key: cord-0939703-b64ijw5o
authors: Reddy, Pavan Kumar; Kuchay, Mohammad Shafi; Mehta, Yatin; Mishra, Sunil Kumar
title: Diabetic ketoacidosis precipitated by COVID-19: A report of two cases and review of literature
date: 2020-08-01
journal: Diabetes Metab Syndr
DOI: 10.1016/j.dsx.2020.07.050
sha: 1584c0b314cfb3f7736b1f18d54f0ee0246a32cb
doc_id: 939703
cord_uid: b64ijw5o

BACKGROUND AND AIMS: The relationship between severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) disease (COVID-19) and diabetes mellitus is bidirectional. On one hand, diabetes mellitus is associated with an increased risk of severe COVID-19. On the other hand, new onset diabetes and severe metabolic complications of pre-existing diabetes, including diabetic ketoacidosis (DKA) have been observed in patients with COVID-19. In this report, we describe two patient with diabetes mellitus who presented to our hospital with DKA. We also reviewed almost all published cases of DKA that had been precipitated by COVID-19. METHODS: Two patients were admitted with DKA, who were diagnosed to have COVID-19 on the basis of real time reverse transcription-polymerase chain reaction (RT-PCR) assay. Detailed history, anthropometry, laboratory investigations, imaging studies, clinical course and management outcomes were documented. RESULTS: First patient (30-year-male) had undiagnosed diabetes and no other comorbidities, and COVID-19 precipitated DKA. He also had COVID-19-associated pneumonia. Second patient (60-year-male) had long duration hypertension with no prior history of diabetes and developed cerebrovascular accident (CVA). He was also diagnosed with COVID-19 (RT-PCR assay) and DKA in the hospital. CVA and COVID-19 could have precipitate DKA. Both patients responded well to treatment and were discharged in a stable condition. CONCLUSIONS: These cases show that COVID-19 can precipitate DKA in a significant number of patients. DKA can occur in patients with pre-existing diabetes or newly diagnosed diabetes. As COVID-19 and diabetes are prevalent conditions, high degree of suspicion is required to diagnose DKA timely in order to improve the prognosis of COVID-19-related diabetic ketoacidosis.

In December 2019, unexplained severe viral pneumonia occurred in Wuhan, Hubei province, in China [1, 2] . A novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was isolated from patients with this pneumonia [3] . Since the COVID-19 pandemic began in China, more than and/or serum HCo3 <18 mmol/L.

Our first patient was a 30-year-old man who presented with general weakness, fever, loss of taste and mild dyspnea of 6 days' duration. He had a history of contact with a COVID-19 patient. He tested positive for SARS COV-2 on RT-PCR assay. He was initially managed at home. However, his condition worsened and presented to our emergency department with progressive breathlessness and unresolved fever. The patient reported no prior history of diabetes or other comorbidities. There was no family history of diabetes. At admission, his blood pressure was 152/84 mmHg, heart rate of 122 beats/min and respiratory rate of 24 breaths/min. His body temperature was 100°F, and oxygen saturation of 90% by pulse oximetry on room air. His investigations ( Table 1 ) revealed random plasma glucose of 555 mg/dL with venous blood gas analysis on room air demonstrating metabolic acidosis (pH-7.07 and HCO3-6.1mmol/L). Urine ketones were present. His glycosylated hemoglobin (HbA1c) was 9.6%. He was diagnosed to have moderate-severe DKA and management was initiated with initial intravenous fluid replacement He improved well with the above management (his metabolic acidosis improved, blood glucose levels stabilised, and blood parameters returned to normal). DKA resolved on the second day. Once patient stabilized, subcutaneous insulin was initiated. He was discharged in a stable condition with adequate education regarding the management of diabetes at home.

Our second patient was a 60-year-old man, who had a long duration hypertension. He had no personal history of diabetes. He presented to our emergency department with sudden onset uneasiness and inability to move the left upper limb associated with weakness of left lower limb. He was not able to walk. His initial blood pressure was 220/180 mm Hg, heart rate 126 beats/min, respiratory rate 26 breaths/min, and body temperature 99°F. His oxygen saturation was 92% by pulse oximetry on room air. Upon admission, random blood glucose was 582 mg/dL and HbA1c was 12.6%. Venous blood gas analysis on room air demonstrated a compensated metabolic acidosis (pH-7.30 and HCO3-13 mmol/L), urine ketones were present (Table 1) 

Herein we report two patients with DKA precipitated by COVID-19 in patients with underlying undiagnosed diabetes. The impact of diabetes on the severity of COVID-19 and occurrence of new onset diabetes and severe metabolic complications of pre-existing diabetes, including DKA and HHS in patients with COVID-19 pose challenges in clinical management [6] . DKA occurs as a result of insulin deficiency and increased counterregulatory responses, which favour the production of ketones. Interleukin-6 (IL-6) levels have been shown to be elevated in both DKA and COVID-19, and may be an important prognostic factor [7] . Both of our cases had elevated IL-6 levels ( Table 1 ). In our cases, there was no previous history of diabetes and the severe DKA episode that occurred leading to hospitalisation in an intensive care setting might be due to the triggering effect of COVID-19 on diabetes. The exact pathogenic mechanisms involved are yet to be determined. However, the role of the inflammatory cytokines released during the viral illness have been implicated.

The interactions between SARS-CoV-2 and the renin angiotensinaldosterone system (RAAS) might provide another mechanism in the pathophysiology of DKA [8] . Angiotensin-converting enzyme 2 (ACE2) is a crucial enzyme in the RAAS system. It catalyzes the conversion of angiotensin II to angiotensin. ACE2 is highly expressed in the lungs and pancreas. It serves as the entry point for SARS-CoV-2. Expression of ACE2 is downregulated after endocytosis of the virus complex [8, 9] . The possible implications of these interactions are twofold. Firstly, entry of SARS-CoV-2 into pancreatic islet cells may directly aggravate beta cell injury [10] .

Secondly, downregulation of ACE2 after viral entry can lead to unopposed angiotensin II, which may impede insulin secretion [11] . These 2 factors might have contributed to the acute worsening of pancreatic beta cell function and precipitated DKA in our patients. In addition, the relationship between SARS-CoV-2 and the RAAS can complicate DKA management. Excessive fluid resuscitation may potentiate acute respiratory distress. Therefore, proper fluid management is vital in these patients. Furthermore, angiotensin II stimulates aldosterone secretion, potentiating the risk of hypokalemia, which may necessitate more potassium supplementation in order to continue intravenous insulin to suppress ketogenesis. To our knowledge few reports of DKA in COVID-19 have been published. Table 2 shows the summary of all the previous published reports [5, 11, 12, 16] .

Emerging information suggests that individuals with diabetes are at increased risk for complications including death among COVID-19 patients. According to a clinical report in China involving 1,099 confirmed COVID-19 patients, diabetes was the second most common comorbidity (16.2%) among severe 173 cases [14] . There are not enough evidences to determine the risk of diabetes for poor outcomes in COVID-19 patients yet, a small study showed that COVID-19 patients with diabetes were not only at higher risk of severe pneumonia but also release excessive inflammatory biomarkers [15] . Our patient 1 also had severe pneumonia based on the HRCT grading. These results suggest that people with comorbidities, especially with diabetes, are CRP, C-reactive protein, IL-6, interleukin-6. Fig. 1 Axial (A) and coronal (B) images of HRCT chest (patient 1) showing ground glass opacities and early consolidation changes in bilateral lower lung fields.

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