|Year : 2020 | Volume
| Issue : 5 | Page : 6-10
In-patient management of hyperglycemia during COVID-19 pandemic
W Y. Khwaja Mohammed Usman1, Radhika Jindal2, Danendra Sahu1, Mohammad Asim Siddiqui1, Subhash Kumar Wangnoo1
1 Apollo Centre for Obesity, Diabetes and Endocrinology, Indraprastha Apollo Hospital, New Delhi, Delhi, India
2 Department of Endocrinology, Safdarjung Hospital and Vardhman Mahavir Medical College, New Delhi, Delhi, India
|Date of Submission||30-Jun-2020|
|Date of Acceptance||16-Jul-2020|
|Date of Web Publication||06-Aug-2020|
Mohammad Asim Siddiqui
Apollo Centre for Obesity, Diabetes and Endocrinology, Indraprastha Apollo Hospital, New Delhi
Source of Support: None, Conflict of Interest: None
The pandemic of COVID-19 has presented new challenges to endocrine physicians and diabetologists in providing care for infected patients with dysglycemia, who may already be having diabetes and who present with newly diagnosed diabetes. The additional burden of metabolic decompensation, effect of treatment on glycemia, and the presence of comorbid complications make the management challenging. The presence of diabetes as a comorbid condition has shown to be associated with poorer outcomes in patients with COVID-19 infection. In addition, the effects of treatments such as the use of medications such as glucocorticoids and hydroxychloroquine may further add to the variability in glycemic control. Appropriate glycemic management leads to improvement in clinical outcomes, which involves intensive bedside glucose monitoring, intravenous and subcutaneous insulin administration, transition from intravenous to subcutaneous insulin, as well as interventions for hypoglycemia events. A uniform treatment protocol related to insulin administration and glucose monitoring is essential for improved clinical outcomes in admitted patients. Where feasible, continuous glucose monitoring systems have been proposed as an option for reducing time spent with patients, but they are not available everywhere and not many personnel are experienced in its usage. In-patient care of diabetes is an important issue that needs to be addressed if it is used in hospitalized patients.
Keywords: COVID-19, diabetes, inpatient hyperglycemia
|How to cite this article:|
Mohammed Usman W Y, Jindal R, Sahu D, Siddiqui MA, Wangnoo SK. In-patient management of hyperglycemia during COVID-19 pandemic. Apollo Med 2020;17, Suppl S1:6-10
|How to cite this URL:|
Mohammed Usman W Y, Jindal R, Sahu D, Siddiqui MA, Wangnoo SK. In-patient management of hyperglycemia during COVID-19 pandemic. Apollo Med [serial online] 2020 [cited 2020 Sep 19];17, Suppl S1:6-10. Available from: http://www.apollomedicine.org/text.asp?2020/17/5/6/291592
| Introduction|| |
The ongoing pandemic of COVID-19 has presented new challenges to the health-care personnel caring for these patients. Available data suggest that most people with COVID-19 have comorbidities, the most prevalent of which are diabetes, cardiovascular disease, and hypertension. Associated comorbidities such as diabetic complications, gender, advanced age, immunocompromised conditions, and patients with a history of organ transplant have a relatively higher mortality, for whom appropriate glycemic management may contribute to a reduction in adverse clinical outcomes.,,, Hyperglycemia increases risk for infections by altering leukocyte function and increasing the virulence of some pathogens, enhances risk for cardiac arrhythmias, prolongs hospital length of stay, and increases mortality, while hypoglycemia in critically ill patients portends a poorer outcome. Rising glucose levels are associated with increased risk of mortality, as well as the risk of dehydration, hypotension, eventual renal shutdown, poor healing, and impaired immune system function.,,,
Managing in-patient glycemia can be challenging and complex for the treating healthcare professionals as it involves frequent bedside blood glucose together measures with structured insulin regimens to avoid glycemic variability. The use of medications which may worsen glycemic control further confounds the problems.
| The Potential Link between Diabetes and COVID-19|| |
The understanding about increased predisposition of diabetes to COVID-19 is based on potential assumptions. The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus hijacks angiotensin-converting-enzyme 2 (ACE2) pathway to gain entry into the target cell which reduces ACE2 expression inducing cellular damage, hyperinflammation, and respiratory failure. Acute hyperglycemia has been shown to upregulate ACE2 expression on cells which might facilitate viral cell entry. Chronic hyperglycemia, on the other hand, causes downregulation of ACE2 expression, making the cells vulnerable to the inflammatory and damaging effect of the virus. Furthermore, the expression of ACE2 on pancreatic β-cells can lead to a direct effect on β-cell function, leading to additional increases in insulin requirements and also new-onset diabetes.,, As of now, there are no indications to discontinue ongoing ACEi therapy.
Another area of interest is the dipeptidyl peptidase-4 (DPP-4) enzyme, a commonly targeted pharmacological enzyme in people with type 2 diabetes, which was identified as a functional receptor for human coronavirus-Erasmus Medical Center (hCoV-EMC), the virus responsible for MERS. Antibodies directed against DPP-4 inhibited hCoV-EMC infection of primary cells. It is still not known whether these also apply to COVID-19 and treatment with DPP-4 inhibitors will influence the course of the infection; however, if these mechanisms do translate to SARS-CoV-2, the use of these agents could reduce DPP-4 concentrations and could provide therapeutic opportunities for the treatment of COVID-19.
| In-Patient Management of Hyperglycemia|| |
The basic principles of in-patient management of glycemia, whether new-onset or already diagnosed diabetes, remain the same. It is imperative that the hospitals dealing with COVID-19 patients follow the available best practice guidelines and can alter them depending on the individual clinical scenarios.
| Noninsulin Therapies|| |
As a rule of thumb, it is recommended to discontinue noninsulin medications and initiate insulin therapy for patients with diabetes or newly recognized hyperglycemia at the time of hospital admission. In patients with milder symptoms, or who are recovering, and not requiring too much of insulin to maintain glycemia within the target range, there is a role for noninsulin therapies. There are several small studies demonstrating safety and efficacy of the DPP-4 inhibitors sitagliptin and linagliptin in selected inpatients with type 2 diabetes.,,, These may be continued in hospitalized patients with type 2 diabetes and milder degrees of hyperglycemia or in the recovery phase of COVID-19 infection in the absence of any contraindications. Use of saxagliptin and alogliptin is not recommended due to concerns of an increased incidence of heart failure., However, use of these medications alone is unlikely to control the sugars; most of the trials with these class of drugs were conducted in combination with correction insulin and several in combination with basal insulin therapy.
Quite a few of patients with diabetes may be on daily or weekly formulations of glucagon-like receptor analogs (GLP1RA). Although there have been a few studies indicating their use in critical care settings, at present, it is advisable to discontinue them in patients with COVID-19. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with the risk for euglycemic diabetic ketoacidosis and volume depletion;, it is advisable to discontinue these class of agents in hospitalized patients.
Sulfonylureas and other insulin secretagogues have a potential to cause severe hypoglycemia – these need to be used cautiously if at all and discontinued for patients with declining renal function, who are elderly, or receiving insulin therapy due to concerns of hypoglycemia. Metformin should be discontinued as it has the potential to precipitate risk of acidosis, in those with hemodynamic instability, hypoxia, and/or severe renal impairment. Thiazolidinediones, although demonstrated to be having anti-inflammatory properties, are associated with fluid retention, aggravating risk for heart failure, and should not be used. There is no available literature for use of alpha-glucosidase inhibitors also [Table 1].
|Table 1: Noninsulin therapies consideration in hospitalized patients with COVID-19|
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| Insulin Therapy|| |
Insulin therapy is the mainstay for managing glycemia in critically ill patients. It is important to remember that there is no ideal protocol for the management of hyperglycemia in the critical patient. In addition, there is no clear evidence demonstrating the benefit of one protocol/algorithm versus the other. Insulin regimens may comprise long-acting and short- or rapid-acting insulin in not so sick patients with or without continuation of ongoing oral antidiabetic agents or intravenous insulin infusions, with the recommended range for achieving glycemic targets 140–180 mg/dl in critically ill patients [Table 2]., Using basal insulin during an intravenous insulin infusion can facilitate transition to SC insulin without rebound hyperglycemia. Use of sliding scale for insulin is not recommended, as leads to variability in glycemia. Glucose monitoring, needed for adjusting insulin requirements to achieve target blood glucose levels, may be done as per the clinical scenario - before meals and at bedtime for patients who are eating; every 4–6 h for patients who are not eating or who are receiving enteral or parenteral nutrition; every hourly or 2ndhourly in patients on insulin infusion. It is important to remember that in patients with critical COVID-19 infections, there is remarkable variability in insulin sensitivity over the course of the illness. In addition, treatment with glucocorticoids, vasopressors, and hydroxychloroquine leads to significant variability in both subcutaneous and intravenous insulin requirements from low to very high. Patients with preexisting chronic kidney disease or who experience acute kidney injury as part of COVID-19 infection may be particularly sensitive to insulin and risk for hypoglycemia.,, For the patients who are already on continuous subcutaneous insulin infusion (CSII), it is advisable to disconnect these devices as the nursing staff may not have adequate training to be proficient with its usage and to remove the infusion catheter also as it may be a potential source of infection. In patients, who are not critically ill, CSII may be continued, but these patients should be monitored frequently to assess changing insulin requirements as per the clinical status.
| Blood Glucose Monitoring|| |
Most of the health-care facilities are using point-of-care glucometers as the standard of care in hospitalized patients, despite identified issues relating to accuracy and precision of several of these devices. It is important to realize that the exposure of health-care staff attending to these patients need to be minimized. One of the ways to do it is to decrease the frequency of blood glucose checking once every 4–6 h when infusion rates are stable. With recent allowances by the Food and Drug Administration for use of continuous glucose monitoring (GGM) devices, some hospitals are using these noninvasive remote monitoring devices for tracking of glycemic data. CGM offers a potential way for facilitating care in COVID-19 patients while also decreasing exposure through reduced frequency of testing. Two such devices are Freestyle Libre and Dexcom G6 continuous glucose monitoring devices which are easy to adapt for use in in-patient settings. The downside is it needs extensive training and education of nursing personnel involved in these projects. The accuracy of CGM can be diminished during the conditions of altered tissue perfusion as well as use of certain medications such as dopamine, heparin, or ascorbic acid, which are commonly being used in these patients, and exposure to radiologic procedures including magnetic resonance imaging, computed tomography scanning, or even routine X-rays can potentially damage sensor components again leading to inaccurate glycemic measures.
Several studies using different CGM devices in critical care areas have demonstrated reductions in nurse time at the bedside, with some but not all studies demonstrating reductions in time spent in hypoglycemia but not mean blood glucose., Importantly, they provide with “tends”, leading to earlier recognition of potential hypoglycemic episodes and “time-in-range” measurements, which further aid in clinical care. Until there are studies validating their safety and efficacy in acute care setting, CGM devices should be viewed as a supplement to and not a replacement for point-of-care glucometers.
| Discharge Planning|| |
Diabetes education and training is a key part of comprehensive diabetes care and should remain a part of discharge planning in patients with diabetes hospitalized with COVID-19 infection. Most of the patients with preexisting diabetes have an appropriate knowledge regarding diabetes self-management at home. Newly diagnosed diabetics need to be counseled regarding the diabetes self-management at home. Patients new to insulin have to be trained for self-administration using devices (vials and syringes, pen devices) they will be using at home. A medication sheet should be provided to the patients and their attendants detailing how and when to take their diabetes medications, monitor blood glucose levels, adjust therapy for low or high blood glucose values, and whom to contact in the event of glycemic emergencies. Explanation regarding recognition and management of hypoglycemia, especially in newly diagnosed diabetes discharged on insulin or insulin secretagogues, is imperative. Where possible and if the patient agrees, teleconsultation is a good option for continuing care.
| Conclusions|| |
In noncritically ill patients, therapeutic strategies aiming to control glycemia should consider use of regimens with low risk of hypoglycemia. They may be continued on already existing treatment with close observation to identify clinical deterioration and modification of treatment as necessary. For critically ill patients, insulin infusions are necessary to control the glycemia for improved clinical outcomes. It is important to remember that no algorithm has shown to be superior to other and they need to be adapted according to the current clinical scenario. Utilization of technological advances such as the use of GGM, remote glucose monitoring, and telemedicine reduces the exposure time of the health-care personnel, and although there are some limitations to its use, it should be used wherever feasible. Discharge planning is an important aspect, especially in newly diagnosed diabetes, and explanation regarding hypoglycemia management is essential.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Chen Y, Gong X, Wang L, Guo J. Effects of hypertension, diabetes and coronary heart disease on COVID-19 diseases severity: A systematic review and meta-analysis. medRxiv; 2020.
Xue T, Li Q, Zhang Q, Lin W, Wen J, Li L, et al
. Blood glucose levels in elderly subjects with type 2 diabetes during COVID-19 outbreak: A retrospective study in a single center. medRxiv 2020.03.31.20048579.
Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med 2020;8:e21.
Andersen CJ, Murphy KE, Fernandez ML. Impact of obesity and metabolic syndrome on immunity. Adv Nutr 2016;7:66-75.
Luzi L, Radaelli MG. Influenza and obesity: Its odd relationship and the lessons for COVID-19 pandemic. Acta Diabetol 2020;57:759-64.
Garg S, Kim L, Whitaker M, O'Halloran A, Cummings C, Holstein R, et al
. Hospitalization rates and characteristics of patients hospitalized with laboratory-confirmed coronavirus disease 2019 – COVID-NET, 14 states, March 1-30, 2020. MMWR Morb Mortal Wkly Rep 2020;69:458-64.
Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler LM, Kitabchi AE. Hyperglycemia: An independent marker of in-hospital mortality in patients with undiagnosed diabetes. J Clin Endocrinol Metab 2002;87:978-82.
Klonoff DC, Umpierrez GE. Letter to the Editor: COVID-19 in patients with diabetes: Risk factors that increase morbidity. Metabolism 2020;108:154224.
Hoffmann M, Kleine-Weber H, Schroeder S, Krüger N, Herrler T, Erichsen S, et al
. SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor. Cell 2020;181:271-8.
Bindom SM, Lazartigues E. The sweeter side of ACE2: Physiological evidence for a role in diabetes. Mol Cell Endocrinol 2009;302:193-202.
Roca-Ho H, Riera M, Palau V, Pascual J, Soler MJ. Characterization of ACE and ACE2 Expression within Different Organs of the NOD Mouse. Int J Mol Sci 2017;18:e563.
Raj VS, Mou H, Smits SL, Dekkers DH, Müller MA, Dijkman R, et al
. Dipeptidyl peptidase 4 is a functional receptor for the emerging human coronavirus-EMC. Nature 2013;495:251-4.
Vasa F. Systematic strategies for improved outcomes for the hyperglycemic hospitalized patient with diabetes mellitus. Am J Cardiol 2005;96:41E-46E.
Iacobellis G. COVID-19 and diabetes: Can DPP4 inhibition play a role? Diabetes Res Clin Pract 2020;162:108125.
Pérez-Belmonte LM, Osuna-Sánchez J, Millán-Gómez M, López-Carmona MD, Gómez-Doblas JJ, Cobos-Palacios L, et al
. Glycaemic efficacy and safety of linagliptin for the management of non-cardiac surgery patients with type 2 diabetes in a real-world setting: Lina-Surg study. Ann Med 2019;51:252-61.
Umpierrez GE, Gianchandani R, Smiley D, Jacobs S, Wesorick DH, Newton C, et al
. Safety and efficacy of sitagliptin therapy for the inpatient management of general medicine and surgery patients with type 2 diabetes: A pilot, randomized, controlled study. Diabetes Care 2013;36:3430-5.
Pasquel FJ, Gianchandani R, Rubin DJ, Dungan KM, Anzola I, Gomez PC, et al
. Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): A multicentre, prospective, open-label, non-inferiority randomised trial. Lancet Diabetes Endocrinol 2017;5:125-33.
Scirica BM, Bhatt DL, Braunwald E, Steg PG, Davidson J, Hirshberg B, et al
. Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus. N Engl J Med 2013;369:1317-26.
Toh S, Hampp C, Reichman ME, Graham DJ, Balakrishnan S, Pucino F, et al
. Risk for hospitalized heart failure among new users of saxagliptin, sitagliptin, and other antihyperglycemic drugs: A retrospective cohort study. Ann Intern Med 2016;164:705-14.
Bornstein SR, Rubino F, Khunti K, Mingrone G, Hopkins D, Birkenfeld AL, et al
. Practical recommendations for the management of diabetes in patients with COVID-19. Lancet Diabetes Endocrinol 2020;8:546-50.
Fleming N, Hamblin PS, Story D, Ekinci EI. Evolving evidence of diabetic ketoacidosis in patients taking sodium-glucose cotransporter 2 inhibitors. J Clin Endocrinol Metab 2020;105:dgaa200.
Koufakis T, Mustafa OG, Ajjan RA, Garcia-Moll X, Zebekakis P, Dimitriadis D, et al
. The use of sodium-glucose co-transporter 2 inhibitors in the inpatient setting: Is the risk worth taking? [published online ahead of print, 2020 Jan 6]. J Clin Pharm Ther 2020;10.1111/jcpt.13107.
Deusenberry CM, Coley KC, Korytkowski MT, Donihi AC. Hypoglycemia in hospitalized patients treated with sulfonylureas. Pharmacotherapy 2012;32:613-7.
Flory JH, Hennessy S, Bailey CJ, Inzucchi SE. Reports of Lactic Acidosis Attributed to Metformin, 2015-2018. Diabetes Care 2020;43:244-6.
Lee SJ, Ha KH, Lee JH, Lee H, Kim DJ, Kim HC. Second-line glucose-lowering drugs added to metformin and the risk of hospitalization for heart failure: A nationwide cohort study. PLoS One 2019;14:e0211959.
Eastman DK, Bottenberg MM, Hegge KA, Ourth H, Kabadi U. Intensive insulin therapy in critical care settings. Curr Clin Pharmacol 2009;4:71-7.
Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, et al
. Management of hyperglycemia in hospitalized patients in non-critical care setting: An endocrine society clinical practice guideline. J Clin Endocrinol Metab 2012;97:16-38.
Firestone RL, Parker PL, Pandya KA, Wilson MD, Duby JJ. Moderate-intensity insulin therapy is associated with reduced length of stay in critically ill patients with diabetic ketoacidosis and hyperosmolar hyperglycemic state. Crit Care Med 2019;47:700-5.
Pérez A, Ramos A, Carreras G. Insulin therapy in hospitalized patients. Am J Ther 2020;27:e71-8.
Finucane FM, Davenport C. Coronavirus and obesity: Could insulin resistance mediate the severity of COVID-19 infection? Front Public Health 2020;8:184.
Gupta R, Misra A. Contentious issues and evolving concepts in the clinical presentation and management of patients with COVID-19 infectionwith reference to use of therapeutic and other drugs used in Co-morbid diseases (Hypertension, diabetes etc). Diabetes Metab Syndr 2020;14:251-4.
Zhou J, Tan J. Diabetes patients with COVID-19 need better blood glucose management in Wuhan, China. Metabolism 2020;107:154216.
Hill MA, Mantzoros C, Sowers JR. Commentary: COVID-19 in patients with diabetes. Metabolism 2020;107:154217.
Klonoff DC, Parkes JL, Kovatchev BP, Kerr D, Bevier WC, Brazg RL, et al
. Investigation of the Accuracy of 18 Marketed Blood Glucose Monitors. Diabetes Care 2018;41:1681-8.
Wallia A, Umpierrez GE, Rushakoff RJ, Klonoff DC, Rubin DJ, Hill Golden S, et al
. Consensus statement on inpatient use of continuous glucose monitoring. J Diabetes Sci Technol 2017;11:1036-44.
Spanakis EK, Levitt DL, Siddiqui T, Singh LG, Pinault L, Sorkin J, et al
. The effect of continuous glucose monitoring in preventing inpatient hypoglycemia in general wards: The glucose telemetry system. J Diabetes Sci Technol 2018;12:20-5.
Leelarathna L, English SW, Thabit H, Caldwell K, Allen JM, Kumareswaran K, et al
. Accuracy of subcutaneous continuous glucose monitoring in critically ill adults: Improved sensor performance with enhanced calibrations. Diabetes Technol Ther 2014;16:97-101.
Brunner R, Kitzberger R, Miehsler W, Herkner H, Madl C, Holzinger U. Accuracy and reliability of a subcutaneous continuous glucose-monitoring system in critically ill patients. Crit Care Med 2011;39:659-64.
Donihi AC. Practical recommendations for transitioning patients with type 2 diabetes from hospital to home. Curr Diab Rep 2017;17:52.
Ghosh A, Gupta R, Misra A. Telemedicine for diabetes care in India during COVID19 pandemic and national lockdown period: Guidelines for physicians. Diabetes Metab Syndr 2020;14:273-6.
[Table 1], [Table 2]