July06, 2022,UK

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Increased DKA and Hyperglycemia During a COVID 19 Surge, a Retrospective Observation.
Eduardo E. Chang M.D. M.B.A 1*, Esther Segura M.D. 2, Sruthi Vellanki, M.D 3, Anup Kumar Trikannad Ashwini Kumar, M.D. 4, David Pham M.D. 5


1. M.B.A. Pulmonary, Sleep, Critical Care Specialist, Adjunct Clinical Assistant Professor of Medicine, University of Indiana School of Medicine, Terra Haute, Indiana.

2. Senior Patient Liaison, Methodist Hospital, Houston Texas.

3. Internal Medicine Specialist, Adjunct Clinical Assistant Professor of Medicine, Indiana University School of Medicine, Terra Haute, Indiana.

4. Internal Medicine Specialist, Clinical Director for Internal Medical Student Clerkships Program, Adjunct Clinical Assistant Professor of Medicine, Indiana University School of Medicine, Terra Haute Indiana.

5. Pulmonary Critical Care Specialist, Allianz Research Institute. Newport Beach, California.

Corresponding Author: Eduardo E. Chang M.D, M.B.A. Pulmonary, Sleep, Critical Care Specialist, Adjunct Clinical Assistant Professor of Medicine, University of Indiana School of Medicine, Terra Haute, Indiana.

Copy Right: © 2022 Eduardo E. Chang M.D, This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Received Date: May 27, 2022

Published Date: June 10, 2022


Abstract

During the middle of a COVID-19 surge a retrospective review of cases in a COVID ICU was performed over a one month of surge. All patients had COVID-19 confirmed by PCR testing and had a degree of respiratory insufficiency ranging from hypoxemia corrected with a minimum of 2 liters of oxygen by nasal cannula up to 100 percent oxygen with mechanical ventilation.  They all had lung protective strategies and mechanical proning.  We saw an average of 20 percent of our patient population having active DKA and a significant increase in hyperglycemia in the rest of the patients.  These findings are consistent with similar observations seen in multiple ICUs in America and the world. Increased morbidity and mortality have been reported in these patients, indicating prompt attention in correcting fluid status, insulin supplementation and electrolyte imbalances as a priority by the intensive care team. Furthermore, all COVID patients receiving steroids as part of the anti-inflammatory therapy should be monitored for abnormal or worsening blood sugars.

Increased DKA and Hyperglycemia During a COVID 19 Surge, a Retrospective Observation.

Patient: Multiple, Retrospective Review of cases over a period of 1 month in the Middle of a COVID 19 Surge.

Final Diagnoses: DKA, COVID-19, Diabetes, Hypoxic Respiratory Failure

MeSH Keywords: DKA, COVID-19, Diabetes, Hypoxic Respiratory Failure, Glycemic Control, Hyperosmolar Hyperglycemia State

Objective: Unusual clinical course


Background

Diabetes has been associated as a major risk factor in developing complications with severe SARS-CoV-2 infection. Most of these patients have DM type 2.  Over the past year there has been an increase in type 2 diabetics presenting with diabetic ketoacidosis (DKA).  Several adult patients with Diabetes Mellitus have presented with COVID related DKA.

DKA is the most common hyperglycemic emergency in the ICU seen in the middle of the surge with Omicron, Delta and with previous COVID strain surges in America. We have seen an increase in diabetic patients presenting concomitant infection with SARS-CoV-2.  The US has surpassed 990,000 fatalities, with over 80 million cases in America. 

There has been an increase in numbers of type 1 and 2 diabetic patients with COVID-19.  These patients have an increased rate of morality compared to non-COVID-19 patients.  Traditional viral infections have increased the likelihood of the destruction of β-cells in people with underlying genetic risk for diabetes.  The unregulated immune response as the virus attaches to the ACE 2 receptors can also cause direct destruction of the pancreatic βeta cells.  SARS-CoV-2 can cause direct destruction of β-cell in the pancreas causing hyperglycemia as further damage of endogenous insulin is exacerbated by direct viral infection.  This can fuel a more robust proinflammatory cytokine response, increase in C reactive protein and pro inflammatory cytokines IL-6 that have been associated with an increased mortality.

Prior to the pandemic, the most common risk factors for admitting DKA patients to the ICUs had been low socioeconomic status, younger age, female patients, and elevated hemoglobin A1C.  It is possible that social isolation itself, self-quarantine and poor access to care or medication can also be contributing factors to increases in DKA during the pandemic.  Prior to COVID, America already had an epidemic of obesity with over 40 percent of its citizens being obese and more than 10 percent of the citizens, over 34 million being diabetic.  As Delta, Omicron and other strains propagated and exerted direct damage to the pancreatic cells causing further decreased insulin production and promoting inflammation. DKA patients have a higher risk and mortality in our hospitals, and ICUs.  The large body habitus, large frame and increased BMI have worse outcomes and can succumb to multiorgan dysfunction.


Methods

A retrospective review of cases during one month in the middle of the pandemic was performed. We had full capacity of 25 ICU beds.  At any one point we had over 20 patients with a blood sugar > 275 mg /dl, average admission of 4-5 new COVID patients per day. I personally rounded on all of them.  Blood Glucose level > 360.  Bicarbonate level less than 19. Anion Gap > 12 on all of them pH less than 7.25 on all of them.  Positive ketonemia or ketonuria. All the patients had the above-mentioned parameters.  These figures represent about 20 percent of all COVID patients seen any day during the week.  All patients had hypoxic respiratory failure requiring supplemental oxygen, high flow or mechanical ventilation. All patients without DKA had blood sugars of > 200.


Results

There was a 20 percent of patient increased in DKA patients in the middle of this surge in our ICU.  These patients had SARS-CoV-2. All had BMI > 30, 75 percent Caucasian and 25 percent Afro-American, 40 percent of the patients had BMI of 35 percent.  All patients were hypoxic, all had ground glass opacities, all were treated with Remdesivir, steroids and antibiotics. All required oxygen supplementation from 28 percent oxygen to 100 percent on the ventilator.  All of them had protracted hospitalizations, and despite the complex management of this group, they all survived, and all were in the acute hospital for more than 2 weeks.  The main limiting factor for discharge was their high oxygen requirements.  All had abnormal HgA1c and were diabetic. Of these patients, 85 percent were not vaccinated, only three had been vaccinated. Of these, 2 had been treated with chemotherapy for lung cancer and 1 with  Rituximab for systemic lupus erythematosus (SLE).  The average age for this cohort was 48.15 years.


Discussion

The observation of this retrospective series reveals many diabetes patients with DKA were admitted during the middle of a surge of both Delta and Omicron strains in a COVID ICU.  All these patients had increased BMI > 35 and all presented hypoxemia. They were all treated with Remdesivir, steroids, fluids, and antibiotics.  All had prolonged hospital admissions of greater than 2 weeks.  Eighty fiver percent (17) of these patients were not vaccinated and fifteen percent (3)   had vaccines. Out of the three that had vaccines, two had underlying malignancy and one was treated with Anti-CD20, Rituximab for SLE.  75 percent were Caucasian, while 25 percent Afro-American.  All had elevated random blood sugars > 350 as well as abnormal HgA1c.  

This data set shows a high number of patients were not vaccinated and it suggests that malignancy or autoimmunity is also a strong comorbidity for COVID-19 patients in the ICU. All patients received fluids and standard insulin replacement to close the anion gap. They were all able to leave the ICU and continue their medical care on a COVID medical unit.


Conclusion

DKA and Diabetes has been reported in the world literature to be more prevalent during the pandemic.  BMI seems to be the highest risk factor. Abnormal blood sugars are also associated with a high mortality.  Any viral infection or secondary infection promotes the pro inflammatory cascade. This increased hyperglycemia, and the direct viral destruction of βeta cells in the pancreas further exacerbate and compound the hyperglycemic effect.  Hydration is necessary with insulin supplementation and replacement.  Most of these patients presented with morbid obesity, representing an independent risk factor of mortality which is compounded by diabetes. Evaluation for end organ damage due to chronic hyperglycemia is recommended.  The use of serial labs, re-expansion of intravascular volume with the adjusted insulin infusion is needed to close the anion gap and subsequently stop glycolysis.  The need for follow up care with endocrinology or primary physicians is necessary and diabetic education should be performed on all patients upon discharge from the ICU.

There appears to be a higher incidence of hyperglycemia associated with ketosis in COVID-19 septic patients. It is unknown if this ketosis is associated with sepsis related syndrome versus diabetic related β-cell destruction.  There is also no long-term data yet on post COVID recovered patients showing increased insulin requirements.  There is a need for further evaluation if insulin deficiency long term is a related effect of post COVID-19 survival.  Another key question to be further evaluated is to see if acute COVID-19 infections will create long term sub-acute diabetes versus long term increased insulin requirements for diabetics. 


References

1. Vellanki, P., & Umpierrez, G. E. (2021). Diabetic ketoacidosis risk during the COVID-19 pandemic. The Lancet. Diabetes & Endocrinology.

2. Nadine E Palermo, Archana R Sadhu, Marie E McDonnell, Diabetic Ketoacidosis in COVID-19: Unique Concerns and Considerations, The Journal of Clinical Endocrinology & Metabolism, Volume 105, Issue 8, August 2020, Pages 2819–2829, https://doi.org/10.1210/clinem/dgaa360

3. Pal, R., Banerjee, M., Yadav, U., & Bhattacharjee, S. (2020). Clinical profile and outcomes in COVID-19 patients with diabetic ketoacidosis: a systematic review of literature. Diabetes & Metabolic Syndrome: Clinical Research & Reviews, 14(6), 1563-1569.

4. Palermo, N. E., Sadhu, A. R., & McDonnell, M. E. (2020). Diabetic ketoacidosis in COVID-19: unique concerns and considerations. The Journal of Clinical Endocrinology & Metabolism, 105(8), 2819-2829.

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