Malnutrition management of hospitalized patients with diabetes/hyperglycemia and COVID-19 infection.

Diabetes mellitus and/or hyperglycemia are highly prevalent medical conditions in patients hospitalized for coronavirus disease 2019 (COVID-19) and are associated with adverse outcomes. In addition, COVID-19 itself can provoke fluctuating and high glucose levels that can be difficult to manage upon hospitalization. Hospitalized patients with COVID-19 are at high risk of malnutrition due to an increase in nutritional requirements and a severe acute inflammatory response. The management of patients with diabetes/hyperglycemia and COVID-19 is challenging and requires a specific nutritional approach, the purpose of which is to fulfill the nutritional requirements while maintaining an optimal glycemic control. In this study, an expert group of nutritional endocrinologists carried out a qualitative literature review and provided recommendations based on evidence and guidelines, when available, or on their own experience. The optimal care based on these recommendations was compared with the routine bedside care as reported by a panel of physicians (mainly, endocrinologists, geriatricians, and internists) treating patients with diabetes/hyperglycemia and COVID-19 in their daily practice. Early screening and diagnosis, a diabetes-specific therapeutic approach, and a close malnutrition monitoring are essential to improve the clinical outcomes of these patients. In conclusion, the proposed recommendations are intended to provide a useful guide on the clinical management of malnutrition in patients with COVID-19 and diabetes/hyperglycemia, in order to improve their outcomes and accelerate their recovery. The comparison of the recommended optimal care with routine clinical practice could aid to identify gaps in knowledge, implementation difficulties, and areas for improvement in the management of malnutrition in this population.

Glucocorticoid-Induced Hyperglycemia Including Dexamethasone-Associated Hyperglycemia in COVID-19 Infection: A Systematic Review.

OBJECTIVE: Optimal glucocorticoid-induced hyperglycemia (GCIH) management is unclear. The COVID-19 pandemic has made this issue more prominent because dexamethasone became the standard of care in patients needing respiratory support. This systematic review aimed to describe the management of GCIH and summarize available management strategies for dexamethasone-associated hyperglycemia in patients with COVID-19. METHODS: A systematic review was conducted using the PubMed/MEDLINE, Cochrane Library, Embase, and Web of Science databases with results from 2011 through January 2022. Keywords included synonyms for "steroid-induced diabetes" or "steroid-induced hyperglycemia." Randomized controlled trials (RCTs) were included for review of GCIH management. All studies focusing on dexamethasone-associated hyperglycemia in COVID-19 were included regardless of study quality. RESULTS: Initial search for non-COVID GCIH identified 1230 references. After screening and review, 33 articles were included in the non-COVID section of this systematic review. Initial search for COVID-19-related management of dexamethasone-associated hyperglycemia in COVID-19 identified 63 references, whereas 7 of these were included in the COVID-19 section. RCTs of management strategies were scarce, did not use standard definitions for hyperglycemia, evaluated a variety of treatment strategies with varying primary end points, and were generally not found to be effective except for Neutral Protamine Hagedorn insulin added to basal-bolus regimens. CONCLUSION: Few RCTs are available evaluating GCIH management. Further studies are needed to support the formulation of clinical guidelines for GCIH especially given the widespread use of dexamethasone during the COVID-19 pandemic.

Early Post-Renal Transplant Hyperglycemia.

CONTEXT: Though posttransplant diabetes mellitus (PTDM, occurring > 45 days after transplantation) and its complications are well described, early post-renal transplant hyperglycemia (EPTH) (< 45 days) similarly puts kidney transplant recipients at risk of infections, rehospitalizations, and graft failure and is not emphasized much in the literature. Proactive screening and management of EPTH is required given these consequences. OBJECTIVE: The aim of this article is to promote recognition of early post-renal transplant hyperglycemia, and to summarize available information on its pathophysiology, adverse effects, and management. METHODS: A PubMed search was conducted for "early post-renal transplant hyperglycemia," "immediate posttransplant hyperglycemia," "post-renal transplant diabetes," "renal transplant," "diabetes," and combinations of these terms. EPTH is associated with significant complications including acute graft failure, rehospitalizations, cardiovascular events, PTDM, and infections. CONCLUSION: Patients with diabetes experience better glycemic control in end-stage renal disease (ESRD), with resurgence of hyperglycemia after kidney transplant. Patients with and without known diabetes are at risk of EPTH. Risk factors include elevated pretransplant fasting glucose, diabetes, glucocorticoids, chronic infections, and posttransplant infections. We find that EPTH increases risk of re-hospitalizations from infections (cytomegalovirus, possibly COVID-19), acute graft rejections, cardiovascular events, and PTDM. It is essential, therefore, to provide diabetes education to patients before discharge. Insulin remains the standard of care while inpatient. Close follow-up after discharge is recommended for insulin adjustment. Some agents like dipeptidyl peptidase-4 inhibitors and glucagon-like peptide-1 receptor agonists have shown promise. The tenuous kidney function in the early posttransplant period and lack of data limit the use of sodium-glucose cotransporter 2 inhibitors. There is a need for studies assessing noninsulin agents for EPTH to decrease risk of hypoglycemia associated with insulin and long-term complications of EPTH.

Thromboembolism risk among patients with diabetes/stress hyperglycemia and COVID-19.

PURPOSE: Individuals with diabetes/stress hyperglycemia carry an increased risk for adverse clinical outcome in case of SARS-CoV-2 infection. The purpose of this study was to evaluate whether this risk is, at least in part, modulated by an increase of thromboembolic complications. METHODS: We prospectively followed 180 hospitalized patients with confirmed COVID-19 pneumonia admitted to the Internal Medicine Units of San Raffaele Hospital. Data from 11 out of 180 patients were considered incomplete and excluded from the analysis. We analysed inflammation, tissue damage biomarkers, hemostatic parameters, thrombotic events (TEs) and clinical outcome according to the presence of diabetes/stress hyperglycemia. RESULTS: Among 169 patients, 51 (30.2%) had diabetes/stress hyperglycemia. Diabetes/stress hyperglycemia and fasting blood glucose (FBG) were associated with increased inflammation and tissue damage circulating markers, higher D-dimer levels, increased prothrombin time and lower antithrombin III activity. Forty-eight venous and 10 arterial TEs were identified in 49 (29%) patients. Diabetes/stress hyperglycemia (HR 2.71, p = 0.001), fasting blood glucose (HR 4.32, p < 0.001) and glucose variability (HR 1.6, p < 0.009) were all associated with an increased risk of thromboembolic complication. TEs significantly increased the risk for an adverse clinical outcome only in the presence of diabetes/stress hyperglycemia (HR 3.05, p = 0.010) or fasting blood glucose ≥7 mmol/L (HR 3.07, p = 0.015). CONCLUSIONS: Thromboembolism risk is higher among patients with diabetes/stress hyperglycemia and COVID-19 pneumonia and is associated to poor clinical outcome. In case of SARS-Cov-2 infection patients with diabetes/stress hyperglycemia could be considered for a more intensive prophylactic anticoagulation regimen.

Clinical Trials of COVID-19 Therapies Should Account for Diabetes and Hyperglycemia.

Complications of Coronavirus Disease 2019 (COVID-19) occur with increased frequency in people admitted to the hospital with diabetes or hyperglycemia. The increased risk for COVID-19 infections in the presence of these metabolic conditions is in part due to overlapping pathophysiologic features of COVID-19, diabetes, and glucose control. Various antiviral treatments are being tested in COVID-19 patients. We believe that in these trials, it will be useful to evaluate treatment effect differences in patients stratified according to whether they have diabetes or hyperglycemia. In this way, it will be possible to better facilitate development of antiviral treatments that are most specifically beneficial for the large subset of COVID-19 patients who have diabetes or hyperglycemia.

Quercetin/Zinc complex and stem cells: A new drug therapy to ameliorate glycometabolic control and pulmonary dysfunction in diabetes mellitus: Structural characterization and genetic studies.

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.

A guidance on diagnosis and management of hyperglycemia at COVID care facilities in India.

BACKGROUND AND AIMS: Diabetes and coronavirus disease 2019 (COVID-19) share a bidirectional relationship. Hyperglycemia occurring in the setting of either previously diagnosed or undiagnosed diabetes is known to be associated with poor outcomes. Here, we aim to provide a simple and practical guidance on the diagnosis and management of hyperglycemia in admitted patients with COVID-19. METHODS: The guidance is formulated based on experience of authors and relevant literature on the subject searched using Pubmed. RESULTS: Every patient admitted to a COVID care facility should be investigated for hyperglycemia using a combination of tests including capillary blood glucose, fasting plasma glucose and HbA1c. Oral glucose lowering drugs can be considered in patients with mild COVID illness who have mild hyperglycemia [pre-meal blood glucose of <180 mg/dl (10 mmol/L) and post-meal blood glucose of <250 mg/dl (13.9 mmol/L)] and no contraindication to the use of these agents.. All patients with moderate-severe disease and/or hyperglycemia of greater severity should be initiated on insulin therapy. Hyperglycemia should be aggressively screened for and managed in patients receiving systemic glucocorticoids. CONCLUSION: This document provides a broad overview on the diagnosis and management of hyperglycemia at COVID care facilities and should be useful to a wide range of healthcare personnel involved in care of patients with COVID-19.

Management of diabetes and hyperglycaemia in the hospital.

Hyperglycaemia in people with and without diabetes admitted to the hospital is associated with a substantial increase in morbidity, mortality, and health-care costs. Professional societies have recommended insulin therapy as the cornerstone of inpatient pharmacological management. Intravenous insulin therapy is the treatment of choice in the critical care setting. In non-intensive care settings, several insulin protocols have been proposed to manage patients with hyperglycaemia; however, meta-analyses comparing different treatment regimens have not clearly endorsed the benefits of any particular strategy. Clinical guidelines recommend stopping oral antidiabetes drugs during hospitalisation; however, in some countries continuation of oral antidiabetes drugs is commonplace in some patients with type 2 diabetes admitted to hospital, and findings from clinical trials have suggested that non-insulin drugs, alone or in combination with basal insulin, can be used to achieve appropriate glycaemic control in selected populations. Advances in diabetes technology are revolutionising day-to-day diabetes care and work is ongoing to implement these technologies (ie, continuous glucose monitoring, automated insulin delivery) for inpatient care. Additionally, transformations in care have occurred during the COVID-19 pandemic, including the use of remote inpatient diabetes management-research is needed to assess the effects of such adaptations.

Importance of hyperglycemia in COVID-19 intensive-care patients: Mechanism and treatment strategy.

This review reported that coronavirus disease 2019 (COVID-19) infected patients with short time bed rest or quarantine and airway inflammation are at more risk of developing hyperglycemia and insulin resistance. This condition can induce oxidative stress, decrease immune system function, impair endothelial function, induce apoptosis, and reduce antioxidant in the lungs. We provide a possible mechanism in severe COVID-19 patients and recommend treatment strategy to reduce mortality rate and prevent adverse outcomes after intensive care unit (ICU).

Continuous Glucose Monitoring in Critically Ill Patients With COVID-19: Results of an Emergent Pilot Study.

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.

Clinical Study of Hyperglycemia and SARS-CoV-2 Infection in Intensive Care Unit Patients.

BACKGROUND/AIM: Reports indicate that coronaviridae may inhibit insulin secretion. In this report we aimed to describe the course of glycemia in critically ill patients with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. PATIENTS AND METHODS: We studied 36 SARS-CoV-2 patients (with no history of diabetes) in one intensive care unit (ICU). All the patients were admitted for hypoxemic respiratory failure; all but four required mechanical ventilation. The mean (±SD) age of the patients was 64.7 (9.7) years; 27 were men; the mean (±SD) duration of ICU stay was 12.9 (8.3 days). RESULTS: Twenty of 36 patients presented with hyperglycemia; brief intravenous infusions of short-acting insulin were administered in six patients. As of May 29 2020, 11 patients had died (seven with hyperglycemia). In 17 patients the Hyperglycemia Index [HGI; defined as the area under the curve of (hyper)glycemia level*time (h) divided by the total time in the ICU] was <16.21 mg/dl (0.90 mmol/l), whereas in three patients the HGI was ≥16.21 mg/dl (0.90 mol/l) and <32.25 mg/dl (1.79 mmol/l). CONCLUSION: In our series of ICU patients with SARS-CoV-2 infection, and no history of diabetes, a substantial number of patients had hyperglycemia, to a higher degree than would be expected by the stress of critical illness, lending credence to reports that speculated a tentative association between SARS-CoV-2 and hyperglycemia. This finding is important, since hyperglycemia can lead to further infectious complications.

Newly-diagnosed diabetes and admission hyperglycemia predict COVID-19 severity by aggravating respiratory deterioration.

AIMS: We investigated whether pre-existing diabetes, newly-diagnosed diabetes, and admission hyperglycemia were associated with COVID-19 severity independently from confounders. METHODS: We retrospectively analyzed data on patients with COVID-19 hospitalized between February and April 2020 in an outbreak hospital in North-East Italy. Pre-existing diabetes was defined by self-reported history, electronic medical records, or ongoing medications. Newly-diagnosed diabetes was defined by HbA1c and fasting glucose. The primary outcome was a composite of ICU admission or death. RESULTS: 413 subjects were included, 107 of whom (25.6%) had diabetes, including 21 newly-diagnosed. Patients with diabetes were older and had greater comorbidity burden. The primary outcome occurred in 37.4% of patients with diabetes compared to 20.3% in those without (RR 1.85; 95%C.I. 1.33-2.57; p < 0.001). The association was stronger for newly-diagnosed compared to pre-existing diabetes (RR 3.06 vs 1.55; p = 0.004). Higher glucose level at admission was associated with COVID-19 severity, with a stronger association among patients without as compared to those with pre-existing diabetes (interaction p < 0.001). Admission glucose was correlated with most clinical severity indexes and its association with adverse outcome was mostly mediated by a worse respiratory function. CONCLUSION: Newly-diagnosed diabetes and admission hyperglycemia are powerful predictors of COVID-19 severity due to rapid respiratory deterioration.

Managing Hyperglycemia in the COVID-19 Inflammatory Storm.

A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (coronavirus disease 2019 [COVID-19]) is now at global pandemic levels causing significant morbidity and mortality. Patients with diabetes are particularly vulnerable and more likely to get severe complications when infected with this virus. Although the information continues to emerge, here we provide our perspective on initial outcomes observed in hospitalized patients with diabetes and the potential role played by the proinflammatory metabolic state in these patients that promotes fertile ground for the virus' inflammatory surge, resulting in severe insulin resistance and severe hyperglycemia. The rapidly evolving renal failure, hypotension, pressor and steroid use, and variable nutritional support further complicates their management. Thus, timely implementation of glucose management protocols addressing these complex scenarios while also following COVID-19-related trajectories in inflammatory biomarkers and being cognizant of the health care provider exposure may substantially affect morbidity and mortality.

COVID-19 in people with diabetes: understanding the reasons for worse outcomes.

Since the initial COVID-19 outbreak in China, much attention has focused on people with diabetes because of poor prognosis in those with the infection. Initial reports were mainly on people with type 2 diabetes, although recent surveys have shown that individuals with type 1 diabetes are also at risk of severe COVID-19. The reason for worse prognosis in people with diabetes is likely to be multifactorial, thus reflecting the syndromic nature of diabetes. Age, sex, ethnicity, comorbidities such as hypertension and cardiovascular disease, obesity, and a pro-inflammatory and pro-coagulative state all probably contribute to the risk of worse outcomes. Glucose-lowering agents and anti-viral treatments can modulate the risk, but limitations to their use and potential interactions with COVID-19 treatments should be carefully assessed. Finally, severe acute respiratory syndrome coronavirus 2 infection itself might represent a worsening factor for people with diabetes, as it can precipitate acute metabolic complications through direct negative effects on ß-cell function. These effects on ß-cell function might also cause diabetic ketoacidosis in individuals with diabetes, hyperglycaemia at hospital admission in individuals with unknown history of diabetes, and potentially new-onset diabetes.

Potential Indirect Effects of the COVID-19 Pandemic on Use of Emergency Departments for Acute Life-Threatening Conditions - United States, January-May 2020.

On March 13, 2020, the United States declared a national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic. Subsequently, states enacted stay-at-home orders to slow the spread of SARS-CoV-2, the virus that causes COVID-19, and reduce the burden on the U.S. health care system. CDC* and the Centers for Medicare & Medicaid Services (CMS)† recommended that health care systems prioritize urgent visits and delay elective care to mitigate the spread of COVID-19 in health care settings. By May 2020, national syndromic surveillance data found that emergency department (ED) visits had declined 42% during the early months of the pandemic (1). This report describes trends in ED visits for three acute life-threatening health conditions (myocardial infarction [MI, also known as heart attack], stroke, and hyperglycemic crisis), immediately before and after declaration of the COVID-19 pandemic as a national emergency. These conditions represent acute events that always necessitate immediate emergency care, even during a public health emergency such as the COVID-19 pandemic. In the 10 weeks following the emergency declaration (March 15-May 23, 2020), ED visits declined 23% for MI, 20% for stroke, and 10% for hyperglycemic crisis, compared with the preceding 10-week period (January 5-March 14, 2020). EDs play a critical role in diagnosing and treating life-threatening conditions that might result in serious disability or death. Persons experiencing signs or symptoms of serious illness, such as severe chest pain, sudden or partial loss of motor function, altered mental state, signs of extreme hyperglycemia, or other life-threatening issues, should seek immediate emergency care, regardless of the pandemic. Clear, frequent, highly visible communication from public health and health care professionals is needed to reinforce the importance of timely care for medical emergencies and to assure the public that EDs are implementing infection prevention and control guidelines that help ensure the safety of their patients and health care personnel.

Proposed guidelines for screening of hyperglycemia in patients hospitalized with COVID-19 in low resource settings.

BACKGROUND AND AIMS: The coronavirus disease 2019 (COVID-19) pandemic has immensely strained healthcare systems worldwide. Diabetes has emerged as a major comorbidity in a large proportion of patients infected with COVID-19 and is associated with poor health outcomes. We aim to provide a practical guidance on screening of hyperglycemia in persons without known diabetes in low resource settings. METHODS: We reviewed the available guidelines on this subject and proposed an algorithm based on simple measures of blood glucose (BG) which can be implemented by healthcare workers with lesser expertise in low resource settings. RESULTS: We propose that every hospitalized patient with COVID-19 infection undergo a paired capillary BG assessment (pre-meal and 2-h post-meal). Patients with pre-meal BG < 7.8 mmol/L (140 mg/dL) and post-meal BG < 10.0 mmol/L (180 mg/dL) may not merit further monitoring. On the other hand, those with one or more value above these thresholds should undergo capillary BG monitoring (pre-meals and 2 hours after dinner) for the next 24 hours. When two or more (≥50%) such values are significantly elevated [pre-meal ≥8.3 mmol/L (150 mg/dL) and post-meal ≥11.1 mmol/L (200 mg/dL)], pharmacotherapy should be immediately initiated. On the other hand, in patients with modest elevation of one or more values [pre-meal 7.8-8.3 mmol/L (140-150 mg/dL) and post-meal 10.0-11.1 mmol/L (180-200 mg/dL)], dietary modifications should be initiated and pharmacotherapy considered only if BG control remains suboptimal. CONCLUSION: We highlight strategies for screening of hyperglycemia in persons without known diabetes treated for COVID-19 infection in low resource settings. This guidance may well be applied to other settings in the near future.

Newly diagnosed diabetes is associated with a higher risk of mortality than known diabetes in hospitalized patients with COVID-19.

AIM: To evaluate the association between different degrees of hyperglycaemia and the risk of all-cause mortality among hospitalized patients with COVID-19. MATERIALS AND METHODS: In a retrospective study conducted from 22 January to 17 March 2020, 453 patients were admitted to Union Hospital in Wuhan, China, with laboratory-confirmed severe acute respiratory syndrome coronavirus 2 infection. Patients were classified into four categories: normal glucose, hyperglycaemia (fasting glucose 5.6-6.9 mmol/L and/or HbA1c 5.7%-6.4%), newly diagnosed diabetes (fasting glucose ≥7 mmol/L and/or HbA1c ≥6.5%) and known diabetes. The major outcomes included in-hospital mortality, intensive care unit (ICU) admission and invasive mechanical ventilation (IMV). RESULTS: Patients with newly diagnosed diabetes constituted the highest percentage to be admitted to the ICU (11.7%) and require IMV (11.7%), followed by patients with known diabetes (4.1%; 9.2%) and patients with hyperglycaemia (6.2%; 4.7%), compared with patients with normal glucose (1.5%; 2.3%), respectively. The multivariable-adjusted hazard ratios of mortality among COVID-19 patients with normal glucose, hyperglycaemia, newly diagnosed diabetes and known diabetes were 1.00, 3.29 (95% confidence interval [CI] 0.65-16.6), 9.42 (95% CI 2.18-40.7) and 4.63 (95% CI 1.02-21.0), respectively. CONCLUSION: We showed that COVID-19 patients with newly diagnosed diabetes had the highest risk of all-cause mortality compared with COVID-19 patients with known diabetes, hyperglycaemia and normal glucose. Patients with COVID-19 need to be kept under surveillance for blood glucose screening.