COVID-19: ISSUES RELATED TO DIABETES MELLITUS IN ADULTS
Deborah J Wexler, MD, MSc, Irl B Hirsch,
MD, Jean E Mulder, MD
Wolters Kluwer Health, Uptodate
Literature review current through: May 2021
This topic last updated: Feb 18, 2021
The care of patients with endocrine disorders during the coronavirus disease 2019 (COVID-19) pandemic poses unique challenges. Patients with diabetes are at risk for more severe illness. COVID-19 appears to precipitate severe manifestations of diabetes, including diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and severe insulin resistance.
This topic will review the care of patients with diabetes during the COVID-19 pandemic. Other important aspects of COVID-19 care are discussed separately.
RISK OF SERVE COVID-19
Severe illness, manifested as the need for hospitalization, intubation, and death, can occur in otherwise healthy individuals of any age, but the risk of severe illness is most pronounced in adults with advanced age or underlying medical comorbidities, including diabetes [1,2].
Patients with type 2 diabetes are more likely to have serious complications, more intensive care unit (ICU) admissions, longer length of stay, and death from COVID-19 [2-7].
- In China, the case fatality rate was 7.3 percent among patients with diabetes (most likely type 2 diabetes) whereas the overall case fatality rate was 2.3 percent .
- In a retrospective study from the United States, the mortality rate was 14.8 percent among patients with diabetes and 28.8 percent in patients with diabetes or uncontrolled hyperglycemia, compared with 6.2 percent without either .
- In a report of a population cohort study from the United Kingdom, the crude mortality rate for patients with type 2 diabetes was 260 per 100,000 persons compared with 27 per 100,000 persons in the overall population without diabetes (adjusted [for age, sex, socioeconomic factors, other comorbidities] odds ratio [OR] 1.80, 95% CI 1.75-1.86) .
There are few data evaluating the risk of severe illness and death in patients with type 1 diabetes. In the population cohort study from the United Kingdom, patients with type 1 diabetes also had an increased risk of in- hospital mortality compared with the general population without known diabetes (crude rate 138 versus 27 per 100,000 persons, adjusted OR 2.86, 95% CI 2.58-3.18) . The United Kingdom study did not report data on people with type 1 diabetes age 49 or younger due to privacy concerns related to small sample size. Therefore, there are limited data in this population, although, if infected, they are likely to have a more prolonged course than similarly healthy people without type 1 diabetes, as is seen in other infections .
Age, obesity, and additional comorbidities are strong correlates of severe disease in diabetes in observational analyses, but the relationship among these risk factors is complex . Both diabetes and obesity appear to be independent risk factors for severe disease, but depending on the population studied and the outcome, one may appear to be stronger than the other. For example, diabetes is positively associated with age, which is a strong predictor of death from COVID-19. Obesity is inversely associated with age, which may reduce its strength as a risk factor for mortality. Nevertheless, obesity, with its proinflammatory state and altered respiratory mechanics, is a strong risk factor for hospital admission, ICU admission, and respiratory failure [11-13].
Role of hyperglycemia — The role of hyperglycemia in the risk of severe infection in patients with diabetes has not been well studied. Poorly controlled diabetes is a risk factor for infection in general. Since COVID-19 can trigger an intense inflammatory response, it has been challenging to disentangle whether hyperglycemia in COVID-19 is a cause, or, as appears more likely, a consequence of severe disease. There are few data evaluating the impact of glycemic control prior to COVID-19 infection on the risk of severe infection. An analysis of national diabetes and mortality data from the United Kingdom before and during the pandemic (over 10,000 COVID-19-related deaths in people with diabetes [predominantly type 2]) showed an association between preceding hyperglycemia and mortality, as illustrated by the following :
- Type 2 diabetes – Mortality risk was higher with glycated hemoglobin (A1C) 7.6 to 8.9 percent (59 to 74 mmol/mol) compared with 6.5 to 7 percent (48 to 53 mmol/mol; hazard ratio [HR] 1.22 [95% CI 1.15-1.30]) and increased as A1C levels rose.
- Type 1 diabetes – Mortality risk was significantly higher with A1C >10 percent (86 mmol/mol) compared with 6.5 to 7 percent (48 to 53 mmol/mol, HR 2.23 [95% CI 50-3.30]).
Elevated body mass index (BMI) was also associated with increased COVID-19 mortality (eg, for BMI 35 to 39.9 kg/m2 compared with 25 to 29.9 kg/m2, HRs 1.72 [95% CI 1.21-2.46] and 1.17 [95% CI 1.08-1.26] for type 1 and type 2 diabetes, respectively).
In a small observational study from France, 1317 patients with diabetes hospitalized with COVID-19, pre-admission A1C was not significantly associated with poor prognosis (mechanical ventilation and/or death within seven days of admission) .
Factors, other than obesity, older age, and associated comorbidities, such as differential expression of angiotensin-converting enzyme (ACE) receptors or other molecular mechanisms, may play a stronger role in COVID-19 outcomes among patients with diabetes .
COVID-19 infection appears to precipitate severe metabolic manifestations of diabetes, including diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and severe insulin resistance , usually in the setting of a severe inflammatory response to the virus in which other inflammatory markers such as interleukin 6 (IL-6) are markedly elevated. Patients may or may not have a history of diabetes . In a systematic review of 19 reports (110 patients with DKA or HHS), 77 percent of patients had pre-existing diabetes .
Sodium-glucose co-transporter 2 (SGLT2) inhibitors can increase the risk of DKA and should be discontinued in ill or hospitalized patients. Glucose levels may be only modestly elevated in patients with SGLT2 inhibitor- associated DKA.
The insulin requirements in patients with COVID-19 and severe insulin resistance are much higher than those generally reported in studies of critically ill patients 
Less severe presentations of newly diagnosed diabetes have also been reported. In a systematic review of eight retrospective cohort studies (3700 patients with severe COVID-19), diabetes was newly diagnosed in 0.6 to 62 percent . Newly diagnosed hyperglycemia may be due to critical illness per se, or there may be direct beta cell injury from SARS-CoV-2 or from the inflammatory response to the virus .
APPROACH TO MANAGEMENT
Outpatient management — In the presence of COVID-19 infection, sick-day management is directed towards preventing hypoglycemia, significant hyperglycemia, and diabetic ketoacidosis (DKA).
- Type 2 diabetes – In the ambulatory setting, patients with type 2 diabetes and COVID-19 may be able to continue their usual diabetes treatment, based on symptoms and, particularly, if they are able to eat (close to their usual diet) and maintain hydration. Blood glucose should be monitored frequently, at least twice daily, and more frequently if needed, particularly for those requiring insulin therapy. Oral and injectable medications may require adjustment based on glucose trends, diet, and symptoms.
- Sulfonylureas or meglitinides – Oral agents that can cause hypoglycemia (eg, sulfonylureas, meglitinides) are not typically administered to patients who are not eating. However, if a patient is experiencing marked hyperglycemia (eg, >200 mg/dL [11.1 mmol/L]), sulfonylureas and meglitinides may be continued, highlighting the important role of self-monitoring of blood
- SGLT2 inhibitors – Sodium-glucose co- transporter 2 (SGLT2) inhibitors (eg, dapagliflozin, canagliflozin, empagliflozin, ertugliflozin) should have a low threshold to be discontinued in patients with COVID-19 who are unable to eat and maintain hydration. SGLT2 inhibitors promote the renal excretion of glucose. They increase calorie losses, risk of dehydration and volume contraction, and genitourinary tract infections. In addition, euglycemic DKA has been reported in patients with both type 1 (during off-label use) and type 2 diabetes who were taking SGLT2 inhibitors. In patients with very mild illness who are maintaining normal diet and fluid intake, SGLT2 inhibitors may be continued.
- DPP-4 inhibitors – Dipeptidyl peptidase 4 (DPP-4) inhibitors should not be used as protection against COVID-19 complications, nor should they be discontinued, excluding known reasons for discontinuation, in those recently contracting COVID-19 DPP-4 has been implicated in the pathogenesis of coronavirus infections, including SARS-CoV-2. The relationship between use of DPP-4 inhibitors and risk of SARS-CoV-2 infection as well as COVID-19 outcomes has been described in population- based observational studies [21,22]. The use of DPP-4 inhibitors was not associated with increased risk of COVID-19 infection or complications in a number of large population trials [21-23]. Some observational studies suggest protective effects with the use of DPP- 4 inhibitors following COVID-19 infection [24,25]. No randomized controlled trials comparing the use of DPP-4 inhibitors with other diabetes drugs on the impact of COVID- 19 infection have been conducted. One major challenge for all such studies is risk of allocation bias, in which older patients or patients with chronic kidney disease (CKD) may be more likely to be prescribed a DPP-4 inhibitor than other glucose-lowering medications. Since these factors may also be associated with COVID-19 outcomes, it can be difficult to eliminate this bias, even with advanced propensity score matching methods.
- GLP-1 receptor agonists – Patients experiencing nausea and diarrhea should withhold glucagon-like peptide 1 (GLP-1) receptor agonists (and possibly metformin).
- For patients who are unable to take their usual diabetes treatment, or if glucose levels remain elevated (>180 to 200 mg/dL [>10 to 11.1 mmol/L]) with usual treatment, once-daily intermediate or long-acting insulin can be initiated.
- All patients should maintain hydration by drinking 8 ounces (approximately 250 mL) of carbohydrate-free fluids (eg, water, broth) every one to two hours, as needed, to match urinary and insensible
- Type 1 diabetes – Patients should always continue basal insulin, even if they are not eating regularly, and perform frequent blood glucose and ketone (urinary/blood) monitoring, particularly with fever and erratic oral
- Continuous glucose monitoring (CGM) or fingerstick capillary glucoses can be checked every two to four hours depending on severity of Of note, medications containing acetaminophen or high-dose vitamin C may cause falsely elevated CGM results with some older CGM devices. This is a dose- dependent effect that results from oxidation of acetaminophen at the CGM electrode.
- If hyperglycemia develops (blood glucose >240 mg/dL [13.4 mmol/L]), advise patients to check urinary or capillary ketones (home testing of blood for beta- hydroxybutyrate is available, but it is used infrequently in adults, at least in the United States).
- The insulin dose is adjusted as needed, based on the measurements of blood glucose and blood or urinary ketones. Insulin requirements may be either increased or decreased during an
- If moderate or large ketones, vomiting, or other symptoms of DKA develop, give supplemental doses of rapid-acting (lispro, aspart, or glulisine) insulin (see ‘DKA/HHS’ below). For insulin pump users, it is usually wise to change the infusion set and site because failure of pump or infusion set is a very common cause of hyperglycemia and ketosis/ketoacidosis in pump
- Advise patients to hydrate by drinking 8 ounces (approximately 250 mL) of carbohydrate-free fluids (eg, water, broth) every For patients with nausea/vomiting or otherwise unable to eat, advise drinking something with carbohydrates (eg, sports drinks, diluted apple juice, clear soda) every four hours.
- If blood ketones remain elevated (>1.5 mmol/L) or urine ketones remain “large” despite extra insulin and hydration, or the patient has ongoing nausea or vomiting and is unable to maintain hydration, the patient should seek urgent medical
Hospitalized patients — For patients with COVID-19 who have laboratory results suggestive of metabolic acidosis on initial laboratory evaluation, we check serum ketones to assess for DKA. The diagnostic criteria proposed by the American Diabetes Association (ADA) for mild, moderate, and severe DKA and hyperosmolar hyperglycemic state (HHS) are shown in the table (table 1). (See ‘DKA/HHS’ below.)
Glycemic targets — In general, the goals of treatment are the same as in other hospitalized patients (eg, avoid severe hyperglycemia, volume depletion, and electrolyte abnormalities; avoid hypoglycemia; ensure adequate nutrition). A blood glucose target of 140 to 180 mg/dL (7.8 to 10 mmol/L) is reasonable for most hospitalized patients. Many patients have severe insulin resistance and require high doses of insulin to achieve these goals.
There are no interventional studies to inform appropriate glycemic targets in patients with COVID-19.
Managing diabetes medications for patients with type 2 diabetes — In the setting of hospitalization for acute illness, oral and non-insulin injectable diabetes agents (ie, GLP- 1 receptor agonists) are often either contraindicated or not well tolerated. Therefore, home diabetes medications are usually discontinued.
- SGLT2 inhibitors should be discontinued due to increased risk of dehydration and volume contraction.
- Metformin is contraindicated in situations in which renal function and/or hemodynamic status is either impaired or threatened, due to the small but increased risk of lactic acidosis, and therefore should be discontinued at least temporarily until the clinical course is more certain.
- GLP-1 receptor agonists often cause nausea and are avoided in the acute care Of note, patients who use long-acting GLP-1 receptor agonists (eg, dulaglutide, semaglutide) may have this medication in their system for the week following the last dose administration .
Hyperglycemia without DKA/HHS – Insulin is the preferred treatment for hyperglycemia in patients hospitalized with moderate to severe COVID-19, even if they do not have diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS). For patients with type 2 diabetes, the need for insulin therapy may be temporary. Patients with type 1 diabetes have an absolute requirement for insulin at all times, whether or not they are eating, to prevent ketosis.
The management of diabetes in hospitalized patients with COVID-19 is similar to the management of other hospitalized patients with diabetes, except for the presence of often extreme, labile insulin resistance that resolves with improvement in COVID-19, and the potential need to minimize injection frequency to maximize safety for health care staff
- Type 2 diabetes (not eating regularly) – Insulin may be given subcutaneously with an intermediate-acting insulin, such as neutral protamine hagedorn (human NPH), or a long- acting (basal) insulin analog, such as glargine or detemir combined with correction insulin (rapid-acting insulin analog [lispro, aspart, glulisine] or regular insulin) every six
- Previously treated with insulin – For patients previously treated with intermediate or long-acting insulin who will not be eating regularly during the hospitalization, reduce the dose by 0 to 50 percent initially, depending on the amount of prandial intake typically covered by the intermediate or long-acting insulin, with correction insulin (rapid-acting or short-acting) administered for blood glucose >150 mg/dL (8.3 mmol/L) (algorithm 1). The basal insulin dose may be adjusted based on
- Previously treated with diet, oral agent, or GLP-1 receptor agonist – For patients with type 2 diabetes previously treated at home with diet, an oral agent, or an injectable GLP-1 receptor agonist who will not be eating regularly during the hospitalization, correction insulin alone may also be used as initial insulin therapy or as a dose-finding strategy (algorithm 1).
- Type 2 diabetes (eating a normal diet) – Some patients with type 2 diabetes and mild to moderate COVID-19 may be able to continue part of their outpatient regimen if glucose is well-controlled and no contraindications are present. However, SGLT2 inhibitors and medications that cause nausea or vomiting (eg, GLP-1 receptor agonists) and, in some cases, metformin, should be discontinued. If glucose levels are poorly controlled (eg, persistently >200 mg/dL [11.1 mmol/L]), discontinue oral agents and begin basal and prandial insulin. A typical starting dose for basal insulin is 0.2 to 0.3 units/kg/day, divided in two doses if NPH or detemir, or administered once daily if glargine; in patients with severe insulin resistance, a higher starting dose may be warranted, or the dose may be rapidly escalated. A typical starting dose for prandial insulin is 0.05 to 0.1 units/kg/meal.
- Type 1 diabetes – Most patients should continue their outpatient regimen, if glucose was well controlled. A modest dose reduction may be necessary if nutritional intake is Never stop basal insulin, even if the patient is not eating. For patients in whom nutritional intake is uncertain, correction insulin every six hours can be administered, as needed, in addition to basal insulin until the patient is eating regularly (algorithm 1).
Most hospitals have protocols for patient self-management of insulin pump therapy. Ideally, patients using an insulin pump may continue, as long as they are clinically stable and assessed to be competent to continue diabetes self-management . If there is a deterioration in their condition, the patient should be transitioned to subcutaneous or intravenous insulin. Similarly, alert, knowledgeable patients may continue use of CGM devices and hybrid closed-loop insulin delivery systems, but given the lack of training of hospital personnel on these devices, endocrinology team consultation is advisable.
The frequency of glucose monitoring depends upon the patient’s status, the results of earlier measurements, and the steps taken as a result of those measurements. CGM is particularly attractive in patients with COVID- 19 as it may decrease the need for frequent self- monitoring of blood glucose, but CGM is not used in most hospitals. For insulin dosing decisions, CGM results require confirmation with standard point-of-care glucose monitoring. Moreover, barriers including lack of reimbursement and familiarity with the technology limit its use in patients who are not already using personal CGM [27,28].
In general, in patients with diabetes (or hyperglycemia) who are eating, blood glucose monitoring should occur just before the meal. In those who are receiving nothing by mouth, the blood glucose monitoring should occur at regular, fixed intervals, usually every six hours. DKA/HHS – Subcutaneous insulin protocols (rather than intravenous insulin infusions) were adopted early in the COVID-19 pandemic to treat mild to moderate diabetic ketoacidosis (DKA) or hyperosmolar hyperglycemic state (HHS), when intravenous insulin was less feasible owing to the need to limit frequency of contact of staff with patients. Subcutaneous insulin protocols for treatment of DKA/HHS require dosing and monitoring every two to four hours, rather than hourly, as is usual in intravenous insulin protocols. Treatment of DKA with subcutaneous insulin has not been evaluated in severely ill patients (with or without COVID-19). In mild DKA, direct comparison of intramuscular, subcutaneous, and intravenous insulin therapy for hemodynamically stable patients with DKA (without COVID-19) shows similar efficacy and safety .
Subcutaneous insulin protocols are best used in patients with mild to moderate DKA without other serious comorbidities. Mild to moderate DKA is generally defined as follows:
- pH ≥7
- Serum bicarbonate ≥10 mEq/L
- Serum potassium ≥3.3 mEq/L
- Awake/alert mental status
Insulin infusions should be used for patients with severe DKA, acute heart failure or coronary syndrome, CKD stage 4 or 5 or end- stage kidney disease (ESKD), acute liver failure or cirrhosis, anasarca, weight >120 kg, treatment with high-dose corticosteroids, or in women who are pregnant. Intravenous insulin infusions for the treatment of DKA and HHS are reviewed separately.
- General principles of subcutaneous insulin protocols – When mild to moderate DKA is treated with subcutaneous insulin, begin (or continue) basal insulin (glargine, detemir, or NPH) at the initiation of treatment (0.15 to 0.3 units/kg), along with rapid-acting insulin. Higher initial doses of basal insulin (eg, 0.3 units/kg/day) may be needed in the setting of severe insulin resistance (obesity, high-dose glucocorticoids). In patients previously treated with intermediate or long- acting insulin, the usual dose of basal insulin can be used to gauge usual insulin requirements and guide insulin dosing. Continue basal insulin every 12 to 24 hours, depending on the insulin formulation used.
When the serum glucose reaches 250 mg/dL (13.9 mmol/L), add dextrose to the intravenous saline solution and adjust the dose of rapid-acting insulin per DKA protocol being followed. Blood glucose in patients taking SGLT2 inhibitors may be normal or minimally elevated (<250 mg/dL [13.9 mmol/L]). In this setting, dextrose is added to intravenous fluids at the initiation of therapy.
In patients with COVID-19, a variety of subcutaneous protocols have been used for DKA , none of which have been formally tested for safety and efficacy. Basal insulin is initiated early in each protocol. Note that doses can be wide-ranging based on starting recommendation and patient weight. It is important to use judgment and consult colleagues when using these protocols . While patients with COVID-19 and diabetes can be quite insulin resistant, meriting high starting doses, individual insulin resistance cannot be predicted at presentation.
- Montefiore DKA protocol
- Intermediate or long-acting insulin – Initiate basal insulin immediately (0.15 to 0.2 units/kg/day), unless the last dose was within 12 hours. Continue every 24 hours .
- Rapid-acting insulin – Initial rapid-acting insulin dose 0.2 units/kg, followed by 0.2 units/kg every four hours. When glucose is <250 mg/dL, decrease to 0.1 units/kg every four hours .
- Mount Sinai COVID-19 DKA protocol
- Intermediate or long-acting insulin – Initiate basal insulin (0.2 units/kg/day). Continue every 24 hours .
- Rapid-acting insulin – Initial rapid-acting insulin dose 0.2 units/kg followed by 0.1 units/kg every three hours if the glucose has decreased by at least 75 mg/dL. If the change in glucose three hours after the initial dose is <75 mg/dL, continue 0.2 units/kg every three When glucose is <250 mg/dL, decrease to 0.1 units/kg every three hours . Continue until resolution of ketoacidosis
- Diabetes UK protocol
- Intermediate or long-acting insulin – Initiate basal insulin (0.15 units/kg). Continue every 24 hours .
- Rapid-acting insulin – Initial dose 0.4 units/kg every four hours. When glucose is <250 mg/dL (13.9 mmol/L), decrease to 0.2 units/kg every four hours . Continue until resolution of ketoacidosis.
Patients treated with an insulin pump should change the infusion set and connectors in case problems with the infusion set caused the DKA. If the pump is functioning correctly with a new infusion set and the DKA is mild, it may be possible in rare situations to use the insulin pump to manage DKA, along with intravenous fluids and electrolyte replacement in a monitored inpatient or observational setting. In most cases, the pump should be removed, and the DKA should be managed with intravenous or subcutaneous regiments per hospital protocol . For patients using a hybrid closed-loop system, we advise using “open loop” until resolution of the DKA. Although there is increasing use of CGM in the hospital with COVID-19 , there are no data about its use in DKA, and we typically do not use it in this setting.
Severe insulin resistance – Severe insulin resistance has been observed in severely ill patients with COVID-19 . The degree of insulin resistance may improve quickly with resolution of COVID-19, resulting in a sudden decrease in insulin requirements (see ‘Hypoglycemia’ below). This has been presumed to be cytokine induced, and it appears to correlate with inflammatory markers such as IL-6. Although insulin resistance can be hard to quantify in clinical practice, in one report from China, an indicator of insulin resistance was associated with severity of illness and mortality . In severely insulin-resistant patients, twice-daily dosing of long-acting insulin (eg, glargine) may be necessary.
Our approach in the most critically ill intensive care unit (ICU) patients, especially those who are intermittently taking nothing by mouth, is to use basal insulin (eg, daily glargine, twice-daily glargine, twice-daily NPH) to cover the basal requirement, with a superimposed insulin infusion to cover the variable insulin requirement. As patients recover, the insulin dose should be rapidly reduced to match requirements and reduce the risk of hypoglycemia.
- Enteral nutrition – The prolonged use of enteral nutrition in association with prolonged respiratory failure in COVID-19 can dramatically increase the insulin requirement in insulin-resistant patients. In patients receiving enteral nutrition, we use NPH twice daily along with regular insulin every six hours, adding the supplemental regular insulin requirement into the subsequent NPH dose. We have observed that insulin requirements can drop dramatically with resolution of illness, even when the patient continues the same formula and rate of enteral nutrition. Thus, insulin management should be re-evaluated daily, taking into account the course of the underlying illness and the nutritional plan.
- Glucocorticoids – Glucocorticoids raise glucose levels in pre-existing diabetes mellitus and may precipitate steroid-induced hyperglycemia in patients without pre-existing diabetes. However, the magnitude of the hyperglycemic response and the duration of the effect depends on the dose and type of glucocorticoids. If dexamethasone is used for treatment of the inflammatory response, we often treat with NPH (0.2 to 0.3 units/kg/day, divided in two doses) at the time of glucocorticoid dosing, adjusting the NPH dose to match glucocorticoid dose and tapering as glucocorticoid dose is tapered.
Hypoglycemia — Although relatively brief and mild hypoglycemia does not usually have clinically significant sequelae, hospitalized patients are particularly vulnerable to severe, prolonged hypoglycemia since they may be unable to sense or respond to the early warning signs and symptoms of low blood glucose. In COVID-19, there is a risk of hypoglycemia when insulin requirements suddenly decrease with resolution of the underlying inflammatory state (and accompanying improvement in insulin resistance).
The risk of hypoglycemia is also increased when caloric intake (including enteral feedings or total parenteral nutrition) is diminished or stopped completely in a patient treated with insulin. In this setting, an intravenous 10 percent dextrose solution, providing a similar number of carbohydrate calories as was being administered via the enteral feeds, should be infused in order to prevent hypoglycemia.
SOCIETY GUIDELINE LINKS
Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately.
- Patients with type 2 diabetes are more likely to have serious complications, more intensive care unit (ICU) admissions, longer length of stay, and die from coronavirus disease 2019 (COVID-19). There are limited data evaluating the risk of severe illness and death in patients with type 1
- COVID-19 infection appears to precipitate severe manifestations of diabetes, including diabetic ketoacidosis (DKA), hyperosmolar hyperglycemic state (HHS), and severe insulin resistance. Patients may or may not have a history of
- Sick-day management is directed towards preventing hypoglycemia, significant hyperglycemia, and
- For patients with a known history of diabetes, or in patients with metabolic acidosis on initial admission laboratory evaluation, assess serum ketones.
- There are no data to inform precise glycemic targets for patients with COVID-19. In general, the goals are the same as in other hospitalized patients (eg, avoid severe hyperglycemia, volume depletion, and electrolyte abnormalities; avoid hypoglycemia; ensure adequate nutrition). A blood glucose target of 140 to 180 mg/dL (7.8 to 10 mmol/L) is reasonable for most hospitalized
- Many oral agents have specific contraindications that may occur in acutely ill or hospitalized patients. Therefore, home diabetes medications are usually discontinued. In particular, sodium-glucose co-transporter 2 (SGLT2) inhibitors should be discontinued due to increased risk of dehydration and volume contraction. Metformin is contraindicated in situations in which renal function and/or hemodynamic status is either impaired or threatened, due to the increased risk of lactic acidosis, and therefore should be discontinued at least temporarily until the clinical course is more certain. Other diabetes medications may not be appropriate due to adverse side-effect profile.
- Insulin is the preferred treatment for hyperglycemia in patients hospitalized with moderate to severe COVID-19. For patients with type 2 diabetes, the need for insulin therapy may be Patients with type 1 diabetes have an absolute requirement for insulin at all times, whether or not they are eating, to prevent ketosis.
- Subcutaneous insulin protocols have been used to treat mild to moderate DKA during the COVID-19 pandemic when intravenous insulin may not be practical owing to the need to limit frequency of contact of staff with patients. In this setting, dosing and monitoring are being performed every two to four hours. Subcutaneous insulin protocols are not used in patients with severe DKA; severe cardiac, renal, or hepatic comorbidities; or in women who are
- Severe insulin resistance has been observed in severely ill patients with COVID-19 The degree of insulin resistance may improve quickly with resolution of COVID-19, resulting in a sudden decrease in insulin requirements.
- Zhou F, Yu T, Du R, et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort Lancet 2020; 395:1054.
- Guo W, Li M, Dong Y, et al. Diabetes is a risk factor for the progression and prognosis of COVID-19. Diabetes Metab Res Rev 2020; :e3319.
- Bode B, Garrett V, Messler J, et al. Glycemic Characteristics and Clinical Outcomes of COVID-19 Patients Hospitalized in the United States. J Diabetes Sci Technol 2020; 14:813.
- Targher G, Mantovani A, Wang XB, et al. Patients with diabetes are at higher risk for severe illness from COVID-19. Diabetes Metab 2020; 46:335.
- https://www.england.nhs.uk/wp- content/uploads/2020/05/Valabhji- COVID-19-and-Diabetes-Paper-2-Full- Manuscript.pdf (Accessed on July 02, 2020).
- Shang J, Wang Q, Zhang H, et al. The Relationship Between Diabetes Mellitus and COVID-19 Prognosis: A Retrospective Cohort Study in Wuhan, China. Am J Med 2021; 134:e6.
- Barron E, Bakhai C, Kar P, et Associations of type 1 and type 2 diabetes with COVID-19-related mortality in England: a whole-population study. Lancet Diabetes Endocrinol 2020; 8:813.
- Wu Z, McGoogan JM. Characteristics of and Important Lessons From the Coronavirus Disease 2019 (COVID-19) Outbreak in China: Summary of a Report of 72 314 Cases From the Chinese Center for Disease Control and JAMA 2020; 323:1239.
- Tatti P, Tonolo G, Zanfardino A, Iafusco Is it fair to hope that patients with Type 1 Diabetes (autoimmune) may be spared by the infection of Covid-19? Med Hypotheses 2020; 142:109795.
- Riddle MC, Buse JB, Franks PW, et al. COVID-19 in People With Diabetes: Urgently Needed Lessons From Early Reports. Diabetes Care 2020; 43:1378.
- Petrilli CM, Jones SA, Yang J, et Factors associated with hospital admission and critical illness among 5279 people with coronavirus disease 2019 in New York City: prospective cohort study. BMJ 2020; 369:m1966.
- Cariou B, Hadjadj S, Wargny M, et al. Phenotypic characteristics and prognosis of inpatients with COVID-19 and diabetes: the CORONADO Diabetologia 2020; 63:1500.
- Hamer M, Gale CR, Kivimäki M, Batty GD. Overweight, obesity, and risk of hospitalization for COVID-19: A community-based cohort study of adults in the United Proc Natl Acad Sci U S A 2020; 117:21011.
- Holman N, Knighton P, Kar P, et al. Risk factors for COVID-19-related mortality in people with type 1 and type 2 diabetes in England: a population-based cohort Lancet Diabetes Endocrinol 2020; 8:823.
- Kim NY, Ha E, Moon JS, et al. Acute Hyperglycemic Crises with Coronavirus Disease-19: Case Reports. Diabetes Metab J 2020; 44:349.
- Rubino F, Amiel SA, Zimmet P, et New- Onset Diabetes in Covid-19. N Engl J Med 2020; 383:789.
- Pal R, Banerjee M, Yadav U, Bhattacharjee S. Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: A systematic review of literature. Diabetes Metab Syndr 2020; 14:1563.
- Wu L, Girgis CM, Cheung COVID-19 and diabetes: Insulin requirements parallel illness severity in critically unwell patients. Clin Endocrinol (Oxf) 2020; 93:390.
- Sathish T, Kapoor N, Cao Y, et al. Proportion of newly diagnosed diabetes in COVID-19 patients: A systematic review and meta-analysis. Diabetes Obes Metab 2021; 23:870.
- Sathish T, Tapp RJ, Cooper ME, Zimmet Potential metabolic and inflammatory pathways between COVID-19 and new- onset diabetes. Diabetes Metab 2021; 47:101204.
- Roussel R, Darmon P, Pichelin M, et al. Use of dipeptidyl peptidase-4 inhibitors and prognosis of COVID-19 in hospitalized patients with type 2 diabetes: A propensity score analysis from the CORONADO Diabetes Obes Metab 2021; 23:1162.
- Zhou JH, Wu B, Wang WX, et al. No significant association between dipeptidyl peptidase-4 inhibitors and adverse outcomes of COVID-19. World J Clin Cases 2020; 8:5576.
- Pérez-Belmonte LM, Torres-Peña JD, López-Carmona MD, et al. Mortality and other adverse outcomes in patients with type 2 diabetes mellitus admitted for COVID-19 in association with glucose- lowering drugs: a nationwide cohort BMC Med 2020; 18:359.
- Mirani M, Favacchio G, Carrone F, et al. Impact of Comorbidities and Glycemia at Admission and Dipeptidyl Peptidase 4 Inhibitors in Patients With Type 2 Diabetes With COVID-19: A Case Series From an Academic Hospital in Lombardy, Diabetes Care 2020; 43:3042.
- Solerte SB, D’Addio F, Trevisan R, et al. Sitagliptin Treatment at the Time of Hospitalization Was Associated With Reduced Mortality in Patients With Type 2 Diabetes and COVID-19: A Multicenter, Case-Control, Retrospective, Observational Study. Diabetes Care 2020; 43:2999.
- Korytkowski M, Antinori-Lent K, Drincic A, et A Pragmatic Approach to Inpatient Diabetes Management during the COVID-19 Pandemic. J Clin Endocrinol Metab 2020; 105.
- Wallia A, Umpierrez GE, Rushakoff RJ, et al. Consensus Statement on Inpatient Use of Continuous Glucose Monitoring. J Diabetes Sci Technol 2017; 11:1036.
- Wang M, Singh LG, Spanakis EK. Advancing the Use of CGM Devices in a Non-ICU Setting. J Diabetes Sci Technol 2019; 13:674.
- Andrade-Castellanos CA, Colunga-Lozano LE, Delgado-Figueroa N, Gonzalez- Padilla DA. Subcutaneous rapid-acting insulin analogues for diabetic Cochrane Database Syst Rev 2016; :CD011281.
- https://professional.diabetes.org/content- page/inpatient-insulin-protocols-covid-19 (Accessed on February 17, 2021).
- Palermo NE, Sadhu AR, McDonnell ME. Diabetic Ketoacidosis in COVID-19: Unique Concerns and Considerations. J Clin Endocrinol Metab 2020; 105.
- https://www.diabetes.org.uk/resources- s3/public/2020- 04/COvID_DKA_SC_v3.3.pdf (Accessed on February 17, 2021).
- Singh LG, Satyarengga M, Marcano I, et al. Reducing Inpatient Hypoglycemia in the General Wards Using Real-time Continuous Glucose Monitoring: The Glucose Telemetry System, a Randomized Clinical Trial. Diabetes Care 2020; 43:2736.
- Ren H, Yang Y, Wang F, et al. Association of the insulin resistance marker TyG index with the severity and mortality of COVID-19. Cardiovasc Diabetol 2020; 19:58.
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