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1.
Lancet Diabetes Endocrinol ; 9(5): 293-303, 2021 05.
Article in English | MEDLINE | ID: covidwho-1531930

ABSTRACT

BACKGROUND: In patients with type 2 diabetes, hyperglycaemia is an independent risk factor for COVID-19-related mortality. Associations between pre-infection prescription for glucose-lowering drugs and COVID-19-related mortality in people with type 2 diabetes have been postulated but only investigated in small studies and limited to a few agents. We investigated whether there are associations between prescription of different classes of glucose-lowering drugs and risk of COVID-19-related mortality in people with type 2 diabetes. METHODS: This was a nationwide observational cohort study done with data from the National Diabetes Audit for people with type 2 diabetes and registered with a general practice in England since 2003. Cox regression was used to estimate the hazard ratio (HR) of COVID-19-related mortality in people prescribed each class of glucose-lowering drug, with covariate adjustment with a propensity score to address confounding by demographic, socioeconomic, and clinical factors. FINDINGS: Among the 2 851 465 people with type 2 diabetes included in our analyses, 13 479 (0·5%) COVID-19-related deaths occurred during the study period (Feb 16 to Aug 31, 2020), corresponding to a rate of 8·9 per 1000 person-years (95% CI 8·7-9·0). The adjusted HR associated with recorded versus no recorded prescription was 0·77 (95% CI 0·73-0·81) for metformin and 1·42 (1·35-1·49) for insulin. Adjusted HRs for prescription of other individual classes of glucose-lowering treatment were as follows: 0·75 (0·48-1·17) for meglitinides, 0·82 (0·74-0·91) for SGLT2 inhibitors, 0·94 (0·82-1·07) for thiazolidinediones, 0·94 (0·89-0·99) for sulfonylureas, 0·94 (0·83-1·07) for GLP-1 receptor agonists, 1·07 (1·01-1·13) for DPP-4 inhibitors, and 1·26 (0·76-2·09) for α-glucosidase inhibitors. INTERPRETATION: Our results provide evidence of associations between prescription of some glucose-lowering drugs and COVID-19-related mortality, although the differences in risk are small and these findings are likely to be due to confounding by indication, in view of the use of different drug classes at different stages of type 2 diabetes disease progression. In the context of the COVID-19 pandemic, there is no clear indication to change prescribing of glucose-lowering drugs in people with type 2 diabetes. FUNDING: None.


Subject(s)
COVID-19/mortality , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/adverse effects , Aged , COVID-19/complications , Cohort Studies , England , Female , Humans , Male , Middle Aged , Proportional Hazards Models
3.
Biomed Pharmacother ; 140: 111685, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1235862

ABSTRACT

Type 2 diabetes mellitus, obesity, hypertension, and other associated metabolic complications have been demonstrated as a crucial contributor to the enhanced morbidity and mortality of patients with coronavirus disease 2019 (COVID-19). Data on the interplay between metabolic comorbidities and the outcomes in patients with COVID-19 have been emerging and rapidly increasing. This implies a mechanistic link between metabolic diseases and COVID-19 resulting in the exacerbation of the condition. Nonetheless, new evidences are emerging to support insulin-mediated aggressive glucose-lowering treatment as a possible trigger of high mortality rate in diabetic COVID-19 patients, putting the clinician in a confounding and difficult dilemma for the treatment of COVID-19 patients with metabolic comorbidities. Thus, this review discusses the pathophysiological link among severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), angiotensin-converting enzyme 2 (ACE2), metabolic complications, and severe inflammation in COVID-19 development, especially in those with multi-organ injuries. We discuss the influence of several routinely used drugs in COVID-19 patients, including anti-inflammatory and anti-coagulant drugs, antidiabetic drugs, renin-angiotensin-aldosterone system inhibitors. Especially, we provide a balanced overview on the clinical application of glucose-lowering drugs (insulin and metformin), angiotensin-converting-enzyme inhibitors, and angiotensin receptor blockers. Although there is insufficient evidence from clinical or basic research to comprehensively reveal the mechanistic link between adverse outcomes in COVID-19 and metabolic comorbidities, it is hoped that the update in the current review may help to better outline the optimal strategies for clinical management of COVID-19 patients with metabolic comorbidities.


Subject(s)
COVID-19/drug therapy , Metabolic Diseases/drug therapy , Pharmaceutical Preparations/administration & dosage , SARS-CoV-2/drug effects , Animals , Comorbidity , Humans , Polypharmacy
5.
Clin Biochem ; 92: 71-76, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1141672

ABSTRACT

Owing to their ease of use, glucose meters are frequently used in research and medicine. However, little is known of whether other non-glucose molecules, besides vitamin C, interfere with glucometry. Therefore, we sought to determine whether other antioxidants might behave like vitamin C in causing falsely elevated blood glucose levels, potentially exposing patients to glycemic mismanagement by being administered harmful doses of glucose-lowering drugs. To determine whether various antioxidants can be detected by seven commercial glucose meters, human blood samples were spiked with various antioxidants ex vivo and their effect on the glucose results were assessed by Parkes error grid analysis. Several of the glucose meters demonstrated a positive bias in the glucose measurement of blood samples spiked with vitamin C, N-acetylcysteine, and glutathione. With the most interference-sensitive glucose meter, non-blood solutions of 1 mmol/L N-acetylcysteine, glutathione, cysteine, vitamin C, dihydrolipoate, and dithiothreitol mimicked the results seen on that glucose meter for 0.7, 1.0, 1.2, 2.6, 3.7 and 5.5 mmol/L glucose solutions, respectively. Glucose meter users should be alerted that some of these devices might produce spurious glucose results not only in patients on vitamin C therapy but also in those being administered other antioxidants. As discussed herein, the clinical relevance of the data is immediate in view of the current use of antioxidant therapies for disorders such as the metabolic syndrome, diabetes, cardiovascular diseases, and coronavirus disease 2019.


Subject(s)
Antioxidants/chemistry , Blood Glucose Self-Monitoring/instrumentation , Blood Glucose/analysis , Acetylcysteine/blood , Acetylcysteine/chemistry , Antioxidants/analysis , Antioxidants/metabolism , Ascorbic Acid/analysis , Ascorbic Acid/blood , Blood Glucose/chemistry , Blood Glucose Self-Monitoring/methods , Glutathione/blood , Glutathione/chemistry , Humans , Point-of-Care Systems
6.
Int J Clin Pharm ; 43(3): 764-767, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1137159

ABSTRACT

Sodium-glucose co-transporter 2 inhibitors (SGLT2i) are a new class of glucose-lowering agents which have changed the landscape of diabetes therapy, due to their remarkable cardiorenal protective properties. The attack of severe acute respiratory syndrome coronavirus 2 on the heart and kidneys shares similarities with diabetes; therefore, the notion that SGLT2i might have a role in the future management of Coronavirus Disease 2019 (COVID-19) is based on a solid pathophysiological hypothesis. SGLT2i have been proved to decrease the expression of proinflammatory cytokines, ameliorate oxidative stress and reduce sympathetic activity, thus resulting in downregulation of both systemic and adipose tissue inflammation. On the other hand, they have been linked to an increased risk of euglycemic diabetic ketoacidosis. Therefore, the efficacy and safety of SGLT2i in COVID-19 are still debatable and remain to be clarified by ongoing randomized trials, to assess whether the benefits of treatment with these drugs outweigh the potential risks.


Subject(s)
COVID-19/complications , Diabetes Mellitus, Type 2/complications , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , COVID-19/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/virology , Humans , Risk Assessment , Sodium-Glucose Transporter 2 Inhibitors/adverse effects
7.
Diabetes Obes Metab ; 23(4): 910-915, 2021 04.
Article in English | MEDLINE | ID: covidwho-1028904

ABSTRACT

AIM: To estimate the proportion of individuals with type 2 diabetes mellitus (T2DM) undergoing changes in glucose-lowering therapy in 2019 and 2020. METHOD: Individuals with T2DM who had at least one consultation in one of 940 general (including diabetologist) practices in Germany between January and July 2019 (N = 79 268) and between January and July 2020 (N = 85 046) were included. Therapy changes were defined as the prescription of new glucose-lowering drugs, with or without the discontinuation of previous treatments (therapy switch and add-on therapy, respectively). The number of T2DM patients with at least one medication regimen change was calculated for the periods 1 January to 14 March in 2019 and 2020, and for the periods 15 March to 31 July in 2019 and 2020. March 2020 corresponded to the beginning of the lockdown in Germany. RESULTS: Overall, there was a decrease in the number of patients with at least one medication regimen change in the period 15 March to 31 July 2019 compared with 15 March to 31 July 2020 (dipeptidyl peptidase-4 inhibitors: -15%; sodium-glucose co-transporter-2 inhibitors: -3%; glucagon-like peptide-1 receptor agonists: 0%; other oral glucose-lowering drugs: -6%; and insulin: -21%). CONCLUSIONS: The coronavirus disease-2019 (COVID-2019) pandemic had a strong impact on glucose-lowering drug use in T2DM patients in Germany. More research is warranted to further investigate the treatment and management of T2DM individuals during the COVID-19 era in Germany and elsewhere.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2/drug therapy , Hypoglycemic Agents/therapeutic use , Adolescent , Adult , Aged , Aged, 80 and over , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Drug Substitution/trends , Drug Therapy, Combination/trends , Female , Germany , Glucagon-Like Peptide-1 Receptor/agonists , Humans , Insulin/therapeutic use , Male , Middle Aged , SARS-CoV-2 , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Young Adult
8.
Free Radic Biol Med ; 161: 84-91, 2020 12.
Article in English | MEDLINE | ID: covidwho-1023568

ABSTRACT

There is a marked variation in mortality risk associated with COVID-19 infection in the general population. Low socioeconomic status and other social determinants have been discussed as possible causes for the higher burden in African American communities compared with white communities. Beyond the social determinants, the biochemical mechanism that predisposes individual subjects or communities to the development of excess and serious complications associated with COVID-19 infection is not clear. Virus infection triggers massive ROS production and oxidative damage. Glutathione (GSH) is essential and protects the body from the harmful effects of oxidative damage from excess reactive oxygen radicals. GSH is also required to maintain the VD-metabolism genes and circulating levels of 25-hydroxyvitamin D (25(OH)VD). Glucose-6-phosphate dehydrogenase (G6PD) is necessary to prevent the exhaustion and depletion of cellular GSH. X-linked genetic G6PD deficiency is common in the AA population and predominantly in males. Acquired deficiency of G6PD has been widely reported in subjects with conditions of obesity and diabetes. This suggests that individuals with G6PD deficiency are vulnerable to excess oxidative stress and at a higher risk for inadequacy or deficiency of 25(OH)VD, leaving the body unable to protect its 'oxidative immune-metabolic' physiological functions from the insults of COVID-19. An association between subclinical interstitial lung disease with 25(OH)VD deficiencies and GSH deficiencies has been previously reported. We hypothesize that the overproduction of ROS and excess oxidative damage is responsible for the impaired immunity, secretion of the cytokine storm, and onset of pulmonary dysfunction in response to the COVID-19 infection. The co-optimization of impaired glutathione redox status and excess 25(OH)VD deficiencies has the potential to reduce oxidative stress, boost immunity, and reduce the adverse clinical effects of COVID-19 infection in the AA population.


Subject(s)
COVID-19/pathology , Glucosephosphate Dehydrogenase Deficiency/genetics , Oxidative Stress/physiology , Reactive Oxygen Species/metabolism , Vitamin D Deficiency/genetics , African Americans/statistics & numerical data , COVID-19/mortality , Cytokine Release Syndrome/pathology , Glucosephosphate Dehydrogenase/genetics , Glucosephosphate Dehydrogenase Deficiency/metabolism , Glutathione/metabolism , Humans , SARS-CoV-2 , Vitamin D/analogs & derivatives , Vitamin D/metabolism
9.
Therapie ; 75(4): 327-333, 2020.
Article in English | MEDLINE | ID: covidwho-1005621

ABSTRACT

According to previous reports, diabetes seems to be a risk factor which worsens the serious clinical events caused by COVID-19. But is diabetes per se a risk factor that increases the probability of getting the virus? This paper will discuss this point. There are not many research data on antidiabetic drugs in this context. The potential influence of glucose-lowering agents on the severity of COVID-19 has not been described yet. Dipeptidylpeptidase-4 (DPP-4) is a cell surface protein ubiquitously expressed in many tissues and it is also a soluble molecule found in serum/plasma fluids. DPP-4 is involved in infection of cells by some viruses. This paper reviews data about the use of DPP-4 inhibitors and others diabetes drugs on COVID-19 patients. As such, no available evidence has yet suggested that glucose-lowering drugs - including those targeting DPP4-related pathways - produce any significant harm or benefit in the context of human infections. However, insulin must remain the first-choice agent in the management of critically ill-hospitalized patients, while it is recommended to suspend other agents in unstable patients. This paper provides related French and international recommendations for people with diabetes who got infected by COVID-19 and upholds that infections may alter glucose control and may require additional vigilance.


Subject(s)
Coronavirus Infections/epidemiology , Diabetes Mellitus/epidemiology , Hypoglycemic Agents/administration & dosage , Pneumonia, Viral/epidemiology , Animals , COVID-19 , Coronavirus Infections/physiopathology , Diabetes Mellitus/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/administration & dosage , Dipeptidyl-Peptidase IV Inhibitors/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Humans , Hypoglycemic Agents/adverse effects , Hypoglycemic Agents/pharmacology , Insulin/administration & dosage , Pandemics , Pneumonia, Viral/physiopathology , Risk Factors , Severity of Illness Index
10.
Front Med (Lausanne) ; 7: 584112, 2020.
Article in English | MEDLINE | ID: covidwho-993375

ABSTRACT

Introduction: COVID-19 is a novel and devastating disease. Its manifestations vary from asymptomatic to lethal. Moreover, mortality rates differ based on underlying health conditions and ethnicity. We investigated the biochemical rationale behind these observations using machine reasoning by the sci.AI system (https://sci.ai/). Facts were extracted and linked from publications available in nlm.nih.gov and Europe PMC to form the dataset which was validated by medical experts. Results: Based on the analysis of experimental and clinical data, we synthesized detailed biochemical pathways of COVID-19 pathogenesis which were used to explain epidemiological and clinical observations. Clinical manifestations and biomarkers are highlighted to monitor the course of COVID-19 and navigate treatment. As depicted in the Graphical Abstract, SARS-CoV-2 triggers a pro-oxidant (PO) response leading to the production of reactive oxygen species (ROS) as a normal innate defense. However, SARS-CoV-2's unique interference with the antioxidant (AO) system, through suppression of nitric oxide (NO) production in the renin- angiotensin-aldosterone system (RAAS), leads to an excessive inflammatory PO response. The excessive PO response becomes critical in cohorts with a compromised AO system such as patients with glucose-6-phosphate dehydrogenase deficiency (G6PDd) where NO and glutathione (GSH) mechanisms are impaired. G6PDd develops in patients with metabolic syndrome. It is mediated by aldosterone (Ald) which also increases specifically in COVID-19. Conclusion: G6PD is essential for an adequate immune response. Both G6PDd and SARS-CoV-2 compromise the AO system through the same pathways rendering G6PDd the Achilles' heel for COVID-19. Thus, the evolutionary antimalarial advantage of the G6PDd cohort can be a disadvantage against SARS-CoV-2.

11.
BMC Med ; 18(1): 359, 2020 11 16.
Article in English | MEDLINE | ID: covidwho-992480

ABSTRACT

BACKGROUND: Limited evidence exists on the role of glucose-lowering drugs in patients with COVID-19. Our main objective was to examine the association between in-hospital death and each routine at-home glucose-lowering drug both individually and in combination with metformin in patients with type 2 diabetes mellitus admitted for COVID-19. We also evaluated their association with the composite outcome of the need for ICU admission, invasive and non-invasive mechanical ventilation, or in-hospital death as well as on the development of in-hospital complications and a long-time hospital stay. METHODS: We selected all patients with type 2 diabetes mellitus in the Spanish Society of Internal Medicine's registry of COVID-19 patients (SEMI-COVID-19 Registry). It is an ongoing, observational, multicenter, nationwide cohort of patients admitted for COVID-19 in Spain from March 1, 2020. Each glucose-lowering drug user was matched with a user of other glucose-lowering drugs in a 1:1 manner by propensity scores. In order to assess the adequacy of propensity score matching, we used the standardized mean difference found in patient characteristics after matching. There was considered to be a significant imbalance in the group if a standardized mean difference > 10% was found. To evaluate the association between treatment and study outcomes, both conditional logit and mixed effect logistic regressions were used when the sample size was ≥ 100. RESULTS: A total of 2666 patients were found in the SEMI-COVID-19 Registry, 1297 on glucose-lowering drugs in monotherapy and 465 in combination with metformin. After propensity matching, 249 patients on metformin, 105 on dipeptidyl peptidase-4 inhibitors, 129 on insulin, 127 on metformin/dipeptidyl peptidase-4 inhibitors, 34 on metformin/sodium-glucose cotransporter 2 inhibitor, and 67 on metformin/insulin were selected. No at-home glucose-lowering drugs showed a significant association with in-hospital death; the composite outcome of the need of intensive care unit admission, mechanical ventilation, or in-hospital death; in-hospital complications; or long-time hospital stays. CONCLUSIONS: In patients with type 2 diabetes mellitus admitted for COVID-19, at-home glucose-lowering drugs showed no significant association with mortality and adverse outcomes. Given the close relationship between diabetes and COVID-19 and the limited evidence on the role of glucose-lowering drugs, prospective studies are needed.


Subject(s)
Coronavirus Infections/mortality , Diabetes Mellitus, Type 2/drug therapy , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Hypoglycemic Agents/standards , Insulin/therapeutic use , Metformin/therapeutic use , Pneumonia, Viral/mortality , Respiration, Artificial/statistics & numerical data , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Aged , Aged, 80 and over , Betacoronavirus , COVID-19 , Cohort Studies , Coronavirus Infections/complications , Coronavirus Infections/therapy , Diabetes Mellitus, Type 2/complications , Drug Therapy, Combination , Female , Hospital Mortality , Hospitalization , Humans , Hypoglycemic Agents/therapeutic use , Intensive Care Units , Length of Stay/statistics & numerical data , Logistic Models , Male , Noninvasive Ventilation/statistics & numerical data , Pandemics , Pneumonia, Viral/complications , Pneumonia, Viral/therapy , Prospective Studies , SARS-CoV-2 , Spain
12.
Curr Pharm Des ; 27(33): 3526-3550, 2021.
Article in English | MEDLINE | ID: covidwho-937333

ABSTRACT

Today, the world is suffering from the pandemic of a novel coronavirus disease (COVID-19), a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This pandemic is the third fatal coronavirus outbreak that has already occurred in the 21st century. Even six months after its emergence, hundreds of thousands of people are still being infected with SARS-CoV-2, and thousands of lives are lost every day across the world. No effective therapy has been approved to date for the treatment of this disease, suggesting the need to broaden the scope in the search for effective treatments. Throughout history, folk medicine has been successfully used to treat various ailments in humans, and Traditional Chinese Medicine has been instrumental in the containment of a number of viral diseases. Owing to their high chemical diversity and safety profiles, natural products offer great promises as potentially effective antiviral drugs. In recent years, a large number of anti-coronaviral phytochemicals with different mechanisms of action have been identified. Among them, tetra-O-galloyl-ß-D-glucose, caffeic acid, and saikosaponin B2 block viral entry. A number of flavonoids inhibit viral proteases. Silvestrol inhibits protein synthesis. Myricetin and scutellarein inhibit viral replication. Emodin, luteolin, and quercetin demonstrate anti-coronaviral activity by inhibiting multiple processes in the virus life cycle. In this review, we critically evaluate the findings of the natural product-based anticoronaviral research that has been published during the last two decades, and attempt to provide a comprehensive description about their utility as potential broad-spectrum anti-coronaviral drugs, examining leads that may guide/facilitate anti-SARS-CoV-2 drug development studies.


Subject(s)
Biological Products , COVID-19 , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Biological Products/pharmacology , Humans , Pandemics , SARS-CoV-2
13.
Nat Rev Endocrinol ; 17(1): 11-30, 2021 01.
Article in English | MEDLINE | ID: covidwho-926817

ABSTRACT

Initial studies found increased severity of coronavirus disease 2019 (COVID-19), caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), in patients with diabetes mellitus. Furthermore, COVID-19 might also predispose infected individuals to hyperglycaemia. Interacting with other risk factors, hyperglycaemia might modulate immune and inflammatory responses, thus predisposing patients to severe COVID-19 and possible lethal outcomes. Angiotensin-converting enzyme 2 (ACE2), which is part of the renin-angiotensin-aldosterone system (RAAS), is the main entry receptor for SARS-CoV-2; although dipeptidyl peptidase 4 (DPP4) might also act as a binding target. Preliminary data, however, do not suggest a notable effect of glucose-lowering DPP4 inhibitors on SARS-CoV-2 susceptibility. Owing to their pharmacological characteristics, sodium-glucose cotransporter 2 (SGLT2) inhibitors might cause adverse effects in patients with COVID-19 and so cannot be recommended. Currently, insulin should be the main approach to the control of acute glycaemia. Most available evidence does not distinguish between the major types of diabetes mellitus and is related to type 2 diabetes mellitus owing to its high prevalence. However, some limited evidence is now available on type 1 diabetes mellitus and COVID-19. Most of these conclusions are preliminary, and further investigation of the optimal management in patients with diabetes mellitus is warranted.


Subject(s)
COVID-19/drug therapy , COVID-19/epidemiology , Diabetes Mellitus, Type 1/drug therapy , Diabetes Mellitus, Type 1/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Angiotensin-Converting Enzyme 2/antagonists & inhibitors , Angiotensin-Converting Enzyme 2/metabolism , Blood Glucose/drug effects , Blood Glucose/metabolism , COVID-19/metabolism , Diabetes Mellitus, Type 1/metabolism , Diabetes Mellitus, Type 2/metabolism , Disease Management , Humans , Hypoglycemic Agents/administration & dosage , Hypoglycemic Agents/metabolism , Risk Factors
14.
J Diabetes Sci Technol ; 14(6): 1065-1073, 2020 11.
Article in English | MEDLINE | ID: covidwho-873877

ABSTRACT

BACKGROUND: Amidst the coronavirus disease 2019 (COVID-19) pandemic, continuous glucose monitoring (CGM) has emerged as an alternative for inpatient point-of-care blood glucose (POC-BG) monitoring. We performed a feasibility pilot study using CGM in critically ill patients with COVID-19 in the intensive care unit (ICU). METHODS: Single-center, retrospective study of glucose monitoring in critically ill patients with COVID-19 on insulin therapy using Medtronic Guardian Connect and Dexcom G6 CGM systems. Primary outcomes were feasibility and accuracy for trending POC-BG. Secondary outcomes included reliability and nurse acceptance. Sensor glucose (SG) was used for trends between POC-BG with nursing guidance to reduce POC-BG frequency from one to two hours to four hours when the SG was in the target range. Mean absolute relative difference (MARD), Clarke error grids analysis (EGA), and Bland-Altman (B&A) plots were calculated for accuracy of paired SG and POC-BG measurements. RESULTS: CGM devices were placed on 11 patients: Medtronic (n = 6) and Dexcom G6 (n = 5). Both systems were feasible and reliable with good nurse acceptance. To determine accuracy, 437 paired SG and POC-BG readings were analyzed. For Medtronic, the MARD was 13.1% with 100% of readings in zones A and B on Clarke EGA. For Dexcom, MARD was 11.1% with 98% of readings in zones A and B. B&A plots had a mean bias of -17.76 mg/dL (Medtronic) and -1.94 mg/dL (Dexcom), with wide 95% limits of agreement. CONCLUSIONS: During the COVID-19 pandemic, CGM is feasible in critically ill patients and has acceptable accuracy to identify trends and guide intermittent blood glucose monitoring with insulin therapy.


Subject(s)
Blood Glucose/analysis , Coronavirus Infections/blood , Coronavirus Infections/therapy , Critical Illness/therapy , Monitoring, Physiologic/instrumentation , Pneumonia, Viral/blood , Pneumonia, Viral/therapy , Adult , Aged , Betacoronavirus/physiology , Blood Glucose/metabolism , Blood Glucose Self-Monitoring/instrumentation , Blood Glucose Self-Monitoring/methods , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/mortality , Critical Illness/epidemiology , Critical Illness/mortality , Diabetes Mellitus/blood , Diabetes Mellitus/diagnosis , Diabetes Mellitus/mortality , Diabetes Mellitus/therapy , Feasibility Studies , Female , Humans , Hyperglycemia/blood , Hyperglycemia/diagnosis , Hyperglycemia/mortality , Hyperglycemia/therapy , Insulin/administration & dosage , Insulin Infusion Systems , Intensive Care Units , Male , Middle Aged , Monitoring, Physiologic/methods , Pandemics , Pilot Projects , Pneumonia, Viral/epidemiology , Pneumonia, Viral/mortality , Point-of-Care Systems , Prognosis , Reproducibility of Results , Retrospective Studies , SARS-CoV-2
17.
Clin Immunol ; 219: 108544, 2020 10.
Article in English | MEDLINE | ID: covidwho-664013

ABSTRACT

Glucose 6-phosphate dehydrogenase (G6PD) deficiency facilitates human coronavirus infection due to glutathione depletion. G6PD deficiency may especially predispose to hemolysis upon coronavirus disease-2019 (COVID-19) infection when employing pro-oxidant therapy. However, glutathione depletion is reversible by N-acetylcysteine (NAC) administration. We describe a severe case of COVID-19 infection in a G6PD-deficient patient treated with hydroxychloroquine who benefited from intravenous (IV) NAC beyond reversal of hemolysis. NAC blocked hemolysis and elevation of liver enzymes, C-reactive protein (CRP), and ferritin and allowed removal from respirator and veno-venous extracorporeal membrane oxygenator and full recovery of the G6PD-deficient patient. NAC was also administered to 9 additional respirator-dependent COVID-19-infected patients without G6PD deficiency. NAC elicited clinical improvement and markedly reduced CRP in all patients and ferritin in 9/10 patients. NAC mechanism of action may involve the blockade of viral infection and the ensuing cytokine storm that warrant follow-up confirmatory studies in the setting of controlled clinical trials.


Subject(s)
Acetylcysteine/therapeutic use , Antioxidants/therapeutic use , Betacoronavirus/pathogenicity , Coronavirus Infections/drug therapy , Cytokine Release Syndrome/drug therapy , Glucosephosphate Dehydrogenase Deficiency/drug therapy , Pneumonia, Viral/drug therapy , Adult , Antirheumatic Agents/therapeutic use , Biomarkers/blood , C-Reactive Protein/metabolism , COVID-19 , Coronavirus Infections/blood , Coronavirus Infections/complications , Coronavirus Infections/virology , Cytokine Release Syndrome/blood , Cytokine Release Syndrome/complications , Cytokine Release Syndrome/virology , Drug Administration Schedule , Ferritins/blood , Fibrin Fibrinogen Degradation Products/metabolism , Glucosephosphate Dehydrogenase Deficiency/blood , Glucosephosphate Dehydrogenase Deficiency/complications , Glucosephosphate Dehydrogenase Deficiency/virology , Humans , Hydroxychloroquine/therapeutic use , Inflammation/prevention & control , Male , Pandemics , Pneumonia, Viral/blood , Pneumonia, Viral/complications , Pneumonia, Viral/virology , SARS-CoV-2 , Treatment Outcome
18.
Acta Clin Belg ; 77(1): 113-117, 2022 Feb.
Article in English | MEDLINE | ID: covidwho-600078

ABSTRACT

OBJECTIVE: Recent publications on Coronavirus Disease-2019 (COVID-19) report that diabetic people with or without co-morbidities are at higher risk of developing severe and/or fatal illnesses. METHOD AND RESULT: We report the first case of a 60-year-old man with a 27-year history of type 1 diabetes mellitus, infected by SARS-CoV-2 presenting with an euglycaemic ketoacidosis and an acute respiratory distress syndrome. CONCLUSION: This case report reminds us of the importance of adjusting more recent glucose-lowering drugs, including sodium-glucose cotransporter 2 inhibitors, in the overall management of type 1 diabetic individuals during the ongoing COVID-19 outbreak. ABBREVIATIONS: COVID-19: Coronavirus disease 2019 (SARS-CoV-2) virus, T1DM: Type 1 diabetes mellitus, T2DM: Type 2 diabetes mellitus, SGLT2i: Sodium-glucose cotransporter 2 inhibitor, DKA: diabetic ketoacidosis, euDKA: euglycaemic diabetic ketoacidosis.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 1 , Diabetes Mellitus, Type 2 , Diabetic Ketoacidosis , Sodium-Glucose Transporter 2 Inhibitors , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 2/complications , Diabetic Ketoacidosis/etiology , Humans , Male , Middle Aged , SARS-CoV-2
19.
Diabetes Metab ; 46(5): 403-405, 2020 10.
Article in English | MEDLINE | ID: covidwho-350547

ABSTRACT

Tocilizumab (TCZ) is used for treating moderate-to-severe Covid-19 pneumonia by targeting interleukin-6 receptors (IL-6Rs) and reducing cytokine release. Yet, in spite of this therapy, patients with vs. patients without diabetes have an adverse disease course. In fact, glucose homoeostasis has influenced the outcomes of diabetes patients with infectious diseases. Of the 475 Covid-19-positive patients admitted to infectious disease departments (University of Bologna, University Vanvitelli of Napoli, San Sebastiano Caserta Hospital) in Italy since 1 March 2020, 31 (39.7%) hyperglycaemic and 47 (60.3%) normoglycaemic patients (blood glucose levels ≥140mg/dL) were retrospectively evaluated at admission and during their hospital stay. Of note, 20 (64%) hyperglycaemic and 11 (23.4%) normoglycaemic patients had diabetes (P<0.01). At admission, hyperglycaemic vs. normoglycaemic patients had fivefold higher IL-6 levels, which persisted even after TCZ administration (P<0.05). Intriguingly, in a risk-adjusted Cox regression analysis, TCZ in hyperglycaemic patients failed to attenuate risk of severe outcomes as it did in normoglycaemic patients (P<0.009). Also, in hyperglycaemic patients, higher IL-6 plasma levels reduced the effects of TCZ, while adding IL-6 levels to the Cox regression model led to loss of significance (P<0.07) of its effects. Moreover, there was evidence that optimal Covid-19 infection management with TCZ is not achieved during hyperglycaemia in both diabetic and non-diabetic patients. These data may be of interest to currently ongoing clinical trials of TCZ effects in Covid-19 patients and of optimal control of glycaemia in this patient subset.


Subject(s)
Anti-Inflammatory Agents/therapeutic use , Antibodies, Monoclonal, Humanized/therapeutic use , Coronavirus Infections , Hyperglycemia , Pandemics , Pneumonia, Viral , Betacoronavirus , COVID-19 , Coronavirus Infections/complications , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Coronavirus Infections/physiopathology , Diabetes Complications , Humans , Hyperglycemia/complications , Hyperglycemia/epidemiology , Interleukin-6/blood , Italy , Pneumonia, Viral/complications , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , Pneumonia, Viral/physiopathology , Retrospective Studies , SARS-CoV-2
20.
Diabetes Care ; 43(7): 1399-1407, 2020 07.
Article in English | MEDLINE | ID: covidwho-272617

ABSTRACT

OBJECTIVE: Diabetes is one of the most distinct comorbidities of COVID-19. Here, we describe the clinical characteristics of and outcomes in patients with diabetes in whom COVID-19 was confirmed or clinically diagnosed (with typical features on lung imaging and symptoms) and their association with glucose-lowering or blood pressure-lowering medications. RESEARCH DESIGN AND METHODS: In this retrospective study involving 904 patients with COVID-19 (136 with diabetes, mostly type 2 diabetes), clinical and laboratory characteristics were collected and compared between the group with diabetes and the group without diabetes, and between groups taking different medications. Logistic regression was used to explore risk factors associated with mortality or poor prognosis. RESULTS: The proportion of comorbid diabetes is similar between cases of confirmed and of clinically diagnosed COVID-19. Risk factors for higher mortality of patients with diabetes and COVID-19 were older age (adjusted odds ratio [aOR] 1.09 [95% CI 1.04, 1.15] per year increase; P = 0.001) and elevated C-reactive protein (aOR 1.12 [95% CI 1.00, 1.24]; P = 0.043). Insulin usage (aOR 3.58 [95% CI 1.37, 9.35]; P = 0.009) was associated with poor prognosis. Clinical outcomes of those who use an ACE inhibitor (ACEI) or angiotensin II type-I receptor blocker (ARB) were comparable with those of patients who do not use ACEI/ARB among COVID-19 patients with diabetes and hypertension. CONCLUSIONS: C-reactive protein may help to identify patients with diabetes who are at greater risk of dying during hospitalization. Older patients with diabetes were prone to death related to COVID-19. Attention needs to be paid to patients with diabetes and COVID-19 who use insulin. ACEI/ARB use showed no significant impact on patients with diabetes and hypertension who have COVID-19.


Subject(s)
Betacoronavirus , Coronavirus Infections/epidemiology , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/epidemiology , Pneumonia, Viral/epidemiology , Age Factors , Aged , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19 , Comorbidity , Female , Glucose/therapeutic use , Humans , Hypertension/epidemiology , Logistic Models , Male , Middle Aged , Odds Ratio , Pandemics , Retrospective Studies , SARS-CoV-2 , Time Factors
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