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1.
Diabetes ; 71(4): 788-794, 2022 04 01.
Article in English | MEDLINE | ID: covidwho-1643401

ABSTRACT

Admission hyperglycemia has emerged worldwide as a predictor of poor coronavirus disease 2019 (COVID-19) outcome. Hyperglycemia leads to a defect in circulating hematopoietic stem/progenitor cells (HSPCs), which, in turn, predicts diabetic complications. Here, we explored whether reduced HSPCs mediated at least part of the prognostic effect of hyperglycemia on COVID-19 outcome. We found that patients with COVID-19 (n = 100) hospitalized in a nonintensive setting displayed dramatically (50-60%) reduced levels of HSPCs measured by flow cytometry as CD34+, CD34+CD45dim, or CD34+CD133+ cells, compared with control subjects (n = 595). This finding was highly significant (all P < 10-10) after multivariable adjustment, or manual 1:1 patient match, or propensity score matching. Admission hyperglycemia (≥7.0 mmol/L) was present in 45% of patients, was associated with a significant further ∼30% HSPCs reduction, and predicted a 2.6-fold increased risk of the primary outcome of adverse COVID-19 course (admittance to the intensive care unit or death). Low HSPCs were also associated with advanced age, higher peak C-reactive protein, and neutrophil-to-lymphocyte ratio. Independently from confounders, 1 SD lower CD34+ HSPCs was associated with a more than threefold higher risk of adverse outcome. Upon formal analysis, reduction of HSPCs was a significant mediator of the admission hyperglycemia on COVID-19 outcome, being responsible for 28% of its prognostic effect.


Subject(s)
COVID-19 , Hyperglycemia , Antigens, CD34/metabolism , Flow Cytometry , Hematopoietic Stem Cells/metabolism , Humans , Hyperglycemia/metabolism
2.
Nat Metab ; 4(1): 29-43, 2022 01.
Article in English | MEDLINE | ID: covidwho-1612214

ABSTRACT

Severe cases of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are associated with elevated blood glucose levels and metabolic complications. However, the molecular mechanisms for how SARS-CoV-2 infection alters glycometabolic control are incompletely understood. Here, we connect the circulating protein GP73 with enhanced hepatic gluconeogenesis during SARS-CoV-2 infection. We first demonstrate that GP73 secretion is induced in multiple tissues upon fasting and that GP73 stimulates hepatic gluconeogenesis through the cAMP/PKA signaling pathway. We further show that GP73 secretion is increased in cultured cells infected with SARS-CoV-2, after overexpression of SARS-CoV-2 nucleocapsid and spike proteins and in lungs and livers of mice infected with a mouse-adapted SARS-CoV-2 strain. GP73 blockade with an antibody inhibits excessive glucogenesis stimulated by SARS-CoV-2 in vitro and lowers elevated fasting blood glucose levels in infected mice. In patients with COVID-19, plasma GP73 levels are elevated and positively correlate with blood glucose levels. Our data suggest that GP73 is a glucogenic hormone that likely contributes to SARS-CoV-2-induced abnormalities in systemic glucose metabolism.


Subject(s)
COVID-19/complications , COVID-19/virology , Glucose/metabolism , Hyperglycemia/etiology , Hyperglycemia/metabolism , Membrane Proteins/metabolism , SARS-CoV-2 , Animals , Biomarkers , Cyclic AMP-Dependent Protein Kinases/metabolism , Diet, High-Fat , Disease Models, Animal , Fasting , Gene Expression , Gluconeogenesis/drug effects , Gluconeogenesis/genetics , Host-Pathogen Interactions , Humans , Hyperglycemia/blood , Liver/metabolism , Liver/pathology , Membrane Proteins/antagonists & inhibitors , Membrane Proteins/blood , Membrane Proteins/genetics , Mice , Mice, Knockout , Organ Specificity/genetics
3.
Front Endocrinol (Lausanne) ; 12: 772865, 2021.
Article in English | MEDLINE | ID: covidwho-1556281

ABSTRACT

The potential relationship between diabetes and COVID-19 has been evaluated. However, new knowledge is rapidly emerging. In this study, we systematically reviewed the relationship between viral cell surface receptors (ACE2, AXL, CD147, DC-SIGN, L-SIGN and DPP4) and SARS-CoV-2 infection risk, and emphasized the implications of ACE2 on SARS-CoV-2 infection and COVID-19 pathogenesis. Besides, we updated on the two-way interactions between diabetes and COVID-19, as well as the treatment options for COVID-19 comorbid patients from the perspective of ACE2. The efficacies of various clinical chemotherapeutic options, including anti-diabetic drugs, renin-angiotensin-aldosterone system inhibitors, lipid-lowering drugs, anticoagulants, and glucocorticoids for COVID-19 positive diabetic patients were discussed. Moreover, we reviewed the significance of two different forms of ACE2 (mACE2 and sACE2) and gender on COVID-19 susceptibility and severity. This review summarizes COVID-19 pathophysiology and the best strategies for clinical management of diabetes patients with COVID-19.


Subject(s)
Angiotensin-Converting Enzyme 2/blood , COVID-19/complications , COVID-19/drug therapy , Diabetes Complications/drug therapy , Diabetes Mellitus/drug therapy , Aged , Animals , Cardiovascular Diseases/complications , Cardiovascular Diseases/drug therapy , Comorbidity , Female , Humans , Hyperglycemia/metabolism , Hypertension , Inflammation , Insulin Resistance , Insulin-Secreting Cells/metabolism , Male , Middle Aged , Obesity/complications , Obesity/drug therapy , Renal Insufficiency, Chronic/complications , Renal Insufficiency, Chronic/drug therapy , Risk , Risk Factors , SARS-CoV-2
4.
Sci Rep ; 11(1): 22860, 2021 11 24.
Article in English | MEDLINE | ID: covidwho-1532106

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.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Hyperglycemia/metabolism , Spike Glycoprotein, Coronavirus/metabolism , Angiotensin-Converting Enzyme 2/physiology , COVID-19/metabolism , COVID-19/pathology , Computational Biology/methods , Computer Simulation , Humans , Hyperglycemia/immunology , Molecular Dynamics Simulation , Protein Binding , SARS-CoV-2/metabolism , SARS-CoV-2/pathogenicity , Spike Glycoprotein, Coronavirus/physiology
5.
Diabetes Metab Syndr ; 15(4): 102188, 2021.
Article in English | MEDLINE | ID: covidwho-1293736

ABSTRACT

AIM: The pandemic has generated the need for COVID-19 patients to be treated as best as possible; however, the effect of these treatments on glycemic control has not yet been taken into account. This article aims to determine whether the daily variation of glucose is influenced by the use of corticosteroids in COVID-19 patients treated in Lima-Peru. METHODOLOGY: A prospective cohort study was undertook, in which glucose was measured four times a day in 53 patients hospitalized due to COVID-19. These values were associated with the use of corticosteroids and adjusted for other socio-educational variables, all by means of PA-GEE models. RESULTS: Nested multivariate analysis of daily glucose variation found that those using corticosteroids increased the daily average glucose as well as the first and last glucose measurements, this is, at 6am and 10pm, respectively (all p-values <0.026). An increase in glucose levels was also observed in those with diabetes (all p-values <0.001). In contrast, we found that there was a decrease in the last glucose measurement of the day in obese patients (p-value = 0.044). CONCLUSIONS: The patients who used corticosteroids for the treatment of COVID-19 increased the average glucose per day, especially in the first and last measurement.


Subject(s)
Adrenal Cortex Hormones/adverse effects , Blood Glucose/analysis , COVID-19/drug therapy , Hyperglycemia/pathology , SARS-CoV-2/isolation & purification , Aged , Blood Glucose Self-Monitoring/methods , COVID-19/epidemiology , COVID-19/virology , Female , Humans , Hyperglycemia/chemically induced , Hyperglycemia/metabolism , Male , Middle Aged , Peru/epidemiology , Prospective Studies
8.
Nat Metab ; 3(6): 774-785, 2021 06.
Article in English | MEDLINE | ID: covidwho-1243313

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) are reported to have a greater prevalence of hyperglycaemia. Cytokine release as a consequence of severe acute respiratory syndrome coronavirus 2 infection may precipitate the onset of metabolic alterations by affecting glucose homeostasis. Here we describe abnormalities in glycometabolic control, insulin resistance and beta cell function in patients with COVID-19 without any pre-existing history or diagnosis of diabetes, and document glycaemic abnormalities in recovered patients 2 months after onset of disease. In a cohort of 551 patients hospitalized for COVID-19 in Italy, we found that 46% of patients were hyperglycaemic, whereas 27% were normoglycaemic. Using clinical assays and continuous glucose monitoring in a subset of patients, we detected altered glycometabolic control, with insulin resistance and an abnormal cytokine profile, even in normoglycaemic patients. Glycaemic abnormalities can be detected for at least 2 months in patients who recovered from COVID-19. Our data demonstrate that COVID-19 is associated with aberrant glycometabolic control, which can persist even after recovery, suggesting that further investigation of metabolic abnormalities in the context of long COVID is warranted.


Subject(s)
Blood Glucose/metabolism , COVID-19/blood , Hyperglycemia/metabolism , COVID-19/complications , COVID-19/virology , Cohort Studies , Humans , Hyperglycemia/complications , Insulin Resistance , Insulin-Secreting Cells/pathology , SARS-CoV-2/isolation & purification
9.
Elife ; 102021 03 15.
Article in English | MEDLINE | ID: covidwho-1196112

ABSTRACT

Measures of lung function are heritable, and thus, we sought to utilise genetics to propose drug-repurposing candidates that could improve respiratory outcomes. Lung function measures were found to be genetically correlated with seven druggable biochemical traits, with further evidence of a causal relationship between increased fasting glucose and diminished lung function. Moreover, we developed polygenic scores for lung function specifically within pathways with known drug targets and investigated their relationship with pulmonary phenotypes and gene expression in independent cohorts to prioritise individuals who may benefit from particular drug-repurposing opportunities. A transcriptome-wide association study (TWAS) of lung function was then performed which identified several drug-gene interactions with predicted lung function increasing modes of action. Drugs that regulate blood glucose were uncovered through both polygenic scoring and TWAS methodologies. In summary, we provided genetic justification for a number of novel drug-repurposing opportunities that could improve lung function.


Chronic respiratory disorders like asthma affect around 600 million people worldwide. Although these illnesses are widespread, they can have several different underlying causes, making them difficult to treat. Drugs that work well on one type of respiratory disorder may be completely ineffective on another. Understanding the biological and environmental factors that cause these illnesses will allow them to be treated more effectively by tailoring therapies to each patient. Reduced lung function is a factor in respiratory disorders and it can have many genetic causes. Studying the genes of patients with reduced lung function can reveal the genes involved, some of which may already be targets of existing drugs for other illnesses. So, could a patient's genetics be used to repurpose existing drugs to treat their respiratory disorders? Reay et al. combined three methods to link genetics and biological processes to the causes of reduced lung function. The results reveal several factors that could lead to new treatments. In one example, reduced lung function showed a link to genes associated with high blood sugar. As such, treatments used in diabetes might help improve lung function in some patients. Reay et al. also developed a scoring system that could predict the efficacy of a treatment based on a patient's genetics. The study suggests that COVID-19 infection could be affected by blood sugar levels too. Chronic respiratory disorders are a critical issue worldwide and have proven difficult to treat, but these results suggest a way to identify new therapies and target them to the right patients. The findings also support a connection between lung function and blood sugar levels. This implies that perhaps existing diabetes treatments ­ including diet and lifestyle changes aimed at reducing or limiting blood sugar ­ could be repurposed to treat respiratory disorders in some patients. The next step will be to perform clinical trials to test whether these therapies are in fact effective.


Subject(s)
Drug Repositioning/methods , Hyperglycemia/genetics , Lung Diseases/drug therapy , Lung Diseases/genetics , Blood Glucose/metabolism , Causality , Databases, Genetic , Genome-Wide Association Study/methods , Humans , Hyperglycemia/metabolism , Hyperglycemia/physiopathology , Lung/drug effects , Lung/physiology , Lung/physiopathology , Lung Diseases/metabolism , Lung Diseases/physiopathology , Multifactorial Inheritance , Phenotype , Polymorphism, Single Nucleotide , Respiratory Function Tests/methods , Transcriptome
10.
PLoS One ; 16(3): e0246265, 2021.
Article in English | MEDLINE | ID: covidwho-1117479

ABSTRACT

Medicinal uses and applications of metals and their complexes are of increasing clinical and commercial importance. The ligation behavior of quercetin (Q), which is a flavonoid, and its Zn (II) (Q/Zn) complex were studied and characterized based on elemental analysis, molar conductance, Fourier-transform infrared (FTIR) spectra, electronic spectra, proton nuclear magnetic resonance (1H-NMR), thermogravimetric analysis, and transmission electron microscopy (TEM). FTIR spectral data revealed that Q acts as a bidentate ligand (chelating ligand) through carbonyl C(4) = O oxygen and phenolic C(3)-OH oxygen in conjugation with Zn. Electronic, FTIR, and 1H-NMR spectral data revealed that the Q/Zn complex has a distorted octahedral geometry, with the following chemical formula: [Zn(Q)(NO3)(H2O)2].5H2O. Diabetes was induced by streptozotocin (STZ) injection. A total of 70 male albino rats were divided into seven groups: control, diabetic untreated group and diabetic groups treated with either MSCs and/or Q and/or Q/Zn or their combination. Serum insulin, glucose, C-peptide, glycosylated hemoglobin, lipid profile, and enzymatic and non-enzymatic antioxidant levels were determined. Pancreatic and lung histology and TEM for pancreatic tissues in addition to gene expression of both SOD and CAT in pulmonary tissues were evaluated. MSCs in combination with Q/Zn therapy exhibited potent protective effects against STZ induced hyperglycemia and suppressed oxidative stress, genotoxicity, glycometabolic disturbances, and structural alterations. Engrafted MSCs were found inside pancreatic tissue at the end of the experiment. In conclusion, Q/Zn with MSC therapy produced a synergistic effect against oxidative stress and genotoxicity and can be considered potential ameliorative therapy against diabetes with pulmonary dysfunction, which may benefit against COVID-19.


Subject(s)
Diabetes Mellitus, Experimental/therapy , Hypoglycemic Agents/therapeutic use , Mesenchymal Stem Cell Transplantation , Quercetin/therapeutic use , Zinc/therapeutic use , Animals , Blood Glucose/analysis , Blood Glucose/metabolism , C-Peptide/blood , C-Peptide/metabolism , Cells, Cultured , Coordination Complexes/chemistry , Coordination Complexes/therapeutic use , Diabetes Mellitus, Experimental/blood , Diabetes Mellitus, Experimental/metabolism , Diabetes Mellitus, Experimental/pathology , Glycated Hemoglobin A/analysis , Glycated Hemoglobin A/metabolism , Hyperglycemia/blood , Hyperglycemia/metabolism , Hyperglycemia/pathology , Hyperglycemia/therapy , Hypoglycemic Agents/chemistry , Insulin/blood , Insulin/metabolism , Lung/drug effects , Lung/metabolism , Lung/pathology , Male , Oxidative Stress/drug effects , Quercetin/analogs & derivatives , Rats , Zinc/chemistry
11.
Eur J Clin Invest ; 50(7): e13262, 2020 Jul.
Article in English | MEDLINE | ID: covidwho-1081113

ABSTRACT

The Covid-19 pandemic confronted us with unknown clinical pictures, also in diabetology and endocrinology. Sharing clinical experiences is therefore of enormous importance. Actually, information about the care given in the Covid-19 ward (in contrast to that provided in the Emergency Room/ICU) is still sparse. The last weeks we built experience and gathered knowledge while giving hospital care to patients who had a pre-existent endocrine disease (and diabetes; most patients suffered from a type two diabetes). In our contribution we presented our insights obtained from this intensive period obtained in the Covid-19 ward.


Subject(s)
Coronavirus Infections/therapy , Diabetes Mellitus, Type 2/drug therapy , Hyperglycemia/drug therapy , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Pneumonia, Viral/therapy , Adrenal Insufficiency/complications , Adrenal Insufficiency/drug therapy , Belgium , Betacoronavirus , Blood Glucose/metabolism , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/metabolism , Diabetes Complications , Diabetes Insipidus/complications , Diabetes Insipidus/therapy , Diabetes Mellitus/drug therapy , Diabetes Mellitus/metabolism , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/metabolism , Disease Management , Glycated Hemoglobin A/metabolism , Hospital Units , Hospitalization , Humans , Hyperglycemia/etiology , Hyperglycemia/metabolism , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/metabolism , SARS-CoV-2
12.
Diabetes Metab Syndr ; 15(2): 499-503, 2021.
Article in English | MEDLINE | ID: covidwho-1071266

ABSTRACT

BACKGROUND AND AIMS: Few studies have reported on the use of continuous glucose monitoring (CGM) during the Covid-19 pandemic. We aimed to examine glycemic control metrics using flash glucose monitoring during insulin treatment and the clinical outcome in hospitalized patients with COVID-19. METHODS: Prospective, single-center cohort of adult patients diagnosed with type 2 diabetes or hyperglycemia and COVID-19 infection treated with basal bolus insulin regimen. Glycemic control was assessed with the use of intermittent Freestyle Libre flash glucose monitoring during the hospital stay. Outcome of interest were time in range [TIR], time above [TAR] and below [TBR] range, glycemic variability [coefficient of variation [% CV]), and differences in a composite of complications including ICU admission, acute respiratory distress syndrome (ARDS) and acute kidney injury. RESULTS: A total of 60 patients were included (44 known diabetes and 16 new onset hyperglycemia). In total 190,080 data points of CGM were available, of which 72.5% of values were within the target area [TIR (70-180 mg/dL)], 22% TAR (>180 mg/dL), and 3% were TBR (<70 mg/dL). During treatment, the coefficient of variation (% CV) was 30%. There were no association with TIR, but patients with TAR >180 mg/dl had higher rates of a composite of complications (22.5% vs 16%, p = 0.04). CONCLUSIONS: Basal bolus insulin regimen was safe and effective in achieving inpatient glycemic control in most patients with COVID-19. The association between TAR and complications indicates the need for improved inpatient glycemic control in hospitalized patients with COVID-19.


Subject(s)
Acute Kidney Injury/epidemiology , Blood Glucose/metabolism , COVID-19/metabolism , Diabetes Mellitus, Type 2/metabolism , Hyperglycemia/metabolism , Hypoglycemic Agents/therapeutic use , Insulin/therapeutic use , Respiratory Distress Syndrome/epidemiology , Aged , COVID-19/complications , Cohort Studies , Colombia/epidemiology , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Female , Glycated Hemoglobin A/metabolism , Glycemic Control , Humans , Hyperglycemia/drug therapy , Hyperglycemia/etiology , Intensive Care Units/statistics & numerical data , Male , Middle Aged , Monitoring, Physiologic , Pilot Projects , Point-of-Care Testing , Prospective Studies , SARS-CoV-2
13.
Diabet Med ; 38(5): e14498, 2021 05.
Article in English | MEDLINE | ID: covidwho-975494

ABSTRACT

AIM: To describe diabetes nurses' perspectives on the impact of the COVID-19 pandemic on people with diabetes and diabetes services across Europe. METHODS: An online survey developed using a rapid Delphi method. The survey was translated into 17 different languages and disseminated electronically in 27 countries via national diabetes nurse networks. RESULTS: Survey responses from 1829 diabetes nurses were included in the analysis. The responses indicated that 28% (n = 504) and 48% (n = 873) of diabetes nurses felt the COVID-19 pandemic had impacted 'a lot' on the physical and psychological risks of people with diabetes, respectively. The following clinical problems were identified as having increased 'a lot': anxiety 82% (n = 1486); diabetes distress 65% (n = 1189); depression 49% (n = 893); acute hyperglycaemia 39% (n = 710) and foot complications 18% (n = 323). Forty-seven percent (n = 771) of respondents identified that the level of care provided to people with diabetes had declined either extremely or quite severely. Self-management support, diabetes education and psychological support were rated by diabetes nurse respondents as having declined extremely or quite severely during the COVID-19 pandemic by 31% (n = 499), 63% (n = 1,027) and 34% (n = 551), respectively. CONCLUSION: The findings show that diabetes nurses across Europe have seen significant increases in both physical and psychological problems in their patient populations during COVID-19. The data also show that clinical diabetes services have been significantly disrupted. As the COVID-19 situation continues, we need to adapt care systems with some urgency to minimise the impact of the pandemic on the diabetes population.


Subject(s)
COVID-19 , Delivery of Health Care , Diabetes Mellitus/physiopathology , Nurse Specialists , Psychological Distress , Anxiety/psychology , Attitude of Health Personnel , Depression/psychology , Diabetes Mellitus/metabolism , Diabetes Mellitus/nursing , Diabetes Mellitus/psychology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 1/nursing , Diabetes Mellitus, Type 1/physiopathology , Diabetes Mellitus, Type 1/psychology , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/nursing , Diabetes Mellitus, Type 2/physiopathology , Diabetes Mellitus, Type 2/psychology , Diabetic Foot/physiopathology , Europe , Humans , Hyperglycemia/metabolism , SARS-CoV-2 , Self-Management , Surveys and Questionnaires
14.
Diabetes Res Clin Pract ; 167: 108338, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-935529

ABSTRACT

AIMS: The objective of this study is to explore the association between documented diabetes, fasting plasma glucose (FPG), and the clinical outcomes of Coronavirus disease 2019 (COVID-19). METHODS: This retrospective study included 255 patients with COVID-19. Of these, 214 were admitted to isolation wards and 41were admitted to intensive care units (ICUs). Demographic, clinical, treatment, and laboratory data were collected and compared between ICU and non-ICU patients. Multivariable logistic regression models were used to explore the risk factors associated with poor clinical outcomes (ICU admission or death). RESULTS: There were significant changes in several clinical parameters in ICU patients (leukopenia, lymphopenia, elevated D-dimer, as well as higher levels of FPG, cardiac troponin, serum ferritin, IL-6, and high-sensitivity C-reactive protein)compared with non-ICU patients. The prevalence of known diabetes was substantially higher in ICU than non-ICU patients (31.7% vs. 17.8%, P = 0.0408). Multivariable regression analysis showed that a history of diabetes [odds ratio (OR), 0.099; 95% confidence interval (CI), 0.016-0.627; P = 0.014], high FPG at admission (OR, 1.587; 95% CI, 1.299-1.939, P < 0.001), high IL-6 (OR, 1.01; 95% CI, 1.002-1.018, P = 0.013), and D-dimer higher than 1 mg/L at admission (OR, 4.341; 95% CI, 1.139-16.547, P = 0.032) were independent predictors of poor outcomes. Cox proportional hazards analysis showed that compared with FPG < 7 mmol/L, FPG levels of 7.0-11.1 mmol/L and ≥ 11.1 mmol/L were associated with an increased hazard ratio (HR) for poor outcome (HR, 5.538 [95% CI, 2.269-13.51] and HR, 11.55 [95% CI, 4.45-29.99], respectively). CONCLUSION: Hyperglycemia and a history of diabetes on admission predicted poor clinical outcomes in COVID-19.


Subject(s)
Blood Glucose/metabolism , Coronavirus Infections/metabolism , Diabetes Mellitus/metabolism , Hyperglycemia/metabolism , Intensive Care Units , Pneumonia, Viral/metabolism , Adult , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , China/epidemiology , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Diabetes Mellitus/epidemiology , Female , Fibrin Fibrinogen Degradation Products/metabolism , Hospitalization , Humans , Hyperglycemia/epidemiology , Interleukin-6/metabolism , Logistic Models , Male , Middle Aged , Mortality , Multivariate Analysis , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Prognosis , Proportional Hazards Models , Retrospective Studies , Risk Factors , SARS-CoV-2 , Severity of Illness Index , Young Adult
15.
Front Endocrinol (Lausanne) ; 11: 574541, 2020.
Article in English | MEDLINE | ID: covidwho-891580

ABSTRACT

Background: Diabetes mellitus is considered a common comorbidity of COVID-19, which has a wide spectrum of clinical manifestations ranging from asymptomatic infection to severe respiratory symptoms and even death. However, the impact of COVID-19 on blood glucose has not been fully understood. This meta-analysis aimed to summarize available data on the association between glycemic parameters and severity of COVID-19. Methods: PubMed, EMBASE, and Cochrane Library were searched from December 1, 2019 to May 15, 2020. Observational studies investigating blood glucose or glycated hemoglobin A1c (HbA1c) according to the severity of COVID-19 were considered for inclusion. Two independent researchers extracted data from eligible studies using a standardized data extraction sheet and then proceeded to cross check the results. Data were pooled using a fixed- or random-effects model to calculate the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Results: Three studies reported blood glucose and HbA1c according to the severity of COVID-19 and were included in this meta-analysis. The combined results showed that severe COVID-19 was associated with higher blood glucose (WMD 2.21, 95% CI: 1.30-3.13, P < 0.001). In addition, HbA1c was slightly higher in patients with severe COVID-19 than those with mild COVID-19, yet this difference did not reach significance (WMD 0.29, 95% CI: -0.59 to 1.16, P = 0.52). Conclusions: This meta-analysis provides evidence that severe COVID-19 is associated with increased blood glucose. This highlights the need to effectively monitor blood glucose to improve prognosis in patients infected with COVID-19.


Subject(s)
Betacoronavirus/isolation & purification , Blood Glucose/analysis , Coronavirus Infections/complications , Glycated Hemoglobin A/analysis , Hyperglycemia/epidemiology , Pneumonia, Viral/complications , COVID-19 , Humans , Hyperglycemia/metabolism , Hyperglycemia/virology , Pandemics , SARS-CoV-2
16.
Diabetes Res Clin Pract ; 167: 108382, 2020 Sep.
Article in English | MEDLINE | ID: covidwho-728513

ABSTRACT

Hyperglycemia with or without blood glucose in diabetes range is an emerging finding not uncommonly encountered in patients with COVID-19. Increasingly, all evidence currently available hints that both new-onset hyperglycemia without diabetes and new-onset diabetes in COVID-19 is associated with a poorer outcome compared with normoglycemic individuals and people with pre-existing diabetes.


Subject(s)
Coronavirus Infections/mortality , Diabetes Mellitus/epidemiology , Hyperglycemia/epidemiology , Pneumonia, Viral/mortality , Betacoronavirus , Blood Glucose/metabolism , COVID-19 , Coronavirus Infections/metabolism , Diabetes Mellitus/diagnosis , Diabetes Mellitus/metabolism , Humans , Hyperglycemia/diagnosis , Hyperglycemia/metabolism , Pandemics , Pneumonia, Viral/metabolism , Prognosis , SARS-CoV-2
17.
Nutrition ; 79-80: 110967, 2020.
Article in English | MEDLINE | ID: covidwho-704014

ABSTRACT

The severe form of coronavirus disease 19 (COVID-19) is characterized by cytokine storm syndrome (CSS) and disseminated intravascular coagulation (DIC). Diabetes, obesity, and hypertension have, as minor common denominators, chronic low-grade inflammation and high plasma myeloperoxidase levels, which could be linked to pulmonary phagocytic hyperactivation and CSS. The hyperactivation of M1 macrophages with a proinflammatory phenotype, which is linked to aerobic glycolysis, leads to the recruitment of monocytes, neutrophils, and platelets from circulating blood and plays a crucial role in thrombo-inflammation (as recently demonstrated in COVID-19) through the formation of neutrophil extracellular traps and monocyte-platelet aggregates, which could be responsible for DIC. The modulation of glucose availability for activated M1 macrophages by means of a eucaloric ketogenic diet (EKD) could represent a possible metabolic tool for reducing adenosine triphosphate production from aerobic glycolysis in the M1 macrophage phenotype during the exudative phase. This approach could reduce the overproduction of cytokines and, consequently, the accumulation of neutrophils, monocytes, and platelets from the blood. Second, an EKD could be advantageous for the metabolism of anti-inflammatory M2 macrophages because these cells predominantly express oxidative phosphorylation enzymes and are best fed by the oxidation of fatty acids in the mitochondria. An EKD could guarantee the availability of free fatty acids, which are an optimal fuel supply for these cells. Third, an EKD, which could reduce high lactate formation by macrophages due to glycolysis, could favor the production of interferon type I, which are inhibited by excessive lactate production. From a practical point of view, the hypothesis, in addition to being proven in clinical studies, must obviously take into account the contraindications of an EKD, particularly type 1 or 2 diabetes treated with drugs that can cause hypoglycemia, to avoid the risk for side effects of the diet.


Subject(s)
COVID-19/complications , Cytokines/metabolism , Diet, Carbohydrate-Restricted , Hyperglycemia/metabolism , Inflammation/prevention & control , Ketosis , Macrophages/metabolism , Blood Glucose/metabolism , Blood Platelets , COVID-19/metabolism , Diabetes Mellitus , Disseminated Intravascular Coagulation , Energy Intake , Glycolysis , Humans , Inflammation/etiology , Inflammation/metabolism , Interferon Type I/metabolism , Ketones/metabolism , Lactic Acid/metabolism , Monocytes , Neutrophils , Pandemics , SARS-CoV-2
18.
Diabetes Metab Syndr ; 14(4): 519-520, 2020.
Article in English | MEDLINE | ID: covidwho-186339

ABSTRACT

BACKGROUND AND AIMS: Administration of corticosteroids is common in obstetric practice. In this concise review we queried on the effects of corticosteroids in pregnancies complicated by SARS-CoV-2. METHODS: We performed a literature search on PubMed, regarding the use of corticosteroids in patients with SARS-CoV-2 infection, in pregnancies complicated by SARS-CoV-2, as well as their impact on glycemia in pregnant women with or without diabetes. Furthermore, we searched for effects of SARS-CoV-2 and of other coronaviridae on insulin secretion and glycemia. RESULTS: SARS-CoV-2 infection appears to be a risk factor for complications in pregnancy. Corticosteroids may not be recommended for treating SARS-CoV-2 pneumonia but they may be needed for at-risk pregnancies. Corticosteroids in pregnancy have a diabetogenic potential. SARS-CoV-2 and other coronaviridae may have effects on glycemia. CONCLUSIONS: Caution should be exercised while using corticosteroids in pregnant women with COVID-19 requiring preterm delivery.


Subject(s)
Adrenal Cortex Hormones/pharmacology , Coronavirus Infections/complications , Diabetes Mellitus/physiopathology , Hyperglycemia/pathology , Hypoglycemia/pathology , Pneumonia, Viral/complications , Pregnancy Complications, Infectious/pathology , Betacoronavirus/drug effects , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/drug therapy , Coronavirus Infections/virology , Female , Homeostasis , Humans , Hyperglycemia/etiology , Hyperglycemia/metabolism , Hypoglycemia/etiology , Hypoglycemia/metabolism , Insulin Secretion/drug effects , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/virology , Pregnancy , Pregnancy Complications, Infectious/etiology , Pregnancy Complications, Infectious/metabolism , SARS-CoV-2
19.
J Med Virol ; 92(7): 770-775, 2020 07.
Article in English | MEDLINE | ID: covidwho-145051

ABSTRACT

Coronavirus disease-2019 (COVID-19) infection and its severity can be explained by the concentration of glycosylated severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) viral particles in the lung epithelium, the concentration of glycosylated angiotensin-converting enzyme receptor 2 (ACE2) in the lung epithelium, and the degree and control of the pulmonary immune response to the SARS-CoV-2 spike protein at approximately day 8 to 10 after symptom onset, which may be related to both. Binding of ACE2 by SARS-CoV-2 in COVID-19 also suggests that prolonged uncontrolled hyperglycemia, and not just a history of diabetes mellitus, may be important in the pathogenesis of the disease. It is tempting to consider that the same mechanism acts in COVID-19 as in SARS, where an overactive macrophage M1 inflammatory response, as neutralizing antibodies to the SARS-CoV-2 spike protein form at day 7 to 10, results in acute respiratory distress syndrome (ARDS) in susceptible patients. It also allows consideration of agents, such as hydroxychloroquine, which may interfere with this overly brisk macrophage inflammatory response and perhaps influence the course of the disease, in particular, those that blunt but do not completely abrogate the M1 to M2 balance in macrophage polarization, as well as viral load, which in SARS appears to be temporally related to the onset of ARDS.


Subject(s)
Antiviral Agents/therapeutic use , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Hydroxychloroquine/therapeutic use , Hyperglycemia/drug therapy , Hyperglycemia/epidemiology , Pandemics , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Angiotensin-Converting Enzyme 2 , Antibodies, Neutralizing/biosynthesis , Antibody-Dependent Cell Cytotoxicity/drug effects , Azithromycin/therapeutic use , Betacoronavirus/drug effects , Betacoronavirus/metabolism , Betacoronavirus/pathogenicity , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/metabolism , Glucose/immunology , Glucose/metabolism , Glycosylation/drug effects , Host-Pathogen Interactions/genetics , Host-Pathogen Interactions/immunology , Humans , Hyperglycemia/complications , Hyperglycemia/metabolism , Incidence , Macrophages/drug effects , Macrophages/immunology , Macrophages/virology , Peptidyl-Dipeptidase A/genetics , Peptidyl-Dipeptidase A/immunology , Peptidyl-Dipeptidase A/metabolism , Pneumonia, Viral/complications , Pneumonia, Viral/metabolism , SARS-CoV-2 , Spike Glycoprotein, Coronavirus/antagonists & inhibitors , Spike Glycoprotein, Coronavirus/genetics , Spike Glycoprotein, Coronavirus/metabolism
20.
Diabet Med ; 37(7): 1094-1102, 2020 07.
Article in English | MEDLINE | ID: covidwho-116685

ABSTRACT

The month of Ramadan forms one of the five pillars of the Muslim faith. Adult Muslims are obligated to keep daily fasts from dawn to sunset, with exceptions. This year Ramadan is due to begin on 23 April 2020 and the longest fast in the UK will be approximately 18 hours in length. In addition, due to the often high-calorie meals eaten to break the fast, Ramadan should be seen as a cycle of fasting and feasting. Ramadan fasting can impact those with diabetes, increasing the risk of hypoglycaemia, hyperglycaemia and dehydration. This year, Ramadan will occur during the global COVID-19 pandemic. Reports show that diabetes appears to be a risk factor for more severe disease with COVID-19. In addition, the UK experience has shown diabetes and COVID-19 is associated with dehydration, starvation ketosis, diabetic ketoacidosis and hyperosmolar hyperglycaemic state. This makes fasting in Ramadan particularly challenging for those Muslims with diabetes. Here, we discuss the implications of fasting in Ramadan during the COVID-19 pandemic and make recommendations for those with diabetes who wish to fast.


Subject(s)
Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/therapy , Fasting/metabolism , Holidays , Islam , Betacoronavirus , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/metabolism , Dehydration/epidemiology , Dehydration/metabolism , Dehydration/prevention & control , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Diabetic Ketoacidosis/epidemiology , Diet Therapy , Disease Management , Fasting/adverse effects , Fluid Therapy , Humans , Hyperglycemia/epidemiology , Hyperglycemia/metabolism , Hyperglycemia/prevention & control , Hyperglycemic Hyperosmolar Nonketotic Coma/epidemiology , Hyperglycemic Hyperosmolar Nonketotic Coma/metabolism , Hypoglycemia/epidemiology , Hypoglycemia/metabolism , Hypoglycemia/prevention & control , Hypoglycemic Agents/therapeutic use , Ketosis/epidemiology , Ketosis/metabolism , Pandemics , Pneumonia, Viral/epidemiology , Pneumonia, Viral/metabolism , Risk Assessment , SARS-CoV-2 , United Kingdom
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