Frequency Of Diabetic Ketoacidosis Research Articles

Impact of the COVID-19 Pandemic on Diabetic Ketoacidosis Patients Treated in a Pediatric Intensive Care Unit: A Single-Center Cross-Sectional Study

Background and Objectives: Diabetic ketoacidosis (DKA) is a common complication of type 1 diabetes mellitus (T1DM) in children. Here, we explored the impact of the coronavirus disease 2019 (COVID-19) pandemic on the occurrence and severity of DKA in children in southern Croatia. Materials and Methods: The demographics and clinical and laboratory findings of all children and adolescents aged 0–18 years diagnosed with DKA and admitted to the pediatric intensive care unit (PICU) of the University Hospital of Split, Croatia from January 2013 to May 2023 were retrospectively collected. The participants were divided into two groups: (1) the pre-pandemic group (presenting before mid-March 2020) and (2) the pandemic group (presenting afterwards). Results: A total of 91 patients were included, 68 in the pre-pandemic and 23 in the pandemic group. The admission rate was similar (<1 patient per month) in both groups. In comparison to pre-pandemic patients, which mostly presented during the summer (52.9%) and winter seasons (23.5%), most pandemic cases occurred in spring (34.8%) and fall (30.4%, p = 0.002). No significant differences between the groups were identified in the severity of DKA, as reflected either by mean pH and median bicarbonate levels or by the proportion of patients with severe DKA. Nevertheless, HbA1c and triglycerides were significantly higher in the pandemic group (12.56% vs. 11.02%, p = 0.002 and 4.95 mmol/L vs. 2.8 mmol/L, p = 0.022, respectively) indicating poorer long-term glycemia. DKA complications were, overall, rare and without significant differences between the groups. Conclusions: The COVID-19 pandemic did not impact overall frequency or severity of DKA in children in southern Croatia. While the seasonal changes in DKA occurrence and a poorer long-term glycemia in pandemic patients may have been influenced by COVID-19 outbreaks and the imposed anti-pandemic measures, further studies are needed to determine if this was a temporary pandemic-related phenomenon or if this trend would persist in the future.

Random C-Peptide and Islet Antibodies at Onset Predict β Cell Function Trajectory and Insulin Dependence in Pediatric Diabetes

ContextIdentification of prognostic biomarkers in pediatric diabetes is important for precision medicine. ObjectiveWe assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes. MethodsWe prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aβ classification system (“A+”: islet autoantibody positive, “β+”: random serum C-peptide≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2h post-prandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6-12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score (T1D GRS2) for each participant, and compared characteristics at baseline, and clinical outcomes at V2. ResultsThe cohort was 50% male. Racial distribution was 76.4% White, 20.8% Black and 2.8% Asian or other races. A total of 46.5% participants were Hispanic. Median age (Q1-Q3) was 12.4 (8.3-14.5) years. The Aβ subgroup frequencies were 46 A+β-(63.9%), 1 A-β-(1.4%), 4 A+β+(5.6%), and 21 A-β+(29.2%). Baseline serum C-peptide correlated with UCPCR at both V1 (r=0.36, p=0.002) and V2 (r=0.47, p<0.001). There were significant subgroup differences in age, race, frequency of diabetic ketoacidosis and T1D GRS2 (p<0.01). At V2, the two β- subgroups had lower UCPCR and higher HbA1c compared with the two β+ subgroups (p<0.001 and p=0.02, respectively). Thirty-eight percent of A-β+ but none of the other subgroups were insulin-independent at V2 (p<0.001). ConclusionsC-peptide and islet autoimmunity at diagnosis define distinct phenotypes and predict beta-cell function and insulin dependence 6-12 months later in racially/ethnically diverse children with new-onset diabetes.

Beyond Infection: Unmasking the Impact of COVID-19 on Diabetes Emergency Trends.

Introduction The relationship between COVID-19 and diabetes has been demonstrated in many studies. However, it is thought that the psycho-socioeconomic effects of the pandemic led to a worsening of glycemic control and an increase in diabetes-associated clinical emergencies in diabetic patients without a diagnosis of COVID-19. Objectives We aimed to reveal the change in the frequency of diabetes-related clinical emergencies before and during the COVID-19 pandemic. Patients and methods The data of the patients requiring endocrinology consultations in Manisa Celal Bayar University Faculty of Medicine Emergency Service between March 2018 and March 2022 were included. In total, 269 consultations were analyzed. The March 2018 - March 2020 period was considered as pre-COVID, and March 2020 - March 2022 as the COVID-19 period. The frequency of diabetes-related conditions between these two periods was compared. Results Compared to the pre-COVID period, there was a significant increase in the frequency of admissions with diabetic ketosis, hyperglycemic hyperosmolar state, hypoglycemia, and hyperglycemia in the COVID-19 period (p=0.022, p=0.037, p=0.044, and p=0.004 respectively). Although an increase was observed in the frequency of diabetic ketoacidosis (DKA) cases, no statistical significance was found. When the mortality data of the patients was evaluated, the total number of deaths was seen to increase significantly in the COVID-19 period (p=0.01). It was observed that the ratio of type 2 diabetes mellitus (DM)/type 1 DM among DKA patients increased significantly in the COVID-19 period (p=0.001). Conclusions It can be concluded that the increasing trend in diabetic emergencies that started even before the pandemic is exacerbated by COVID-19, especially in patients with poor glycemic control.

Tacrolimus related diabetic ketoacidosis and hyperglycaemic hyperosmolar nonketotic syndrome: an observational, retrospective, pharmacovigilance study

ABSTRACT Background Information on the incidence and risk factors for diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar nonketotic syndrome (HHNS) caused by tacrolimus has rarely been reported. This study aims to assess the spectrum of DKA/HHNS associated with tacrolimus. Methods We conducted an observational, retrospective pharmacovigilance study using the Food and Drug Administration adverse event reporting system (FAERS) database. We employed the information component (IC) and reporting odds ratio (ROR) to evaluate the association between tacrolimus and DKA/HHNS. Results A total of 232 events were identified as tacrolimus-related DKA/HHNS, 186 cases from DKA and 54 cases from HHNS. The frequency of tacrolimus-associated DKA and HHNS was found to be significantly higher compared to all other drugs. Specifically, HHNS was significantly associated with tacrolimus based on its ROR and IC. There were no significant differences in death and non-death cases in gender, age group, year of reporting and region of reporting. Conclusion Our study showed that DKA and HHNS were associated with tacrolimus use. Healthcare professionals should be aware of the possibility of DKA/HHNS following tacrolimus administration, as they were associated with an increased risk of mortality in transplant recipients.

Clinical features, biomarkers and diabetic ketoacidosis at diagnosis of type 1 diabetes among children and adolescents in Sana’a, Yemen

IntroductionThere is little published information on type 1 diabetes (T1D) in children in Yemen. We aimed to identify the clinical characteristics, biomarkers and diabetic ketoacidosis (DKA) at diagnosis of T1D...

Diabetic Ketoacidosis and Adverse Outcomes Among Pregnant Individuals With Pregestational Diabetes in the United States, 2010-2020.

To assess the frequency of, risk factors for, and adverse outcomes associated with diabetic ketoacidosis (DKA) at delivery hospitalization among individuals with pregestational diabetes (type 1 and 2 diabetes mellitus) and secondarily to evaluate the frequency of and risk factors for antepartum and postpartum hospitalizations for DKA. We conducted a serial, cross-sectional study using the Agency for Healthcare Research and Quality's Healthcare Cost and Utilization Project Nationwide Readmissions Database from 2010 to 2020 of pregnant individuals with pregestational diabetes hospitalized for delivery. The exposures were 1) sociodemographic and clinical risk factors for DKA and 2) DKA. The outcomes were DKA at delivery hospitalization, maternal morbidity (nontransfusion severe maternal morbidity (SMM), critical care procedures, cardiac complications, acute renal failure, and transfusion), and adverse pregnancy outcomes (preterm birth, hypertensive disorders of pregnancy, and cesarean delivery) and secondarily DKA at antepartum and postpartum hospitalizations. Of 392,796 deliveries in individuals with pregestational diabetes (27.2% type 1 diabetes, 72.8% type 2 diabetes), there were 4,778 cases of DKA at delivery hospitalization (89.1% type 1 diabetes, 10.9% type 2 diabetes). The frequency of DKA at delivery hospitalization was 1.2% (4.0% with type 1 diabetes, 0.2% with type 2 diabetes), and the mean annual percentage change was 10.8% (95% CI, 8.2-13.2%). Diabetic ketoacidosis at delivery hospitalization was significantly more likely among those who had type 1 diabetes compared with those with type 2 diabetes, who were younger in age, who delivered at larger and metropolitan hospitals, and who had Medicaid insurance, lower income, multiple gestations, and prior psychiatric illness. Diabetic ketoacidosis during the delivery hospitalization was associated with an increased risk of nontransfusion SMM (20.8% vs 2.4%, adjusted odds ratio [aOR] 8.18, 95% CI, 7.20-9.29), critical care procedures (7.3% vs 0.4%, aOR 15.83, 95% CI, 12.59-19.90), cardiac complications (7.8% vs 0.8%, aOR 8.87, 95% CI, 7.32-10.76), acute renal failure (12.3% vs 0.7%, aOR 9.78, 95% CI, 8.16-11.72), and transfusion (6.2% vs 2.2%, aOR 2.27, 95% CI, 1.87-2.75), as well as preterm birth (31.9% vs 13.5%, aOR 2.41, 95% CI, 2.17-2.69) and hypertensive disorders of pregnancy (37.4% vs 28.1%, aOR 1.11, 95% CI, 1.00-1.23). In secondary analyses, the overall frequency of antepartum DKA was 3.1%, and the mean annual percentage change was 4.1% (95% CI, 0.3-8.6%); the overall frequency of postpartum DKA was 0.4%, and the mean annual percentage change was 3.5% (95% CI, -1.6% to 9.6%). Of 3,092 antepartum hospitalizations among individuals with DKA, 15.7% (n=485) had a recurrent case of DKA at delivery hospitalization. Of 1,419 postpartum hospitalizations among individuals with DKA, 20.0% (n=285) previously had DKA at delivery hospitalization. The above risk factors for DKA at delivery hospitalization were similar for DKA at antepartum and postpartum hospitalizations. The frequency of DKA at delivery hospitalization and antepartum hospitalizations for DKA increased between 2010 and 2020 among deliveries in individuals with pregestational diabetes in the United States. Diabetic ketoacidosis is associated with an increased risk of maternal morbidity and adverse pregnancy outcomes. Risk factors for DKA at delivery were similar to those for DKA during the antepartum and postpartum periods.

Impact of Thyroid Autoimmunity on the Clinical and Biochemical Characteristics of Type 1 Diabetes Mellitus Patients.

Type 1 diabetes mellitus (T1DM) is frequently associated with other autoimmune disorders that are characterized by the presence of organ-specific autoantibodies. Autoimmune thyroid disease (AIT) is the most frequent autoimmune disorder associated with T1DM. Thyroid peroxidase antibodies (TPOAb) serve as a marker for diagnosing AIT. Prior research indicates that thyroid dysfunction can negatively impact linear growth and glycemic control in subjects with T1DM. The present study was done to determine the impact of thyroid autoimmunity on the clinical and biochemical characteristics of patients with newly diagnosed T1DM. In this single-center, hospital-based, observational cross-sectional study, we enrolled 70 patients with newly diagnosed T1DM ≤18 years of age. Type 1 diabetes mellitus was diagnosed based on the acute onset of osmotic symptoms with or without diabetic ketoacidosis (DKA), severe hyperglycemia (blood glucose >13.9 mmol/l (>250 mg/dl)), and insulin requirement from the onset of diabetes. Secondary diabetes, pancreatic diabetes (Type 3c), and maturity-onset diabetes of the young (MODY) were excluded. Participants were screened for AIT disease using TPOAb testing. Based on the presence or absence of TPOAb, the participants were categorized into two groups: Group A comprised individuals with T1DM who tested positive for TPOAb, while Group B consisted of those who tested negative for TPOAb. Out of 70 patients, 41.4% were girls and 58.6% were boys, with a mean age of 9.8±4.4 years. The prevalence of TPOAb among the cohort was 18.6%. A significant majority of patients (71.4%), presented with DKA. Group A showed significantly lower mean height standard deviation scores (SDS) compared to Group B (-0.3±0.6 vs. -0.8±0.5, p = 0.004), but no differences in weight SDS or BMI SDS. Hemoglobin A1C (HbA1c) levels, C-peptide levels, and frequency of DKA did not differ between groups. Group A had higher mean thyroid-stimulating hormone (TSH) levels (4.8±3.7 µU/ml vs. 2.6±1.5 µU/ml, p = 0.001) and a greater proportion of patients with TSH levels above the upper limit of normal compared to Group B (38.4% vs. 7.1%, p = 0.008). Additionally, Group A exhibited a higher frequency of glutamic acid decarboxylase antibody (GADA) positivity compared to Group B (46.1% vs. 17.5%, p = 0.04). Patients positive for TPOAb exhibited significantly lower height SDS compared to TPOAb-negative patients. Additionally, T1DM patients with TPOAb positivity showed an increased frequency of GADA compared to those without TPOAb. However, no significant differences were found in HbA1c levels, C-peptide levels, or hematological parameters between TPOAb-positive and TPOAb-negative patients. These findings emphasize the impact of TPOAb on growth parameters in T1DM and advocate for routine screening of TPOAb in all T1DM patients, starting at the time of diabetes diagnosis.

RE: Comment On: Change in the Frequency of Diabetic Ketoacidosis in Children with Newly Diagnosed Type 1 Diabetes in the Central Anatolia Region of Türkiye Over the Years Before and After the Coronavirus Disease 2019 Pandemic.

Cite this article as: Koca SB, Takcı MZ, Deniz R, Özcan S, Çeleğen M, Dursun A. RE: Comment on: Change in the frequency of diabetic ketoacidosis in children with newly diagnosed type 1 diabetes in the Central Anatolia region of Turkey over the years before and after the coronavirus disease 2019 pandemic: A single-center experience. Turk Arch Pediatr. Published online May 6, 2024, doi: 10.5152/TurkArchPediatr.2024.246202.

Comment On: Change in the Frequency of Diabetic Ketoacidosis in Children with Newly Diagnosed Type 1 Diabetes in the Central Anatolia Region of Türkiye Over the Years Before and After the Coronavirus Disease 2019 Pandemic: A Single-Center Experience.

Comment On: Change in the Frequency of Diabetic Ketoacidosis in Children with Newly Diagnosed Type 1 Diabetes in the Central Anatolia Region of Türkiye Over the Years Before and After the Coronavirus Disease 2019 Pandemic: A Single-Center Experience.

Exploring ketoacidosis frequency and risk factors in childhood-onset type 1 diabetes: an 8-year retrospective study (2011-2018) at a tertiary paediatric hospital in Tripoli, Libya.

Diabetic ketoacidosis (DKA) stands as a critical, acute complication of type 1 diabetes. Despite its severity, there exists a dearth of data concerning the frequency and prevalence of DKA at the onset of type 1 diabetes in Libyan children. This study aimed to ascertain the frequency of DKA during the initial presentation of type 1 diabetes among children aged 0.5-14 years admitted to Tripoli Children's Hospital between 2011 and 2018. Employing a retrospective approach, the study examined the proportion of children with newly diagnosed type 1 diabetes who presented with DKA. Data analysis included estimating DKA frequency concerning age at presentation, sex, and age groups. The comparative analysis involved assessing DKA frequency between 0.5 and <2 and 2-14 years age groups. Logistic regression analysis evaluated the impact of age group, sex, and family history of type 1 diabetes on DKA and severe DKA occurrence. Among 497 children with newly diagnosed type 1 diabetes, 39.2 % presented with DKA, of these 44.5 % had severe DKA. Females exhibited a higher DKA rate than males (OR 1.63, 95 % CI 1.13-2.34, p=0.009). Very young children (0.5 to <2 years) presented with DKA more frequently than those aged 2-14 years (OR 4.73, 95 % CI 2.65-8.47, p<0.001), and they were more likely to present in severe DKA (63.9 vs. 39.1 %, [OR 7.26, 95 % CI 3.65-14.41, p<0.001]). The frequency of DKA at type 1 diabetes onset among children admitted to Tripoli Children's Hospital is notably high, with nearly half of the DKA episodes categorized as severe. Very young children notably demonstrated a fivefold increase in the likelihood of presenting with DKA.

Diabetic Ketoacidosis in Type 1 Diabetes Onset in Latin American Children

ObjectiveTo describe the patterns of diabetic ketoacidosis (DKA) occurrence in children newly diagnosed with type 1 diabetes (T1DM) across several Latin American pediatric diabetes centers from 2018 to 2022. MethodsA retrospective chart review included children under 18 with new-onset T1DM from 30 Latin American pediatric diabetes centers (Argentina, Chile, and Peru) between 30 December 2018 and 30 December 2022. Multiple logistic regression models examined the relationships between age, gender, medical insurance, BMI, and DKA at new-onset T1DM. As far as we know, there are no large studies in Latin American countries exploring the patterns of DKA in new-onset T1DM. ResultsA total of 2,026 (983 females) children, median age 9.12 (5.8 -11.7) years with new-onset-T1DM were included. Approximately 50% had no medical insurance. Mean glucose values were 467 mg/dL, pH 7.21, bicarbonate 13 mEq/L, HbA1c 11.3%, and BMI 18. The frequency of DKA was 1,229 (60.7%), out of which only 447 (36%) were severe. There was a significant decrease in the frequency of DKA as age increased: 373 (70.2%) in children under 6, 639 (61.6%) in those between 6 and 12, 217 and (47.5%) in those over 12. Children with medical insurance (58.8%) had a significantly lower frequency of DKA than those without (62.7%). The multiple logistic regression models showed that DKA was significantly and inversely associated with age [OR, 0.72 (95% CI 0.60–0.86)], BMI [OR, 0.95 (95% CI 0.92–0.99)], and medical insurance [OR, 0.75 (95% CI 0.60–0.94)] adjusted for sex. ConclusionLatin American children with new-onset T1DM exhibited a substantial occurrence of DKA. Younger ages and the lack of medical insurance were significantly associated with DKA in new-onset T1DM.

Change in the Frequency of Diabetic Ketoacidosis in Children with Newly Diagnosed Type 1 Diabetes in the Central Anatolia Region of Turkey over the Years Before and After the Coronavirus Disease 2019 Pandemic: A Single-Center Experience.

The number of admissions for severe diabetic ketoacidosis (DKA) in children with newly diagnosed type 1 diabetes (T1D) increased during the coronavirus disease 2019 pandemic. We aimed to investigate whether there has been a change in this situation in recent years. All children with T1D who were diagnosed in our tertiary hospital between 2019 and 2023 were included. Plasma insulin, C-peptide, hemoglobin A1c (HbA1c), and antibodies against thyroid peroxidase, thyroglobulin, insulin, islet cell, glutamic acid decarboxylase, tissue transglutaminase IgA, and endomysium IgA were measured. The frequency of moderate-severe acidosis at admission, which increased after pandemic period compared to the pre-pandemic period, returns to its previous levels over time but still shows a statistical difference compared to the pre-pandemic period (P = .012). Age, blood gas pH and HCO3 level, C-peptide, HbA1c, and length of stay of children at the time of admission were compared year by year (years 2019-2023). No statistical differences were observed (P = .509, P = .181, P = .069, P = .469, P = .346, P = .946), respectively. A significant difference was observed in venous glucose (P .001) and insulin (P = .001) according to years. Also, no significant difference was found about the degree of acidosis according to age (P = .334). Although the frequency of DKA in children with newly-diagnosed T1D increased in the first years of the pandemic, it has been decreasing over t.

Characterization of newly diagnosed type 1 diabetes in children and adolescents from 2017 to 2022 in China: a single-center analysis

ObjectiveThis study investigated the characteristics of newly diagnosed type 1 diabetes mellitus (T1DM) related to autoimmunity and the frequency of diabetic ketoacidosis (DKA) in children and adolescents from 2017–2022 in China.Research design and methodsSingle-center regional data from the Department of Pediatric Endocrinology, Tongji Hospital, were used to compare 88 children and adolescents newly diagnosed with T1DM from 2020 to 2022 (i.e. during the COVID-19 pandemic in China) and 76 children and adolescents diagnosed with T1DM from 2017 to 2019. Auto-antibodies, including glutamic acid decarboxylase-65 and insulin auto-antibodies, were detected by enzyme-linked immunoassays. DKA was defined as a pH < 7.3 and/or a bicarbonate level < 15 mmol/L.ResultsThe median age of the 164 children and adolescents newly diagnosed with T1DM from 2017 to 2022 was 7.0 years (interquartile range [IQR]: 3.8–10.0 years; 51.83% male). The mean annual incidence of T1DM was 2.98 per 1,000,000 child years. The estimated frequency of auto-antibody positivity was 51.22% (n = 84), and there was no difference between the 2020–2022 group and 2017–2019 group (55.68% [n = 49] vs. 46.5% [n = 35]; p = 0.219). The frequency of DKA among the entire cohort was 57.93% (n = 95), and peaked in 2020 at 78.9% (15/19 patients). The frequency of DKA was not significantly higher in the 2020–2022 group compared with the 2017–2019 group (60.23% [n = 53] vs. 55.26% [n = 42]; p = 0.521). We found no significant difference in the frequency of DKA between patients who were negative vs. positive for auto-antibodies in the 2020–2022 group (64.10% [n = 25] vs. 57.14% [n = 28], p > 0.05). The C-peptide level and HbA1c (%) were positively correlated with onset age (R1 = 0.389, p < 0.01; R2 = 0.371, p < 0.01), and the estimated mean C-peptide level was 0.26 ng/ml (IQR: 0.2–0.4 ng/ml) in patients with DKA and 0.370 ng/ml (IQR: 0.2–0.6 ng/ml) in patients without DKA (p = 0.044).ConclusionsThis study showed the annual incidence of T1DM was 2.98 per 1,000,000 child years, gradually increased over the study period, and there was no significant increase in T1DM with auto-antibody positivity in children and adolescents newly diagnosed from 2020–2022 in China compared with the previous 3 years. Furthermore, the frequency of DKA was peaked in 2020, and were not significantly different between patients who were negative vs. positive for auto-antibodies.

Glycemic variability and time in range among children with type 1 diabetes on insulin pump during the Covid-19 pandemic in Egypt; single center experience

BackgroundCovid-19 has impacted the lives of individuals worldwide especially those with chronic illnesses. Children with type 1 diabetes (T1DM) are at risk of glycemic deterioration during the Covid-19 pandemic. However, some studies reported glycemic improvement in these children during the pandemic.AimTo assess the impact of Covid-19 on glycemic control and acute complications among children with T1DM on insulin pump in Egypt.MethodologyForty-two children with T1DM on insulin pump for at least 1 year were assessed during the period from June 2020 to May 2021 for insulin requirements, insulin-pump problems, frequency of diabetic-ketoacidosis (DKA), hypoglycemia and HbA1C. Continuous-glucose monitoring was done using Medtronic i-pro device for 5 days. Data were compared to those obtained from the patients’ medical records 1 year previously.ResultUpon comparing data during Covid-19 pandemic with previous data from 12–24 months before Covid-19, there was a significant small increase in the mean total daily insulin dose from 0.83 ± 0.28 to 0.88 ± 0.30 U/kg/day with a similar small increase in the mean basal percentage from 51.19 ± 3.46 to 52.74 ± 4.31. Interestingly, the median time in range showed small increase from 53 (IQR 47–61) to 57.0 (IQR 51–73), the mean coefficient of variation showed small decrease from 42.10 ± 9.90 to 38.20 ± 8.12 and the mean HbA1C significantly decreased from 8.8 ± 1.3 (72.31 ± 16.78 mmol/ml) to 7.8 ± 1.2 mg/dl (61.31 ± 16.62 mmol/mol). Twenty-nine children (69%) had insulin-pump problems in the form of skin irritation (31%), skin infection (7.1%) and pump Set/Site occlusion (31%).ConclusionNo safety issues and overall glycemic improvement were reported among the children with T1DM on insulin pump therapy from this single center during the covid-19 pandemic.

Diabetic ketoacidosis and cognitive impairment in children and adolescents

The aim of the literature review was to highlight modern scientific sources on the formation and clinical manifestations of cognitive impairment in children and adolescents with type 1 diabetes mellitus (DM) after diabetic ketoacidosis (DKA). Type 1 DM is one of the most prevalent endocrine disorders in childhood and adolescence. DKA is the most common acute complication of type 1 DM that may cause cognitive impairment. Cerebral edema is the main cause of cerebral vascular insufficiency in patients with DKA. However, the mechanisms underlying the development of cognitive dysfunction in DKA have not been fully elucidated.The leading hypotheses include development of neuroinflammation, oxidative stress, disruption of neurogenesis, and neurodegeneration. Hypoxic – ischemic injury and changes in the brain neuroanatomy may also cause cognitive dysfunction. Disruption of some brain structures has been reported after DKA episodes, primarily affecting the white matter. Clinical studies in the pediatric population support the presence of a correlation between the severity and frequency of DKA and the severity of cognitive impairment. Cognitive dysfunction in children and adolescents after a DKA episode can manifest through decreased attention, impaired memory and executive function, and reduced IQ. The earliest possible diagnosis of cognitive impairment in pediatric patients with symptoms of DKA in the context of type 1 DM can improve the treatment prognosis for this endocrinopathy.

Characterisation and clinical outcomes in children and adolescents with diabetes according to newly defined subgroups: a cohort study from the DPV registry

Personalised therapy has emerged as a possibly more efficient approach taking disease heterogeneity into account. The aim of this study was to determine whether recently described subgroups of childhood diabetes have prognostic association with diabetes-specific complications and, therefore, might be a basis for personalised therapies. We applied a previously developed subgroup classification to pediatric patients (diabetes onset <18 years) from the prospective Diabetes Patient Follow-up (DPV) registry with documented data between January 1, 2000 and March 31, 2022, from diabetes centers in Germany, Austria, Switzerland, and Luxembourg. The classification required information on islet autoantibody status, age, haemoglobin A1c (HbA1c), and body-mass index (BMI-SDS) at disease manifestation, as well as follow up data after 2 and after 4 years, which was available in 22,719 patients. Patients without documented data on these parameters were excluded from the analysis. The cumulative risk of severe hypoglycemia, diabetic ketoacidosis (DKA), retinopathy, and nephropathy were analysed by Kaplan-Meier analyses over a median follow-up of 6.8 years (IQR 4.8-9.6). Patients were classified into 10 subgroups (P1-P7 islet autoantibody-positive, n=19,811; N1-N3 islet autoantibody-negative, n=2908). The groups varied markedly with respect to specific acute and chronic complications. Severe hypoglycemia was a characteristic feature in young islet autoantibody-positive subgroups P1, P3, P4 (10-year risk 46, 46 and 47%) and the islet autoantibody-negative groups N1, N2 (43 and 46%). Nephropathy was identified in patient groups P2 and P5 (10-year risk 16%), which had features of moderate disease such as preserved C-peptide, low HbA1c, and very low frequency of DKA at diabetes onset. Group P7, which was defined by a high BMI, was associated with poor metabolic control, DKA, and retinopathy. In contrast, islet autoantibody-negative patients with high BMI (N3) had a low risk for all four complications. Subgrouping of childhood diabetes at diabetes onset provided prognostic value for the development of acute and chronic diabetes-specific complications. The DPV initiative is supported by The German Ministry of Education and Research (BMBF) within the German Center for Diabetes Research, the diabetes surveillance of the Robert Koch Institute, the German Diabetes Association (DDG) and INNODIA.

The Interplay Between COVID-19 and Pediatric Endocrine Disorders. What have we Learned After More than Three Years of the Pandemic?

As an increased body of COVID-19 related research is now available, it becomes apparent that the effects of COVID-19 extend beyond that of the respiratory system. Among others, the endocrine system is particularly vulnerable to perturbation from the COVID-19 infection. The present scoping review summarizes the bidirectional relationship between COVID-19 and endocrine system in children and adolescents, by describing both the possible susceptibility of children and adolescents without endocrinopathies to endocrine disorders following COVID-19 infection, but also the potential susceptibility to COVID-19 infection and severe infection, or the aggravation of endocrine dysfunction in patients with pre-existing endocrine diseases. Data suggest increased obesity and diabetes rates, as well as increased severity and frequency of diabetic ketoacidosis following COVID-19 infection. Conversely, patients with diabetes and obesity may experience a more severe course of COVID-19 infection. However, in the majority of cases, children and adolescents with well-managed and regulated endocrine disorders do not appear to be at increased risk of infection or severe infection from COVID-19. Thus, adhering to the appropriate "sick day management rules", maintaining adequate supply of medications and supplies, keeping close contact with the therapeutic team and seeking medical help without delay when needed, are the main recommendations for a safe outcome. Additional lessons learnt during the pandemic include the risk for mental health diseases caused by children's disrupted routine due to COVID-19 related protective measures and the importance of adopting alternative communication options, such as telehealth visits, in order to ensure uninterrupted endocrine care.

The Effect of the SARS-CoV-2 Pandemic on Presentation with Diabetic Ketoacidosis in Children with New Onset Type 1 Diabetes Mellitus

Diabetic ketoacidosis (DKA) is a life-threatening, acute complication of type 1 diabetes mellitus (T1DM). Infection is the most common precipitating factor for DKA, being responsible for more than 50% of such complications. The frequency and severity of DKA in children with T1DM, before and during the coronavirus disease 2019 outbreak were evaluated and compared with pre-pandemic presentation and severity rates. In total, 199 patients younger than 18 years were included in the study. Patients were divided into two groups: the Coronavirus disease-2019 (COVID-19) pandemic group (new onset T1DM presenting from March 2020 to March 2021; the control group included new onset T1DM from March 2016 to March 2020. The rate of DKA at presentation was similar (p=0.393) during the pandemic period (58.3%) compared to the pre-pandemic years (44.8-64.3%). Although the percentage of DKA was similar, the rate of severe DKA in the COVID-19 group was higher than previous years. Although not significant, the duration of diabetes symptoms was longer in the COVID-19 period than the previous years. This study suggests that the rate of severe DKA, but not the overall rate of DKA, has increased during the COVID-19 pandemic compared to the prior four years. This may be due to the behavior of the parents of sick children and the limited access to the healthcare system. Despite this limited access, parental concern may have been sufficiently high to seek medical attention for their children, avoiding an increased frequency of DKA as the first presentation of new-onset T1DM.

The Impact of COVID 19 on Glycemic Control in Children with Type 1 Diabetes on Insulin Pump Therapy: A Single Centre Study

Background Children with type 1 diabetes (T1DM) are at risk of glycemic deterioration during the COVID-19 pandemic due to several factors. However, some studies reported glycemic improvement in these children. Aim To assess the impact of COVID-19 on children with T1DM on insulin pump in terms of glycemic control and insulin therapy adjustments. Methodology Forty-two children with T1DM on insulin pump (Medtronic) for at least 3 months were recruited from the Pediatric and Adolescent Diabetes Unit (PADU), Ain-Shams University, Cairo, Egypt. They were assessed for insulin requirements, frequency of diabetic ketoacidosis and clinically significant hypoglycemia. Auxological parameters, HbA1c and lipid profile were assessed. Continuous glucose monitoring was performed using Medtronic i-pro device for 5 days for each patient. Data were compared to previous patients’ data obtained from their medical records. Study period was performed between 29/6/2020 until 29/12/2020. Results This study was carried out on 42 children with T1DM on insulin pump (15 males and 27 females with a male to female ratio of 1: 1.8) with a mean age of 11.31± 3.28 years, mean BMI of 18.80± 3.35 and mean disease duration of 4.40± 2.93 years. The mean insulin requirements of the studied children before the COVID- 19 pandemic was 0.83 ± 0.28 U/kg/d, range 0.5- 1.8 U/Kg/d with a mean basal percentage of 51.19 ± 3.46 %, range 45-60 % .As regards the laboratory data of the studied children with a mean HbA1c of 9.0±1.2%, range: 7-11.8%, mean fasting cholesterol of 184.88 ± 27.03 mg/dl, range: 142-233 mg/dl, mean fasting triglycerides of 89.81 ± 32.69 mg/dl, range: 43-148 mg/dl, mean LDL of 87.77±9.97 mg/dl, range: 68-98 mg/dl, mean HDL of 58.33± 12.28, range: 32-83 and median UACR was 13(10-21.9) mg/g, range: 7.0-94. There was a statistically significant increase in the total daily insulin units(P = 0.001), basal percentage (P = 0.011) and time in range (p = 0.009) with a significant decrease in the frequency of DKA (P = 0.001), hypoglycemia (P = 0.004), HbA1c (p = 0.001) and glycemic variability (p = 0.001) after the COVID-19 pandemic. Conclusion Glycemic control improved during the COVID-19 pandemic among children with T1DM on insulin pump therapy reflected by improvement in TIR and decrease in glycemic variability. Declarations Conflicts of interest disclosure The authors declare that they have no conflict of interest. Funding sources No funding sources

Comparison of Diabetic Ketoacidosis Characteristics During- and Before the COVID-19 Pandemic.

Despite evidence about the relationship between diabetic ketoacidosis (DKA) and infectious diseases, our knowledge of DKA during the coronavirus disease 2019 (COVID-19) pandemic remains unclear. This study aimed to compare the DKA situation among individuals with type 1 diabetes mellitus (T1DM) and type 2 diabetes mellitus (T2DM) during the COVID-19 pandemic compared to pre-pandemic. This retrospective-longitudinal study included individuals with T1DM and T2DM hospitalized with newly diagnosed DKA before (March to August 2018 and 2019) and during (March to August 2020 and 2021) the COVID-19 pandemic. Demographics, the frequency of new-onset diabetes mellitus (DM) and new-onset DKA, days of hospitalization, DKA severity, laboratory tests, and mortality were assessed. Of 162 patients with DKA, 139 patients were newly diagnosed. The frequency of individuals with new-onset DM had increased during the pandemic compared to pre-pandemic (P = 0.047). Moreover, new-onset DKA was higher in 2020 and 2021 versus 2019 and 2018 (P = 0.002). Significantly, there were no T2DM patients with DKA in pre-pandemic, but DKA admissions in people with T2DM increased in 2021 (P < 0.001). The severity of new-onset DKA had increased during the pandemic compared to pre-pandemic (P = 0.000). However, there was no significant difference between pre-and the pandemic regarding mortality (P = 0.981). Additionally, hospitalization length (P = 0.043) and mortality (P = 0.038) were higher in patients with T2DM compared to T1DM. During the COVID-19 pandemic, the frequency of DKA and its severity was higher than in pre-pandemic, and COVID-19 can be more life-threatening in patients with T2DM. Therefore, healthcare providers should be alert to DKA, especially in patients with T2DM.