma ◽  
K. R. Raveendra ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Lipid Profile ◽  
Lifestyle Changes ◽  
Secondary Outcome ◽  
Oral Glucose ◽  
Double Blind Study ◽  
Beneficial Effects ◽  
Glucose Levels ◽  
Blood Glucose Levels ◽  
Normal Ranges

<p>Individuals suffering from Type 2 diabetes develop prediabetes before progression of diabetes. In case of prediabetes people, the blood glucose levels are higher than normal but not sufficient to be diagnosed as diabetes. On the basis of existing reports on Sesame extract, SesaVita<sup>TM</sup> which is an herbal food supplement containing Sesame seeds (<em>Sesamum indicum</em> L.) extract may provide an option for management of prediabetes. The objective of this study was to determine the beneficial effects of SesaVita<sup>TM</sup> in prediabetes and mild to moderate hyperlipidemia subjects. This randomized, placebo-controlled, double-blind study comprised of 13 female and 07 male patients with prediabetes and mild to moderate hyperlipidemia, aged between 18 and 65 years. Twenty subjects were randomized to receive SesaVita<sup>TM</sup> (500 mg/day) or placebo along with therapeutic lifestyle changes for 6 weeks. The primary outcome was the measure of efficacy in terms of change in serum lipid profile and glycaemic levels on week 3 and 6. Secondary outcome measures include safety and tolerability evaluated by physical examination and clinical laboratory evaluations. Improvements in lipid profile and glycaemic levels were observed in SesaVita<sup>TM</sup> treated group when compared with placebo and baseline. A statistical significant reduction was observed in low density lipoprotein cholesterol (LDL-C), total cholesterol (TC), oral glucose tolerance test (OGTT) and fasting blood sugar (FBS) levels during week 3 and 6 when treated with SesaVita<sup>TM</sup> extract.<em> </em>No adverse events occurred and all safety parameters were within normal ranges during the study. This study revealed that the treatment with SesaVita<sup>TM</sup> was safe and well tolerated;<em> </em>may be beneficial in the management of prediabetes and mild-to-moderate hyperlipidemia.</p>

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