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 Table of Contents  
REVIEW ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 2  |  Page : 58-64

Management of diabetes in patients with coronavirus disease 2019: A practical approach


Department of Medicine, Hamad Medical Corporation; Department of Medicine, Weill Cornell Medical College, Doha, Qatar

Date of Submission27-Apr-2020
Date of Acceptance30-Apr-2020
Date of Web Publication22-May-2020

Correspondence Address:
Dr. Mohsen S Eledrisi
Department of Medicine, Hamad Medical Corporation, P. O. Box 3050, Doha
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/LJMS.LJMS_34_20

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  Abstract 


Coronavirus disease 2019 (COVID-19) has emerged as a rapidly transmissible communicable disease around the globe. Diabetes is reported as a common morbidity in patients with COVID-19, has been associated with worse clinical outcomes, and may lead to higher mortality. Because the disease has variable presentations varying from mild respiratory symptoms to pneumonia and respiratory failure, proper care of patients with diabetes in this context should cover both outpatient and inpatient sectors. Outpatient management in acutely ill patients includes frequent home glucose monitoring; holding certain medications including metformin, sodium glucose co-transporter 2 inhibitors, and glucagon-like peptide-1 receptor agonists that may cause unwanted side effects such as dehydration and resulting acute kidney injury; continuation and adjustment of insulin therapy; and patient education on indications to seek medical assistance. Inpatient glucose management of patients admitted with COVID-19 involves holding noninsulin medications, monitoring blood glucose, and starting insulin if glucose levels are not in target. Intravenous insulin is recommended for critically ill patients with uncontrolled glucose. Universal measures should include assurance of continuity of care, adherence to therapy, and self-management education using connected health models and telemedicine. Patients with diabetes are considered a vulnerable group during periods of epidemics, and clear recommendations and pathways are essential to assure patients' safety.

Keywords: Coronavirus disease 2019, diabetes, glucose management


How to cite this article:
Eledrisi MS, Elzouki AN. Management of diabetes in patients with coronavirus disease 2019: A practical approach. Libyan J Med Sci 2020;4:58-64

How to cite this URL:
Eledrisi MS, Elzouki AN. Management of diabetes in patients with coronavirus disease 2019: A practical approach. Libyan J Med Sci [serial online] 2020 [cited 2020 Sep 18];4:58-64. Available from: http://www.ljmsonline.com/text.asp?2020/4/2/58/284687




  Introduction Top


The World Health Organization declared coronavirus disease 2019 (COVID-19), a disease caused by the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), a public health emergency of international concern, and on March 11, 2020, the epidemic was upgraded to a pandemic. The disease has arisen as a rapidly spreading communicable disease affecting more than 200 countries across the globe. The disease severity has varied from mild upper respiratory tract symptoms to pneumonia, respiratory failure, and death. Prior studies with respiratory tract infection outbreaks including Severe acute respiratory syndrome-related coronavirus (SARS-CoV), influenza A virus type H1N1, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) revealed that the presence of diabetes is associated with worse clinical outcomes and confers high mortality rates.[1],[2],[3],[4] COVID-19 is distinguished from those viral respiratory infections by its high rates of transmissibility and global spread. This puts a high number of patients with diabetes at risk for acquiring the infection. In addition, the current regulations in many countries involving lockdown and quarantine measures may impose real challenges to patients' health including interruption of continuity of medical care and medication supply, change in daily lifestyle habits, and adverse psychological consequences, resulting in the deterioration of glucose control and higher risk of diabetes complications.

Individuals with diabetes carry a higher risk of infections, especially bacterial and viral lower respiratory tract infections and urinary tract infections as well as infection-related mortality.[5],[6],[7],[8] The presence of uncontrolled glucose in patients with diabetes is associated with adverse infection-related outcomes. Hyperglycemia in hospitalized patients leads to increased rates of infection, higher mortality, longer hospital length of stay, and higher health-care resource utilization.[9],[10],[11],[12] There is some evidence suggesting that glucose control may reduce the risk of infections, particularly in hospitalized patients.[13],[14],[15],[16] In this article, we review the available epidemiological data on patients with diabetes infected with COVID-19 and discuss management issues pertinent to glucose control and preventive strategies to assure patient safety during and after the pandemic.


  Epidemiological Data on Diabetes in Patients With Coronavirus Disease 2019 Top


There is no conclusive evidence, so far, that patients with diabetes are at higher risk for acquiring COVID-19. Available data demonstrate that diabetes confers a higher risk for the severity of the disease and possibly higher mortality rates. The overall proportions of diabetes in patients with COVID-19 were 2%–20% in China[17],[18],[19],[20],[21],[22],[23],[24],[25],[26] and 8.9%–35.5% in Italy.[27],[28],[29],[30] The percentage of patients with diabetes was 22.2% in those who required admission to the intensive care unit (ICU) compared to only 5.9% in those who did not require ICU care.[17] In a large nationwide cohort of patients with COVID-19 in China, the overall percentage of diabetes was 7.4%; patients with diabetes formed 16.2% of severe cases and 27% of patients met the criteria of a primary outcome of admission to the ICU, use of mechanical ventilation, or death.[22] A study of patients with COVID-19 who were admitted to the ICU found that diabetes was a concurrent medical condition in 17% of patients and that 22% of patients who did not survive had diabetes.[24] A meta-analysis showed that the presence of diabetes was associated with a twofold increase in the risk of severe disease or requirement of admission to the ICU.[25]

Diabetes appears to also confer a high risk of mortality in patients with COVID-19 in some studies,[22],[24] but not others.[26],[31] An analysis of a sample of 355 patients with COVID-19 who died in Italy revealed that almost all patients (99.2%) had at least one comorbid chronic condition.[28] Diabetes was the most common chronic condition constituting 35.5% of this cohort of patients. Other comorbid conditions included ischemic heart disease, active cancer, atrial fibrillation, stroke, and dementia. It was suggested that the presence of these comorbid conditions might have increased the risk of mortality independent of COVID-19 infection.

Data on glucose control in patients with diabetes who are infected with COVID-19 are very limited. A retrospective study from China evaluated glucose control in 29 patients with known Type 2 diabetes who were admitted with COVID-19 to a designated isolation medical facility.[32] Using the definition of adequate glucose control as preprandial capillary glucose values of <7.8 mmol/L and postprandial glucose values of <10 mmol/L, the investigators reported that out of a total of 881 capillary glucose tests, 56.6% showed abnormal levels, including 29.4% of the preprandial values and 64.5% of the postprandial tests. They also reported that 10.3% of the patients suffered at least one episode of hypoglycemia (defined as <3.9 mmol/L). The study did not report details on patients' medical conditions and outcomes.


  Management of Glucose during Coronavirus Disease 2019 Illness Top


Patients with diabetes may develop the following abnormalities during acute illness: significant hyperglycemia, diabetic ketoacidosis due to inadequate insulin supplementation, hypoglycemia, or ketosis independent of hyperglycemia.

Hyperglycemia is common among patients with diabetes during acute illness or hospitalization. This has been attributed to increases in circulating concentrations of counterregulatory stress hormones such as cortisol, epinephrine, glucagon, and growth hormone.[33] In addition, cytokines, as mediators of the systemic inflammatory response, may have hyperglycemic effects through the stimulation of counterregulatory hormone secretion. During illness, patients with diabetes may show greater glucose response to counterregulatory hormones and may not sufficiently increase insulin secretion as a compensatory response due to the underlying insulin resistance and impaired insulin secretion.[33] Other factors that contribute to hyperglycemia during acute illness include decreased level of activity, glucocorticoid therapy, continuous enteral nutrition, and parenteral nutrition.[34] Hyperglycemia has been shown to have harmful effects on the vascular, hemodynamic, and immune systems. Neutrophil chemotaxis, phagocytosis, intracellular bactericidal activity, and cell-mediated immunity are impaired during hyperglycemia in patients with diabetes.[35],[36] Several studies have shown that hyperglycemia is associated with poor outcomes in hospitalized patients, particularly higher rates of infections, adverse medical outcomes, prolonged hospital length of stay, and increased mortality.[10],[11],[12],[37],[38],[39],[40] Associations between high glucose levels and the risk of death remain significant even after adjusting for the severity of illness.[40] On the other hand, hypoglycemia can occur due to reduced oral intake of carbohydrates because of decreased appetite, nausea, or vomiting, resulting in decreased insulin requirements. Hypoglycemia in the hospital due to diabetes treatment or nondiabetes causes is associated with increased mortality.[41],[42] Hypoglycemia is viewed as a severe consequence of abnormal metabolism and/or diabetes treatment and can be an indicator for the severity of the underlying disease rather than the cause of mortality.[43]

Diabetic ketoacidosis can occur due to intercurrent illness in patients with Type 1 diabetes as well as those with Type 2 diabetes due to significant hyperglycemia and the failure to use appropriate doses of supplemental insulin.[44] Sodium glucose co-transport-2 (SGLT2) inhibitors, a class of medications prescribed for Type 2 diabetes and recently for Type 1 diabetes, are associated with increased risk of diabetic ketoacidosis, particularly during periods of acute illness.[45]

Outpatient management of glucose in patients with coronavirus disease 2019

Patients with diabetes who get infected with COVID-19 and have mild symptoms may not need admission to the hospital and are generally managed at home or at a quarantine facility. These patients should be aware of the possibility of developing disturbances of blood glucose levels because of the illness. Frequent monitoring of home glucose (every 2–4 h) helps to detect abnormal glucose values (hyperglycemia or hypoglycemia) and make decisions regarding the management and the need to contact the medical team. Patients should be advised to keep enough supply of their medications including noninsulin drugs and insulin and its necessary supplies, blood glucose meter materials (strips and lancets), and, if advised by the physician, ketone testing materials (urine or blood). If there is significant illness resulting in decreased oral intake or vomiting, patients are advised to drink fluids (such as water or sugar-free drinks) at least 100 ml every hour, to consume carbohydrate meals to prevent hypoglycemia and ketosis, and to consider stopping the following medications after consulting their physicians: metformin, SGLT2 inhibitors, and glucagon-like peptide-1 receptor agonists.[46] If the patient does not have access to blood glucose monitoring, education should be provided about the symptoms of hyperglycemia such as polyuria, polydipsia, and tiredness, and immediate medical care should be sought if any of these symptoms develops. Patients who are on insulin regimens should continue the basal (long or intermediate acting) component and if blood glucose is persistently high, the dose can be increased by 10%–20% while the meal (rapid or short acting) insulin is adjusted according to home blood glucose values as per a corrective insulin algorithm as advised by the treating physician. If there is hypoglycemia, basal insulin doses should be reduced by 20%.

Patients with Type 1 diabetes should check their ketones (blood or urine) along with monitoring of blood glucose every 2–4 h. Basal insulin should be continued while the change in the dose of meal insulin is calculated depending on the clinical condition, blood glucose levels, amount of ketones, and patient's corrective insulin algorithm.[47],[48] If the high glucose is associated with negative or trace ketones on urine testing or <1.5 mmol/L on blood testing, it is recommended to give 10% of the usual total daily insulin dose as rapid or short-acting insulin. If the amount of ketones is moderate or large on urine testing or >3 mmol/L on blood testing, it is recommended to give 20% of the usual total daily insulin dose as rapid or short-acting insulin. Additional doses of supplemental meal insulin can be given according to the corrective insulin algorithm advised by the treating physician. Patients should seek medical assistance if the blood glucose remains persistently elevated (>13 mmol/L); if ketones continue to be present after 4–6 h; if they are unable to keep oral feeding; or if any acute symptoms such as dyspnea, chest pain, high fever, or persistent vomiting develops. [Table 1] provides a summary on sick day rules during acute illness at outpatient setting for patients with diabetes infected with COVID-19.
Table 1: Sick day rules for acutely ill patients with diabetes infected with coronavirus disease 2019

Click here to view


Inpatient management of glucose in patients with coronavirus disease 2019

Patients with diabetes are frequently admitted to the hospital, usually for the treatment of conditions other than the diabetes. It was found that 30% of patients with Type 2 diabetes and 25% with Type 1 diabetes required a hospital admission during 1 year and that patients with uncontrolled glucose were at the highest risk for admission.[49] The main goal of glucose management in patients with diabetes in the hospital is to maintain adequate glucose control so that the extremes of glucose disturbances – hyperglycemia and hypoglycemia – can be prevented. Other objectives include maintaining adequate nutrition, assessment and addressing patient educational needs, and ensuring appropriate discharge plans. Inpatient glucose control is challenged by hyperglycemia induced by the acute illness and the risk of hypoglycemia aggravated by glucose-lowering medications, decreased appetite, and change in diet during hospitalization. Evaluation of glucose control should be part of the routine assessment of patients with diabetes upon admission to the hospital. This includes recent levels of hemoglobin A1c and home blood glucose levels. Capillary blood glucose should be monitored on admission and during the hospitalization period. The frequency of monitoring is decided by the patient's clinical status, initial glucose values, and type of diabetes therapy. In general, capillary glucose is measured initially before meals in patients who are eating and every 6 h in patients who are kept on no oral feeding.[43] The frequency of glucose monitoring can be increased in patients who have significantly high glucose values particularly if they are on subcutaneous insulin, patients on intravenous insulin, and if a change in the clinical condition warrants further glucose testing. On the other hand, the frequency of glucose monitoring can be decreased in patients who are not on insulin and have glucose levels at target. A target blood glucose range of 7.8–10 mmol/L is recommended for the majority of noncritically ill patients, while more tighter goal, such as 6.1–7.8 mmol/L, may be appropriate for selected patients such as those who are clinically stable, not elderly, do not have multiple comorbidities, or not at high risk for significant hypoglycemia. The glucose target for critically ill patients is 7.8–10 mmol/L.[43] On the other side, the goal should be set at higher levels for dependent elderly patients and those with severe comorbidities or advanced diabetes complications where the potential risk of hypoglycemia may outweigh any potential benefit; in such patients, glucose targets can relaxed up to 12 mmol/L.

The choice of the type of glucose-lowering agents in patients with Type 2 diabetes during hospitalization depends on the previous type of treatment and glucose control before hospitalization as well as blood glucose levels during the hospital stay. Insulin remains the preferred agent for use during hospitalization for patients previously treated with noninsulin agents. Some clinicians recommend continuing oral glucose-lowering agents in patients who had previous adequate glucose control, have stable medical condition, and are taking oral meals. For patients who had adequate glucose control on noninsulin agents before hospitalization, glucose levels should be monitored during hospitalization after stopping the prior diabetes therapy. The routine use of sliding scale insulin with no background basal insulin is not recommended and has resulted in higher rates of hyperglycemia.[43],[50] If glucose control was adequate before hospitalization or is not known and admission glucose values are reasonable, it may be acceptable to implement a sliding scale for 1 or 2 days until the overall glucose control in the hospital becomes clear. If glucose levels are persistently above 10 mmol/L, insulin should be started. The initial insulin regimen should consist of a basal insulin (long-acting such as glargine, detemir, or degludec once daily or intermediate acting as Neutral Protamine Hagedorn (NPH) twice daily) at a starting dose of 0.1 units per kilogram body weight. In addition, supplemental insulin is given as meal insulin (short acting as regular or rapid acting as aspart, glulisine, or lispro) based on an algorithm that initiates treatment with if glucose level is more than 10 mmol/L. The dose of supplemental insulin depends on previous insulin doses, calculated insulin requirement, and suspected patient's sensitive to insulin. If glucose values remain above target on this basal plus supplemental insulin regimen, particularly if patients are on regular meals, scheduled meal insulin should be added before meals at a frequency of one, two, or three times daily depending on glucose levels.

Insulin should be continued in patients who were on insulin regimens before hospital admission. Basal insulin is continued while meal insulin is held initially if patients are not eating. The recommended insulin doses depend on glucose control prior to hospitalization. If glucose control was acceptable before hospital admission, insulin doses are usually reduced by 25% while patients are in the hospital. If glucose was not adequately controlled before hospitalization, insulin doses can be continued at the same doses with plans to make adjustment according to glucose values in the hospital. Consideration should be given to patients who have uncontrolled glucose on premixed or only basal insulin to change their regimen to basal + meal insulin. For critically ill patients with uncontrolled glucose of >10 mmol/L, an intravenous insulin infusion is recommended to achieve a target glucose of 7.8–10 mmol/L[43],[50] along with more frequent monitoring of blood glucose (every 1 to 2 h initially and then every 4 h once glucose values are stable).

Other considerations in patients admitted with COVID-19 include the use of some medications that can affect glucose control. Glucocorticoids, which are known to induce hyperglycemia, have been frequently used in patients with COVID-19 who are severely ill and those admitted to ICUs. On the other hand, hydroxychloroquine, which can cause hypoglycemia, is commonly used by many medical centers for hospitalized patients with COVID-19. Therefore, patients who are prescribed these medications should be closely monitored for glucose disturbances along with implementation of proper management plans. At the time of hospital discharge, patients should have clear plans that include appropriate diabetes management depending on the overall assessment of glucose control, patient education, and proper transition to the outpatient care. [Figure 1] summarizes glucose management of patients with diabetes admitted with COVID-19.
Figure 1: Inpatient glucose management of patients with diabetes and COVID-19

Click here to view



  Special Considerations for Diabetes Care during the Coronavirus Disease 2019 Pandemic Top


Many countries have recommended social distancing and lockdown for the general population in an attempt to reduce the spread of the virus. This can adversely affect people with diabetes in many ways. Refills of diabetes medications and medications for other chronic conditions that are common in patients with diabetes such as hypertension, cardiovascular disease, and dyslipidemia; insulin supplies; and blood glucose testing supplies can be interrupted during this unusual situation. Quarantine and lockdown measures are commonly associated with reduced physical activity and change in food supply and type which can affect glucose control. Loss of access to direct outpatient care including patient care and education will interrupt usual diabetes care measures and prohibit patients from receiving proper self-management education, particularly on sick day management because access to helplines (by phone, E-mail) and telemedicine services may not be available in all areas during the pandemic. Many patients will be facing the uncertainties of handling emerging issues such as changes in glucose control and blood pressure levels; development of issues related to diabetes such as foot care, eye care, pregnancy, and sick day management if they get infected with COVID-19; or any other acute illness. It is important to also consider psychological factors related to the current pandemic. Patients with diabetes are at increased risk for mental disorders, particularly anxiety and depression.[51] Adherence to medical management can be affected by psychological factors and can worsen during and after periods of disasters.[52],[53] All the above-mentioned factors can result in worsening of glucose control with increased risk of diabetes complications during periods of unusual situations such as natural disasters and war conflicts[54],[55],[56] and should be considered during the current COVID-19 pandemic.

In this context, a clinical guide was issued jointly by authorities in the United Kingdom including the Royal College of Physicians, Association of British Clinical Diabetologists, and National Health System for the management of people with diabetes during the COVID-19 pandemic.[57] The guide outlines considerations for the best local solutions to continue the proper management of people with diabetes while protecting resources for the response to CoV. It notes that currently 18% of hospital beds in the United Kingdom are occupied by patients with diabetes, who are more likely to have severe manifestations of COVID-19; it is projected that the percentage is likely to increase, so inpatient diabetes services will need to continue and potentially increase capacity. For secondary care, the guide recommends remote contact (through phones, E-mails, or virtual technology) as much as possible for routine care of patients with Type 2 as well as those with Type 1 diabetes. At the same time, assessment of individual risk factors and clinical needs are required to help decide which patients may require physical attendance for proper clinical care. The guide suggests that multidisciplinary team diabetes foot services, selected pregnancy and diabetes services, and helplines for acute diabetes-related problems may need to continue at full capacity. For primary care, the recommendation is to consider routine diabetes care delivered remotely in the context of broader long-term condition management and prioritization, taking into account individual risk factors and clinical needs.


  Conclusion Top


Diabetes is a risk factor for worse clinical outcomes in patients with COVID-19. It remains to be confirmed whether diabetes is associated with higher mortality in this disease. Management of diabetes depends on the clinical condition of infected patients. For those with mild symptoms who do not require hospital care, it is imperative to follow sick day rules for the management of glucose including frequent blood glucose testing, holding certain noninsulin diabetes medications, using supplemental insulin if needed, and appreciate the proper time to seek medical assistance. Inpatient management follows the same recommendations as other acute medical conditions. Clear recommendations on proper and regular follow-up either remotely or face to face if needed for patients with diabetes during the COVID-19 pandemic are essential to assure continuity of care and patient safety.

Financial support and sponsorship

Nil.

Conflicts of interest

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