key: cord-1022625-ixs9vpk2
authors: Al‐Abdulrazzaq, Dalia; Alkandari, Abdullah; Alhusaini, Fatemah; Alenazi, Naser; Gujral, Unjali P.; Narayan, K. M. Venkat; Al‐Kandari, Hessa
title: Higher rates of diabetic ketoacidosis and admission to the paediatric intensive care unit among newly diagnosed children with type 1 diabetes in Kuwait during the COVID‐19 pandemic
date: 2021-10-25
journal: Diabetes Metab Res Rev
DOI: 10.1002/dmrr.3506
sha: cfeec16b462027e7e00d8c32f979139a0e50d2fb
doc_id: 1022625
cord_uid: ixs9vpk2

INTRODUCTION: The COVID‐19 pandemic might have a multifaceted effect on children with type 1 diabetes (T1D), either directly through infection itself or indirectly due to measures implemented by health authorities to control the pandemic. OBJECTIVE: To compare data on children newly diagnosed with T1D in Kuwait during the COVID‐19 pandemic to the pre‐pandemic period. RESEARCH DESIGN AND METHODS: We analysed data on children aged 12 years or less registered in the Childhood‐Onset Diabetes electronic Registry (CODeR) in Kuwait. Data were incidence rate (IR), diabetic ketoacidosis (DKA), and its severity and admission to the paediatric intensive care unit (PICU). RESULTS: The IR of T1D was 40.2 per 100,000 (95% CI; 36.0–44.8) during the COVID‐19 pandemic period and was not statistically different from pre‐pandemic. A higher proportion of incident T1D cases presented with DKA and were admitted to the PICU during the pandemic (52.2% vs. 37.8%: p ˂ 0.001, 19.8% vs. 10.9%; p = 0.002, respectively). The COVID‐19 pandemic was positively associated with presentation of DKA and admission to PICU (AOR = 1.73; 95% CI, 1.13–2.65; p = 0.012, AOR = 2.04; 95% CI, 1.13–3.67; p = 0.018, respectively). Children of families with a positive history for diabetes were less likely to present with DKA and get admitted to the PICU during the COVID‐19 pandemic (AOR = 0.38; 95% CI, 0.20–0.74; p = 0.004, AOR = 0.22; 95% CI, 0.08–0.61; p = 0.004, respectively). CONCLUSION: High rates of DKA at presentation and admission to PICU in incident T1D cases during the COVID‐19 pandemic warrant further studies and effective mitigation efforts through increasing awareness, early detection, and timely intervention.

We analysed data on children aged 12 years or less (official age range definition of paediatric patients in the country) registered in the Childhood-Onset Diabetes electronic Registry (CODeR) in Kuwait.

CODeR is a prospective population-based diabetes registry and is a country-wide surveillance system in Kuwait, with validated high Children younger than 6 months were excluded due to the diagnosis of neonatal diabetes in this age group.

Data were extracted using standard registry data forms. The forms included baseline information at the time of diagnosis such as demographic information, anthropometric measures (weight, height, and body mass index [BMI] ) expressed as standard deviation (SDS) z-scores according to WHO child growth standards. 13 Information on PICU admission, family history of diabetes in first degree relatives, haemoglobin A1C (HbA1C) and venous gas (pH and bicarbonate in mmol/L) were also collected. The 2018 International Society of Paediatric and Adolescent diabetes (ISPAD) guidelines 14 were used to confirm diagnosis of T1D in registered children that is, characterised by the presence by one or more pancreatic antibodies. DKA was defined as venous pH < 7.3 or serum bicarbonate <15 mmol/L and further categorised as mild (venous pH < 7.3, serum bicarbonate <15 mmol/L), moderate (pH < 7.2, serum bicarbonate <10 mmol/L) or severe (pH < 7.1, serum bicarbonate <5 mmol/L). 10 pandemic and 0 = pre-pandemic) to be the main explanatory variable while DKA (1 = yes 0 = no) was a main outcome variable. Age, gender, BMI z-score, and family history of diabetes were all considered potential confounders ( Table 2 ). The same analysis was repeated with severe DKA (1 = yes 0 = no) and PICU admission (1 = yes 0 = no) as main outcome variables (Table 2) . Furthermore, multiple logistic regression was used to explore the association between baseline characteristics and DKA, severe DKA, and PICU admission during the pandemic versus the pre-pandemic period (Table 3 ). This analysis was exploratory and guided by clinical judgement and the literature. 15, 16 The study was approved by the Standing committee for coordination of health and medical research at the MOH (#1569/2020).

The study was performed in accord with the Declaration of Helsinki.

A total of 324 children aged 6 months to 12 years were newly diagnosed with T1D during the first 12 months of the COVID-19 pandemic period in Kuwait (males, n = 151, 46.6% and females, n = 173, 53.4%), compared to a total of 303 children during 12 months of the pre-pandemic period. Baseline characteristics of newly diagnosed children with T1D during the COVID-19 pandemic period in comparison to the pre-pandemic period are shown in Table 2 . No When the analysis was repeated with severe DKA as an outcome variable, the COVID-19 pandemic period was not associated with severe DKA. Table 3 

In this study compared children newly diagnosed with T1D for 12 months during the COVID-19 pandemic to their counterparts diagnosed in the 12 months prior to the pandemic using data from a validated national surveillance system in Kuwait. 11, 12 We did not find any evidence for an increase in T1D incidence among children during the pandemic period. However, children diagnosed with T1D during the pandemic were more likely to present with DKA and get admitted to the PICU. Family history of diabetes was found to reduce the risk of presentation with DKA and admission to the PICU during the COVID-19 pandemic period.

Results of our study found no evidence for higher incidence of T1D among children during the pandemic period compared to the prepandemic period. Similarly, a report from Germany based on a shorter period of analysis (March to May 2020) found no short-term effect of the COVID-19 pandemic on T1D incidence in children. 17 However, a multicentre regional study from the United Kingdom reported that from March to June 2020, there was an apparent increase in children newly diagnosed with T1D in two regional units with 10

cases each compared to two and four cases, respectively, during the same period in the previous 5 years. 18 These reports compared data over a shorter duration of time, and therefore may not represent true changes in incidence. Our results add further evidence that during the first 12 months of the COVID-19 pandemic the overall incidence of T1D did not significantly increase compared to previous years.

We also noted a trend indicating an accumulative increase in the number of children diagnosed with T1D as the pandemic continued during the first three 3-month intervals (quarters) of the study period followed by a decrease in the last quarter. Such trends might be corresponding to the overall COVID-19 case-load in the country among all age groups (Information on COVID-19 status in Kuwait obtained from https://corona.e.gov.kw/en). Although this observation is speculative, however it raises questions about potential multifaceted connections between incident T1D and COVID-19.

Unfortunately, any direct connection between COVID-19 infection and onset of T1D could not be evaluated in the present study as COVID-19 testing was not available nor done for all newly diagnosed children with T1D during the pandemic. While we found an accumulative increase in the incidence of T1D in the first three quarters during the COVID-19 pandemic, we did not find any significant differences between quarters with regard to HbA1C, BMI a-scores, presentation with DKA and its severity, or admission to PICU. To the best of our knowledge, it is the first in the Middle East region and one of the first internationally to report on a longer period of the COVID-19 pandemic (12 months). Additionally, our data are from a validated nation-wide surveillance system (8) . Limitations of our study include lack of data on socioeconomic status and residual β-cell function (c-peptide levels) which might confound the results and influence DKA and its severity. Furthermore, lack of data on COVID-19 status on children at the time of diagnosis which limits further study on direct impact of the infection on newly diagnosed T1D in children.

In conclusion, very high rates of DKA at presentation and admission to PICU in children newly diagnosed with T1D during the COVID-19 pandemic warrant further studies and effective mitigation efforts through increasing awareness, early detection, and timely

intervention that need to be prioritised.

Non autoimmune type 1B diabetes after mild COVID-19: report of three cases. Diabetes

Covid-19 and diabetes mellitus: unveiling the interaction of two pandemics

Psychological stress and type 1 diabetes mellitus: what is the link?

Reduction of hypoglycaemia, lifestyle modifications and psychological distress during lockdown following SARS-CoV-2 outbreak in type 1 diabetes

Effects of COVID-19 lockdown on glucose control: continuous glucose monitoring data from people with diabetes on intensive insulin therapy

Glucose control in diabetes during home confinement for the first pandemic wave of COVID-19: a meta-analysis of observational studies

The impact of COVID-19 lockdown on metabolic control and access to healthcare in people with diabetes: the CONFI-DIAB cross-sectional study

Missing during COVID-19 lockdown: children with onset of type 1 diabetes

Rates of diabetic ketoacidosis: international comparison with 49,859 pediatric patients with type 1 diabetes from England

ISPAD clinical practice consensus guidelines 2018: diabetic ketoacidosis and the hyperglycemic hyperosmolar state

Incidence of type 1 diabetes has doubled in Kuwaiti children 0-14 years over the last 20 years

Incidence of type 2 diabetes in Kuwaiti children and adolescents: results from the childhood-onset diabetes electronic registry (CODeR)

WHO child growth standards based on length/height, weight and age

ISPAD clinical practice consensus guidelines 2018: definition, epidemiology, and classification of diabetes in children and adolescents

Variation between countries in the frequency of diabetic ketoacidosis at first presentation of type 1 diabetes in children: a systematic review

Ketoacidosis at first presentation of type 1 diabetes mellitus among children: a study from

Did the COVID-19 lockdown affect the incidence of pediatric type 1 diabetes in Germany? Diabetes Care

New-onset type 1 diabetes in children during COVID-19: multicenter regional findings in the U. K. Diabetes Care

Ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes during the COVID-19 pandemic in Germany

Increased DKA at presentation among newly diagnosed type 1 diabetes patients with or without COVID-19: data from a multi-site surveillance registry

The impact of COVID-19 pandemic lockdown on the incidence of new-onset type 1 diabetes and ketoacidosis among Saudi children

Increased paediatric presentations of severe diabetic ketoacidosis in an Australian tertiary centre during the COVID-19 pandemic

Delayed access or provision of care in Italy resulting from fear of COVID-19

Medical expenditures associated with diabetes acute complications in privately insured U. S. youth. Diabetes Care

How to cite this article

Higher rates of diabetic ketoacidosis and admission to the paediatric intensive care unit among newly diagnosed children with type 1 diabetes in Kuwait during the COVID-19 pandemic

The authors would like to thank Dr. Azza Al Shaltout for founding and establishing the CODeR project. The authors would like toThe authors declare that they have no competing interests.

The study was approved by the Standing committee for coordination of health and medical research at the Ministry of Health of Kuwait (MOH) (#1569/2020).The study was performed in accord with the Declaration of Helsinki.The data used in this study was completely anonymised without any possibility to re-identify subjects.A waiver of consent was granted by the Standing committee for coordination of health and medical research at the MOH.

All authors have contributed significantly to this manuscript and in keeping with the latest guidelines of the International Committee of Medical Journal Editors. Authors contributions were as follows: Dalia Al-Abdulrazzaq was principal investigator of this project, she was responsible for the conception, planning, data management and analysis, and conducting the study. She had drafted this manuscript.Abdullah Alkandari was responsible for the data analysis. Fatemah Alhusaini and Naser Alenazi were responsible for data collection and data management. Hessa Al-Kandari had participated in the planning, data management, and conducting the study. Unjali P. Gujral and K.M. Venkat Narayan had participated in writing the manuscript. All coauthors had participated in reviewing the manuscript.

The data that support the findings of this study are available from the MOH and DDI but restrictions apply to the availability of these data, which were used under licence for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of the MOH and DDI.

https://orcid.org/0000-0002-4613-865XK. M. Venkat Narayan https://orcid.org/0000-0001-8621-5405

The peer review history for this article is available at https://publons. com/publon/10.1002/dmrr.3506.