Link Between Diabetes and COVID-19 Is Credible, but Clinical Implications Are Unclear
The FLARE Four
- Observational data indicate that patients with diabetes are at higher risk of SARS-CoV-2 infection, severe COVID-19 illness and death than patients without diabetes
- Whether intrinsic properties of SARS-CoV-2 interact with diabetes and make presentations more severe has yet to be determined
- It is possible that a vicious cycle, where virulence properties of SARS-CoV-2 and acutely impaired glycemic control in patients with diabetes, directly contributes to the morbidity and mortality of COVID-19
- It is unclear whether alternative protocols for blood glucose management in critically ill patients with COVID-19 would improve outcomes
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Case series consistently identify diabetes mellitus as a risk factor for severe COVID-19. In a fast literature update posted on April 28, 2020, Janaki D. Vakharia, MD, a fellow in adult and pediatric endocrinology at Massachusetts General Hospital, discusses that issue and the related question of whether having COVID-19 makes diabetes presentations more severe.
Observational Data
In all but one of nine relevant studies in China, Italy and the U.S., the prevalence of diabetes in patients with COVID-19 was higher than that in the general population. (Most studies did not distinguish type 1 from type 2 diabetes.)
Further, patients with diabetes appear to be at higher risk of severe COVID-19 and death. No causal relationship has been established.
How Might Diabetes Exacerbate COVID-19?
Hyperglycemia is known to be capable of increasing the severity of viral infections. Based on in vitro studies of influenza, it may also promote viral replication.
Another hypothesis is that diabetes modulates the expression of angiotensin-converting enzyme 2 (ACE2), the principal cell-surface receptor for SARS-CoV-2.
COVID-19 and Diabetes Control
Acute infection is a known trigger for diabetic ketoacidosis. COVID-19 may predispose patients to severe hyperglycemia and ketoacidosis like any other acute infection or it may uniquely increase the risk.
There is a hypothesis that coronaviruses can cause transient beta-cell dysfunction, leading to acute hyperglycemia and relative insulin deficiency. This is supported by a study of 39 SARS patients with no history of diabetes. Twenty of them developed diabetes, all but two transiently. Furthermore, ACE2 has been identified in the pancreas of SARS patients.
A feedback loop might develop where SARS-CoV-2 infection leads to severe hyperglycemia, which leads to the upregulation of ACE2 in various organs, which leads to further viral entry and further inflammation.
Conclusions
Further study will reveal whether alternative blood glucose management protocols are needed in critically ill COVID-19 patients or whether clinicians should simply practice with a heightened awareness of potential complications from diabetes.
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Learn more about diabetes research at Mass General