Hyperglycemia and COVID-19: Why Management of Glucose Levels Is Essential

woman in hospital bed
An infected patient in quarantine lying in bed in hospital, coronavirus concept.
Hyperglycemia may worsen outcomes in COVID-19 due to a rapid inflammatory response and increased glycosylation of the ACE2 receptor.

Researchers have found that hyperglycemia in patients with novel coronavirus disease 2019 (COVID-19) is linked to significantly worse outcomes, indicating a need for early normalization of glucose levels.1 In one study of 1122 patients with COVID-19 treated in 88 hospitals across the United States, the presence of diabetes or uncontrolled hyperglycemia was linked to a longer length of hospital stay and higher mortality risk (28.8% vs 6.2% in the comparison group without hyperglycemia). Antonio Ceriello, MD, head of the diabetes department at the Scientific Institute for Research, Hospitalization, and Healthcare Multimedica in Milan, Italy, commented on this association and emphasized the need for rapid glucose control in patients with COVID-19 in an editorial published in Diabetes Research and Clinical Practice.2

Dr Ceriello proposed that a rapid inflammatory response and increased glycosylation of the angiotensin-converting enzyme 2 (ACE2) receptor may increase COVID-19 disease severity given a higher propensity for cellular intrusion of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) via the ACE2 receptor. These factors may explain why hyperglycemia affects COVID-19 prognosis. Dr Ceriello added that it is the amount of glycosylated ACE2, not just the amount of ACE2, that is associated with viral binding and fusion.2

In the same editorial article, he suggested that “a fast normalization of hyperglycemia during COVID-19 may [result] in a decrease of inflammatory cytokines release and in a lower ACE2 binding capacity for the virus, two facts which consistently might help in improving the prognosis in people affected by SARS-CoV- 2.”

We interviewed Dr Ceriello to learn more about these associations.

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What are implications for glucose control in the management of critical care patients with COVID-19?

It is already know that hyperglycemia in people in the intensive care unit (ICU) worsens the prognosis. In the case of COVID-19, there are at least 2 more reasons why hyperglycemia can be dangerous: it produces a huge cytokine release and favors the nonenzymatic glycosylation of the ACE2 receptor.

The glycosylation of ACE2, a reaction that can be induced by hyperglycemia, is needed for the linkage of the virus to this cellular receptor. This mechanism, at the very early stage, is reversible.

Would you consider normalization of hyperglycemia at hospital admission to be one of the most important steps in caring for a patient with COVID-19? Should more attention be paid to elevated glucose levels in patients without diabetes?

Yes, for the aforementioned reasons. It is even more important in patients without diabetes.

How have hyperglycemia algorithms been adjusted at your institution to rapidly normalize glucose levels in the ICU setting, if at all?

We are following the Updated Yale Insulin Infusion Protocol for managing hyperglycemia during critical illness.

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1. Bode B, Garrett V, Messler J, et al. Glycemic characteristics and clinical outcomes of COVID-19 patients hospitalized in the United States [published online April 12, 2020]. J Diabetes Sci Technol. 2020; in press.

2. Ceriello A. Hyperglycemia and the worse prognosis of COVID-19. Why a fast blood glucose control should be mandatory [published online April 28, 2020]. Editorial. Diabetes Res Clin Pract. doi:10.1016/j.diabres.2020.108186