Endos Discuss Diabetic Ketoacidosis in COVID-19, Dexamethasone

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A new article in the Journal of Clinical Endocrinology & Metabolism (JCEM) addresses unique concerns and considerations regarding diabetic ketoacidosis (DKA) in the setting of COVID-19.

Corresponding author Marie E. McDonnell, MD, director of the diabetes program at Brigham and Women's Hospital, Boston, Massachusetts, discussed the recommendations with Medscape Medical News and also spoke about the news this week that the corticosteroid dexamethasone reduced death rates in severely ill patients with COVID-19.

The full JCEM article, by lead author Nadine E. Palermo, DO, Division of Endocrinology, Diabetes, and Hypertension, also at Brigham and Women's Hospital, covers DKA diagnosis and triage, and emphasizes that usual hospital protocols for DKA management may need to be adjusted during COVID-19 to help preserve personal protective equipment and ICU beds.

"Hospitals and clinicians need to be able to quickly identify and manage DKA in COVID patients to save lives. This involves determining the options for management, including when less intensive subcutaneous insulin is indicated, and understanding how to guide patients on avoiding this serious complication," McDonnell said in an Endocrine Society statement.

What About Dexamethasone for Severe COVID-19 in Diabetes?

The new article briefly touches on the fact that upward adjustments to intensive intravenous insulin therapy for DKA may be necessary in patients with COVID-19 who are receiving concomitant corticosteroids or vasopressors.

But it was written prior to the June 16 announcement of the "RECOVERY" trial results with dexamethasone. The UK National Health Service immediately approved the drug's use in the COVID-19 setting, despite the fact that there has been no published article on the findings yet.

McDonnell told Medscape Medical News that she would need to see formal results to better understand exactly which patients were studied and which ones benefitted.

"The peer review will be critical. It looks as if it only benefits people who need respiratory support, but I want to understand that in much more detail," she said. "If they all had acute respiratory distress syndrome (ARDS)," that's different.

"There are already some data supporting steroid use in ARDS," she noted, but added that not all of it suggests benefit.

She pointed to one of several studies now showing that diabetes, and hyperglycemia among people without a prior diabetes diagnosis, are both strong predictors of mortality in hospitalized patients with COVID-19.

"There was a very clear relationship between hyperglycemia and outcomes. We really shouldn't put people at risk until we have clear data," she said.

If, once the data are reviewed and appropriate dexamethasone becomes an established treatment for severe COVID-19, hyperglycemia would be a concern among all patients, not just those with previously diagnosed diabetes, she noted.

"We know a good number of people with prediabetes develop hyperglycemia when put on steroids. They can push people over the edge. We're not going to miss anybody, but treating steroid-induced hyperglycemia is really hard," McDonnell explained.

She also recommended 2014 guidance from Diabetes UK and the Association of British Clinical Diabetologists, which addresses management of inpatient steroid-induced DKA in patients with and without pre-existing diabetes.

Another major concern, she said, is "patients trying to get dexamethasone when they start to get sick," because this is not the right population to use this agent.

"We worry about people who do not need this drug. If they have diabetes they put themselves at risk of hyperglycemia, which then increases the risk of severe COVID-19. And then they're also putting themselves at risk of DKA. It would just be bad medicine," she said.

Managing DKA in the Face of COVID-19: Flexibility Is Key

In the JCEM article, Palermo and colleagues emphasizes that the usual hospital protocols for DKA management may need to be adjusted during COVID-19 in the interest of reducing transmission risk and preserving scare resources.

They provide evidence for alternative treatment strategies, such as the use of subcutaneous rather than intravenous insulin when appropriate.

"We wanted to outline when exactly you should consider nonintensive management strategies for DKA," McDonnell further explained to Medscape Medical News.

"That would include those with mild or some with moderate DKA...The idea is to remind our colleagues about that, because hospitals tend to operate on a protocol-driven algorithmic methodology, they can forget to step off the usual care pathway even if evidence supports that," she said.

But on the other hand, she also said that in some very complex or severely ill patients with COVID-19, classical intravenous insulin therapy makes the most sense even if their DKA is mild.

The Outpatient Setting: Prevention and Preparation

The new article also addresses several concerns regarding DKA prevention in the outpatient setting.

As with other guidelines, it includes a reminder that patients with diabetes should be advised to discontinue sodium-glucose cotransporter 2 (SGLT2) inhibitors if they become ill with COVID-19, especially if they're not eating or drinking normally, because they raise the risk for DKA.

Also, for patients with type 1 diabetes, particularly those with a history of repeated DKA, "this is the time to make sure we reach out to patients to refill their insulin prescriptions and address issues related to cost and other access difficulties," McDonnell said.

The authors also emphasize that insulin starts and education should not be postponed during the pandemic. "Patients identified as meeting criteria to start insulin should be referred for urgent education, either in person or, whenever possible and practical, via video teleconferencing," they urge.

McDonnell has reported receiving research funding from Novo Nordisk. The other two authors have reported no relevant financial relationships.

J Clin Endocrinol Metab. Published online June 18, 2020. Abstract

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