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Year : 2021  |  Volume : 8  |  Issue : 2  |  Page : 110-113

Surge in diabetic ketoacidosis in children with Type 1 diabetes during COVID-19 pandemic – A report from a tertiary care center in Pune, India

Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune, Maharashtra, India

Date of Submission11-Oct-2020
Date of Decision18-Dec-2020
Date of Acceptance28-Dec-2020
Date of Web Publication10-Mar-2021

Correspondence Address:
Dr. Bhakti Sarangi
Department of Pediatrics, Bharati Vidyapeeth Medical College and Hospital, Pune - 411 043, Maharashtra
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jpcc.jpcc_160_20

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As the COVID-19 pandemic evolves, an increasing number of concurrent associations are being reported including several postinfectious phenomena. The role of diabetes mellitus (DM) and its implications in increased severity and mortality of adults with COVID-19 is established. COVID-19 is known to cause hyperglycemia and worsen glycemic control in adults with active infection. However, the association in pediatric population is not well established. The interplay between biological, psychosocial, and economic factors for increased association of COVID-19 with Type 1 DM and/or presentation with diabetic ketoacidosis (DKA) is not clear. We briefly describe a surge in the number of children with DKA as experienced in our center in the course of the ongoing pandemic with a brief evaluation of all the abovementioned factors.

Keywords: Children, COVID-19, diabetic ketoacidosis

How to cite this article:
Shankar GH, Sharma V, Sarangi B, Walimbe A, Prithvichandra Markal K C, Reddy VS. Surge in diabetic ketoacidosis in children with Type 1 diabetes during COVID-19 pandemic – A report from a tertiary care center in Pune, India. J Pediatr Crit Care 2021;8:110-3

How to cite this URL:
Shankar GH, Sharma V, Sarangi B, Walimbe A, Prithvichandra Markal K C, Reddy VS. Surge in diabetic ketoacidosis in children with Type 1 diabetes during COVID-19 pandemic – A report from a tertiary care center in Pune, India. J Pediatr Crit Care [serial online] 2021 [cited 2022 Dec 6];8:110-3. Available from: http://www.jpcc.org.in/text.asp?2021/8/2/110/311054

Type 1 diabetes mellitus (DM) is established as one of the most common chronic diseases of childhood. In India, over the years, developing health-care facilities, greater awareness among health-care personnel, more trained specialists, and access to better communication and technology have contributed to the increase in early diagnosis and better survival of children with Type 1 DM. There is mounting evidence that in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, DM as a comorbidity contributes to severity of infection and mortality in adults.[1] For instance, a systematic review by Abdi et al. on the relationship between DM and COVID-19 found that severity as well as mortality was higher in diabetic patients with COVID-19 with patients who died having a prevalence up to and greater than 3 times that of the general population.[2]

Information has been forthcoming mostly about Type 2 DM, though Type 1 DM cases have been reported as well to exacerbate the morbidity.[1] The severity in adults with Type 2 DM has been attributed to the syndromic nature of the disease encompassing hyperglycemia, older age, hypertension, obesity, and cardiovascular disease as other key determinants. The emerging relationship between COVID-19 and hyperglycemia resulting in ketoacidosis and other metabolic problems is a complex one. Ketosis and ketoacidosis is more commonly present in patients with COVID-19 infection.[3] Similarly, an unexpectedly higher mortality is reported with this combination of COVID-19 and diabetic ketoacidosis (DKA) as opposed to patients admitted previously only with DKA, one of the contributing factors being concurrent acute kidney injury.[4]

In the pediatric age group as well, an increase in incidence of severe DKA at diagnosis has been reported during the COVID-19 period in comparison with previous years. Data from the German Diabetes Prospective Follow-up Registry have shown that the percentage of children presenting in DKA has increased compared to previous years, reasons for which included reduced medical care and fear of reporting to health-care settings with the ongoing pandemic.[5] From a tertiary care center in Pune (the current epicenter of the pandemic in India), we report our experience with the surge of DKA cases from May to August of 2020.

Ten admissions were noted during this period of 3 months with DKA associated with Type 1 DM, with families of all children hailing from areas with high disease burden (containment zones). The mean age of presentation was 12.1 years. Six were girls. Five children tested positive for COVID-19 infection by reverse transcriptase real-time polymerase chain reaction (RT-PCR) of nasopharyngeal swab and two tested negative. Three did not undergo RT-PCR testing [Table 1]. Six children were newly diagnosed DM while the remaining were known diabetics. DKA by the International Society for Pediatric and Adolescent Diabetes criteria was mild in two, moderate in three, and severe in five cases. Three out of five COVID-19-positive children had accompanying fever while two were asymptomatic. Among the children who were on treatment with insulin, two had precipitation of ketoacidosis due to noncompliance/poor technique of insulin administration whereas one child had pump failure which could not be rectified due to unavailability of services during the lockdown. Swabs were not sent for the three cases. One of those presented with DKA in the initial period and did not have features to suggest an ongoing infection, while one had an obvious precipitating cause of insulin pump failure and the last one took leave against medical advice. All children who present with new-onset DM and any child with DKA are now screened for COVID-19 even if asymptomatic, and thus, two asymptomatic infections were picked up. One child (Patient 10) took leave against medical advice and hence could not be completely evaluated. It is interesting to note that among the five patients who were proven to have COVID-19, the infection itself was mild, without significant elevation of C-reactive protein (>100 mg/L), and did not contribute to increased morbidity. None had respiratory involvement or clinical/laboratory features suggestive of hyperinflammatory syndrome temporally associated with COVID-19. DKA resolved in an average of 33 h among the cases, and those who were positive for COVID-19 could not be distinguished from others in terms of severity and time to resolution within this small cohort. The average glycated hemoglobin (HbA1c) at admission was 14.1. There was no mortality.
Table 1: Clinical profile and laboratory parameters of children in the study

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As opposed to the previous 3 years, where the mean of number of DKA cases annually in our unit was 14, the initial phase of the pandemic with the lockdown in place showed a surge of ten cases in 4 months. It is well established that DKA can be the presenting manifestation of new-onset Type 1 DM in up to 70% of cases, and with the pandemic in full swing, psychosocial factors may have contributed significantly to the surge in DKA cases. Viral infections, including enteroviruses, rotavirus, mumps, and cytomegalovirus, have been previously linked with the development of Type 1 DM.[6],[7] The development of autoantibodies has been shown to correlate with the seasonal pattern of enteroviral infections in genetically susceptible children in the Finnish population.[8] However, subclinical insulitis occurs unapparent for a long period of time prior to the onset of hyperglycemia[9] which becomes precipitate with a viral insult. Expression of angiotensin-converting enzyme 2 (ACE2) receptors which facilitate SARS-CoV viral entry on pancreatic β-cells may affect their function due to a direct effect.[10] The resulting decrease in insulin production may be the final compromise in an already ongoing process of hyperglycemia as evidenced by the significantly elevated HbA1c in these children. It is interesting to note that HbA1c was elevated not only in the newly diagnosed cases but also in the previously known cases of DM suggesting preexisting poor glycemic control with further decompensation in the pandemic due to the proposed contributing factors.

Although DM is a pro-inflammatory and a pro-thrombotic state, unlike adults,[1] children with DKA and COVID-19 in this small series of cases were not noted to have increased severity of infectious or respiratory manifestations. An anticipated hyperinflammatory process was not present as well though rarely reported.[11] The differential expression of ACE2 receptors in different organs may help explain the phenomenon, though more data are necessary to consider the same mechanism.

The economic and psychosocial impact of the ongoing pandemic cannot be underestimated. It has already been reported that tertiary care centers are seeing a severe decrease in the number of referrals for DM.[12] The same has been attributed to limited access to tertiary health-care facilities and a fear of approaching hospitals treating COVID-19 patients. The re-distribution of available health-care resources to serve in the pandemic has further added to these limitations in terms of patients being unable to access routine subspecialty services or follow up with the same. Among those who do present, progress to DKA is more common. Our unit experience suggests that the fear of being infected with COVID-19 in the hospital is playing a significant role. Ancillary biomedical technology services are also not at full capacity and add to the woes.

Building a concerted database with nationwide data, focused research on the complex variables that affect the interplay between the immunologic, genetic, and epidemiologic factors will throw more light on these issues.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Apicella M, Campopiano MC, Mantuano M, Mazoni L, Coppelli A, Del Prato S. COVID-19 in people with diabetes: Understanding the reasons for worse outcomes. Lancet Diabetes Endocrinol 2020;8:782-92.  Back to cited text no. 1
Abdi A, Jalilian M, Sarbarzeh PA, Vlaisavljevic Z. Diabetes and COVID-19: A systematic review on the current evidences. Diabetes Res Clin Pract 2020;166:108347.  Back to cited text no. 2
Li J, Wang X, Chen J, Zuo X, Zhang H, Deng A. COVID-19 infection may cause ketosis and ketoacidosis. Diabetes Obes Metab 2020;22:1935-41.  Back to cited text no. 3
Chamorro-Pareja N, Parthasarathy S, Annam J, Hoffman J, Coyle C, Kishore P. Letter to the editor: Unexpected high mortality in COVID-19 and diabetic ketoacidosis. Metabolism 2020;110:154301.  Back to cited text no. 4
Kamrath C, Mönkemöller K, Biester T, Rohrer TR, Warncke K, Hammersen J, et al. Ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes during the COVID-19 pandemic in Germany. JAMA 2020;324:801-4.  Back to cited text no. 5
Lönnrot M, Lynch KF, Elding Larsson EH, Lernmark Å, Rewers MJ, Törn C, et al. Respiratory infections are temporally associated with initiation of type 1 diabetes autoimmunity: The TEDDY study. Diabetologia 2017;60:1931-40.  Back to cited text no. 6
Karaoglan M, Eksi F. The coincidence of newly diagnosed type 1 diabetes mellitus with IgM antibody positivity to enteroviruses and respiratory tract viruses. J Diabetes Res 2018;2018:8475341.  Back to cited text no. 7
Kimpimäki T, Kupila A, Hämäläinen AM, Kukko M, Kulmala P, Savola K, et al. The first signs of beta-cell autoimmunity appear in infancy in genetically susceptible children from the general population: The Finnish type 1 diabetes prediction and prevention study. J Clin Endocrinol Metab 2001;86:4782-8.  Back to cited text no. 8
Coppieters KT, Boettler T, von Herrath M. Virus infections in type 1 diabetes. Cold Spring Harb Perspect Med 2012;2:a007682.  Back to cited text no. 9
Orioli L, Hermans MP, Thissen JP, Maiter D, Vandeleene B, Yombi JC. COVID-19 in diabetic patients: Related risks and specifics of management. Ann Endocrinol (Paris) 2020;81:101-9.  Back to cited text no. 10
Daniel S, Gadhiya B, Parikh A, Joshi P. COVID-19 in a child with diabetic ketoacidosis: An instigator, a deviator or a spectator. Indian Pediatr 2020;57:969-70.  Back to cited text no. 11
Dayal D, Gupta S, Raithatha D, Jayashree M. Missing during COVID-19 lockdown: Children with onset of type 1 diabetes. Acta Paediatr 2020;109:2144-6.  Back to cited text no. 12


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