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2.
J Steroid Biochem Mol Biol ; 213: 105957, 2021 10.
Article in English | MEDLINE | ID: covidwho-1561628

ABSTRACT

This review examines the beneficial effects of ultraviolet radiation on systemic autoimmune diseases, including multiple sclerosis and type I diabetes, where the epidemiological evidence for the vitamin D-independent effects of sunlight is most apparent. Ultraviolet radiation, in addition to its role in the synthesis of vitamin D, stimulates anti-inflammatory pathways, alters the composition of dendritic cells, T cells, and T regulatory cells, and induces nitric oxide synthase and heme oxygenase metabolic pathways, which may directly or indirectly mitigate disease progression and susceptibility. Recent work has also explored how the immune-modulating functions of ultraviolet radiation affect type II diabetes, cancer, and the current global pandemic caused by SARS-CoV-2. These diseases are particularly important amidst global changes in lifestyle that result in unhealthy eating, increased sedentary habits, and alcohol and tobacco consumption. Compelling epidemiological data shows increased ultraviolet radiation associated with reduced rates of certain cancers, such as colorectal cancer, breast cancer, non-Hodgkins lymphoma, and ultraviolet radiation exposure correlated with susceptibility and mortality rates of COVID-19. Therefore, understanding the effects of ultraviolet radiation on both vitamin D-dependent and -independent pathways is necessary to understand how they influence the course of many human diseases.


Subject(s)
COVID-19/prevention & control , Diabetes Mellitus, Type 1/prevention & control , Diabetes Mellitus, Type 2/prevention & control , Multiple Sclerosis/prevention & control , Neoplasms/prevention & control , Sunlight , Vitamin D/metabolism , Alcohol Drinking/adverse effects , COVID-19/immunology , COVID-19/pathology , COVID-19/virology , Dendritic Cells/immunology , Dendritic Cells/radiation effects , Diabetes Mellitus, Type 1/immunology , Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/immunology , Diabetes Mellitus, Type 2/pathology , Disease Progression , Disease Susceptibility , Heme Oxygenase (Decyclizing)/genetics , Heme Oxygenase (Decyclizing)/immunology , Humans , Multiple Sclerosis/immunology , Multiple Sclerosis/pathology , Neoplasms/immunology , Neoplasms/pathology , Nitric Oxide Synthase/genetics , Nitric Oxide Synthase/immunology , SARS-CoV-2/pathogenicity , SARS-CoV-2/radiation effects , Sedentary Behavior , T-Lymphocytes/immunology , T-Lymphocytes/radiation effects , Vitamin D/immunology
3.
Sci Rep ; 11(1): 17968, 2021 09 09.
Article in English | MEDLINE | ID: covidwho-1402115

ABSTRACT

The impact of overlapping risk factors on coronavirus disease (COVID-19) severity is unclear. To evaluate the impact of type 2 diabetes (T2D) and obesity on COVID-19 severity, we conducted a cohort study with 28,095 anonymized COVID-19 patients using data from the COVID-19 Research Database from January 1, 2020 to November 30, 2020. The mean age was 50.8 ± 17.5 years, and 11,802 (42%) patients were male. Data on age, race, sex, T2D complications, antidiabetic medication prescription, and body mass index ≥ 30 kg/m2 (obesity) were analysed using Cox proportional hazard models, with hospitalization risk and critical care within 30 days of COVID-19 diagnosis as the main outcomes. The risk scores were 0-4 for age ≥ 65 years, male sex, T2D, and obesity. Among the participants, 11,294 (61.9%) had obesity, and 4445 (15.8%) had T2D. T2D, obesity, and male sex were significantly associated with COVID-19 hospitalization risk. Regarding hospitalization risk scores, compared with those for hospitalization risk score 0 and critical care risk score 0, hazard ratios [95% confidence intervals] were 19.034 [10.470-34.600] and 55.803 [12.761-244.015] (P < 0.001) (P < 0.001), respectively, for risk score 4. Complications from diabetes and obesity increased hospitalization and critical care risks for COVID-19 patients.


Subject(s)
COVID-19/pathology , Critical Care/statistics & numerical data , Diabetes Mellitus, Type 2/pathology , Obesity/pathology , Severity of Illness Index , Aged , Aging/pathology , COVID-19/drug therapy , Diabetes Complications/pathology , Female , Hospitalization/statistics & numerical data , Humans , Hypoglycemic Agents/therapeutic use , Intensive Care Units/statistics & numerical data , Male , Metformin/therapeutic use , Middle Aged , Risk Factors , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , United States
4.
FEBS J ; 288(17): 5042-5054, 2021 Sep.
Article in English | MEDLINE | ID: covidwho-1295003

ABSTRACT

The COVID-19 pandemic has highlighted the vulnerability of people with diabetes mellitus (DM) to respiratory viral infections. Despite the short history of COVID-19, various studies have shown that patients with DM are more likely to have increased hospitalisation and mortality rates as compared to patients without. At present, the mechanisms underlying this susceptibility are unclear. However, prior studies show that the course of COVID-19 disease is linked to the efficacy of the host's T-cell responses. Healthy individuals who can elicit a robust T-cell response are more likely to limit the severity of COVID-19. Here, we investigate the hypothesis that an impaired T-cell response in patients with type 2 diabetes mellitus (T2DM) drives the severity of COVID-19 in this patient population. While there is currently a limited amount of information that specifically addresses T-cell responses in COVID-19 patients with T2DM, there is a wealth of evidence from other infectious diseases that T-cell immunity is impaired in patients with T2DM. The reasons for this are likely multifactorial, including the presence of hyperglycaemia, glycaemic variability and metformin use. This review emphasises the need for further research into T-cell responses of COVID-19 patients with T2DM in order to better inform our response to COVID-19 and future disease outbreaks.


Subject(s)
COVID-19/immunology , Diabetes Mellitus, Type 2/immunology , Hyperglycemia/immunology , T-Lymphocytes/immunology , COVID-19/complications , COVID-19/pathology , COVID-19/virology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/virology , Humans , Hyperglycemia/complications , Hyperglycemia/pathology , Hyperglycemia/virology , Pandemics , SARS-CoV-2/pathogenicity , T-Lymphocytes/virology
5.
Diabetes Metab Syndr ; 15(4): 102143, 2021.
Article in English | MEDLINE | ID: covidwho-1286293

ABSTRACT

BACKGROUND AND AIMS: We studied the profile and outcome of patients hospitalized for coronavirus disease-19 (COVID-19) infection with and without type 2 diabetes (T2DM). METHODS: In this observational study, clinical details of patients with COVID-19, identified by Reverse Transcription - Polymerase Chain Reaction admitted to 4 hospitals in Chennai, Tamil Nadu, India were collected from May to November 2020. A total of 845 (n = 423 with diabetes, n = 422 without diabetes) were selected for the analysis. Clinical details, biochemical and radiological investigations, diabetes treatment, intensive care, mortality and other adverse outcomes were recorded. Patients with clinical history of T2DM, glycosylated haemoglobin (HbA1c) of ≥6.5% (48 mmol/mol) and/or random blood glucose ≥200 mg/dl (11.1 mmol/l) were included. Statistical analyses were done using chi-square or 't' test and multiple logistic regression analysis. RESULTS: At admission, patients with T2DM were older (p < 0.0001), had higher co-morbidities such as coronary artery disease (p = 0.02), hypertension (p < 0.0001), hypothyroidism (p = 0.03) and renal disorders (p = 0.01) than non-diabetes persons. Requirement for intensive care was higher among them. Acute renal injury or failure, pneumonia and myocardial infarction developed in higher percentage of T2DM. Mortality was significantly higher in T2DM (10.2% vs 5.9%, p = 0.02). However, in the multiple logistic regression analysis, only age (p < 0.0001) and renal disorders (p = 0.002) were significantly associated with mortality. CONCLUSION: Our study showed that mortality was associated with higher age and renal disorders but did not show an association with diabetes, among patients hospitalized for COVID-19 infection.


Subject(s)
COVID-19/complications , Diabetes Mellitus, Type 2/pathology , Hospitalization/statistics & numerical data , SARS-CoV-2/isolation & purification , COVID-19/transmission , COVID-19/virology , Case-Control Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/virology , Female , Humans , India/epidemiology , Male , Middle Aged , Prognosis , Risk Factors
6.
Front Immunol ; 12: 651728, 2021.
Article in English | MEDLINE | ID: covidwho-1190315

ABSTRACT

The coronavirus infectious disease 2019 (COVID-19) pandemic has hit the world, affecting health, medical care, economies and our society as a whole. Furthermore, COVID-19 pandemic joins the increasing prevalence of metabolic syndrome in western countries. Patients suffering from obesity, type II diabetes mellitus, cardiac involvement and metabolic associated fatty liver disease (MAFLD) have enhanced risk of suffering severe COVID-19 and mortality. Importantly, up to 25% of the population in western countries is susceptible of suffering from both MAFLD and COVID-19, while none approved treatment is currently available for any of them. Moreover, it is well known that exacerbated innate immune responses are key in the development of the most severe stages of MAFLD and COVID-19. In this review, we focus on the role of the immune system in the establishment and progression of MAFLD and discuss its potential implication in the development of severe COVID-19 in MAFLD patients. As a result, we hope to clarify their common pathology, but also uncover new potential therapeutic targets and prognostic biomarkers for further research.


Subject(s)
Adaptive Immunity/immunology , COVID-19/immunology , COVID-19/pathology , Fatty Liver/immunology , Immunity, Innate/immunology , Angiotensin-Converting Enzyme 2/immunology , Angiotensin-Converting Enzyme 2/metabolism , CD4-Positive T-Lymphocytes/immunology , CD8-Positive T-Lymphocytes/immunology , Diabetes Mellitus, Type 2/pathology , Fatty Liver/pathology , Humans , Liver/immunology , Liver/pathology , Obesity/pathology , Risk Factors , SARS-CoV-2/immunology , Severity of Illness Index
7.
Int J Environ Res Public Health ; 18(8)2021 04 15.
Article in English | MEDLINE | ID: covidwho-1186956

ABSTRACT

Background: The aim of this study was to investigate the effect of the coronavirus disease (COVID-19) pandemic restrictions on the change in muscle mass in older patients with type 2 diabetes (T2D), who were not infected with COVID-19. Methods: In this retrospective cohort study, data were obtained from outpatients who underwent bioelectrical impedance analysis at least twice before April 2020 and at least once thereafter. Skeletal muscle mass index (SMI, kg/m2) was calculated as appendicular muscle mass (kg) divided by height squared (m2). Change in SMI (kg/m2/year) was calculated as (follow-up SMI-baseline SMI/follow-up period). The differences between the changes in SMI before and after the start of the COVID-19 pandemic were evaluated using paired t test. Results: This study recruited 56 patients, with a mean (SD) age of 75.2 (7.1) years. SMI changed from 6.7 (0.9) to 6.8 (0.9) kg/m2 before the COVID-19 pandemic, whereas SMI changed from 6.8 (0.9) to 6.6 (0.9) kg/m2 after the start of the COVID-19 pandemic. SMI decreased after the start of the COVID-19 pandemic compared with before the pandemic (-0.117 (0.240) vs. 0.005 (0.289) kg/m2/year, p = 0.049). This decrease was observed in men (-0.159 (0.257) vs. 0.031 (0.325) kg/m2/year, p = 0.038), patients with poor glycemic control (-0.170 (0.264) vs. 0.031 (0.285) kg/m2/year, p = 0.042), and those with a long diabetes duration (-0.153 (0.229) vs. 0.082 (0.291) kg/m2, p = 0.049). Conclusions: The COVID-19 pandemic restrictions caused muscle mass loss in older patents with T2D. Actions, including recommendation of exercise and adequate diet intake, are needed to prevent loss of muscle mass.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Sarcopenia , Aged , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/pathology , Humans , Male , Muscle, Skeletal , Pandemics , Retrospective Studies , SARS-CoV-2 , Sarcopenia/epidemiology
8.
Front Cell Infect Microbiol ; 11: 590874, 2021.
Article in English | MEDLINE | ID: covidwho-1158345

ABSTRACT

Gut microbiome alterations may play a paramount role in determining the clinical outcome of clinical COVID-19 with underlying comorbid conditions like T2D, cardiovascular disorders, obesity, etc. Research is warranted to manipulate the profile of gut microbiota in COVID-19 by employing combinatorial approaches such as the use of prebiotics, probiotics and symbiotics. Prediction of gut microbiome alterations in SARS-CoV-2 infection may likely permit the development of effective therapeutic strategies. Novel and targeted interventions by manipulating gut microbiota indeed represent a promising therapeutic approach against COVID-19 immunopathogenesis and associated co-morbidities. The impact of SARS-CoV-2 on host innate immune responses associated with gut microbiome profiling is likely to contribute to the development of key strategies for application and has seldom been attempted, especially in the context of symptomatic as well as asymptomatic COVID-19 disease.


Subject(s)
COVID-19/pathology , Dysbiosis/microbiology , Gastrointestinal Microbiome/immunology , Gastrointestinal Tract/microbiology , Immunity, Innate/immunology , Angiotensin-Converting Enzyme 2/biosynthesis , Angiotensin-Converting Enzyme 2/genetics , Angiotensin-Converting Enzyme 2/metabolism , Bacteria/metabolism , COVID-19/therapy , Cardiovascular Diseases/pathology , Diabetes Mellitus, Type 2/pathology , Gastrointestinal Tract/immunology , Gastrointestinal Tract/metabolism , Gene Expression/genetics , Humans , Leukocyte L1 Antigen Complex/biosynthesis , Obesity/pathology , Probiotics/pharmacology , SARS-CoV-2/immunology , Severity of Illness Index
9.
Biochim Biophys Acta Mol Basis Dis ; 1867(4): 166044, 2021 04 01.
Article in English | MEDLINE | ID: covidwho-1103717

ABSTRACT

Diabetes-associated morbidity and mortality is predominantly due to complications of the disease that may cause debilitating conditions, such as heart and renal failure, hepatic insufficiency, retinopathy or peripheral neuropathy. Fibrosis, the excessive and inappropriate deposition of extracellular matrix in various tissues, is commonly found in patients with advanced type 1 or type 2 diabetes, and may contribute to organ dysfunction. Hyperglycemia, lipotoxic injury and insulin resistance activate a fibrotic response, not only through direct stimulation of matrix synthesis by fibroblasts, but also by promoting a fibrogenic phenotype in immune and vascular cells, and possibly also by triggering epithelial and endothelial cell conversion to a fibroblast-like phenotype. High glucose stimulates several fibrogenic pathways, triggering reactive oxygen species generation, stimulating neurohumoral responses, activating growth factor cascades (such as TGF-ß/Smad3 and PDGFs), inducing pro-inflammatory cytokines and chemokines, generating advanced glycation end-products (AGEs) and stimulating the AGE-RAGE axis, and upregulating fibrogenic matricellular proteins. Although diabetes-activated fibrogenic signaling has common characteristics in various tissues, some organs, such as the heart, kidney and liver develop more pronounced and clinically significant fibrosis. This review manuscript summarizes current knowledge on the cellular and molecular pathways involved in diabetic fibrosis, discussing the fundamental links between metabolic perturbations and fibrogenic activation, the basis for organ-specific differences, and the promises and challenges of anti-fibrotic therapies for diabetic patients.


Subject(s)
Diabetes Mellitus, Type 1/pathology , Diabetes Mellitus, Type 2/pathology , Animals , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Disease Progression , Epigenesis, Genetic , Fibroblasts/metabolism , Fibroblasts/pathology , Fibrosis , Glucose/genetics , Glucose/metabolism , Humans , Inflammation/genetics , Inflammation/metabolism , Inflammation/pathology , Signal Transduction
11.
Cell Metab ; 33(2): 258-269.e3, 2021 02 02.
Article in English | MEDLINE | ID: covidwho-1064967

ABSTRACT

Corticosteroid therapy is now recommended as a treatment in patients with severe COVID-19. But one key question is how to objectively identify severely ill patients who may benefit from such therapy. Here, we assigned 12,862 COVID-19 cases from 21 hospitals in Hubei Province equally to a training and a validation cohort. We found that a neutrophil-to-lymphocyte ratio (NLR) > 6.11 at admission discriminated a higher risk for mortality. Importantly, however, corticosteroid treatment in such individuals was associated with a lower risk of 60-day all-cause mortality. Conversely, in individuals with an NLR ≤ 6.11 or with type 2 diabetes, corticosteroid treatment was not associated with reduced mortality, but rather increased risks of hyperglycemia and infections. These results show that in the studied cohort corticosteroid treatment is associated with beneficial outcomes in a subset of COVID-19 patients who are non-diabetic and with severe symptoms as defined by NLR.


Subject(s)
Adrenal Cortex Hormones/therapeutic use , COVID-19/drug therapy , Lymphocytes/cytology , Neutrophils/cytology , Adrenal Cortex Hormones/adverse effects , Area Under Curve , COVID-19/mortality , COVID-19/pathology , COVID-19/virology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Humans , Hyperglycemia/complications , Hyperglycemia/pathology , Length of Stay , Proportional Hazards Models , ROC Curve , Risk Factors , SARS-CoV-2/isolation & purification , Severity of Illness Index , Survival Rate , Treatment Outcome
13.
Cells ; 9(11)2020 11 13.
Article in English | MEDLINE | ID: covidwho-927551

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) was declared a pandemic by the WHO on 19 March 2020. This pandemic is associated with markedly elevated blood glucose levels and a remarkable degree of insulin resistance, which suggests pancreatic islet ß-cell dysfunction or apoptosis and insulin's inability to dispose of glucose into cellular tissues. Diabetes is known to be one of the top pre-existing co-morbidities associated with the severity of COVID-19 along with hypertension, cardiocerebrovascular disease, advanced age, male gender, and recently obesity. This review focuses on how COVID-19 may be responsible for the accelerated development of type 2 diabetes mellitus (T2DM) as one of its acute and suspected long-term complications. These observations implicate an active role of metabolic syndrome, systemic and tissue islet renin-angiotensin-aldosterone system, redox stress, inflammation, islet fibrosis, amyloid deposition along with ß-cell dysfunction and apoptosis in those who develop T2DM. Utilizing light and electron microscopy in preclinical rodent models and human islets may help to better understand how COVID-19 accelerates islet and ß-cell injury and remodeling to result in the long-term complications of T2DM.


Subject(s)
Apoptosis , Coronavirus Infections/pathology , Diabetes Mellitus, Type 2/pathology , Pneumonia, Viral/pathology , Animals , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/virology , Diabetes Mellitus, Type 2/complications , Humans , Insulin-Secreting Cells/cytology , Insulin-Secreting Cells/metabolism , Metabolic Syndrome/complications , Metabolic Syndrome/pathology , Oxidative Stress , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/virology , Renin-Angiotensin System/physiology , SARS-CoV-2
14.
Endokrynol Pol ; 71(5): 367-375, 2020.
Article in English | MEDLINE | ID: covidwho-895590

ABSTRACT

INTRODUCTION: The objective of this paper was to investigate the clinical features and pulmonary CT imaging features of COVID-19 patients with diabetes mellitus. MATERIAL AND METHODS: From January 16, 2020 to March 28, 2020, among the 568 cases of COVID-19 patients diagnosed in Xiaogan Central Hospital, 64 cases of COVID-19 patients with diabetes were selected as the diabetic group, and 64 cases of COVID-19 patients with age and gender matching without diabetes were selected as the non-diabetic group, and their clinical data and pulmonary CT characteristics were retrospectively analysed. RESULTS: Compared with the non-diabetic group, the proportion of patients in the diabetic group with chronic underlying disease was higher, and they were in more a serious condition at admission. Inflammation index and characteristics of glycolipid metabolism results showed that COVID-19 patients with diabetes mellitus were more likely to have elevated inflammatory markers and hypercoagulability, accompanied by hypoproteinaemia and glucose and lipid metabolism disorders. Treatment and clinic outcome results showed that the time of nucleic acid turning negative in the diabetic group was significantly longer than that in the non-diabetic group. Radiological data showed that COVID-19 combined with diabetes prolonged the time of detoxification in patients. CONCLUSION: COVID-19 patients with diabetes mellitus and chronic hypertension are associated with increased inflammatory markers and disorders of glucose and lipid metabolism. These patients tend to develop serious diseases, especially the rapid progression of CT lesions in the lungs of patients with a wide range ofinvolvement, and prolonged absorption and detoxification time.


Subject(s)
Betacoronavirus , Coronavirus Infections/diagnostic imaging , Diabetes Mellitus, Type 2/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Adult , Aged , COVID-19 , COVID-19 Testing , Clinical Laboratory Techniques , Coronavirus Infections/complications , Coronavirus Infections/diagnosis , Coronavirus Infections/pathology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/pathology , Female , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/pathology , Retrospective Studies , Risk Factors , SARS-CoV-2 , Tomography, X-Ray Computed
16.
BMC Endocr Disord ; 20(1): 155, 2020 Oct 16.
Article in English | MEDLINE | ID: covidwho-873974

ABSTRACT

BACKGROUND: Detailed description of hyperglycemia management in diabetic patients infected with SARS-CoV-2 remain limited, although patients with diabetes show higher complication and mortality rate than patients without diabetes. Transient non-severe increased insulin requirement in patients hospitalized for medical conditions such as sepsis or myocardial infarction is a well-known phenomenon. However, extremely high-dose insulin requirement remains a very rarely reported entity. Here, we report the case of an extreme and transitory insulin requirement episode in a type 2 diabetic patient presenting an acute respiratory distress syndrome caused by SARS-CoV-2. CASE PRESENTATION: A 57-year-old man resident in Geneva, Switzerland, previously known for type 2 diabetes for 3 years was admitted for an aggravation of his dyspnea. His type 2 diabetes was treated only with metformin and his latest Hb1Ac was 6.1%. Chest CT SCAN showed a bilateral multilobar ground-glass opacification. Twenty-four hours after his admission he presented a worsening of dyspnea and severe hypoxemia requiring a transfer to the intensive care unit rapidly followed by oro-tracheal intubation for mechanical ventilation support. A bronchoalveolar lavage was performed and test of SARS-CoV-2 by RT-qPCR assay was positive. At day 3, he presented a rapidly progressive insulin requirement at a rate of up to 50 units/hour intravenous insulin aspart. Despite the high insulin doses, he maintained an elevated plasma glucose level at 270 mg/dL on average. His extremely high-dose insulin requirement "resolved" at day 9, and the insulin infusion rate was rapidly reduced. CONCLUSIONS: This case may reflect a specific and profound impact of SARS-CoV-2 on metabolic homeostasis, in particular in diabetic patients that appear more prone to complications of COVID-19 infection. Yet, the mechanisms behind this remain to be elucidated. The optimal management of hyperglycemia of diabetic patients infected with SARS-CoV-2 has yet not be defined, however insulin remain the mainstay of treatment approach. Report of extreme dysregulation of chronic conditions such as diabetes in patients with COVID-19 may help clinicians to better take care of patients during the pandemic of SARS-CoV-2. To the best of our knowledge this is the first description of extremely high-dose insulin requirement in patient with COVID-19.


Subject(s)
Betacoronavirus/isolation & purification , Coronavirus Infections/complications , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Pneumonia, Viral/complications , COVID-19 , Coronavirus Infections/transmission , Coronavirus Infections/virology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/pathology , Diabetes Mellitus, Type 2/virology , Dose-Response Relationship, Drug , Humans , Male , Middle Aged , Pandemics , Pneumonia, Viral/transmission , Pneumonia, Viral/virology , Prognosis , SARS-CoV-2
17.
J Diabetes Res ; 2020: 8205261, 2020.
Article in English | MEDLINE | ID: covidwho-852770

ABSTRACT

The coronavirus disease 2019 (COVID-19) pandemic continues to cause havoc to many countries of the globe, with no end in sight, due to nonavailability of a given vaccine or treatment regimen. The pandemic has so far had a relatively limited impact on the African continent, which contributes more than 93% of global malaria burden. However, the limited burden of COVID-19 pandemic on the African region could have long-term implications on the health and wellbeing of affected inhabitants due to its malaria-endemic status. Malaria causes recurrent insulin resistance with episodes of infection at relatively low parasitaemia. Angiotensin-converting enzyme 2 (ACE2) which is widely distributed in the human body is implicated in the pathogenesis of malaria, type 2 diabetes mellitus (T2DM), and COVID-19. Use of ACE2 by the COVID-19 virus induces inflammation and oxidative stress, which can lead to insulin resistance. Although COVID-19 patients in malaria-endemic African region may not exhibit severe signs and symptoms of the disease, their risk of exhibiting heightened insulin resistance and possible future development of T2DM is high due to their prior exposure to malaria. African governments must double efforts at containing the continued spread of the virus without neglecting existing malarial control measures if the region is to avert the plausible long-term impact of the pandemic in terms of future development of T2DM.


Subject(s)
Coronavirus Infections/epidemiology , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/pathology , Endemic Diseases , Malaria/epidemiology , Pneumonia, Viral/epidemiology , Africa/epidemiology , Angiotensin-Converting Enzyme 2 , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , Betacoronavirus/physiology , COVID-19 , Coronavirus Infections/complications , Diabetes Mellitus, Type 2/complications , Disease Progression , Humans , Insulin Resistance/physiology , Malaria/complications , Pandemics , Peptidyl-Dipeptidase A/physiology , Pneumonia, Viral/complications , Prediabetic State/epidemiology , Prediabetic State/pathology , Prediabetic State/virology , Renin-Angiotensin System/drug effects , Renin-Angiotensin System/physiology , SARS-CoV-2
18.
Mech Ageing Dev ; 192: 111363, 2020 12.
Article in English | MEDLINE | ID: covidwho-797286

ABSTRACT

Neprilysin (NEP) is an integral membrane-bound metallopeptidase with a wide spectrum of substrates and physiological functions. It plays an important role in proteolytic processes in the kidney, cardiovascular regulation, immune response, cell proliferation, foetal development etc. It is an important neuropeptidase and amyloid-degrading enzyme which makes NEP a therapeutic target in Alzheimer's disease (AD). Moreover, it plays a preventive role in development of cancer, obesity and type-2 diabetes. Recently a role of NEP in COVID-19 pathogenesis has also been suggested. Despite intensive research into NEP structure and functions in different organisms, changes in its expression and regulation during brain development and ageing, especially in age-related pathologies, is still not fully understood. This prevents development of pharmacological treatments from various diseases in which NEP is implicated although recently a dual-acting drug sacubitril-valsartan (LCZ696) combining a NEP inhibitor and angiotensin receptor blocker has been approved for treatment of heart failure. Also, various natural compounds capable of upregulating NEP expression, including green tea (EGCG), have been proposed as a preventive medicine in prostate cancer and AD. This review summarizes the existing literature and our own research on the expression and activity of NEP in normal brain development, ageing and under pathological conditions.


Subject(s)
Aging/immunology , Alzheimer Disease/immunology , COVID-19/immunology , Diabetes Mellitus, Type 2/immunology , Gene Expression Regulation, Enzymologic/immunology , Gene Expression Regulation, Neoplastic/immunology , Neoplasm Proteins/immunology , Neoplasms/immunology , Neprilysin/immunology , SARS-CoV-2/immunology , Aging/pathology , Alzheimer Disease/pathology , Animals , COVID-19/pathology , Diabetes Mellitus, Type 2/pathology , Humans , Neoplasms/pathology
19.
Diabetes Res Clin Pract ; 169: 108454, 2020 Nov.
Article in English | MEDLINE | ID: covidwho-778739

ABSTRACT

AIMS: To evaluate whether subjects with diabetes hospitalized for Coronavirus disease-19 (Covid-19) represent a subgroup of patients with high-risk clinical features compared to patients with diabetes without Covid-19. METHODS: In this case-control study 79 patients with type 2 diabetes out of 354 adults hospitalized for Covid-19 and 158 controls with type 2 diabetes but without Covid-19, matched for age and gender, were enrolled. Medical history and concomitant therapies were retrieved from medical charts and compared between cases and controls, controlling for confounders. RESULTS: Fully-adjusted multivariate logistic regression model showed that previous CVD history did not differ between patients with and without Covid-19 (odds ratio 1.40, 95% confidence interval [CI]: 0.59-3.32, p = 0.45). A higher prevalence of chronic obstructive pulmonary disease (COPD) (OR 3.72, 95%CI: 1.42-9.72, p = 0.007) and of chronic kidney disease (CKD) (OR 3.08, 95%CI: 1.18-8.06, p = 0.022) and a lower prevalence of ever smokers (OR 0.30, 95%CI: 0.13-0.67, p = 0.003), of users of lipid lowering agents (OR 0.26, 95%CI: 0.12-0.54, p < 0.001), and of anti-hypertensive drugs (OR 0.39, 95%CI: 0.16-0.93, p = 0.033) were found among cases. CONCLUSIONS: CVD prevalence does not differ between people with diabetes with and without Covid-19 requiring hospitalization. An increased prevalence of COPD and of CKD in Covid-19 patients with type 2 diabetes is suggested. These findings aid to clarify the relationship between underlying conditions and SARS-CoV-2 infection in the high-risk group of patients with diabetes.


Subject(s)
COVID-19/complications , Diabetes Mellitus, Type 2/pathology , Pulmonary Disease, Chronic Obstructive/pathology , Renal Insufficiency, Chronic/pathology , SARS-CoV-2/isolation & purification , Aged , Aged, 80 and over , COVID-19/transmission , COVID-19/virology , Case-Control Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/virology , Female , Hospitalization , Humans , Incidence , Italy/epidemiology , Male , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/virology , Renal Insufficiency, Chronic/epidemiology , Renal Insufficiency, Chronic/virology
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