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| CASE REPORT |
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| Year : 2023 | Volume
: 22
| Issue : 3 | Page : 388-391 |
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Management Difficulties in the Coexistence of Covid-19 Infection and Diabetic Ketoacidosis (Case Report; Two Children with Newly Diagnosed Diabetes)
Fatma Özgüç Comlek1, Gülsüm Sönmez2
1 Division of Pediatric Endocrinology, Gaziantep Children's Hospital, Gaziantep, Turkey
2 Division of Pediatric Infection Diasese, Gaziantep Children's Hospital, Gaziantep, Turkey
| Date of Submission | 04-Dec-2021 |
| Date of Decision | 22-Feb-2023 |
| Date of Acceptance | 24-Feb-2023 |
| Date of Web Publication | 4-Jul-2023 |
Correspondence Address:
Fatma Özgüç Comlek
Clinics of Paediatric Endocrinology, Gaziantep Children's Hospital, Gaziantep
Turkey
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/aam.aam_250_21
 Abstract | | |
Two 8-year-old girls were admitted to the emergency department with diabetic ketoacidosis (DKA) approximately 10 days apart. The patients with resistant severe acidosis and high infection parameters were diagnosed with COVID-19 by real-time reverse transcription-polymerase chain reaction test. Accompanying pneumonia was observed in one of the patients. Here, we aimed to discuss the difficulties in the management of patients with a new diagnosis of DKA with COVID-19 infection. In addition, we wanted to emphasize that COVID-19 infection may be effective in the development of diabetes in patients with a genetic predisposition.
| Abstract in French | | |
Résumé
Deux filles de 8 ans ont été admises aux urgences avec une acidocétose diabétique (ACD) à environ 10 jours d'intervalle. Les patients présentant une acidose sévère résistante et des paramètres d'infection élevés ont reçu un diagnostic de COVID-19 par un test de réaction en chaîne par transcription inverse et polymérase en temps réel. Une pneumonie d'accompagnement a été observée chez l'un des patients. Ici, nous avons cherché à discuter des difficultés de prise en charge des patients avec un nouveau diagnostic d'ACD avec infection au COVID-19. De plus, nous voulions souligner que l'infection au COVID-19 peut être efficace dans le développement du diabète chez les patients présentant une prédisposition génétique.
Mots-clés: Covid-19, Jacétoacidose diabétique, nouvelle
Keywords: COVID-19, diabetic ketoacidosis, new
How to cite this article:
Comlek FÖ, Sönmez G. Management Difficulties in the Coexistence of Covid-19 Infection and Diabetic Ketoacidosis (Case Report; Two Children with Newly Diagnosed Diabetes). Ann Afr Med 2023;22:388-91 |
How to cite this URL:
Comlek FÖ, Sönmez G. Management Difficulties in the Coexistence of Covid-19 Infection and Diabetic Ketoacidosis (Case Report; Two Children with Newly Diagnosed Diabetes). Ann Afr Med [serial online] 2023 [cited 2023 Sep 26];22:388-91. Available from: https://www.annalsafrmed.org/text.asp?2023/22/3/388/380155 |
| Introduction | |  |
In December 2019, severe cases of viral pneumonia of unexplained etiology were seen in Wuhan, Hubei province of China.[1] A novel coronavirus, named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), was isolated from these pneumonia patients.[1] Recent research has revealed that advanced age or the presence of underlying conditions such as cardiovascular disease, hypertension, diabetes mellitus, and obesity are risk factors for serious illness and death in COVID-19 patients.[2] Several case reports have also been published, showing that COVID-19 can trigger diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state in patients with poorly controlled diabetes and newly diagnosed diabetes.[3],[4] Here, we report two confirmed cases of COVID-19 infection presenting to our emergency department (ED) with DKA.
| Case Reports | | |
Case 1
An 8.5-year-old female patient presented to the ED in March 2021 with complaints of rapid breathing, unresponsiveness to audible stimuli, and a tendency to sleep. She had no known disease to explain her condition. She had no relatives with diabetes. In her physical examination, her heart rate was 121/min, respiratory rate: 45/min, blood pressure: 90/55 mmHg, oral mucosa was dry, and capillary filling time: 4 s. The tachypneic patient was performing Kussmaul breathing. The patient's Gloskow coma score was 11. Body weight was 25 kg (−0.68 SDS), height: 127 cm (−0.62 SDS). In the laboratory evaluation, venous blood gas analysis showed metabolic acidosis (Ph: 6.85, bicarbonate: 5.7 mmol/L, anion gap: −29.5 mmol/L), serum glucose 503 mg/dl and 3+ ketonuria, 3+ glucosuria, and none proteinuria in urine. Other laboratory results are in [Table 1]. In line with these findings, the patient was diagnosed with DKA, and her treatment was initiated in the pediatric intensive care unit and was first given a saline infusion at a dose of 10 ml/kg in 1 h. Empirical antibiotic therapy was started because of elevated C-reactive protein (CRP): 19.5 mg/dl (N: 0.01–6) and increased body temperature (38.1°). Subsequently, the presence of Possible COVID-19 infection was evaluated by reverse transcription-polymerase chain reaction (RT-PCR). After saline loading, 0.1 unit/kg/h insulin infusion and fluid were started with the DKA protocol according to International Society for Pediatric and Adolescent Diabetes (ISPAD) 2018.[5] In the follow-up, the potassium content in the fluid was adjusted to 40 meq/L–50 meq/L, depending on the serum potassium course. Sodium bicarbonate was given as a 1 h infusion at a dose of 1 meq/kg to her, whose blood pH (PH <6.9) value did not improve at the 2nd h of the follow-up. Although there was a decrease in blood glucose monitoring, the patient's acidosis did not improve, and the COVID-19 RT-PCR test was positive in the 5th-h follow-up. Pneumonic infiltrations were observed in the chest radiography [Figure 1] of the patient, who was receiving oxygen therapy between 8 and 10 lt/min with high-flow nasal cannula since the oxygen saturation was between 85% and 90% in room air, and it was evaluated as COVID-19 pneumonia. The patient was consulted with pediatric infectious diseases. With the recommendation of a pediatric infection specialist, ritonavir/lopinavir treatments were started according to the Turkish (TR) Ministry of Health Guidelines. Long-acting glargine insulin was administered subcutaneously to the patient at the 8th hour of follow-up, as recommended in many studies, while severe acidosis continued and she was receiving parenteral insulin infusion.[4],[5] During the follow-up, no decrease in the Glasgow coma scale was observed, and the patient's acidosis resolved at approximately 24 h (blood pH >7.3 and serum bicarbonate >15). She, who was followed up in the ward of COVID-19 patients, continued to need oxygen therapy for 2 more days. Her islet cell antibody (ICA): 94.2 U/ml (0–24) and, anti-GAD antibody: 66.7 IU/ml (0–17) were positive. After blood glucose regulation was provided, and diabetes education was completed, she was discharged on the 8th day with multiple insulin doses. | Figure 1: Case 1 – Chest radiography, there is a difference in aeration between the two lungs, and the aeration is reduced on the left
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Case 2
An 8-year-old girl presented to the ED with complaints of vomiting, inability to feed, and deterioration in general condition. She had no medical history to explain these complaints. She had no relatives with diabetes. On physical examination, she was susceptible to drowsiness with audible stimulus response. Her Glasgow coma scale was 10. Her heart rate was 115/min, blood pressure: 100/60 mmHg, respiratory rate 39/min, and Kussmaul breathing pattern was observed. Metabolic acidosis was detected in blood gas analysis (PH: 6.78, bicarbonate: 1.8 mmol/L, and anion gap: −33). Serum glucose level was 672 mg/dl and she had +4 ketonuria and + 3 glucosuria in her urine. Body weight was 23 kg (−0.78 SDS), and height: 124 cm (−0.9 SDS). Based on these findings, the patient was diagnosed with DKA and was followed up in the pediatric intensive care unit. Empirical antibiotherapy was initiated, whose her CRP value was high: 18.3 mg/L (N: 0.01–6), and an RT-PCR test was performed for COVID-19 infection. There was no infiltration focus on chest radiography [Figure 2]. Other laboratory results are in [Table 1]. The patient was first given saline infusion at a dose of 10 ml/kg in 1 h. Afterward, fluid infusion and insulin were started with a dose of 0.1 unit/kg/h with the DKA protocol according to ISPAD 2018 guidelines.[6] Bicarbonate infusion was given at a dose of 1 meq/kg in the 1st h because of very severe acidosis and low bicarbonate value (PH <6.9). Bicarbonate was given again to the patient whose bicarbonate level did not improve in the control venous blood gas analysis 1 h later (PH <6.9). At approximately the 4th h of the follow-up, the patient who was COVID-19 RT-PCR positive was started on ritonavir/lopinavir treatment with pediatric infectious diseases. She, whose oxygen saturation is generally between 95% and 98% in room air, was given 4–5/L high-flow oxygen support through nasal cannula. The potassium level was gradually increased up to 70 meq/L in the fluid of the patient who had a decrease in her serum potassium (2.7 mmol/L) during the follow-up. Long-acting glargine insulin subcutan was administered to her, whose severe acidosis continued in the 8th-h follow-up. In addition, magnesium sulfate infusion was administered at a dose of 50 mg/kg in order to benefit from its effect of reducing insulin resistance due to the serum magnesium level in the lower limit of normal.[7] After these treatments, the recovery process of the patient was faster. The DKA status improved within approximately 24 h. She, who was followed up in the COVID service afterward, did not need oxygen. Her ICA: 63.5.2 U/ml (0–24) and anti-GAD antibody: 95.6 IU/ml (0–17) were positive. After completing her diabetes education, she was discharged on the 7th day with multiple insulin therapy.
| Discussion | | |
The virus that causes COVID-19 infection (SARS-CoV-2) binds to angiotensin-converting enzyme 2 (ACE2) receptors. These receptors are expressed in important metabolic organs and tissues such as pancreatic beta cells, small intestine, adipose tissue, and kidneys.[8] Therefore, it is conceivable that SARS-CoV-2 could induce pleiotropic changes in glucose metabolism, which could complicate the pathophysiology of preexisting diabetes or lead to new disease mechanisms.[9]
Viral infections are well known to be associated with the development of pancreatic autoantibodies that cause type 1 diabetes (T1D) in genetically predisposed individuals, and coronaviruses were identified as one of the culprit pathogens in the TEDDY study.[10] The diabetes antibodies of our patients were also positive.
In addition, serious metabolic complications of preexisting diabetes, including DKA and hyperosmolarity, which require extremely high doses of insulin, have been reported, as well as the existence of an association between COVID-19 and new-onset T1D.[9] Our patients did not need high-dose insulin.
While there are many publications addressing the management challenge of co-existence of COVID-19 and DKA, perhaps the most innovative and practical may be the administration of long-acting subcutaneous insulin, such as glargine, in the early stages of DKA treatment. Thus, it is aimed at preventing the relapse of ketoacidosis and/or significant hyperglycemia.[4] We applied glargine insulin subcutaneous at approximately the 8th h (0.25U/kg/dose) of DKA treatment in both of our patients. Although we gave bicarbonate in the first 2 h of the treatment in both of our patients, the persistent low blood pH value (PH <6.9) showed rapid improvement at approximately 8 h of follow-up after long-acting subcutaneous glargine [Chart 1].
Furthermore, SARS-CoV-2 reduces ACE2 expression and ultimately leads to increased aldosterone secretion and decreased angiotensin II, which can cause renal potassium loss. This may require further potassium supplementation to maintain the necessary intravenous insulin to suppress ketogenesis.[11] In our second patient, high doses of potassium replacement were required during insulin infusion. The fact that high potassium replacement was not required in our first patient may be the reason for this in some predisposition conditions that require further investigation of COVID-19 disease.
With all of this, what we have learned so far is insufficient to understand whether this incipient diabetes is the classic T1D or a new form of diabetes. It is also unclear whether severe COVID-19-induced hyperglycemia, which is noticed in some people, will improve in the long-term, as seen in diabetes caused by SARS-CoV-1.[12] In addition, since the presence of COVID-19 infection accompanying DKA causes resistant metabolic acidosis, parenteral insulin infusion, and simultaneous subcutaneous long-acting insulin therapy were required in addition to bicarbonate therapy. Although we observed that long-acting subcutaneous glargine insulin therapy was beneficial in the early period in both of our patients, large-scale studies are needed on this subject.
An international group of diabetes researchers has created a global registry of patients with diabetes associated with COVID-19 under the title CoviDiab Project (covidien.e-dendrite.com) to address some of these issues. The purpose of the registry is to identify the characteristics and phenotype of new-onset diabetes defined by a history of hyperglycemia, negative diabetes, confirmed COVID-19, and normal glucose hemoglobin level.[10] We think that our cases will contribute to this study.
| Conclusion | | |
COVID-19 infection is a worldwide health emergency with many uncertainties in terms of its etiopathogenesis, complications, mortality, and adequate treatment development.
According to endocrinologists, the correlation between COVID-19 and incipient diabetes remains unresolved, especially in children. The cases we report here show a unique presentation of the DKA that triggered the diagnosis of COVID-19, especially in childhood. Therefore, our clinical cases are potentially raising the global record of cases of diabetes associated with COVID-19 (CoviDiab project) and provide a basis for further research seeking to understand the relationship between diabetes and COVID-19 in the pediatric population. We also believe that the new practices we try in managing our cases will be helpful for possible similar cases.
Currently, more attention is needed to improve the prognosis of COVID-19-associated DKA, and care must be taken to provide healthy diabetes education to the affected child and family.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understand that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Nil.
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1]
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