Diabetes Ther https://doi.org/10.1007/s13300-020-00966-z REVIEW Inpatient Hyperglycemia Management and COVID-19 Virginia Bellido . Antonio Pérez Received: September 10, 2020 / Accepted: November 3, 2020 Ó The Author(s) 2020 ABSTRACT with COVID-19. The shortage of personal pro- tective equipment, the need to prevent staff Diabetes is one of the most common comor- exposure, or the fact that many of the health- bidities in hospitalized patients with coron- care professionals might be relatively unfamiliar avirus disease 2019 (COVID-19). Inpatient with the management of hyperglycemia may hyperglycemia during this pandemic has been lead to worse glycemic control and, conse- associated with worse outcomes, so it is quently, a worse prognosis. In order to reduce mandatory to implement effective glycemic these barriers, we intend to adapt established control treatment approaches for inpatients recommendations to manage hyperglycemia during this pandemic in critical and noncritical care settings. V. Bellido Department of Endocrinology and Nutrition, Cruces University Hospital, Vizcaya, Spain Keywords: COVID-19; Diabetes; Hospitalized; V. Bellido Hyperglycemia; Inpatient; Insulin therapy; Biocruces Bizkaia Health Research Institute, Vizcaya, SARS-CoV-2 Spain V. Bellido University of the Basque Country (UPV/EHU), Vizcaya, Spain A. Pérez (&) Department of Endocrinology and Nutrition, Santa Creu I Sant Pau Hospital, Barcelona, Spain e-mail: aperez@santpau.cat A. Pérez Sant Pau Institute of Biomedical Research, Barcelona, Spain A. Pérez Autonomous University of Barcelona, Barcelona, Spain A. Pérez CIBER de Diabetes Y Enfermedades Metabólicas Asociadas (CIBERDEM), Barcelona, Spain Diabetes Ther found diabetes to be a major risk factor for dis- Key Summary Points ease severity and mortality [3, 4]. Patients with diabetes and/or uncontrolled hyperglycemia are Diabetes is one of the most common more than twice as likely to be admitted to comorbidities in hospitalized patients intensive care units (ICU) and mortality is up to with coronavirus disease 2019 (COVID- three times higher compared to patients with- 19). out diabetes and/or uncontrolled hyper- glycemia [5]. Inpatient hyperglycemia during the It is well established that inpatient hyper- COVID-19 pandemic has been associated glycemia, with or without known diabetes, with worse outcomes, but improvement contributes to a significant increase in morbid- of glycemic control can reduce ity, mortality, length of hospital stay, and complications associated with healthcare costs, and that better glycemic con- hyperglycemia. trol improves clinical outcomes [6–8]. This was Effective glycemic control treatment also evident in prior coronavirus infection out- approaches for inpatients with COVID-19 breaks like the severe acute respiratory syn- are needed while, at the same time, drome (SARS) [9]. limiting the exposure of healthcare Several mechanisms have linked hyper- professionals. An individualized approach glycemia to the worse prognosis of COVID-19. adapting the established These mechanisms include those related to recommendations for the management of hyperglycemia and glycemic control as well as hyperglycemia in hospitalized patients the impaired immune and inflammatory may reduce the barriers during COVID-19 response caused by hyperglycemia [10]. Poor pandemic. glycemic control has been associated with worse outcomes, including higher resource utiliza- tion, prolonged length of hospitalization, mul- ti-organ injuries, and higher mortality [10–13]. Hyperglycemia in patients with and without diabetes can also have a negative impact on the DIGITAL FEATURES efficacy of COVID-19 therapies, such as tocili- zumab [14]. Frequent comorbidities associated This article is published with digital features, with diabetes, such as obesity and hypertension, including a summary slide, to facilitate under- have also been associated with poor prognosis standing of the article. To view digital features [15]. However, a recent study has shown that for this article go to https://doi.org/10.6084/ diabetes is associated with poor early outcomes m9.figshare.13182836. among hospitalized patients with COVID-19, after adjustment for obesity [16]. In addition, accelerated respiratory deterioration has INTRODUCTION recently been identified as another mechanism whereby hyperglycemia can lead to worse out- Diabetes is one of the most common comor- comes of COVID-19 [17]. bidities of coronavirus disease 2019 (COVID- While some of these mechanisms remain to 19), caused by severe acute respiratory syn- be elucidated, it seems clear that optimizing drome coronavirus 2 (SARS-CoV-2) infection. glycemic control can be crucial to improve The prevalence of diabetes among people COVID-19 outcomes. Well-controlled blood affected by COVID-19 is not higher than that glucose (BG) levels, defined as BG between 70 observed in the general population, suggesting and 180 mg/dL (3.9 and 10.0 mmol/L) have that diabetes does not increase the risk of SARS- been associated with reduced medical inter- CoV-2 infection, but can worsen the outcome of ventions, major organ injuries, and all-cause the disease [1, 2]. In fact, clinical studies have mortality [11]. In fact, for every 10 mg/dL Diabetes Ther (0.6 mmol/L) drop in glucose levels between In this clinical scenario, there is an urgent admission and 18 days, an 11% relative decrease need to implement effective glycemic control in severe disease risk has been described in treatment approaches for inpatients with patients with hyperglycemia [10]. COVID-19 [25]. However, no data is available The limited data available suggest that gly- regarding the most appropriate management of cemic control in patients with COVID-19 is hyperglycemia in patients infected by SARS- inadequate. An observational study that evalu- CoV-2. Until then, given the aforementioned ated glycemic control among hospitalized challenges, we intend to adapt established rec- patients with COVID-19, diabetes, and acute ommendations to manage hyperglycemia dur- hyperglycemia described 39.1% of BG values ing this pandemic in critical and noncritical above 180 mg/dL (10.0 mmol/L) and 37.8% of care settings. In Table 1 we summarize the main the time of admission spent with a mean BG recommendations for the management of above 180 mg/dL (10.0 mmol/L) [12]. Another hyperglycemia in critically ill and noncritically study showed 56.6% of capillary BG tests above ill patients with COVID-19 according to their the recommended target of 140–180 mg/dL clinical situation. This article is based on pre- (7.8–10.0 mmol/L) [18]. This may be due to viously conducted studies and does not contain high levels of stress, inflammation, a cytokine- any studies with human participants or animals mediated insulin-resistant state and lack of performed by any of the authors. adequate protocols for glucose management [19]. It is also possible that the SARS coronavirus can penetrate into pancreatic islets and damage MANAGEMENT beta cells leading to insulin deficiency, thereby OF HYPERGLYCEMIA IN CRITICAL aggravating the course of diabetes and trigger- PATIENTS WITH COVID-19 ing acute hyperglycemia even in people without diabetes [20, 21]. This is supported by the Glycemic Targets observation of frequent cases of ketosis and severe diabetic ketoacidosis (DKA) at the time of Glycemic control goals in the ICU have been hospital admission [22]. On the other hand, a the subject of debate during the past 2 decades. rather large number or hypoglycemic episodes It is generally accepted that intensive glycemic at hospital admission have also been reported, control [80–110 mg/dL (4.4–6.1 mmol/L)] com- probably favored by COVID-19-induced anor- pared to moderate control [140–180 mg/dL exia without concomitant adaptation of glu- (7.8–10.0 mmol/L)] does not provide any bene- cose-lowering drugs [18, 20]. There are other fit and in fact can increase the risk of hypo- factors associated with BG fluctuation that are glycemia and even mortality [26, 27]. There is especially relevant in patients with diabetes and agreement that glucose levels above 180 mg/dL COVID-19, such as the use of glucocorticoids, (10.0 mmol/L) may increase the risk of hospital that can lead to large glycemic excursions complications. However, the lower limit for which should be considered in setting the glycemia target is less well established and val- insulin pattern [23]. ues greater than 110 mg/dL (6.1 mmol/L) are In addition, healthcare workers can face generally recommended in order to minimize challenges that need careful attention. Special- the risks of hypoglycemia [7]. The GLUCO- ists from all disciplines may have to manage CABG study showed a significant reduction in patients with COVID-19 outside of their usual complications among patients undergoing specialty areas and, therefore, clinicians rela- coronary artery bypass graft surgery without tively unfamiliar with managing hyperglycemia diabetes comparing a glucose target of may be required to do so [24]. The shortage of 100–140 mg/dL (5.6–7.8 mmol/L) to a target of personal protective equipment and the need to 141–180 mg/dL (7.8–10.0 mmol/L) [28], and the prevent healthcare workers’ exposure can also results of Krinsley et al.’s study in critically ill hinder glycemic control in patients with patients support a BG target of 80–140 mg/dL COVID-19. Diabetes Ther Table 1 Hyperglycemia management in critically and noncritically ill patients with COVID-19 Glycemic targets Clinical situation Insulin regimen BG monitoring Critically ill 140–180 mg/dL* Hemodynamically unstable Continuous Every hour patients (7.8–10.0 mmol/ Parenteral nutrition intravenous insulin L) infusion Unstable insulin requirements Corticosteroid therapy Hemodynamically stable Subcutaneous insulin Every 4–6 h Stable insulin requirements Basal-correction or basal-bolus- correction Noncritically 110–180 mg/dL** T1D Not oral intake Basal-correction Every 4–6 h## ill patients (6.1–10.0 mmol/ T2D on Oral intake Basal-bolus- Before meals and at L) oral correction bedtime## agents ± insulin T2D on Glycemia at admission Correction insulin Before meals and at diet \ 180 mg/dL before meals or bedtime or every Unknown (10.0 mmol/L) every 6 h# 6 h## DM Glycemia at admission Basal-bolus- Before meals and at [ 180 mg/dL correction bedtime## (10.0 mmol/L) BG blood glucose, T1D type 1 diabetes, T2D type 2 diabetes, DM diabetes mellitus *110–140 mg/dL (6.1–7.8 mmol/L) may be reasonable for selected patients, as long as it can be achieved without significant hypoglycemia **110–140 mg/dL (6.1–7.8 mmol/L) may be reasonable for stable patients with mild disease and previous tight glycemic control. BG levels [ 180 mg/dL (7.8 mmol/L) might be acceptable for patients who are at high risk of hypoglycemia or who have limited life expectancy # To calculate insulin requirements during the first 24 h. Then intensify to a basal-correction or basal-bolus regimen ## Consider the use of continuous glucose monitoring if feasible to limit fingersticks (4.4–7.8 mmol/L) for patients without diabetes data, like those established for outpatient dia- and with diabetes when HbA1c is less than 7% betes management, support a potential benefit (53 mmol/mol), but 110–160 mg/dL (6.1– of a personalized glycemic target in critically ill 8.9 mmol/L) in those with HbA1c levels of at patients. least 7% (53 mmol/mol) [29]. Also deserving Clinical guidelines recommend maintaining attention is the fact that glycemic variability per glucose levels between 140 and 180 mg/dL se has been associated with higher mortality (7.8–10.0 mmol/L) for most critically ill patients rates than hyperglycemia in septic patients [30]. [32] and more stringent goals of 110–140 mg/dl It has therefore been suggested that glycemic (6.1–7.8 mmol/L) may be reasonable for selec- variability has to be part of the management of ted patients, as long as they can be achieved hyperglycemia, even in ICU patients [31]. These without significant hypoglycemia [7, 28, 29]. In Diabetes Ther accordance with Pasquel et al. [33], we consider considered instead of intravenous insulin infu- that these recommendations could be extended sion and check BG levels four times a day to critical patients with COVID-19. together with other nursing activities to reduce the need to enter a patient’s room. Transfer Insulin Therapy from intravenous to subcutaneous insulin administration will be recommended when the Insulin should be the treatment of choice for patient is clinically stable [37, 38]. The initial critically ill patients with COVID-19. The main dose of subcutaneous insulin administration at aims of a safe and effective insulin regimen the time of transition can be determined as should be to reduce contact frequency, reduce 60–80% of the insulin administered intra- glucose variability, minimize risk of severe venously during the preceding 24 h. To avoid hypoglycemia, and improve overall glycemic rebound hyperglycemia after transition, a suffi- control [34]. As a result of the stress caused by cient duration of overlap with the insulin SARS-CoV-2 infection and other factors, such as infusion and the subcutaneous insulin admin- continuous tube feeding in patients on artificial istration is required. Short-acting insulin can be ventilation and the risk of hypoglycemia when administered 1 to 2 h and long-acting insulin 2 tube feeding is interrupted, or the use of high to 3 h prior to discontinuation of intravenous doses of corticosteroids, patients may suffer insulin administration. from great glycemic excursions [34]. To achieve glycemic targets, continuous intravenous insu- MANAGEMENT lin infusion, based on validated written or computerized protocols, is the most effective OF HYPERGLYCEMIA method [7, 35, 36]. The protocols that do not IN NONCRITICAL PATIENTS need a calculation of insulin doses (printed with WITH COVID-19 decision columns and computerized protocols) are preferable to those that require calculations Glycemic Targets to decide the dose. Training of physicians and especially nurses in the efficient use of the The American Diabetes Association (ADA) pro- protocol as well as predefining adjustments poses the range of 140–180 mg/dL (7.8– before important changes in BG and/or situa- 10.0 mmol/L) as a target level of BG for the tions in which corticosteroids, vasopressors, majority of noncritically ill patients [39]. How- parenteral nutrition, etc., are removed or added ever, the ideal glucose goals for noncritically ill is important for protocol safety. However, the patients remain undefined, and current recom- main factor that contributes to the safety of the mendations are based mostly on retrospective protocol is the frequency of glycemic monitor- studies, clinical experience, and judgment [7]. ing. The majority of insulin infusion protocols Evidence regarding appropriate glycemic demand a minimum of hourly glucose moni- targets for hospitalized patients with COVID-19 toring for successful glycemic target achieve- is lacking. As mentioned before, BG levels ment while reducing the risk of hypoglycemia. maintained between 70 and 180 mg/dL (3.9 and Checking glucose levels with a meter and test 10.0 mmol/L) have been associated with better strips requires caregivers to enter a patient’s clinical outcomes [11]. Premeal and fasting BG room. In order to minimize healthcare workers’ values below 140 mg/dL (7.8 mmol/L) with exposure when managing hyperglycemia in maximal random BG below 180 mg/dL critically ill patients with COVID-19, for (10.0 mmol/L) might be appropriate in hemodynamically stable patients who are not stable patients with mild disease and previous on parenteral nutrition or high-dose corticos- tight glycemic control, while glucose levels teroids, we recommend that the use of subcu- above 180 mg/dL (10.0 mmol/L) might be taneous basal-bolus-correction or basal- acceptable in patients who are at high risk of correction insulin regimens should be hypoglycemia or who have limited life Diabetes Ther expectancy, as a way of minimizing the risk of patients with hyperglycemia and diabetes in hypoglycemia [7]. noncritical care setting [32, 36]. There is no data regarding the most appropriate regimen for Insulin Therapy patients with COVID-19, but the importance of achieving good glycemic control is evident [10]. There are limited data available about the effi- A lot of evidence supports the use of basal- cacy and safety of non-insulin agents in hospi- bolus regimens in noncritically ill patients. talized patients, almost restricted to dipeptidyl Randomized clinical trials have shown that peptidase 4 (DPP4) inhibitors [40–44]. These basal-bolus treatment improves glycemic con- agents in combination with basal insulin may trol and reduces the rate of hospital complica- represent an alternative in patients with tions compared with reactive, or sliding-scale, COVID-19 and mild to moderate hyperglycemia insulin regimens [8, 52]. Compared to premixed [33]. DPP4 inhibitors have also been suggested insulin (70/30 NPH/regular insulin), a basal- to have a protective effect on COVID-19 [45]. bolus regimen has shown comparable glycemic However, recent studies found no association control, but significantly fewer hypoglycemic between the use of DPP4 inhibitors before episodes in medical and surgical patients [53]. A admission and COVID-19 prognosis [20, 46, 47]. basal plus regimen compared with a standard Moreover, we still do not have data on their use basal-bolus regimen in medical and surgical in hospitalized patients with COVID-19, and patients with type 2 diabetes treated with diet, they may not be available in many hospitals. oral antidiabetic agents, or low-dose insulin The incorporation of non-insulin drugs expands resulted in a similar improvement in glycemic the therapeutic options and consequently the control without differences in hypoglycemia complexity of the prescription, which can be [54]. As for the types of insulin, regimens using especially difficult when clinicians are unfa- insulin analogues and human insulin result in miliar with managing hyperglycemia. Gluca- similar glycemic control in the hospital setting gon-like peptide 1 (GLP-1) receptor agonists [55]. However, NPH insulin-based basal-bolus could be an attractive option, but they may regimens have been largely supplanted by increase the risk of gastrointestinal side effects insulins analogue because of a perceived lower [48]. Metformin and sodium-glucose cotrans- risk of hypoglycemia and because NPH insulin porter 2 (SGTL2) inhibitors should be discon- usually cannot be administered once daily. tinued at admission, because of the risk of lactic There are limited data regarding the use of new acidosis and DKA, respectively [49]. Some basal insulin analogues in the hospital setting. A authors hypothesized that SGLT2 inhibitors recent study comparing glargine U300 and could be effective in patients with hypoxemia glargine U100 in a basal-bolus regimen in gen- and interstitial lung edema due to SARS-CoV-2 eral medical and surgical patients with type 2 infection [50, 51]. Experience with three hos- diabetes resulted in similar glycemic control, pitalized patients without diabetes has been but significantly lower rates of clinically signif- reported, showing no beneficial effects with the icant hypoglycemia [BG below 54 mg/dL use of SGLT2 inhibitors [50]. All other oral (3 mmol/L)] with the use of glargine U300 [56]. agents, such as sulfonylureas or thiazolidine- In line with this study, another recent study in diones, should also be discontinued at people with type 2 diabetes insufficiently con- admission. trolled with basal insulin and/or non-insulin Insulin is still considered the most appro- antidiabetic drugs, the COBALTA trial, confirms priate pharmacologic agent for effectively con- the efficacy and safety of insulin glargine U300 trolling glycemia in hospital. Several regimens during hospitalization. This study also demon- have proven to be effective for achieving and strates that therapy intensification at discharge maintaining glycemic control. Current clinical with glargine U300 is an effective strategy, guidelines recommend basal-bolus insulin regi- improving HbA1c by 1.6% at months 3 and 6 mens as the standard care for hospitalized post discharge with an adequate safety profile and a high degree of treatment satisfaction [57]. Diabetes Ther On the basis of these results, an insulin reg- healthcare workers caring for them [60]. Nev- imen with basal, prandial, and correction com- ertheless, a way to monitor BG remotely, from ponents would be the preferred treatment for outside the isolated rooms, is required [59]. This noncritically ill hospitalized patients with could be achieved by using BG meters that COVID-19 and good nutritional intake, and transmit the data via Bluetooth to an app or to a basal insulin or a basal plus correction for cloud. However, the use of continuous glucose patients with poor oral intake or those in which monitoring (CGM) might be the ideal way to oral intake cannot be ensured [32]. Prolonged monitor BG in patients with COVID-19. It use of sliding-scale insulin regimens as the sole would allow, on the one hand, remote moni- treatment of hyperglycemia is strongly dis- toring; on the other hand, it would help to couraged [32]. enable BG control with low variability in the intended target range [31]. Insulin Therapy in Glucocorticoid- Inpatient clinical trials have tested the Induced Hyperglycemia accuracy, safety, and efficacy of CGM technol- ogy in hospital, in both critical and noncritical The use of glucocorticoid therapy can aggravate patients [61–63]. Some experiences have already or precipitate hyperglycemia in hospitalized been reported in noncritical patients with patients with COVID-19 with and without COVID-19 with type 1 and type 2 diabetes, with known diabetes [58]. Regarding the use of high the use of Guardian Connect (Medtronic), with doses of corticosteroids in these patients, some significant improvement in mean glucose levels authors have described their experience adding in all patients [59]. The main challenges for the NPH insulin in a dose of 20–30 units in the use of CGM in hospital include training morning in addition to the current insulin healthcare workers, the need for calibration regimen as an efficient strategy to minimize the procedures with some CGM systems, and cost. impact of steroids on BG values [34]. In our There are some systems such as FreeStyle Libre experience, the best option is to add the calcu- or Dexcom G6 that do not require BG calibra- lated increase in insulin dose, considering body tion, minimizing risk of staff exposure and weight and glucocorticoid dose, to the patient’s burden. Recently, the FDA approved the use of usual total dose, distributing it according to the both FreeStyle Libre and Dexcom for inpatient usual insulin regimen and glucocorticoid use during the COVID-19 healthcare crisis in schedule [23]. noncritically ill patients, but not in the criti- cally ill [64–66]. Both systems can securely transmit glucose measurement data to digitally GLUCOSE MONITORING connected devices. As far as we know, no IN HOSPITAL IN PATIENTS experiences have been reported with the use of these two CGM systems in hospitalized patients WITH COVID-19 with COVID-19. Some issues should be taken into account Maintaining an adequate glycemic control with the use of CGM systems in patients with usually requires multiple daily glucose mea- COVID-19. Hypoxemia and possible reduction surements, which can be a challenge in patients in peripheral perfusion could interfere with the under strict isolation. The implementation of accuracy of interstitial glucose measurement, technology that minimizes staff exposure while especially in critically ill patients [67]. Acet- maintaining standard of care for hospitalized aminophen, a commonly used antipyretic in patients with diabetes is essential [59]. patients with COVID-19, can interfere with The US Food and Drug Administration (FDA) CGM readings in some systems and may cause a recognizes that home-use BG meters may be CGM to overestimate glucose [68] (not in Free- used by patients with diabetes who are hospi- Style Libre or Dexcom G6). Glucose values in talized because of COVID-19 to check their own patients wearing a device that may be impacted BG levels and provide the readings to the Diabetes Ther by acetaminophen should be interpreted with aforementioned barriers during the COVID-19 caution. pandemic. The use of subcutaneous insulin Regarding ICU patients, the integration of regimens in clinically stable patients may facil- computer-guided insulin infusion with CGM or itate the reduction of the number of BG con- further development of new automated insulin trols and, therefore, the exposure of the staff. In delivery systems may be ideal [33]. Data about the same way, the implementation of technol- the use of hybrid closed-loop insulin infusion ogy that allows BG remote monitoring could systems in critically ill patients are scarce. help to limit fingersticks to check BG and, However, two recent cases of type 1 diabetes in consequently, minimize staff exposure. The patients with COVID-19 using t:slim Control IQ FDA approved the use of both FreeStyle Libre hybrid closed-loop system have been described, and Dexcom for inpatient use during the with optimal glycemic levels and minimal COVID-19 healthcare crisis. Further research variability [34]. However, we will have to wait regarding the evaluation of these changes in for more data on its efficacy and safety in criti- care is warranted in order to adapt our cally ill patients before we can recommend its protocols. use. Both the use of CGM systems and the use of hybrid closed-loop insulin infusion systems ACKNOWLEDGEMENTS would require specific protocols for guidance, as well as access to specialist care [69]. Having an endocrinologist on consult, even over the Funding. Support from Sanofi was received phone or virtually, could help with all the for the development of the manuscript and approaches proposed [19, 70]. funding the journal’s Rapid Service Fee, but the opinions represent those of authors and not Sanofi. CONCLUSIONS Authorship. All named authors meet the Improvement of glycemic control can reduce International Committee of Medical Journal complications associated with hyperglycemia in Editors (ICMJE) criteria for authorship for this hospitalized patients infected by SARS-CoV-2. article, take responsibility for the integrity of Effective glycemic control treatment approa- the work, and have given their approval for this ches for inpatients with COVID-19 are needed version to be published. while, at the same time, limiting the exposure of healthcare professionals. Although we do not Disclosures. Virginia Bellido has served as a yet have data regarding the optimal glycemic consultant for or received research support, targets for inpatients with COVID-19, it is clear lecture fees or travel reimbursement from that extremes of BG can lead to poor outcomes, Abbott, Sanofi Aventis, Novo Nordisk, Eli Lilly, and that insulin is the most appropriate treat- MSD, Boehringer Ingelheim, Esteve, Novartis, ment for effectively controlling glycemia in and Astra Zeneca. hospital. A target glucose range of 110–180 mg/ Antonio Pérez has served as a consultant for or dL (6.1–10.0 mmol/L) may be appropriate for received research support, lecture fees or travel most critically and noncritically ill patients, reimbursement from Sanofi Aventis, Almirall, individualized according to patient characteris- Novo Nordisk, Eli Lilly, MSD, Boehringer Ingel- tics and clinical situation. A continuous intra- heim, Esteve, Gilead, Novartis, Amgen, Menar- venous insulin infusion and scheduled basal- ini, and Astra Zeneca. bolus correction insulin are the preferred regi- mens for glycemic control in critically and Compliance with Ethics Guidelines. This noncritically ill hospitalized patients, respec- article is based on previously conducted studies tively. An individualized approach adapting the and does not contain any studies with human established recommendations may reduce the Diabetes Ther participants or animals performed by any of the and practical considerations. Diabetes Metab Syndr. authors. 2020;14:303–10. 6. Umpierrez GE, Isaacs SD, Bazargan N, You X, Thaler Data Availability. Data sharing is not LM, Kitabchi AE. Hyperglycemia: an independent applicable to this article as no datasets were marker of in-hospital mortality in patients with generated or analyzed during the current study. undiagnosed diabetes. J Clin Endocrinol Metab. 2002;87:978–82. Open Access. This article is licensed under a 7. Pérez A, Ramos A, Carreras G. Insulin therapy in Creative Commons Attribution-NonCommer- hospitalized patients. Am J Ther. 2020;27:e71–8. cial 4.0 International License, which permits any non-commercial use, sharing, adaptation, 8. Umpierrez GE, Smiley D, Jacobs S, et al. Random- ized study of basal-bolus insulin therapy in the distribution and reproduction in any medium inpatient management of patients with type 2 dia- or format, as long as you give appropriate credit betes undergoing general surgery (RABBIT 2 sur- to the original author(s) and the source, provide gery). Diabetes Care. 2011;34:256–61. a link to the Creative Commons licence, and 9. Yang JK, Feng Y, Yuan MY, et al. Plasma glucose indicate if changes were made. The images or levels and diabetes are independent predictors for other third party material in this article are mortality and morbidity in patients with SARS. included in the article’s Creative Commons Diabet Med. 2006;23:623–8. licence, unless indicated otherwise in a credit 10. Sardu C, D’Onofrio N, Balestrieri ML, et al. Out- line to the material. If material is not included comes in patients with hyperglycemia affected by in the article’s Creative Commons licence and Covid-19: can we do more on glycemic control? your intended use is not permitted by statutory Diabetes Care. 2020;43(7):1408–15. regulation or exceeds the permitted use, you 11. Zhu L, She Z-G, Cheng X, et al. Association of blood will need to obtain permission directly from the glucose control and outcomes in patients with copyright holder. To view a copy of this licence, COVID-19 and pre-existing type 2 diabetes. Cell visit http://creativecommons.org/licenses/by- Metab. 2020;31(6):1068–77.e3. nc/4.0/. 12. 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