What Every Diabetologist Should Know about SARS-CoV-2: State of Knowledge at the Beginning of 2021.
TL;DR: In this paper, the authors present new research about the epidemiology of COVID-19 in a group of patients with diabetes, which details the mortality and prognosis in such patients, as well as the relationship between COVID19 and the diseases most often coexisting with diabetes: obesity, atherosclerosis, hypertension and increased risk for infection.
Abstract: For almost a year, the major medical problem has been the pandemic caused by the SARS-CoV-2 virus. People with diabetes who contract COVID-19 are likely to experience more serious symptoms than patients without diabetes. This article presents new research about the epidemiology of COVID-19 in a group of patients with diabetes. It details the mortality and prognosis in such patients, as well as the relationship between COVID-19 and the diseases most often coexisting with diabetes: obesity, atherosclerosis, hypertension, and increased risk for infection. It also details how the virus infects and affects patients with hyperglycemia. The context of glycation and receptors for advanced glycation products (RAGE) seems to be of particular importance here. We also present a hypothesis related to the cause-and-effect axis-it turns out that diabetes can be both the cause of the more difficult course of COVID-19 and the result of SARS-CoV-2 infection. The last part of this article discusses the impact of antihyperglycemic drugs on the development of COVID-19 and other pharmacological implications, including which non-classical antihyperglycemic drugs seem to be effective in both the treatment of coronavirus infection and glucose homeostasis, and what strategies related to RAGE and glycation should be considered.
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TL;DR: In this article, the concentration of different AGEs and their receptors for 58 serum samples was determined by ELISA and by spectrofluorimetric methods, and a new class of AGE was also marked: melibiose-derived glycation product (MAGE).
Abstract: Glycation is a non-enzymatic process involving the reaction of reducing sugars or reactive oxoaldehyde with proteins, lipids or nucleic acids, which results in the formation of advanced glycation end products (AGEs). The presented work discusses the glycation process in people with advanced stage of type 1 or type 2 diabetes. The concentration of different AGEs and their receptors for 58 serum samples was determined by ELISA and by spectrofluorimetric methods. In addition to fluorescent low molecular weight and protein-bound AGEs, we have also marked a new class of AGEs: melibiose-derived glycation product (MAGE). Our attention was also focused on the two groups of AGEs receptors: scavenger receptors (SR-A and SR-B) and RAGE. The correlation between the SR-AI scavenging receptors concentration and the fluorescence of AGEs as well as diabetes biological markers: GFR, creatinine contentration and HbA1c was demonstrated. A relationship between the concentration of AGEs and their receptors was also found in serum sample of patients treated with the metformin and aspirin. Furthermore, the concentration of SR-AI scavenger and the fluorescence of total AGEs was significantly lower in treated patients than in non treated patients. AGEs have also been found to contribute to the development of cardiovascular disease, atherosclerosis and diabetic complications, what could be deduced from the correlation of AGEs level and HDL cholesterol or uric acid level. Thus, it was confirmed that AGEs are involved in the pathomechanism of diabetes and other degenerative diseases. Nowadays, it is believed that AGEs due to the long time remaining in the body may be an important diagnostic marker. Their determination may allow monitoring the progression of the disease and the effectiveness of the therapy.
40 citations
TL;DR: A summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of CO VID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ are presented.
Abstract: Although coronavirus disease 2019 (COVID-19)-related major health consequences involve the lungs, a growing body of evidence indicates that COVID-19 is not inert to the pancreas either. This review presents a summary of the molecular mechanisms involved in the development of pancreatic dysfunction during the course of COVID-19, the comparison of the effects of non-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on pancreatic function, and a summary of how drugs used in COVID-19 treatment may affect this organ. It appears that diabetes is not only a condition that predisposes a patient to suffer from more severe COVID-19, but it may also develop as a consequence of infection with this virus. Some SARS-CoV-2 inpatients experience acute pancreatitis due to direct infection of the tissue with the virus or due to systemic multiple organ dysfunction syndrome (MODS) accompanied by elevated levels of amylase and lipase. There are also reports that reveal a relationship between the development and treatment of pancreatic cancer and SARS-CoV-2 infection. It has been postulated that evaluation of pancreatic function should be increased in post-COVID-19 patients, both adults and children.
25 citations
TL;DR: In this paper , the authors investigated the health-promoting activities of methanolic extracts of Ajwa date seed and fruit pulp extracts through in vitro studies and found that Ajwa dates have high nutritional value and are reported to possess antioxidant, anti-inflammatory, and antitumor properties.
Abstract: Simple Summary Most diseases result in an imbalance of antioxidant defense, inflammatory responses, and membrane permeabilization. The current therapeutic modules of disease prevention are not fully effective and have some adverse effects on physiological parameters. In this vista, medicinal plants and their active compounds have proven to be effective against disease prevention and treatment. Ajwa dates have high nutritional value and are reported to possess antioxidant, anti-inflammatory, and antitumor properties. In the current in vitro study, Ajwa fruit pulp and seed extract were found to have strong antioxidant properties, stabilize the RBC membrane, and have a good protective capacity against protein denaturation. Besides this, the seed extract prevents glucose-mediated browning of BSA as well as inhibiting the development of cross-amyloid and AGEs formations. Molecular docking results confirm the interaction between functional residues of antioxidant enzymes and components of Ajwa fruit pulp and seed contents. Therefore, the consumption of Ajwa dates can be beneficial in disease prevention and treatment. However, more detailed study is required based on pharmacological aspects to determine the mechanisms of action of Ajwa dates’ components in disease prevention. Abstract This study investigated the health-promoting activities of methanolic extracts of Ajwa date seed and fruit pulp extracts through in vitro studies. These studies confirmed potential antioxidant, anti-hemolytic, anti-proteolytic, and anti-bacterial activities associated with Ajwa dates. The EC50 values of fruit pulp and seed extracts in methanol were reported to be 1580.35 ± 0.37 and 1272.68 ± 0.27 µg/mL, respectively, in the DPPH test. The maximum percentage of hydrogen peroxide-reducing activity was 71.3 and 65.38% for both extracts at 600 µg/mL. Fruit pulp and seed extracts inhibited heat-induced BSA denaturation by 68.11 and 60.308%, heat-induced hemolysis by 63.84% and 58.10%, and hypersalinity-induced hemolysis by 61.71% and 57.27%, and showed the maximum anti-proteinase potential of 56.8 and 51.31% at 600 μg/mL, respectively. Seed and fruit pulp inhibited heat-induced egg albumin denaturation at the same concentration by 44.31 and 50.84%, respectively. Ajwa seed showed minimum browning intensity by 63.2%, percent aggregation index by 64.2%, and amyloid structure by 63.8% at 600 μg/mL. At 100 mg/mL, Ajwa seed extract exhibited good antibacterial activity. Molecular docking analysis showed that ten active constituents of Ajwa seeds bind with the critical antioxidant enzymes, catalase (1DGH) and superoxide dismutase (5YTU). The functional residues involved in such interactions include Arg72, Ala357, and Leu144 in 1DGH, and Gly37, Pro13, and Asp11 in 5YTU. Hence, Ajwa dates can be used to develop a suitable alternative therapy in various diseases, including diabetes and possibly COVID-19-associated complications.
15 citations
TL;DR: In this article, a computational analysis was performed based on the X-ray crystallographic structure of the Spike Receptor-Binding Domain (RBD)-ACE2 system to evaluate the interaction between human ACE2 receptor and SARS-CoV-2 Spike protein under different conditions of hyperglycemic environment.
Abstract: The worse outcome of COVID-19 in people with diabetes mellitus could be related to the non-enzymatic glycation of human ACE2, leading to a more susceptible interaction with virus Spike protein. We aimed to evaluate, through a computational approach, the interaction between human ACE2 receptor and SARS-CoV-2 Spike protein under different conditions of hyperglycemic environment. A computational analysis was performed, based on the X-ray crystallographic structure of the Spike Receptor-Binding Domain (RBD)-ACE2 system. The possible scenarios of lysine aminoacid residues on surface transformed by glycation were considered: (1) on ACE2 receptor; (2) on Spike protein; (3) on both ACE2 receptor and Spike protein. In comparison to the native condition, the number of polar bonds (comprising both hydrogen bonds and salt bridges) in the poses considered are 10, 6, 6, and 4 for the states ACE2/Spike both native, ACE2 native/Spike glycated, ACE2 glycated/Spike native, ACE2/Spike both glycated, respectively. The analysis highlighted also how the number of non-polar contacts (in this case, van der Waals and aromatic interactions) significantly decreases when the lysine aminoacid residues undergo glycation. Following non-enzymatic glycation, the number of interactions between human ACE2 receptor and SARS-CoV-2 Spike protein is decreased in comparison to the unmodified model. The reduced affinity of the Spike protein for ACE2 receptor in case of non-enzymatic glycation may shift the virus to multiple alternative entry routes.
9 citations
TL;DR: Type 2 diabetes in patients with coronavirus disease-19 (COVID-19) is associated with worse prognosis because of the use of sodium-glucose cotransporter 2 inhibitors, and SGLT2i and DPP-4i use was associated with higher risk of incident severe CO VID-19.
Abstract: Abstract Aims Type 2 diabetes (T2DM) in patients with coronavirus disease-19 (COVID-19) is associated with a worse prognosis. We separately investigated the associations between the use of sodium-glucose cotransporter 2 inhibitors (SGLT2i), glucagon-like peptide-1 receptor agonists (GLP-1 RA), and dipeptidyl peptidase-4 inhibitors (DPP-4i), and the risk of COVID-19 hospitalization and death. Methods and results Patients with T2DM registered in the Swedish National Patient Registry and alive on 1 February 2020 were included. ‘Incident severe COVID-19’ was defined as the first hospitalization and/or death from COVID-19. A modified Poisson regression approach was applied to a 1:1 propensity score-matched population receiving vs. not receiving SGLT2i, GLP-1 RA, and DPP-4i to analyse the associations between their use and (I) incident severe COVID-19 and (II) risk of 30-day mortality in patients hospitalized for COVID-19. Among 344 413 patients, 39 172 (11%) were treated with SGLT2i, 34 290 (10%) with GLP-1 RA, and 53 044 (15%) with DPP-4i; 9538 (2.8%) had incident severe COVID-19 by 15 May 2021. SGLT2i and DPP-4i were associated with a 10% and 11% higher risk of incident severe COVID-19, respectively, whereas there was no association for GLP-1 RA. DPP-4i was also associated with a 10% higher 30-day mortality in patients hospitalized for COVID-19, whereas there was no association for SGLT2i and GLP-1 RA. Conclusion SGLT2i and DPP-4i use were associated with a higher risk of incident severe COVID-19. DPP-4i use was associated with higher 30-day mortality in patients with COVID-19, whereas SGLT2i use was not. No increased risk for any outcome was observed with GLP-1 RA.
3 citations
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TL;DR: The epidemiological and clinical characteristics of novel coronavirus (2019-nCoV)-infected pneumonia in Wuhan, China, and hospital-associated transmission as the presumed mechanism of infection for affected health professionals and hospitalized patients are described.
Abstract: Importance In December 2019, novel coronavirus (2019-nCoV)–infected pneumonia (NCIP) occurred in Wuhan, China. The number of cases has increased rapidly but information on the clinical characteristics of affected patients is limited. Objective To describe the epidemiological and clinical characteristics of NCIP. Design, Setting, and Participants Retrospective, single-center case series of the 138 consecutive hospitalized patients with confirmed NCIP at Zhongnan Hospital of Wuhan University in Wuhan, China, from January 1 to January 28, 2020; final date of follow-up was February 3, 2020. Exposures Documented NCIP. Main Outcomes and Measures Epidemiological, demographic, clinical, laboratory, radiological, and treatment data were collected and analyzed. Outcomes of critically ill patients and noncritically ill patients were compared. Presumed hospital-related transmission was suspected if a cluster of health professionals or hospitalized patients in the same wards became infected and a possible source of infection could be tracked. Results Of 138 hospitalized patients with NCIP, the median age was 56 years (interquartile range, 42-68; range, 22-92 years) and 75 (54.3%) were men. Hospital-associated transmission was suspected as the presumed mechanism of infection for affected health professionals (40 [29%]) and hospitalized patients (17 [12.3%]). Common symptoms included fever (136 [98.6%]), fatigue (96 [69.6%]), and dry cough (82 [59.4%]). Lymphopenia (lymphocyte count, 0.8 × 109/L [interquartile range {IQR}, 0.6-1.1]) occurred in 97 patients (70.3%), prolonged prothrombin time (13.0 seconds [IQR, 12.3-13.7]) in 80 patients (58%), and elevated lactate dehydrogenase (261 U/L [IQR, 182-403]) in 55 patients (39.9%). Chest computed tomographic scans showed bilateral patchy shadows or ground glass opacity in the lungs of all patients. Most patients received antiviral therapy (oseltamivir, 124 [89.9%]), and many received antibacterial therapy (moxifloxacin, 89 [64.4%]; ceftriaxone, 34 [24.6%]; azithromycin, 25 [18.1%]) and glucocorticoid therapy (62 [44.9%]). Thirty-six patients (26.1%) were transferred to the intensive care unit (ICU) because of complications, including acute respiratory distress syndrome (22 [61.1%]), arrhythmia (16 [44.4%]), and shock (11 [30.6%]). The median time from first symptom to dyspnea was 5.0 days, to hospital admission was 7.0 days, and to ARDS was 8.0 days. Patients treated in the ICU (n = 36), compared with patients not treated in the ICU (n = 102), were older (median age, 66 years vs 51 years), were more likely to have underlying comorbidities (26 [72.2%] vs 38 [37.3%]), and were more likely to have dyspnea (23 [63.9%] vs 20 [19.6%]), and anorexia (24 [66.7%] vs 31 [30.4%]). Of the 36 cases in the ICU, 4 (11.1%) received high-flow oxygen therapy, 15 (41.7%) received noninvasive ventilation, and 17 (47.2%) received invasive ventilation (4 were switched to extracorporeal membrane oxygenation). As of February 3, 47 patients (34.1%) were discharged and 6 died (overall mortality, 4.3%), but the remaining patients are still hospitalized. Among those discharged alive (n = 47), the median hospital stay was 10 days (IQR, 7.0-14.0). Conclusions and Relevance In this single-center case series of 138 hospitalized patients with confirmed NCIP in Wuhan, China, presumed hospital-related transmission of 2019-nCoV was suspected in 41% of patients, 26% of patients received ICU care, and mortality was 4.3%.
16,635 citations
TL;DR: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for d
Abstract: Background: Hospitalised COVID-19 patients are frequently elderly subjects with co-morbidities receiving polypharmacy, all of which are known risk factors for d
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TL;DR: A two-dose regimen of BNT162b2 conferred 95% protection against Covid-19 in persons 16 years of age or older and safety over a median of 2 months was similar to that of other viral vaccines.
Abstract: Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and the resulting coronavirus disease 2019 (Covid-19) have afflicted tens of millions of people in a world...
10,274 citations
TL;DR: This integrating paradigm provides a new conceptual framework for future research and drug discovery in diabetes-specific microvascular disease and seems to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain.
Abstract: Diabetes-specific microvascular disease is a leading cause of blindness, renal failure and nerve damage, and diabetes-accelerated atherosclerosis leads to increased risk of myocardial infarction, stroke and limb amputation. Four main molecular mechanisms have been implicated in glucose-mediated vascular damage. All seem to reflect a single hyperglycaemia-induced process of overproduction of superoxide by the mitochondrial electron-transport chain. This integrating paradigm provides a new conceptual framework for future research and drug discovery.
8,289 citations
TL;DR: Just under half a billion people are living with diabetes worldwide and the number is projected to increase by 25% in 2030 and 51% in 2045, with the prevalence higher in urban than rural areas, and in high-income than low-income countries.
4,865 citations