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Inpatient Diabetes and Hyperglycemia Management Protocol in the COVID-19 Era

  • Faisal A. Aljehani
    Correspondence
    Corresponding author at: Division of Endocrinology, Diabetes & Metabolic Diseases, Medical University of South Carolina, Clinical Sciences Building, CSB 96 Jonathan Lucas Street, Floor: 8th Floor Suite: 822, MSC Code: 624, Charleston, SC 29425, United States.
    Affiliations
    Division of Endocrinology, Diabetes and Metabolic Diseases, Medical University of South Carolina, Clinical Sciences Building, CSB 96 Jonathan Lucas Street, Floor: 8th Floor Suite: 822, MSC Code: 624, Charleston, SC 29425, United States

    Ralph H. Johnson Veteran Affairs Medical Center, 109 Bee Street, Charleston, SC 29401, United States

    University of Jeddah, Hamzah Ibn Al Qasim Street, Al Sharafeyah, Jeddah 23218, Saudi Arabia
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  • Katalina Funke
    Affiliations
    Division of Endocrinology, Diabetes and Metabolic Diseases, Medical University of South Carolina, Clinical Sciences Building, CSB 96 Jonathan Lucas Street, Floor: 8th Floor Suite: 822, MSC Code: 624, Charleston, SC 29425, United States

    Ralph H. Johnson Veteran Affairs Medical Center, 109 Bee Street, Charleston, SC 29401, United States
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  • Kathie L. Hermayer
    Affiliations
    Division of Endocrinology, Diabetes and Metabolic Diseases, Medical University of South Carolina, Clinical Sciences Building, CSB 96 Jonathan Lucas Street, Floor: 8th Floor Suite: 822, MSC Code: 624, Charleston, SC 29425, United States

    Ralph H. Johnson Veteran Affairs Medical Center, 109 Bee Street, Charleston, SC 29401, United States
    Search for articles by this author
      Dear Editor
      Diabetes and hyperglycemia are among the most common problems in hospitalized patients.
      Their management may be challenging due to high volume demand, the limited number of specialty providers, and lack of knowledge or availability of standardized protocols. Insulin is one of the most crucial and effective medications used to treat hyperglycemia in health care systems but is also one of the most frequently involved in creating safety problems if not properly administered and monitored. Human error and possible miscommunication between the different layers of health care providers play a major role in the mismanagement of hyperglycemia among hospitalized patients. Standardizing common processes and procedures are strategies to improve human factors in the health care environment. Examples include avoiding reliance on memory by providing an updated, comprehensively reviewed, and simplified diagram that explains the steps of a process or procedure. Here we present a flow chart (Fig. 1) for the management of diabetes and hyperglycemia in non-critically ill patients as an attempt to standardize a protocol that may be used across different services in the hospital without the need of a diabetes specialist.
      Fig 1
      Figure 1Inpatient diabetes/hyperglycemia management protocol for non-critically ill patients in COVID-19 era.
      Abbreviations: A1C, hemoglobin A1c; AC, before meals; BG, blood glucose; BID, twice daily; DKA, diabetes ketoacidosis; DM, diabetes mellitus; HS, bedtime; HHS, hyperosmolar hyperglycemic state; IV, intravenous; NPO, nothing by mouth; SQ, subcutaneous; TDD, total daily dose; Q4h, every four hours; QD, once daily.
      * Degree of hyperglycemia definition adapted from Pasquel 2019.
      ** Discharge recommendations adapted from Umpierrez 2014.
      References:
      1. Pasquel FJ, Fayfman M, Umpierrez GE. Debate on insulin vs non-insulin use in the hospital setting-is it time to revise the guidelines for the management of inpatient diabetes? Current Diabetes Reports. 2019;19(9):65.
      2. Umpierrez GE, Smiley D, Jacobs S, et al. Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery). Diabetes Care. 2011;34(2):256‐261. doi:10.2337/dc10–1407
      3. Inzucchi SE. Clinical practice. Management of hyperglycemia in the hospital setting. The New England Journal of Medicine. 2006;355(18):1903–11. doi:10.1056/NEJMcp060094
      4. Umpierrez GE, Reyes D, Smiley D, et al. Hospital discharge algorithm based on admission HbA1c for the management of patients with type 2 diabetes. Diabetes Care. 2014;37(11):2934‐2939. doi:10.2337/dc14–0479.
      Recent studies suggest that patients with diabetes may be at a higher risk of severe COVID-19 infection.
      • Guan W.J.
      • Ni Z.Y.
      • Hu Y.
      • et al.
      Clinical characteristics of coronavirus disease 2019 in China.
      At present, establishing a diagram that can be used anywhere in the hospital became a necessity since the COVID-19 global pandemic has added major challenges to a complex problem. Therefore, it is essential to adequately treat hospitalized patients while protecting health care workers and minimizing contact exposure due to a lack of personal protective equipment and available staff. Additionally, patients who do not have diabetes, but may be at higher risk for diabetes, should be monitored closely for the development of hyperglycemia. Due to the cytokine storm and pronounced inflammation associated with COVID-19, steroids may be used which result in increased hyperglycemia and the subsequent need to promote euglycemia using either SQ or IV insulin. Clinicians caring for patients with COVID-19 need to be aware of these possible outcomes.
      • Bornstein S.R.
      • Rubino F.
      • Khunti K.
      • et al.
      Practical recommendations for the management of diabetes in patients with COVID-19.
      • Korytkowski M.
      • Antinori-Lent K.
      • Drincic A.
      • et al.
      A pragmatic approach to inpatient diabetes management during the COVID-19 pandemic.
      • Pasquel F.J.
      • Umpierrez G.E.
      Individualizing inpatient diabetes management during the coronavirus disease 2019 pandemic.
      Strategies include lessening the frequency of blood glucose (BG) checks in patients receiving SQ insulin regimens or insulin infusions and attempting treatment of diabetic ketoacidosis/hyperosmolar hyperglycemic state (DKA/HHS) with a SQ insulin regimen. Diabetes self-management has been considered in the past to be safe and effective in select patients,
      American Diabetes Association. 15
      Diabetes care in the hospital: standards of medical care in diabetes-2020.
      and consideration should be given to allow a patient with intact mental status and adequate diabetes management skills to administer insulin and measure blood glucose. This would include permitting patients to continue to use and manage outpatient continuous glucose monitoring devices (CGM) and insulin pumps if they are well controlled and without contraindications such as DKA/HHS, undergoing a procedure or surgery, encephalopathy or sedation which may prevent their ability to adequately manage their CGM or insulin pump.
      Insulin dosing may be challenging for providers in hospitalized patients; however, studies have shown that weight-based dosing is an effective and safe way to estimate insulin needs. Here in Table 1, we suggest a dosing approach adapted from Magaji and Johnston
      • Magaji V.
      • Johnston J.M.
      Inpatient management of hyperglycemia and diabetes.
      and Umpierrez et al.
      • Umpierrez G.E.
      • Hellman R.
      • Korytkowski M.T.
      • et al.
      Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline.
      Total daily dose (TDD) of insulin should be given as 50% basal insulin and 50% prandial insulin. We suggest considering basal insulin with correction scale instead of correction scale only; this is based on the ADA recommendations and multiple studies that were included in a meta-analysis.
      American Diabetes Association. 15
      Diabetes care in the hospital: standards of medical care in diabetes-2020.
      ,
      • Christensen M.B.
      • Gotfredsen A.
      • Norgaard K
      Efficacy of basal-bolus insulin regimens in the inpatient management of non-critically ill patients with type 2 diabetes: a systematic review and meta-analysis.
      Prandial insulin should be considered if needed to treat postprandial hyperglycemia. For correction scale insulin, we suggest using an approach included in Table 2, but other approaches are available and may be used.
      • Umpierrez G.E.
      • Hellman R.
      • Korytkowski M.T.
      • et al.
      Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline.
      However, due to the possible lack of PPE and staff exposure, modifications are made to these regimens, to minimize risk for all involved in caring for patients with COVID-19.
      • Pasquel F.J.
      • Umpierrez G.E.
      Individualizing inpatient diabetes management during the coronavirus disease 2019 pandemic.
      Daily insulin adjustments may be a challenging task. There are no validated protocols for these adjustments. However, an approach based on an extensive literature review is outlined in Fig. 1. Other daily insulin strategies may be followed such as the protocol employed in the RABBIT 2 trial.
      • Umpierrez G.E.
      • Smiley D.
      • Jacobs S.
      • et al.
      Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery).
      TABLE 1Total daily dose (TDD)* of insulin estimates in non-critically ill patients.
      TDD for insulinPatient group
      0.4 unit/kg body weight- Normal BMI if admission BG 140–200 mg/dl and A1c is controlled
      0.5 unit/kg body weight- Normal BMI if admission BG >200 mg/dl and/or A1c is not controlled

      - BMI 25–30
      0.2–0.3 unit/kg body weightConditions with high risk of hypoglycemia:

      - Age >70

      - Liver disease (AKI or CKD especially on HD)

      - Liver disease

      - Underweight
      0.6 unit/kg body weightConditions associated with Insulin resistance:

      - BMI>30

      - Glucocorticosteroids therapy.
      Abbreviations: A1c, hemoglobin A1c; AKI, acute kidney injury; BG, blood glucose; BMI, body mass index; CKD, chronic kidney disease; HD, hemodialysis.
      *Total daily dose (TDD) of insulin should be given as 50% basal insulin and, if needed, 50% prandial insulin.
      Table 1 References:
      1. Magaji V, Johnston JM. Inpatient management of hyperglycemia and diabetes. Clinical Diabetes. 2011;29(1):3.
      2. Umpierrez GE, Hellman R, Korytkowski MT, Kosiborod M, Maynard GA, Montori VM, et al. Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline. J Clin Endocrinol Metab. 2012;97(1):16–38.
      TABLE 2Insulin correction scale parameters.
      BG mg/dLUnits of insulin
      Daytime: ACNighttime: HSLow doseMedium doseHigh dose
      141–170171–220123
      171–220221–270246
      221–270271–320369
      271–320321–3704812
      321–370371–42051015
      Abbreviations: AC, before meals; BG, blood glucose; HS, bed time.
      The use of non-insulin anti-diabetic medications is another treatment option and should be considered if available. Metformin should be stopped in patients with suspected or COVID-19 positive patients due to the risk of dehydration and lactic acidosis.
      • Bornstein S.R.
      • Rubino F.
      • Khunti K.
      • et al.
      Practical recommendations for the management of diabetes in patients with COVID-19.
      • Korytkowski M.
      • Antinori-Lent K.
      • Drincic A.
      • et al.
      A pragmatic approach to inpatient diabetes management during the COVID-19 pandemic.
      • Pasquel F.J.
      • Umpierrez G.E.
      Individualizing inpatient diabetes management during the coronavirus disease 2019 pandemic.
      Sulfonylurea therapy needs to be used with caution in patients with declining renal function, the elderly and those prone for hypoglycemia, so it is best to avoid their use in patients infected with COVID-19.
      • Bornstein S.R.
      • Rubino F.
      • Khunti K.
      • et al.
      Practical recommendations for the management of diabetes in patients with COVID-19.
      • Korytkowski M.
      • Antinori-Lent K.
      • Drincic A.
      • et al.
      A pragmatic approach to inpatient diabetes management during the COVID-19 pandemic.
      • Pasquel F.J.
      • Umpierrez G.E.
      Individualizing inpatient diabetes management during the coronavirus disease 2019 pandemic.
      Sodium-glucose-co-transporter 2 inhibitors carry a risk of dehydration, diabetic ketoacidosis and genitourinary infections, so these drugs should be discontinued in suspected or high risk COVID-19 patients. These drugs include canagliflozin, dapagliflozin, ertugliflozin and empagliflozin.
      • Bornstein S.R.
      • Rubino F.
      • Khunti K.
      • et al.
      Practical recommendations for the management of diabetes in patients with COVID-19.
      • Korytkowski M.
      • Antinori-Lent K.
      • Drincic A.
      • et al.
      A pragmatic approach to inpatient diabetes management during the COVID-19 pandemic.
      • Pasquel F.J.
      • Umpierrez G.E.
      Individualizing inpatient diabetes management during the coronavirus disease 2019 pandemic.
      Glucagon-like peptide-1-receptor agonists may be associated with dehydration, nausea and vomiting. Since patients infected with COVID-19 may suddenly experience deterioration in their clinical status, it is advisable to stop these agents upon admission to the hospital or continue their use with extreme caution. These agents include albiglutide, dulaglutide, exenatide-extended release, liraglutide, lixisenatide, and semaglutide.
      • Bornstein S.R.
      • Rubino F.
      • Khunti K.
      • et al.
      Practical recommendations for the management of diabetes in patients with COVID-19.
      • Korytkowski M.
      • Antinori-Lent K.
      • Drincic A.
      • et al.
      A pragmatic approach to inpatient diabetes management during the COVID-19 pandemic.
      • Pasquel F.J.
      • Umpierrez G.E.
      Individualizing inpatient diabetes management during the coronavirus disease 2019 pandemic.
      Based on multiple randomized controlled trials, dipeptidyl peptidase 4 (DDP-4) inhibitors alone or combined with basal insulin could be considered as a safe and effective inpatient glycemic control strategy for patients with mild to moderate hyperglycemia. These agents include alogliptin, linagliptin, saxagliptin and sitagliptin. DDP-4 inhibitors alone have the potential to decrease hypoglycemia, insulin dose and use, and frequency of blood glucose checks.
      • Pasquel F.J.
      • Gianchandani R.
      • Rubin D.J.
      • et al.
      Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial.
      • Perez-Belmonte L.M.
      • Osuna-Sanchez J.
      • Millan-Gomez M.
      • et al.
      Glycaemic efficacy and safety of linagliptin for the management of non-cardiac surgery patients with type 2 diabetes in a real-world setting: Lina-Surg study.
      • Vellanki P.
      • Rasouli N.
      • Baldwin D.
      • et al.
      Glycaemic efficacy and safety of linagliptin compared to basal-bolus insulin regimen in patients with Type 2 diabetes undergoing non-cardiac surgery: a multicenter randomized clinical trial.
      Caution should be used in patients at high risk for heart failure given the FDA warning for this class of medications, although various cardiovascular outcome trials and a recent meta-analysis failed to show a significant increase of heart failure in patients treated with DDP-4 inhibitors.
      • Singh A.K.
      • Singh R.
      Heart failure hospitalization with DPP-4 inhibitors: a systematic review and meta-analysis of randomized controlled trials.
      Experts have suggested that we need to revise guidelines to allow more usage of non-insulin anti-diabetic medications for hospitalized patients.
      • Pasquel F.J.
      • Fayfman M.
      • Umpierrez G.E
      Debate on insulin vs non-insulin use in the hospital setting-is it time to revise the guidelines for the management of inpatient diabetes?.
      Given the dire situation presented by the COVID-19 global pandemic, we should accelerate this dialog to assess the positive impact that may be provided by utilization of agents requiring less monitoring, fewer healthcare provider contacts, and a lower risk of hypoglycemia. Health care providers and the community as a whole have entered uncharted territory during the COVID-19 pandemic, which has resulted in the development of innovations in delivering medical care while maintaining maximum patient and provider safety, which is a critical and challenging task.

      Author Contributions

      All authors contributed equally on this paper.

      Acknowledgments

      The authors would like to thank Dr. Maria Lopes-Virella for her support and assistance in editing the flow chart algorithm.

      References

        • Guan W.J.
        • Ni Z.Y.
        • Hu Y.
        • et al.
        Clinical characteristics of coronavirus disease 2019 in China.
        N Engl J Med. 2020; 382: 1708-1720
        • Bornstein S.R.
        • Rubino F.
        • Khunti K.
        • et al.
        Practical recommendations for the management of diabetes in patients with COVID-19.
        Lancet Diabetes Endocrinol. 2020; 8: 546-550
        • Korytkowski M.
        • Antinori-Lent K.
        • Drincic A.
        • et al.
        A pragmatic approach to inpatient diabetes management during the COVID-19 pandemic.
        J Clin Endocrinol Metab. 2020;
        • Pasquel F.J.
        • Umpierrez G.E.
        Individualizing inpatient diabetes management during the coronavirus disease 2019 pandemic.
        J Diabetes Sci Technol. 2020; 14: 705-707
        • American Diabetes Association. 15
        Diabetes care in the hospital: standards of medical care in diabetes-2020.
        Diabetes Care. 2020; 43: S193-202
        • Magaji V.
        • Johnston J.M.
        Inpatient management of hyperglycemia and diabetes.
        Clin Diabetes. 2011; 29: 3-9
        • Umpierrez G.E.
        • Hellman R.
        • Korytkowski M.T.
        • et al.
        Management of hyperglycemia in hospitalized patients in non-critical care setting: an endocrine society clinical practice guideline.
        J Clin Endocrinol Metab. 2012; 97: 16-38
        • Christensen M.B.
        • Gotfredsen A.
        • Norgaard K
        Efficacy of basal-bolus insulin regimens in the inpatient management of non-critically ill patients with type 2 diabetes: a systematic review and meta-analysis.
        Diabetes Metab Res Rev. 2017; 33: e2885
        • Umpierrez G.E.
        • Smiley D.
        • Jacobs S.
        • et al.
        Randomized study of basal-bolus insulin therapy in the inpatient management of patients with type 2 diabetes undergoing general surgery (RABBIT 2 surgery).
        Diabetes Care. 2011; 34: 256-261
        • Pasquel F.J.
        • Gianchandani R.
        • Rubin D.J.
        • et al.
        Efficacy of sitagliptin for the hospital management of general medicine and surgery patients with type 2 diabetes (Sita-Hospital): a multicentre, prospective, open-label, non-inferiority randomised trial.
        Lancet Diabetes Endocrinol. 2017; 5: 125-133
        • Perez-Belmonte L.M.
        • Osuna-Sanchez J.
        • Millan-Gomez M.
        • et al.
        Glycaemic efficacy and safety of linagliptin for the management of non-cardiac surgery patients with type 2 diabetes in a real-world setting: Lina-Surg study.
        Ann Med. 2019; 51: 252-261
        • Vellanki P.
        • Rasouli N.
        • Baldwin D.
        • et al.
        Glycaemic efficacy and safety of linagliptin compared to basal-bolus insulin regimen in patients with Type 2 diabetes undergoing non-cardiac surgery: a multicenter randomized clinical trial.
        Diabetes Obes Metab. 2018;
        • Singh A.K.
        • Singh R.
        Heart failure hospitalization with DPP-4 inhibitors: a systematic review and meta-analysis of randomized controlled trials.
        Indian J Endocrinol Metab. 2019; 23: 128-133
        • Pasquel F.J.
        • Fayfman M.
        • Umpierrez G.E
        Debate on insulin vs non-insulin use in the hospital setting-is it time to revise the guidelines for the management of inpatient diabetes?.
        Curr Diab Rep. 2019; 19: 65