key: cord-0683835-n227rsc7
authors: Croft, Alexander; Bucca, Antonino; Jansen, Jaclyn H.; Motzkus, Christine; Herbert, Audrey; Wang, Alfred; Hunter, Benton R.
title: First-time Diabetic Ketoacidosis in Type 2 Diabetics with COVID-19 Infection: A Novel Case Series
date: 2020-07-08
journal: J Emerg Med
DOI: 10.1016/j.jemermed.2020.07.017
sha: 27555ab467e8b57ff98bc45c8088c31b10ca910b
doc_id: 683835
cord_uid: n227rsc7

Abstract Background SARS-CoV-2 is a novel coronavirus first diagnosed in US hospitals in January 2020. Typical presenting symptoms include fever, dry cough, dyspnea, and hypoxia. However, several other symptoms have been reported, including fatigue, weakness, diarrhea, and abdominal pain. We have identified a series of patients with diabetic ketoacidosis (DKA) likely precipitated by COVID-19. Case Series We describe five patients with previously known type 2 diabetes and no history of DKA, who presented to the emergency department with new-onset DKA and COVID-19. Why should an emergency physician be aware of this? Diabetes mellitus is a known risk factor for poor outcomes in viral respiratory illnesses, including COVID-19. Infection may precipitate DKA in patients with type 2 diabetes. Aggressive management of these patients is recommended; however, management guidelines have not yet been put forth for this unique subset of patients.

cases triggered by infection. 5 DKA confers a mortality rate of approximately 5%, but notably higher 50 mortality rates occur in the elderly and patients with concurrent acute illnesses. 5 The overall mortality in 51 patients with COVID-19 is likely to be approximately 1-3%. However, among patients with diabetes, 52 mortality may be over 7%, and likely higher in the elderly diabetic population. 3, 6 We are unaware of any 53 reports of DKA among COVID-19 patients or the associated mortality risk. It is unknown whether the 54 mortality of these two conditions is additive or even exponential. Given the high-risk nature of both DKA 55 and COVID-19, it is paramount that DKA be quickly recognized in patients with concern for COVID-19 56 and conversely that COVID-19 is considered as a precipitant for DKA.

To our knowledge, there are no reported cases of new-onset DKA in patients with DM2 and 58 COVID-19 infection. In this novel case series, we report five patients who presented to the emergency 59 department (ED) with a spectrum of respiratory complaints and were found to be in DKA, likely 60 precipitated by COVID-19.

This case series was granted exempt status by the local Institutional Review Board. Table 1 62 provides demographic and laboratory details for each patient. Figure 1 shows the chest x-ray findings of 63 the presented cases.

Case 1

A 55-year old African-American male with DM2 was brought in from home for altered mental 66 status and hypoxia. He reported a cough for several days prior, and on the day of presentation had become 67 confused. His initial prehospital oxygen saturation was 35%. He was given oxygen via non-rebreather 68 mask and brought to the ED, where he was persistently hypoxic to 66% and was subsequently intubated. (Table 1) . She was tachycardic but normotensive, with tachypnea and moderate respiratory distress. She 84 was started on an intravenous insulin drip and IV crystalloid fluids in addition to antibiotics and hydroxychloroquine for multifocal pneumonia. She was admitted to a medical ward, her anion gap closed, 86 and she was transitioned to subcutaneous insulin before being discharged from the hospital. She tested 87 positive for COVID-19 on hospital day 2. Upon follow up, she was doing well at home. 

He was started on an intravenous insulin drip and given crystalloid fluids. He was admitted to a 94 medical ward where his anion gap resolved, and he was transitioned to a subcutaneous insulin regimen.

He tested positive for COVID-19 on hospital day 2 and was discharged on hospital day 3. He has 96 remained stable and recently was seen for follow up with improved glycemic control.

Case 4:

A 45-year-old Hispanic female with a history of DM2, non-adherent with medication, presented 99 to the ED with concerns for COVID-19 after developing headache, myalgias, anorexia, and fever. She 100 had previously been managed with oral antihyperglycemics but had stopped taking her medications two 101 months prior to presentation.

The patient was ill-appearing, with tachypnea and clinical dehydration. Initial laboratory 103 findings showed DKA. She was admitted to a medical ward and treated with intravenous insulin and 104 crystalloid fluids. Her anion gap resolved after twelve hours, and she was transitioned to a subcutaneous 105 insulin regimen. Her COVID-19 testing returned positive on hospital day two. She was discharged after 106 two days and has not returned to the ED. 

Initial laboratory studies (Table 1) 134 may play a role in the insulin dysregulation seen in these patients. 10 Another possibility is that these 135 patients were sustaining pancreatic injury to beta-islet cells, as a recent study has shown a high rate of 136 pancreatic injury in COVID-19 infection. 11 It is important to note that in our case series, all patients had 137 a relatively high hemoglobin A1c, ranging from 9.5 to 11.9 This may suggest that suboptimal glucose 138 control predisposes to more severe forms of COVID-19 or to the precipitation of DKA. We also note that 

H1N1 Influenza Infection Complicated 183 with diabetic ketoacidosis

Connecting type 1 and type 2 diabetes through innate immunity

Dysregulation of immune response in patients with COVID-188 19 in Wuhan

Mechanisms of inflammatory responses and development of 190 insulin resistance: How are they interlinked?

Journal Pre-proof Pancreatic injury 192 patterns in patients with COVID-19 pneumonia

Management of Critically Ill Adults with COVID-19

Conflicts of Interest: 199 No authors have any conflicts of interest

Figure 1: Features of chest radiograph of selected cases. (A) Case 1, bilateral interstitial 202 opacifications with endotracheal tube in place. (B) Case 2, mild interstitial prominence of left 203 lower lobe

In the midst of the current pandemic, COVID-19 infection should be considered as a possible