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1.
BMJ Open Diabetes Res Care ; 10(3)2022 05.
Article in English | MEDLINE | ID: covidwho-1883277

ABSTRACT

INTRODUCTION: Various studies have shown a number of glycemic parameters to improve over several weeks in people with type 1 diabetes during the first surge of the COVID-19 pandemic. Whether and to what extent such improvement is sustained during following COVID-19 surges remains unknown. Therefore, the aim of this study was to investigate glycemic parameters during the first year of the COVID-19 pandemic in people with type 1 diabetes and to determine factors associated with glycemic improvement. RESEARCH DESIGN AND METHODS: This was an observational cohort study in people with type 1 diabetes, aged ≥16 years. We compared glycated hemoglobin (HbA1c) and flash glucose monitoring (FGM) downloads between the prelockdown period and approximately 1 year thereafter. Using logistic regression analysis, we assessed associations between an HbA1c reduction of at least 0.5% (~5.5 mmol/mol) with baseline clinical characteristics and self-reported changes in psychological well-being and lifestyle behavior related to COVID-19. RESULTS: A total of 437 participants were included. As compared with prepandemic data, 1 year after the start of the COVID-19 pandemic and associated lockdowns, HbA1c had decreased from 7.9%±1.1% (63±12 mmol/mol) to 7.5%±1.0% (59±11 mmol/mol) (p<0.001), whereas time in range increased from 55.8%±16.7% to 58.6%±16.7% (p=0.004) and time below (<3.9 mmol/L) and above (>13.9 mmol/L) range and glucose variability all decreased (all p<0.05). FGM use, higher HbA1c at baseline and current smoking were independently associated with an HbA1c decrease of at least 0.5%, whereas self-reported changes in psychological well-being and lifestyle behavior related to the first surge of the COVID-19 pandemic and associated lockdowns were not. CONCLUSIONS: The COVID-19 pandemic and related lockdown measures were associated with improvement in glucometrics, including HbA1c and FGM data, in individuals with type 1 diabetes, particularly in FGM users, those with higher HbA1c at baseline or current smokers.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 1 , Blood Glucose , Blood Glucose Self-Monitoring , COVID-19/epidemiology , Communicable Disease Control , Diabetes Mellitus, Type 1/epidemiology , Glucose , Humans , Pandemics
2.
Biosensors (Basel) ; 12(5)2022 Apr 29.
Article in English | MEDLINE | ID: covidwho-1875480

ABSTRACT

Glucose management indicator (GMI) is frequently used as a substitute for HbA1c, especially when using telemedicine. Discordances between GMI and HbA1c were previously mostly reported in populations with type 1 diabetes (T1DM) using real-time CGM. Our aim was to investigate the accordance between GMI and HbA1c in patients with diabetes using intermittent scanning CGM (isCGM). In this retrospective cross-sectional study, patients with diabetes who used isCGM >70% of the time of the investigated time periods were included. GMI of four different time spans (between 14 and 30 days), covering a period of 3 months, reflected by the HbA1c, were investigated. The influence of clinical- and isCGM-derived parameters on the discordance was assessed. We included 278 patients (55% T1DM; 33% type 2 diabetes (T2DM)) with a mean HbA1c of 7.63%. The mean GMI of the four time periods was between 7.19% and 7.25%. On average, the absolute deviation between the four calculated GMIs and HbA1c ranged from 0.6% to 0.65%. The discordance was greater with increased BMI, a diagnosis of T2DM, and a greater difference between the most recent GMI and GMI assessed 8 to 10 weeks prior to HbA1c assessment. Our data shows that, especially in patients with increased BMI and T2DM, this difference is more pronounced and should therefore be considered when making therapeutic decisions.


Subject(s)
Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Blood Glucose , Blood Glucose Self-Monitoring , Cross-Sectional Studies , Diabetes Mellitus, Type 1/diagnosis , Diabetes Mellitus, Type 1/therapy , Diabetes Mellitus, Type 2/diagnosis , Glucose , Glycated Hemoglobin A/analysis , Humans , Obesity , Retrospective Studies
3.
Front Endocrinol (Lausanne) ; 13: 869451, 2022.
Article in English | MEDLINE | ID: covidwho-1869369

ABSTRACT

Aim: We explored the prospective relationship between continuous glucose monitoring (CGM) metrics and clinical outcomes in patients admitted to the intensive care unit (ICU). Materials and Methods: We enrolled critically ill patients admitted to the medical ICU. Patients with an Acute Physiology and Chronic Health Evaluation (APACHE) score ≤9 or ICU stay ≤48 h were excluded. CGM was performed for five days, and standardized CGM metrics were analyzed. The duration of ICU stay and 28-day mortality rate were evaluated as outcomes. Results: A total of 36 patients were included in this study (age [range], 49-88 years; men, 55.6%). The average APACHE score was 25.4 ± 8.3; 33 (91.7%) patients required ventilator support, and 16 (44.4%) patients had diabetes. The duration of ICU stay showed a positive correlation with the average blood glucose level, glucose management indicator (GMI), time above range, and GMI minus (-) glycated hemoglobin (HbA1c). Eight (22.2%) patients died within 28 days, and their average blood glucose levels, GMI, and GMI-HbA1c were significantly higher than those of survivors (p<0.05). After adjustments for age, sex, presence of diabetes, APACHE score, and dose of steroid administered, the GMI-HbA1c was associated with the risk of longer ICU stay (coefficient=2.34, 95% CI 0.54-4.14, p=0.017) and higher 28-day mortality rate (HR=2.42, 95% CI 1.01-5.76, p=0.046). Conclusion: The acute glycemic gap, assessed as GMI-HbA1c, is an independent risk factor for longer ICU stay and 28-day mortality rate. In the ICU setting, CGM of critically ill patients might be beneficial, irrespective of the presence of diabetes.


Subject(s)
Blood Glucose , Diabetes Mellitus , Aged , Aged, 80 and over , Blood Glucose Self-Monitoring , Critical Illness/therapy , Female , Glucose , Glycated Hemoglobin A/analysis , Glycemic Index , Humans , Male , Middle Aged , Pilot Projects , Prospective Studies
4.
Nat Metab ; 4(5): 547-558, 2022 May.
Article in English | MEDLINE | ID: covidwho-1830111

ABSTRACT

The severity and mortality of COVID-19 are associated with pre-existing medical comorbidities such as diabetes mellitus. However, the underlying causes for increased susceptibility to viral infection in patients with diabetes is not fully understood. Here we identify several small-molecule metabolites from human blood with effective antiviral activity against SARS-CoV-2, one of which, 1,5-anhydro-D-glucitol (1,5-AG), is associated with diabetes mellitus. The serum 1,5-AG level is significantly lower in patients with diabetes. In vitro, the level of SARS-CoV-2 replication is higher in the presence of serum from patients with diabetes than from healthy individuals and this is counteracted by supplementation of 1,5-AG to the serum from patients. Diabetic (db/db) mice undergo SARS-CoV-2 infection accompanied by much higher viral loads and more severe respiratory tissue damage when compared to wild-type mice. Sustained supplementation of 1,5-AG in diabetic mice reduces SARS-CoV-2 loads and disease severity to similar levels in nondiabetic mice. Mechanistically, 1,5-AG directly binds the S2 subunit of the SARS-CoV-2 spike protein, thereby interrupting spike-mediated virus-host membrane fusion. Our results reveal a mechanism that contributes to COVID-19 pathogenesis in the diabetic population and suggest that 1,5-AG supplementation may be beneficial to diabetic patients against severe COVID-19.


Subject(s)
COVID-19 , Diabetes Mellitus, Experimental , Animals , Glucose , Humans , Mice , SARS-CoV-2 , Spike Glycoprotein, Coronavirus
5.
Sci Rep ; 12(1): 7158, 2022 05 03.
Article in English | MEDLINE | ID: covidwho-1821606

ABSTRACT

A major obstacle to tackling the growing burden of chronic disease in South Africa is lack of testing, particularly where individuals face multiple barriers to accessing health services. We conducted a pilot study to evaluate a cardiometabolic self-measurement kit, including assessment of blood pressure, obesity and urine analysis, amongst adults in Soweto, South Africa. Participants (N = 94) were recruited by researchers during community health screening and were provided with a home test kit including a tablet with self-measurement instructions. The participants entered their results on the tablet and, on completion, the researcher immediately repeated the measurements. We interviewed 10% of participants to understand their experience and views of the kits. Concordance correlation coefficients ranged from 0.78 for waist circumference to 0.93 for height, while the overall percentage agreement ranged from 80.5% for both urine protein and urine glucose testing to 91.4% for the identification of central obesity (ratio of waist circumference to height of ≥ 0.5). Participants saw the need for self-testing and found the process for the most part simple, though urine testing and height self-assessment presented some challenges. This pilot study suggests that self-assessment at home has the potential to facilitate the identification of individuals at risk for cardiometabolic disease in low-income settings, adding to a growing body of evidence on the use of self-testing in disease prevention and detection. However, we would not recommend self-testing for urine glucose and protein without further study.


Subject(s)
COVID-19 , Cardiovascular Diseases , Adult , Cardiovascular Diseases/diagnosis , Cardiovascular Diseases/epidemiology , Glucose , Humans , Obesity/diagnosis , Obesity/epidemiology , Pandemics , Pilot Projects , Reproducibility of Results , Self-Assessment , South Africa/epidemiology
6.
Int J Environ Res Public Health ; 19(9)2022 04 28.
Article in English | MEDLINE | ID: covidwho-1820232

ABSTRACT

Those infected by COVID-19 develop various kinds of complications with varying degrees of severity. For this reason, it is necessary to evaluate its analytical values to predict and reduce the risks and complications derived from this pathology. A cross-sectional study was carried out a population in Almeria (south-eastern Spain) who had a positive Polymerase Chain Reaction test result from 1 March 2020 to 30 November 2020. The study involved 4575 patients, with 1346 who were asymptomatic, 1653 mildly symptomatic (no hospitalisation needed) and 1576 severely symptomatic (symptomatic patients hospitalised). Laboratory values for D-dimer, glucose, serum ferritin, and C-reactive protein were analysed. The mean age of the participants in the study was 53.60 (16.89) years old. A total of 70.6% of the patients were symptomatic, of which 36.1% had mild symptoms. For all of the laboratory predictors analysed (D-dimer, glucose, serum ferritin, and C-reactive protein), it was found that severe alterations in the parameters were more frequent in severely symptomatic patients with statistically significant differences (p < 0.001), although these alterations also occurred in asymptomatic patients. Age correlated with analytical values (D-dimer, glucose, serum ferritin, and C-reactive protein) with statistically significant differences. Patients with severe symptoms presented alterations in the analytical values of D-dimer, glucose, serum ferritin, and C-reactive protein. Asymptomatic patients presented alterations in the analysed parameters, though with less frequency and severity than patients with severe symptoms.


Subject(s)
COVID-19 , Biomarkers , C-Reactive Protein/analysis , COVID-19/diagnosis , Cross-Sectional Studies , Ferritins , Fibrin Fibrinogen Degradation Products , Glucose , Humans , Middle Aged , Retrospective Studies , SARS-CoV-2
7.
BMC Emerg Med ; 22(1): 68, 2022 04 29.
Article in English | MEDLINE | ID: covidwho-1817182

ABSTRACT

BACKGROUND: COVID-19 remains a major healthcare concern. Vital signs are routinely measured on admission and may provide an early, cost-effective indicator of outcome - more so in developing countries where such data is scarce. We sought to describe the association between six routinely measured admission vital signs and COVID-19 mortality, and secondarily to derive potential applications for resource-limited settings. METHODS: Retrospective analysis of consecutive patients admitted to King Edward VIII Hospital, South Africa, with COVID-19 during June-September 2020 was undertaken. The sample was subdivided into survivors and non-survivors and comparisons made in terms of demographics and admission vital signs. Univariate and multivariate analysis of predictor variables identified associations with in-hospital mortality, with the resulting multivariate regression model evaluated for its predictive ability with receiver operating characteristic (ROC) curve analysis. RESULTS: The 236 participants enrolled comprised 153(77.54%) survivors and 53(22.46%) non-survivors. Most participants were Black African(87.71%) and female(59.75%) with a mean age of 53.08(16.96) years. The non-survivor group demonstrated a significantly lower median/mean for admission oxygen saturation (%) [87(78-95) vs. 96(90-98)] and diastolic BP (mmHg) [70.79(14.66) vs. 76.3(12.07)], and higher median for admission respiratory rate (breaths/minute) [24(20-28) vs. 20(20-23)] and glucose (mmol/l) [10.2(6.95-16.25) vs. 7.4(5.5-9.8)]. Age, oxygen saturation, respiratory rate, glucose and diastolic BP were found to be significantly associated with mortality on univariate analysis. A log rank test revealed significantly lower survival rates in patients with an admission oxygen saturation < 90% compared with ≥90% (p = 0.001). Multivariate logistic regression revealed a significant relationship between age and oxygen saturation with in-hospital mortality (OR 1.047; 95% CI 1.016-1.080; p = 0.003 and OR 0.922; 95% CI 0.880-0.965; p = 0.001 respectively). A ROC curve analysis generated an area under the curve (AUC) of 0.778 (p < 0.001) when evaluating the predictive ability of oxygen saturation, respiratory rate, glucose and diastolic BP for in-hospital death. This improved to an AUC of 0.832 (p < 0.001) with the inclusion of age. CONCLUSION: A multivariate regression model comprising admission oxygen saturation, respiratory rate, glucose and diastolic BP (with/without age) demonstrated promising predictive capacity, and may provide a cost-effective means for early prognostication of patients admitted with COVID-19 in resource-limited settings.


Subject(s)
COVID-19 , Cross-Sectional Studies , Female , Glucose , Hospital Mortality , Humans , Middle Aged , Retrospective Studies , Vital Signs
8.
Sci Rep ; 12(1): 6890, 2022 04 27.
Article in English | MEDLINE | ID: covidwho-1815590

ABSTRACT

2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo. On the other hand, it is known that 2DG given continuously can have severe detrimental effects on the rodent heart. Here, we show that the principal effect of an extended, intermittent 2DG treatment on mice is to augment the mitochondrial respiratory chain proteome in the heart; importantly, this occurs without vacuolization, hypertrophy or fibrosis. The increase in the heart respiratory chain proteome suggests an increase in mitochondrial oxidative capacity, which could compensate for the energy deficit caused by the inhibition of glycolysis. Thus, 2DG in the murine heart appears to induce a metabolic configuration that is the opposite of SARS-CoV-2 infected cells, which could explain the compound's ability to restrict the propagation of the virus to the benefit of patients with COVID-19 disease.


Subject(s)
COVID-19 , Glucose , Animals , COVID-19/drug therapy , Deoxyglucose/pharmacology , Electron Transport , Glucose/metabolism , Humans , Mice , Proteome/metabolism , SARS-CoV-2
9.
Biosensors (Basel) ; 12(4)2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1792819

ABSTRACT

A simple, selective, and quantitative platform for point-of-care diagnostic of COVID-19 is urgently needed as a complement in areas where resources are currently relatively scarce. To meet the needs of early diagnosis and intervention, a proof-of-concept demonstration of a universal personal glucose meter-based nucleic acid assay platform (PGM-NAAP) is presented, which converts to SARS-CoV-2 detection from glucose detection. By using magnetic bead separation together with the hand-held PGM for quantitative readout, PGM-NAAP achieves the 98 pM limit of detection for a sequence related to SARS-CoV-2. The ability to discriminate target nucleic acid from genomic DNA, the satisfactory spike recoveries of saliva and serum samples, as well as the good stability all together suggest the potential of the PGM-NAAP for the screening and diagnosis of suspected patients during the outbreaks of COVID-19 in resource-limited settings without sophisticated instruments. On the basis of these findings, PGM-NAAP can be expected to provide an accurate and convenient path for diagnosis of disease-associated nucleic acid.


Subject(s)
COVID-19 , Nucleic Acids , COVID-19/diagnosis , Glucose , Humans , Nucleic Acid Amplification Techniques , Point-of-Care Systems , SARS-CoV-2/genetics
10.
Int J Environ Res Public Health ; 19(7)2022 04 01.
Article in English | MEDLINE | ID: covidwho-1785648

ABSTRACT

Postprandial hyperglycemia can be corrected by exercise; however, the effect of home-based high-intensity interval exercise (HIIE), a new time-efficient exercise, on glycemic control is unclear. This study aimed to investigate the effect of home-based HIIE on postprandial hyperglycemia. Twelve young adult males (mean age: 24.3 ± 2.3 y) with postprandial hyperglycemia that had not yet led to diabetes completed home-based HIIE, moderate-intensity continuous exercise (MICE), and control conditions on separate days, randomly. The intervention began 30 min after the start of a standardized meal intake, with 11 min of HIIE completed at maximal effort in the home-based HIIE condition, 30 min of running performed at 50% maximum oxygen uptake in the MICE condition, or 30 min of sitting at rest completed in the control condition. The participants sat at rest after each intervention for up to 120 min. Interstitial fluid glucose concentrations were measured using a continuous glucose monitoring system that scanned every 15 min for up to 2 h after the meal. The glucose concentrations after the meal were significantly lower in the home-based HIIE and MICE conditions than in the control condition (p < 0.001). There were no significant differences in the glucose concentrations between the home-based HIIE and MICE conditions. In conclusion, home-based HIIE was able to correct postprandial hyperglycemia.


Subject(s)
Glucose , Hyperglycemia , Blood Glucose , Blood Glucose Self-Monitoring , Humans , Hyperglycemia/prevention & control , Male , Oxygen , Oxygen Consumption , Young Adult
11.
Diabetes Metab Syndr ; 16(3): 102439, 2022 Mar.
Article in English | MEDLINE | ID: covidwho-1773263

ABSTRACT

BACKGROUND AND AIMS: We investigate the impact of blood glucose on mortality and hospital length of stay (HLOS) among COVID-19 patients. METHODS: Retrospective study of 456 patients with confirmed COVID-19 and glycemic dysregulation in the New York City area. RESULTS: We found that impaired glucose adjusted for other organs systems involved (OR:1.87; 95% CI:1.36-2.57, p < 0.001), increased glucose nadir (OR:34.28; 95% CI:3.97-296.05, p < 0.01) and abnormal blood glucose levels at discharge (OR:5.07; 95% CI:2.31-11.14, p < 0.001) were each significantly associated with increased odds for mortality. New or higher from baseline insulin requirement during hospitalization (OR:0.34; 95% CI:0.15-0.78; p < 0.05) was significantly associated with decreased odds for mortality. Increased glucose peak (B = 0.001, SE=<0.001, p < 0.001), new or higher from baseline insulin requirement during hospitalization (B = 0.11, SE = 0.03, p < 0.001), and increased days to dysglycemia (B = 0.15, SE = 0.04, p < 0.001) were each significantly associated with increased HLOS. Increased glucose nadir (B = -0.67, SE = 0.07, p < 0.001), insulin intravenous drip (B = -0.10, SE = 0.05, p < 0.05), and increased proportion days endocrine system involved (B = -0.25, SE = 0.06, p < 0.001) were each significantly associated with decreased HLOS. CONCLUSION: Glucose dysregulation adversely affects mortality and HLOS in COVID-19. These data can help clinicians to guide patient treatment and management in COVID-19 patients.


Subject(s)
COVID-19 , Blood Glucose , Glucose , Hospitalization , Hospitals , Humans , Length of Stay , Retrospective Studies
12.
Elife ; 112022 03 23.
Article in English | MEDLINE | ID: covidwho-1761118

ABSTRACT

The SARS-CoV-2 pandemic continues to rage around the world. At the same time, despite strong public health measures and high vaccination rates in some countries, a post-COVID-19 syndrome has emerged which lacks a clear definition, prevalence, or etiology. However, fatigue, dyspnea, brain fog, and lack of smell and/or taste are often characteristic of patients with this syndrome. These are evident more than a month after infection, and are labeled as Post-Acute Sequelae of CoV-2 (PASC) or commonly referred to as long-COVID. Metabolic dysfunction (i.e., obesity, insulin resistance, and diabetes mellitus) is a predisposing risk factor for severe acute COVID-19, and there is emerging evidence that this factor plus a chronic inflammatory state may predispose to PASC. In this article, we explore the potential pathogenic metabolic mechanisms that could underly both severe acute COVID-19 and PASC, and then consider how these might be targeted for future therapeutic approaches.


Subject(s)
COVID-19/complications , Disease Susceptibility , Energy Metabolism , COVID-19/epidemiology , COVID-19/etiology , COVID-19/metabolism , COVID-19/therapy , Diabetes Mellitus, Type 2 , Disease Management , Glucose/metabolism , Glucose Intolerance , Humans , Insulin Resistance , Islets of Langerhans/metabolism , Liver/metabolism , Metabolic Syndrome/epidemiology , Metabolic Syndrome/etiology , Metabolic Syndrome/metabolism , Metabolic Syndrome/therapy , Risk Assessment , Risk Factors , T-Lymphocytes/immunology , T-Lymphocytes/metabolism
13.
Nutrients ; 14(6)2022 Mar 15.
Article in English | MEDLINE | ID: covidwho-1742570

ABSTRACT

In December 2019, 27 cases of pneumonia were reported in Wuhan. In 2020, the causative agent was identified as a virus called SARS-CoV-2. The disease was called "coronavirus disease 2019" (COVID-19) and was determined as a Public Health Emergency. The main measures taken to cope with this included a state of lockdown. The aim of this study was to assess how the unhealthy lifestyles that ensued influenced different parameters. A prospective study was carried out on 6236 workers in a Spanish population between March 2019 and March 2021. Anthropometric, clinical, and analytical measurements were performed, revealing differences in the mean values of anthropometric and clinical parameters before and after lockdown due to the pandemic, namely increased body weight (41.1 ± 9.9-43.1 ± 9.9), BMI (25.1 ± 4.7-25.9 ± 4.7), and percentage of body fat (24.5 ± 9.1-26.9 ± 8.8); higher total cholesterol levels, with a statistically significant increase in LDL levels and a reduction in HDL; and worse glucose levels (90.5 ± 16.4-95.4 ± 15.8). Lockdown can be concluded to have had a negative effect on health parameters in both sexes in all age ranges, causing a worsening of cardiovascular risk factors.


Subject(s)
COVID-19 , Glucose , Adult , Blood Pressure , COVID-19/epidemiology , Communicable Disease Control , Female , Humans , Lipids , Longitudinal Studies , Male , Pandemics , Prospective Studies , SARS-CoV-2
14.
Nutrients ; 13(11)2021 Nov 08.
Article in English | MEDLINE | ID: covidwho-1732137

ABSTRACT

Associations between habitual dietary intake of minerals and glucose metabolism have been extensively studied in relation to metabolic disorders. However, similar research has yet to be conducted in individuals after acute pancreatitis (AP). The main aim was to investigate the associations between habitual intake of 13 minerals and glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Associations between the dietary intake of minerals and markers of glucose metabolism (glycated haemoglobin and fasting plasma glucose) were also studied. The EPIC-Norfolk food frequency questionnaire was used in a cross-sectional fashion to determine the habitual intake of 13 dietary minerals. ANCOVA as well as multiple linear regression analyses were conducted and five statistical models were built to adjust for covariates. The study included 106 individuals after AP. In the NODAP group, intake of 4 minerals was significantly less when compared with the NAP group: iron (B = -0.076, p = 0.013), nitrogen (B = -0.066, p = 0.003), phosphorous (B = -0.046, p = 0.006), and zinc (B = -0.078, p = 0.001). Glycated haemoglobin was significantly associated with iodine intake (B = 17.763, p = 0.032) and manganese intake (B = -17.147, p = 0.003) in the NODAP group. Fasting plasma glucose was significantly associated with manganese intake (B = -2.436, p = 0.027) in the NODAP group. Habitual intake of minerals differs between individuals with NODAP, T2DM, and NAP. Prospective longitudinal studies and randomised controlled trials are now warranted to further investigate the associations between mineral intake and NODAP.


Subject(s)
Diabetes Mellitus/etiology , Diet , Minerals/administration & dosage , Pancreatitis/complications , Prediabetic State/etiology , Biomarkers/blood , Blood Glucose/metabolism , Cross-Sectional Studies , Diabetes Mellitus/metabolism , Diabetes Mellitus, Type 2/metabolism , Female , Glucose/metabolism , Humans , Insulin/blood , Male , Middle Aged , Pancreatitis/metabolism , Prediabetic State/metabolism , Prospective Studies
15.
Cells ; 11(6)2022 03 09.
Article in English | MEDLINE | ID: covidwho-1731953

ABSTRACT

The infection with SARS-CoV-2 impairs the glucose-insulin axis and this contributes to oxidative (OS) and nitrosative (NSS) stress. Here, we evaluated changes in glucose metabolism that could promote the loss of redox homeostasis in COVID-19 patients. This was comparative cohort and analytical study that compared COVID-19 patients and healthy subjects. The study population consisted of 61 COVID-19 patients with and without comorbidities and 25 healthy subjects (HS). In all subjects the plasma glucose, insulin, 8-isoprostane, Vitamin D, H2S and 3-nitrotyrosine were determined by ELISA. The nitrites (NO2-), lipid-peroxidation (LPO), total-antioxidant-capacity (TAC), thiols, glutathione (GSH) and selenium (Se) were determined by spectrophotometry. The glucose, insulin and HOMA-IR (p < 0.001), 8-isoprostanes, 3-nitrotyrosine (p < 0.001) and LPO were increased (p = 0.02) while Vitamin D (p = 0.01), H2S, thiols, TAC, GSH and Se (p < 0.001) decreased in COVID-19 patients in comparison to HS. The SARS-CoV-2 infection resulted in alterations in the glucose-insulin axis that led to hyperglycemia, hyperinsulinemia and IR in patients with and without comorbidities. These alterations increase OS and NSS reflected in increases or decreases in some oxidative markers in plasma with major impact or fatal consequences in patients that course with metabolic syndrome. Moreover, subjects without comorbidities could have long-term alterations in the redox homeostasis after infection.


Subject(s)
COVID-19 , Hyperglycemia , Insulin Resistance , Selenium , Antioxidants/metabolism , Glucose , Glutathione/metabolism , Homeostasis , Humans , Hyperglycemia/complications , Insulin/metabolism , Oxidation-Reduction , Oxidative Stress , SARS-CoV-2 , Sulfhydryl Compounds , Vitamin D , Vitamins
18.
J Cell Mol Med ; 26(4): 1144-1155, 2022 02.
Article in English | MEDLINE | ID: covidwho-1685345

ABSTRACT

High glucose (HG) is one of the basic factors of diabetic nephropathy (DN), which leads to high morbidity and disability. During DN, the expression of glomerular glucose transporter 1 (GLUT1) increases, but the relationship between HG and GLUT1 is unclear. Glomerular mesangial cells (GMCs) have multiple roles in HG-induced DN. Here, we report prominent glomerular dysfunction, especially GMC abnormalities, in DN mice, which is closely related to GLUT1 alteration. In vivo studies have shown that BBR can alleviate pathological changes and abnormal renal function indicators of DN mice. In vitro, BBR (30, 60 and 90 µmol/L) not only increased the proportion of G1 phase cells but also reduced the proportion of S phase cells under HG conditions at different times. BBR (60 µmol/L) significantly reduced the expression of PI3K-p85, p-Akt, p-AS160, membrane-bound GLUT1 and cyclin D1, but had almost no effect on total protein. Furthermore, BBR significantly declined the glucose uptake and retarded cyclin D1-mediated GMC cell cycle arrest in the G1 phase. This study demonstrated that BBR can inhibit the development of DN, which may be due to BBR inhibiting the PI3K/Akt/AS160/GLUT1 signalling pathway to regulate HG-induced abnormal GMC proliferation and the cell cycle, supporting BBR as a potential therapeutic drug for DN.


Subject(s)
Berberine , Diabetes Mellitus , Diabetic Nephropathies , Animals , Berberine/pharmacology , Cell Cycle , Cell Division , Cell Proliferation , Diabetes Mellitus/pathology , Diabetic Nephropathies/pathology , Glucose/metabolism , Glucose Transporter Type 1/genetics , Glucose Transporter Type 1/metabolism , Mesangial Cells/metabolism , Mice , Phosphatidylinositol 3-Kinases/metabolism , Proto-Oncogene Proteins c-akt/metabolism
19.
Life Sci ; 295: 120411, 2022 Apr 15.
Article in English | MEDLINE | ID: covidwho-1683412

ABSTRACT

AIMS: Virus-infected host cells switch their metabolism to a more glycolytic phenotype, required for new virion synthesis and packaging. Therefore, we investigated the effect and mechanistic action of glycolytic inhibitor 2-Deoxy-d-glucose (2-DG) on virus multiplication in host cells following SARS-CoV-2 infection. MAIN METHODS: SARS-CoV-2 induced change in glycolysis was examined in Vero E6 cells. Effect of 2-DG on virus multiplication was evaluated by RT-PCR (N and RdRp genes) analysis, protein expression analysis of Nucleocapsid (N) and Spike (S) proteins and visual indication of cytopathy effect (CPE), The mass spectrometry analysis was performed to examine the 2-DG induced change in glycosylation status of receptor binding domain (RBD) in SARS-CoV-2 spike protein. KEY FINDINGS: We observed SARS-COV-2 infection induced increased glucose influx and glycolysis, resulting in selectively high accumulation of the fluorescent glucose analog, 2-NBDG in Vero E6 cells. 2-DG inhibited glycolysis, reduced virus multiplication and alleviated cells from virus-induced cytopathic effect (CPE) in SARS-CoV-2 infected cells. The progeny virions produced from 2-DG treated cells were found unglycosylated at crucial N-glycosites (N331 and N343) of the receptor-binding domain (RBD) in the spike protein, resulting in production of defective progeny virions with compromised infective potential. SIGNIFICANCE: The mechanistic study revealed that the inhibition of SARS-COV-2 multiplication is attributed to 2-DG induced glycolysis inhibition and possibly un-glycosylation of the spike protein, also. Therefore, based on its previous human trials in different types of Cancer and Herpes patients, it could be a potential molecule to study in COVID-19 patients.


Subject(s)
COVID-19/drug therapy , Deoxyglucose/pharmacology , SARS-CoV-2/drug effects , SARS-CoV-2/pathogenicity , Adenosine Triphosphate/metabolism , Animals , Antiviral Agents/pharmacology , COVID-19/metabolism , COVID-19/virology , Cell Proliferation/drug effects , Cell Survival/drug effects , Chlorocebus aethiops , Glucose/metabolism , Glycolysis/drug effects , Glycosylation , Host-Pathogen Interactions/drug effects , Mannose/pharmacology , SARS-CoV-2/physiology , Spike Glycoprotein, Coronavirus/metabolism , Vero Cells , Virion/drug effects , Virion/pathogenicity , Virus Replication/drug effects
20.
Int J Mol Sci ; 22(16)2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1662663

ABSTRACT

Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin.


Subject(s)
Antiviral Agents/pharmacology , Coxsackievirus Infections/diet therapy , Enterovirus C, Human/drug effects , N-Acetylneuraminic Acid/pharmacology , Conjunctivitis, Acute Hemorrhagic/drug therapy , Conjunctivitis, Acute Hemorrhagic/metabolism , Conjunctivitis, Acute Hemorrhagic/virology , Coxsackievirus Infections/metabolism , Coxsackievirus Infections/virology , Glucose/metabolism , Humans , Lectins/metabolism , Ligands , Polysaccharides/metabolism , Receptors, Virus/metabolism
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