The COVID-19 pandemic has raised concerns about potential links between SARS-CoV-2 infection and autoimmune diseases. This study investigated changes in the incidence rate (IR) of autoimmune diseases among children following the pandemic's onset.

A retrospective cross-sectional study analyzed data from Clalit Health Services, Israel's largest healthcare provider, examining the IR of different autoimmune diseases in children aged 0-18. The study compared pre-pandemic (2019) with pandemic/post-pandemic periods (2020-2023), encompassing a cohort of over 1.5 million children.

Significant IR increases were observed across multiple autoimmune diseases. Rheumatic diseases (Juvenile Idiopathic Arthritis, Systemic Lupus Erythematosus, Henoch Schoenlein Purpura (HSP)) showed consistent increases, with HSP demonstrating the most pronounced trend. Endocrine disorders exhibited diverse patterns, with autoimmune thyroid diseases and Type 1 diabetes showing overall increases, while diabetic ketoacidosis exhibited an initial spike followed by a decline. Gastrointestinal diseases displayed heterogeneous patterns; Celiac disease and Ulcerative colitis showed general increases, Crohn's disease showed a downward trend, and autoimmune hepatitis exhibited an initial significant decrease followed by a significant increase. Dermatological conditions, including Psoriasis and Vitiligo, demonstrated consistent elevations throughout 2020-2023. Immune Thrombocytopenia Purpura showed initial decreases followed by significant increases in 2022-2023.

This comprehensive analysis reveals significant changes in pediatric autoimmune disease incidence following the COVID-19 pandemic, suggesting potential associations between SARS-CoV-2 infection and autoimmune dysregulation. The diverse patterns observed across different conditions highlight the complex interplay between viral infection and autoimmunity, emphasizing the need for continued surveillance and investigation of long-term immunological consequences of COVID-19 in pediatric populations.

Diabetic ketoacidosis (DKA) is a complication of uncontrolled diabetes mellitus, with a known increase in severity and incidence during the COVID-19 pandemic. Our institution also observed a rise in pediatric DKA cases in our largely underserved patient population. We hypothesized that the impact would be more pronounced in Black patients due to prepandemic healthcare inequities.

To investigate this, we confirmed the increased number of severe DKA cases in our pediatric patients during the pandemic and then stratified data to compare laboratory values between Black and White patients. We analyzed patients with a DKA diagnosis admitted to our institution's pediatric intensive care unit (PICU) prior to the pandemic (March 2016 to December 2017) and during its peak (March 2020 to December 2021).

Our data demonstrated more cases of severe DKA overall during 2020-2021 and when compared to prepandemic years, a statistically significant increase in severity for Black, but not White patients.

Type 1 diabetes (T1D) is an autoimmune condition affecting approximately 1.5 million children and adolescents worldwide, with an incidence of approximately 2-3% each year and rising. During the recent COVID-19 pandemic, a significant increase in incidence of T1D in children and adolescents was observed in numerous countries worldwide, with an increased number of newly-diagnosed cases presenting with diabetic ketoacidosis. The increased frequency of T1D presenting with diabetic ketoacidosis has been attributed not only to the SARS-CoV-2 virus itself but also to the restrictions imposed by the pandemic. The shift to telemedicine and unwillingness to seek medical care due to fear of infection contributed to delayed diagnosis and more severe disease presentation. Furthermore, the periods of lockdown that were implemented during the pandemic presented multiple challenges for children and adolescents living with T1D and disrupted the management of their condition. Changes in physical activity and diet as well as shortage of medical supplies during that period have been linked to worsening of glycemic control, which were at least partly offset by increased parental involvement and use of telemedicine.

Both the global prevalence of diabetes and the frequency of natural and man-made disasters are increasing. Of all chronic diseases, the consequences of sudden loss of medical supplies are most serious for those with diabetes, with people living with type 1 diabetes being at risk of death within a few days without insulin. This review considers how to prepare for and respond to sudden reductions in medical supplies to those with diabetes. Recent experiences with the COVID-19 pandemic in India, the war in Ukraine and the war/blockade in the Tigray region of Ethiopia are described, and the importance of prevention, preparedness, response and recovery are discussed. It is hoped that lessons from these and other disasters and ongoing advocacy and other actions may help to mitigate the risks of significant morbidity and mortality for people with diabetes in disaster-impacted regions across the world.

Autoimmune disorders, including type 1 diabetes mellitus (T1DM) and systemic lupus erythematosus (SLE), are influenced by a combination of genetic, environmental, and immunological factors. Among these, stress, both physical and psychological, has been increasingly recognized as a significant contributor to disease onset and progression. This review explores the current literature on the relationship between stress and autoimmune diseases, focusing on the neuroendocrine pathways, such as the hypothalamic-pituitary-adrenal (HPA) axis, and the effects of glucocorticoids on immune modulation. These mechanisms contribute to clinical manifestations, such as disease flares or progression, highlighting the impact of stress on patient outcomes. Evidence suggests that psychological stress can precipitate the onset of T1DM in genetically predisposed individuals, with immune disruptions occurring before diagnosis. In SLE, both acute and chronic stress, particularly trauma-induced stress, has been linked to increased disease activity and flare-ups, largely due to stress-induced immune dysregulation that disrupts the balance between pro-inflammatory and anti-inflammatory cytokines. Despite the substantial evidence supporting the role of stress in autoimmune disease exacerbation, further research is necessary to fully understand the mechanisms by which stress influences autoimmune diseases and to develop effective stress management.

Cardiovascular involvement in Multisystem Inflammatory Syndrome in Children (MIS-C), a potential consequence of coronavirus disease-2019 (COVID-19), is common. Conventional transthoracic echocardiography (TTE) provides primary data on the function of the left and right ventricles, while Speckle Tracking Echocardiography (STE) is more sensitive. This study aims to assess longitudinal cardiac function using STE in these patients. This longitudinal study was conducted from late 2021 to early 2022 at Imam Hossein Children's Hospital, Isfahan. Cardiac function was assessed by STE at the time of diagnosis and again two months later. Demographics, clinical characteristics, ECG interpretations, imaging studies, and serum cardiac marker levels were collected. Thirty-five pediatric patients with a mean age of 5.1 years (range: 4 months to 17 years) were included and prospectively followed. Twenty-nine of them, comprising 14 males (48.3%) and 15 females (51.7%), underwent STE and were compared with 29 healthy age- and sex-matched children. Factors related to adverse events included reduced myocardial function, enlarged left atrium or ventricle, and mitral regurgitation (MR). Patients with comorbidities affecting strain measurements were excluded from the strain analyses. A significant difference was observed between the groups in regional strains in the basal and apical septal and middle lateral regions. Global strain rate (GLS) and strain rates were not significantly different but were still lower than the control group. Twenty percent of patients had abnormal GLS but normal left ventricular ejection fraction (LVEF). All patients exhibited reduced segmental myocardial strain in at least one segment. Four out of 26 recovered patients without comorbidities had abnormal GLS at follow-up, despite normal LVEF. STE proves more useful than conventional echocardiography in patients with MIS-C, revealing subclinical cardiac injury in the acute and post-acute phases.

Patients with Diabetic ketoacidosis (DKA) have increased critical illness and mortality during coronavirus diseases 2019 (COVID-19). The aim of our study was to develop a predictive model for the occurrence of critical illness and mortality in COVID-19 patients with DKA utilizing machine learning. Blood samples and clinical data from 242 COVID-19 patients with DKA collected from December 2022 to January 2023 at Second Xiangya Hospital. Patients were categorized into non-death (n = 202) and death (n = 38) groups, and non-severe (n = 146) and severe (n = 96) groups. We developed five machine learning-based prediction models-Extreme Gradient Boosting (XGB), Logistic Regression (LR), Random Forest (RF), Support Vector Machine (SVM), and Multilayer Perceptron (MLP)-to evaluate the prognosis of COVID-19 patients with DKA. We employed 5-fold cross-validation for model evaluation and used the Shapley Additive Explanations (SHAP) algorithm for result interpretation to ensure reliability. The LR model demonstrated the highest accuracy (AUC = 0.933) in predicting mortality. Additionally, the LR model excelled (AUC = 0.898) in predicting progression to severe disease. This study developed a machine learning-based predictive model for the progression to severe disease or death in COVID-19 patients with DKA, which can serve as a valuable tool to guide clinical treatment decisions.

Diabetic ketoacidosis is the most common acute complication in children and adolescents with type 1 diabetes, and contributes significantly to morbidity, mortality, and healthcare burden. This review aims to explore the multifaceted aspects of severe diabetic ketoacidosis in pediatric age, including its epidemiology, pathogenesis, risk factors, complications and emphasizing advances in prevention strategies. Incidence rates vary due to influences from geographic, socioeconomic, cultural and demographic factors. Pathogenesis is linked to insulin deficiency and an excess of counter-regulatory hormones, which disrupt glucose, protein, and lipid metabolism, causing hyperglycemia, ketosis, acidosis, dehydration, and electrolyte imbalances. According to the International Society for Pediatric and Adolescent Diabetes guidelines, severe diabetic ketoacidosis is characterized by a pH < 7.1 or bicarbonate < 5 mmol/L. This condition can lead to a wide range of life-threatening complications, including cerebral edema that represents the leading cause of death. Several prevention strategies, including awareness campaigns, early diagnosis of diabetes, regular monitoring and management, effective insulin therapy, education, access to healthcare and technological assistance, may contribute to reduce the risk of severe diabetic ketoacidosis episodes in children and adolescents.

Diabetes is undeniably a pandemic of the 21st century. Although type 1 diabetes mellitus (T1DM) only represents 10% of all diabetes cases, it dominates the pediatric population. The number of T1DM cases is accelerating, and Poland is one of the countries with the fastest increase in incidence.

To evaluate the epidemiological situation in T1DM in Podlaskie region, Poland.

The study included 777 patients (369 girls and 408 boys) under 18. Incidence rates were calculated and standardized to an age-matched population (general population of Poland 2010).

We showed an upward trend in the number of cases during the analyzed period (R2 = 0.6, p = 0.001). The average incidence rate grew during the study period from 19.22/100,000 in 2010 to 34.11/100,000 in 2022, a 1.77-fold increase over the study period. The youngest age group (0-4 years old) showed the most prominent, nearly 2.3-fold rise, from 9.86/100,000 in 2010 to 22.56/100,000 in 2022. We have also demonstrated the possible impact of the COVID pandemic - after a decrease in 2020 we observed an increase of the incidence rate in 2021 up to 38.05/100,000 and in 2022 to 34/100,000.

The incidence of type 1 diabetes in Podlaskie Voivodeship, Poland, continues its upward trend. Various factors may influence this, but the potential impact of the COVID-19 pandemic is worth considering.

The coronavirus disease 2019 (COVID-19) pandemic has been linked to an increased incidence of diabetes and diabetic ketoacidosis (DKA). However, the relationship between COVID-19 infection and progression to type 1 diabetes (T1D) in children has not been well defined.

To evaluate the influence of COVID-19 infection and inactivated vaccine administration on the progression of T1D among Chinese children.

A total of 197 newly diagnosed patients with T1D were retrospectively enrolled from Children's Hospital of Fudan University between September 2020 and December 2023. The patients were divided into three groups based on their history of COVID-19 infection and vaccination: the infection group, the vaccination-only group, and the non-infection/non-vaccination group. Comprehensive clinical assessments and detailed immunological evaluations were performed to delineate the characteristics and immune responses of these groups.

The incidence of DKA was significantly higher in the COVID-19 infection group (70.2%) compared to the non-infection/non-vaccination group (62.5%) and vacscination-only group (45.6%; P = 0.015). Prior COVID-19 infection was correlated with increased DKA risk (OR: 1.981, 95%CI: 1.026-3.825, P = 0.042), while vaccination was associated with a reduced risk (OR: 0.558, 95%CI: 0.312-0.998, P = 0.049). COVID-19 infection mildly altered immune profiles, with modest differences in autoantibody positivity, lymphocyte distribution, and immunoglobulin levels. Notably, HLA-DR3 positive children with a history of COVID-19 infection had an earlier T1D onset and lower fasting C-peptide levels than the HLA-DR3 negative children with a history of infection (both P < 0.05).

COVID-19 infection predisposes children to severe T1D, characterized by enhanced DKA risk. Inactivated vaccination significantly lowers DKA incidence at T1D onset. These findings are valuable for guiding future vaccination and T1D risk surveillance strategies in epidemic scenarios in the general pediatric population.

This systematic review aims to collect and examine recent research findings regarding hypophysitis in COVID-19 patients.

We conducted a comprehensive literature review in English on the topic "Hypophysitis in COVID-19," using the MEDLINE (PubMed) database in July 2024. The selected articles were systematically tabulated and we have assessed in this review patient demographics, symptom presentation, imaging results, diagnosis, clinical management, and outcomes.

Seven reported cases of post-COVID-19 hypophysitis were identified, comprising 4 (57%) females and 3 (43%) males, with a median age of 37 years. The interval between COVID-19 infection symptoms and the onset of hypophysitis ranged from 2 to 3 weeks. Initial symptoms included frontal headache in 4 (57%) cases and polyuria and polydipsia in 3 (43%) cases. Anterior or posterior hypopituitarism was observed in 6 (85%) patients. Radiological findings varied: 2 (28.5%) cases showed panhypophysitis, 3 (43%) cases exhibited gland enlargement with homogeneous contrast enhancement on magnetic resonance imaging (MRI), 1 case involved the loss of the posterior pituitary bright spot, and 1 case involved pituitary apoplexy/enlargement of the gland and infundibulum. No pituitary biopsies were performed. Four (57%) patients received glucocorticoid (GC) treatment. Long-term follow-up was documented in only one case, a 16-year-old female followed for 2 years reporting complete clinical and radiological resolution.

Although rare, hypophysitis related to COVID-19 is documented in the literature exhibiting distinct characteristics such as a homogeneous gender prevalence, an average age of onset around 35 years, and primary symptoms of headache, polyuria, and polydipsia which are indicative of angiotensin-vasopressin deficiency. This is in contrast with primary autoimmune hypophysitis characterized by a female prevalence and typical symptoms with headache and visual impairment. Longer-term follow-up of these patients is needed to better understand the potential lasting impact on pituitary function and radiological improvement. Future research should also explore the presence of anti-pituitary antibodies and the other possible pathophysiological mechanisms potentially involved in these cases.

Predicting post-COVID-19 diabetes is crucial for enhancing patient care and public health. This study investigates the role of metabolic factors in predicting the glycemic outcomes in patients recovering from moderate to severe COVID-19.

We conducted a retrospective analysis of 135 patients without pre-existing diabetes, selected from a cohort of 1980 individuals hospitalized between January 2020 and December 2022. Metabolic parameters, including blood glucose, Homeostasis Model Assessment of Insulin Resistance (HOMA-IR), Triglyceride/Glucose (TyG) index, and high-sensitivity C-reactive protein (hs-CRP), were assessed at discharge and followed up after 4 months (T4) and 12 months (T12).

Statistical analysis revealed significant correlations of initial glycemia, HOMA-IR, and hs-CRP with the subsequent glycemic levels at T4 and T12. Multiple regression analysis confirmed that initial glycemia, HOMA-IR, and hs-CRP were strong predictors of elevated glycemia, while the TyG index did not show a significant predictive value. Conventional diabetes risk factors, including body mass index (BMI) and lipid profiles, showed low predictive power for post-COVID-19 glycemia.

This research highlights the critical role of metabolic and inflammatory pathways in managing glycemic control in COVID-19 patients. Markers like blood glucose, HOMA-IR, and hs-CRP are significant predictors of blood glucose levels, while the TyG index appears less helpful in this context. Early, targeted interventions based on these markers can improve patient outcomes and reduce the risk of post-COVID-19 complications like diabetes.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single-cell RNA sequencing (scRNA-seq) analysis of human islets exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis. To distinguish viral versus proinflammatory-macrophage-mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both β cells and endothelial cells compared with separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory-macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune-cell-mediated host damage and uncovered the mechanism of β cell damage during viral exposure.

To determine the incidence and presenting features of type 1 diabetes mellitus and diabetic ketoacidosis in a paediatric population serviced by a regional health service in Queensland, Australia.

All patients less than 16 years old diagnosed with type 1 diabetes mellitus between 01 January 2015 and 31 December 2021 were included in this retrospective, observational study. The electronic medical records of each patient were reviewed to collect data on demographics, presentation and ongoing diabetes care.

Sixty-four paediatric patients were diagnosed with type 1 diabetes mellitus during the study period, giving an incidence of 25 cases per 100 000 person years. Half the patients presented with diabetic ketoacidosis, with 14 (22% of the total cohort) presenting in severe diabetic ketoacidosis. There was no significant increase in the incidence of type 1 diabetes mellitus or proportion of patients with diabetic ketoacidosis across the years of the study. Patients that had a delayed diagnosis had an increased likelihood of presenting with severe diabetic ketoacidosis.

Incidence of type 1 diabetes mellitus in the paediatric population in this regional centre in Queensland, Australia, is similar to national data. High proportions of patients presenting with diabetic ketoacidosis and severe diabetic ketoacidosis were identified in the study population, with delayed diagnosis, a risk factor for severe diabetic ketoacidosis.

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.

Environmental factors, in particular viral infections, are thought to have an important role in the pathogenesis of type 1 diabetes mellitus (T1DM). The COVID-19 pandemic reinforced this hypothesis as many observational studies and meta-analyses reported a notable increase in the incidence of T1DM following infection with SARS-CoV-2 as well as an association between SARS-CoV-2 infection and the risk of new-onset T1DM. Experimental evidence suggests that human β-cells express SARS-CoV-2 receptors and that SARS-CoV-2 can infect and replicate in β-cells, resulting in structural or functional alterations of these cells. These alterations include reduced numbers of insulin-secreting granules, impaired pro-insulin (or insulin) secretion, and β-cell transdifferentiation or dedifferentiation. The inflammatory environment induced by local or systemic SARS-CoV-2 infection might result in a set of signals (such as pro-inflammatory cytokines) that lead to β-cell alteration or apoptosis or to a bystander activation of T cells and disruption of peripheral tolerance that triggers autoimmunity. Other mechanisms, such as viral persistence, molecular mimicry and activation of endogenous human retroviruses, are also likely to be involved in the pathogenesis of T1DM following SARS-CoV-2 infection. This Review addresses the issue of the involvement of SARS-CoV-2 infection in the development of T1DM using evidence from epidemiological, clinical and experimental studies.

We aimed to evaluate the effect of light-dark cycle alteration and soft drink consumption on the acceleration of type 1 diabetes mellitus (T1DM) development among non-obese diabetic (NOD) mice model.

We exposed female NOD and C57BL/6 mice from the age of 5 weeks to either adlib soft drink consumption and/or T20 light-dark cycle alteration until the development of diabetes, or the mice reached the age of 30 weeks. Each group consisted of 7-15 mice. We monitored weight, length, blood glucose level, and insulin autoantibody (IAA) levels weekly.

Out of 75 NOD and 22 C57BL/6 mice, 41 NOD mice developed diabetes, and 6 mice died between 7 and 8 weeks of age. The mean time to development of T1DM among NOD control mice was 20 weeks. The time to development of T1DM was accelerated by two weeks in the NOD mice exposed to light-dark cycle alteration, hazard ratio of 2.65,95th CI (0.70, 10.04) p = 0.15). The other groups developed T1DM, similar to the control group.

There was a trend toward earlier development of T1DM among NOD mice exposed to light-dark cycle alteration, but this difference was not statistically significant. Further studies are needed to confirm our findings using larger sample sizes and different animal species.

Hyperglycemia, and exacerbation of pre-existing deficits in glucose metabolism, are manifestations of the post-acute sequelae of SARS-CoV-2. Our understanding of metabolic decline after acute COVID-19 remains unclear due to the lack of animal models. Here, we report a non-human primate model of metabolic post-acute sequelae of SARS-CoV-2 using SARS-CoV-2 infected African green monkeys. Using this model, we identify a dysregulated blood chemokine signature during acute COVID-19 that correlates with elevated and persistent hyperglycemia four months post-infection. Hyperglycemia also correlates with liver glycogen levels, but there is no evidence of substantial long-term SARS-CoV-2 replication in the liver and pancreas. Finally, we report a favorable glycemic effect of the SARS-CoV-2 mRNA vaccine, administered on day 4 post-infection. Together, these data suggest that the African green monkey model exhibits important similarities to humans and can be utilized to assess therapeutic candidates to combat COVID-related metabolic defects.

This review explores the immunomodulatory potential of Teplizumab and its impact on pancreatic β-cell function in T1D. Characterized by the autoimmune destruction of insulin-producing beta cells, T1D's management involves maintaining glycemic control through exogenous insulin. Teplizumab, a humanized monoclonal antibody targeting the CD3 antigen, has shown promise in delaying T1D onset and preserving residual β-cell function. The review employs a narrative approach, synthesizing evidence from diverse clinical trials and studies gathered through a meticulous literature search. It scrutinizes Teplizumab's mechanisms of action, including its influence on autoreactive CD8 + T cells and regulatory T cells, offering insights into its immunological pathways. The synthesis of findings from various trials demonstrates Teplizumab's efficacy in preserving C-peptide levels and reducing exogenous insulin requirements, particularly in recent-onset T1D. Considering Teplizumab's real-world implications, the paper addresses potential obstacles, including side effects, patient selection criteria, and logistical challenges. It also emphasizes exploring combination therapies and personalized treatment strategies to maximize Teplizumab's benefits. The review contributes a nuanced perspective on Teplizumab's clinical implications and future directions in T1D management, bridging theoretical understanding with practical considerations.

Viral respiratory infections may precipitate type 1 diabetes (T1D). A possible association between the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus responsible for COVID-19, and the incidence of T1D is being determined. This study was carried out using Portuguese registries, aiming at examining temporal trends between COVID-19 and T1D.

Hospital data, comparing the incidence before and during the COVID-19 pandemic, from children and young adults diagnosed with new-onset T1D, was acquired beginning in 2017 and until the end of 2022. Data was obtained from nine different Portuguese hospital units. The impact of the COVID-19 pandemic, beginning in March 2020, was assessed comparing the annual numbers of new-onset T1D cases. The annual median levels of glucose, glycated hemoglobin (HbA1c) and fasting C-peptide at T1D diagnosis were compared. The annual number of diabetic ketoacidosis (DKA) episodes among new T1D cases was also assessed at two centers.

In total, data from 574 newly diagnosed T1D patients was analyzed, including 530 (92.3%) children. The mean ages for child and adult patients were 9.1 (SD 4.4) and 32.8 (SD 13.6) years, respectively. 57.8% (331/573) were male, one patient had unknown sex. The overall median (25-75 percentiles) levels of glucose, HbA1c and fasting C-peptide at diagnosis were 454 mg/dL (356-568), 11.8% (10.1-13.4) and 0.50 µg/L (0.30-0.79), respectively. DKA at T1D diagnosis was present in 48.4% (76/157). For eight centers with complete 2018 to 2021 data (all calendar months), no overall significant increase in T1D cases was observed during the COVID-19 pandemic, i.e. 90 cases in 2018, 90 cases in 2019, 112 in 2020 and 100 in 2021 (P for trend = 0.36). Two of the centers, Faro (CHUA) and Dona Estefânia (CHULC) hospitals, did however see an increase in T1D from 2019 to 2020. No significant changes in glucose (P = 0.32), HbA1c (P = 0.68), fasting C-peptide (P = 0.20) or DKA frequency (P = 0.68) at the time of T1D diagnosis were observed over the entire study period.

The T1D incidence did not increase significantly, when comparing the years before and during the COVID-19 pandemic, nor did key metabolic parameters or number of DKA episodes change.

There is a paucity of human models to study immune-mediated host damage. Here, we utilized the GeoMx spatial multi-omics platform to analyze immune cell changes in COVID-19 pancreatic autopsy samples, revealing an accumulation of proinflammatory macrophages. Single cell RNA-seq analysis of human islets exposed to SARS-CoV-2 or Coxsackievirus B4 (CVB4) viruses identified activation of proinflammatory macrophages and β cell pyroptosis. To distinguish viral versus proinflammatory macrophage-mediated β cell pyroptosis, we developed human pluripotent stem cell (hPSC)-derived vascularized macrophage-islet (VMI) organoids. VMI organoids exhibited enhanced marker expression and function in both β cells and endothelial cells compared to separately cultured cells. Notably, proinflammatory macrophages within VMI organoids induced β cell pyroptosis. Mechanistic investigations highlighted TNFSF12-TNFRSF12A involvement in proinflammatory macrophage-mediated β cell pyroptosis. This study established hPSC-derived VMI organoids as a valuable tool for studying immune cell-mediated host damage and uncovered mechanism of β cell damage during viral exposure.

Glycosylated hemoglobin (HbA1c) is commonly used as a monitoring tool in diabetes. Due to the potential influence of insulin resistance (IR), HbA1c level may fluctuate over a person's lifetime. This study explores the long-term tracking of HbA1c level in individuals diagnosed with type 1 diabetes mellitus (T1DM) from infancy to early adulthood.

The HbA1c levels in 275 individuals (121 males, 43.8%) diagnosed with T1DM were tracked for an average of 9.4 years. The distribution of HbA1c levels was evaluated according to age with subgroups divided by gender, use of continuous glucose monitoring (CGM), and the presence of complications.

HbA1c levels were highest at the age of 1 year and then declined until age 4, followed by a significant increase, reaching a maximum at ages 15-16 years. The levels subsequently gradually decreased until early adulthood. This pattern was observed in both sexes, but it was more pronounced in females. Additionally, HbA1c levels were higher in CGM nonusers compared with CGM users; however, regardless of CGM usage, an age-dependent pattern was observed. Furthermore, diabetic complications occurred in 26.8% of individuals, and the age-dependent pattern was observed irrespective of diabetic complications, although HbA1c levels were higher in individuals with diabetic complications.

HbA1c levels vary throughout the lifespan, with higher levels during adolescence. This trend is observed regardless of sex and CGM usage, potentially due to physiological IR observed during adolescence. Hence, physiological IR should be considered when interpretating HbA1c levels during adolescence.

Multicenter international clinical trials demonstrated the clinical safety and efficacy by using stem cell educator therapy to treat type 1 diabetes (T1D) and other autoimmune diseases. Previous studies characterized the peripheral blood insulin-producing cells (PB-IPC) from healthy donors with high potential to give rise to insulin-producing cells. PB-IPC displayed the molecular marker glucose transporter 2 (GLUT2), contributing to the glucose transport and sensing. To improve the clinical efficacy of stem cell educator therapy in the restoration of islet β-cell function, we explored the GLUT2 expression on PB-IPC in recent onset and longstanding T1D patients. In the Food and Drug Administration (FDA)-approved phase 2 clinical studies, patients received one treatment with the stem cell educator therapy. Peripheral blood mononuclear cells (PBMC) were isolated for flow cytometry analysis of PB-IPC and other immune markers before and after the treatment with stem cell educator therapy. Flow cytometry revealed that both recent onset and longstanding T1D patients displayed very low levels of GLUT2 on PB-IPC. After the treatment with stem cell educator therapy, the percentages of GLUT2+CD45RO+ PB-IPC were markedly increased in these T1D subjects. Notably, we found that T1D patients shared common clinical features with patients with other autoimmune and inflammation-associated diseases, such as displaying low or no expression of GLUT2 on PB-IPC at baseline and exhibiting a high profile of the inflammatory cytokine interleukin (IL)-1β. Flow cytometry demonstrated that their GLUT2 expressions on PB-IPC were also markedly upregulated, and the levels of IL-1β-positive cells were significantly downregulated after the treatment with stem cell educator therapy. Stem cell educator therapy could upregulate the GLUT2 expression on PB-IPC and restore their function in T1D patients, leading to the improvement of clinical outcomes. The clinical data advances current understanding about the molecular mechanisms underlying the stem cell educator therapy, which can be expanded to treat patients with other autoimmune and inflammation-associated diseases.

Metabolic Syndrome (MetS), diabetes, and other noncommunicable diseases (NCDs) have been a major focus of research in recent decades as the prevalence of these conditions continues to rapidly increase globally. However, the timing and patterns of development from metabolic risk factors to disease states are less well understood and are especially critical to understand in low- and middle-income countries (LMICs) and populations undergoing epidemiological transitions.

Nationally representative sociodemographic, anthropometric, and point-of-care biomarker data from the 2016 Tunisian Health Examination Survey (n = 8170) were used to determine the prevalence of diabetes and MetS components in Tunisia and to investigate associations between glycated hemoglobin (HbA1c) and MetS components (blood pressure [BP], HDL cholesterol [HDL], triglycerides [TG], and waist circumference [WC]) in participants aged 15-97 years old. To better understand how sustained metabolic dysregulation and disease states impact these associations, diabetic and nondiabetic groups were analyzed separately.

The overall prevalence of diabetes based on measured HbA1c was 18.2%. The diabetic groups had a higher prevalence of each individual MetS component, and significantly higher (BP, TG, WC, and HbA1c) and lower (HDL) values than the nondiabetic groups. Yet, there were a higher number of significant associations between HbA1c and MetS components found in nondiabetic women and men when compared to diabetic women and men. HbA1c was positively associated with the cumulative number of MetS components, irrespective of diabetes status in men and women.

The prevalence of both diabetes and MetS components (particularly low HDL cholesterol and elevated TG) is high among the Tunisian population. More MetS components were associated with HbA1c in nondiabetic individuals, showing a strong connection between the development of MetS components and diabetes. However, once the diabetes disease state manifests, there is more variability in the relationships. These results show the potential for HbA1c to be an indicator of metabolic health below clinical disease cutoffs, which may allow insights into the physiological changes that precipitate the emergence of diabetes.

Past literature on the development of type 1 diabetes (T1D) and type 2 diabetes (T2D) has emphasized the influence of exogenous factors, including viral infections, in the development of these conditions. The coronavirus disease 2019 (COVID-19) pandemic again highlighted the complicated connection between viral infection and the development of diabetes. The complex interplay of proinflammatory, genetic, and socioeconomic factors can help explain the increased incidence of T1D and T2D during the pandemic. Proposed pathophysiological mechanisms connecting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to T1D include the expression of angiotensin enzyme 2 receptors on pancreatic islet cells, resultant proinflammatory states, and potential transient damage caused by viral entry. The intricate web of genetic factors, social determinants of health (including the rise of obesity), and the impact of proinflammatory states during SARS-CoV-2 infection on insulin resistance suggests mechanisms linking SARS-CoV-2 infection to the development of diabetes. [Pediatr Ann. 2024;53(7):e258-e263.].

This study reports the prevalence and characteristics related to the development of thyroid autoimmunity among children newly diagnosed with type I diabetes (T1D) during the COVID-19 pandemic in Kuwait.

This is a prospective observational study of all children under age 14 years newly diagnosed with T1D in Kuwait. We define the duration of the COVID-19 pandemic from the official declaration of the first identified positive COVID-19 case on 24 February 2020 until 31 December 2022. For comparison, we use the time period directly before the COVID-19 pandemic, 1 January 2017 to 23 February 2020.

One thousand twenty-four (1024) children newly diagnosed with T1D in Kuwait during the study period were included. Among newly diagnosed children, 20.3% tested positive for thyroid antibodies during the COVID-19 pandemic, compared with 14.5% during the pre-pandemic period (p = 0.015). Children with positive COVID-19 status were more likely to present with thyroid antibodies (p = 0.035). After adjusting for other characteristics, patients diagnosed with T1D during the COVID-19 pandemic had double the odds of testing positive for thyroid antibodies (Adjusted odds ratio = 2.173, 95%CI: 1.108, 4.261, p = 0.024).

Incident cases of T1D during the COVID-19 pandemic may be different in aetiology or contextual factors leading to a higher risk of thyroid autoimmunity. Longitudinal studies are needed to understand the role of COVID-19 in the onset and progression of T1D and on thyroid autoimmunity and disease.

Type 2 diabetes (T2D) is a growing concern among the pediatric population. During the coronavirus disease 2019 (COVID-19) pandemic, the incidence of pediatric T2D increased. This was more notable among males and Black people. Increased rates of T2D may be due to rising obesity rates observed during the pandemic, behavioral and nutritional changes due to the lockdown, and decreased structure typically provided by in-person schooling. New-onset T2D presentations are more severe than in years prior to the pandemic, with higher initial hemoglobin A1C levels and increased rates of diabetic ketoacidosis. Increased severity in presentation may be due to hesitation in seeking care, increased virtual care, and limited access to health care resources. The pathophysiology of the relationship between T2D and COVID-19 in youth is not clear at this time. More studies are needed to understand the true long-term impact of the COVID-19 pandemic on T2D in youth. [Pediatr Ann. 2024;53(7):e249-e253.].

Celiac disease (CD) is among the diseases most commonly associated with type 1 diabetes (T1D). This study aimed to evaluate the worldwide practices and attitudes of physicians involved in pediatric diabetes care regarding diagnosing and managing CD in children with T1D.

The 30-item survey was conducted between July and December 2023 aimed at targeting pediatricians with special interest in T1D and CD. It was shared by the JENIOUS - young investigators group of the International Society of Pediatric and Adolescent Diabetes (ISPAD) - and the YES - early career group of the European Society for Pediatric Endocrinology (ESPE).

Overall, 180 physicians (67.8% female) from 25 countries responded. Among respondents, 62.2% expected sustaining optimal glycemic control in children with T1D and CD (T1D + CD) to be more difficult than in children with T1D alone. Majority (81.1%) agreed that more specific guidelines are needed. The follow-up routine for patients with T1D + CD differed, and one-quarter of physicians scheduled more frequent follow-up checkups for these patients. Seventy percent agreed multidisciplinary outpatient clinics for their follow-up is needed. In the multivariate ordinal logistic regression model, a statistically significant predictor of a higher degree of practice according to ISPAD 2022 guidelines was a higher level of country income (OR = 3.34; p < 0.001).

These results showed variations in physicians' practices regarding managing CD in children with T1D, emphasizing the need for more specific guidelines and intensive education of physicians in managing this population, especially in lower-income countries. Our data also suggest the implementation of multidisciplinary outpatient clinics for their follow-up.

Emerging publications indicate that diabetes predisposes patients with COVID-19 to more severe complications, which is partly attributed to inflammatory condition. In the current review, we reviewed recent published literature to provide evidence on the role of insulin resistance (IR) in diabetes, the association between diabetes and COVID-19 severity and mortality, the impact of COVID-19 infection on incident new-onset diabetes, mechanisms responsible for IR in COVID-19 patients, and the predictive value of different surrogates of IR in COVID-19.

The literature search performs to find out studies that have assessed the association between IR surrogates and morbidity and mortality in patients with COVID-19.

We showed that there is a bulk of evidence in support of the fact that diabetes is a potent risk factor for enhanced morbidity and mortality in COVID-19 patients. COVID-19 patients with diabetes are more prone to remarkable dysglycemia compared to those without diabetes, which is associated with an unfavourable prognosis. Furthermore, SARS-COV2 can make patients predispose to IR and diabetes via activating ISR, affecting RAAS signaling pathway, provoking inflammation, and changing the expression of PPARɣ and SREBP-1. Additionally, higher IR is associated with increased morbidity and mortality in COVID-19 patients and different surrogates of IR can be utilized as a prognostic biomarker for COVID-19 patients.

Different surrogates of IR can be utilized as predictors of COVID-19 complications and death.

To assess the incidence trends in type 1 diabetes among children and adolescents across Europe during the period from 1994 to 2022 using a systematic methodology.

Cross-sectional or follow-up studies reporting population-based incidence rates (IRs) of European children and adolescents diagnosed aged <15 years with type 1 diabetes were included. The Mantel‒Haenszel or DerSimonian and Laird random-effects method was used to compute the pooled IR estimates and their 95% confidence intervals (CIs). Subgroup analyses were conducted by study year, biological sex, age group (0-4, 5-9, and 10-14 years), country, and European regions.

A total of 75 studies (219,331 children and adolescents aged 0-14 years) with data from 32 countries were included. Generally, a high overall rate of increase in type 1 diabetes incidence has been shown in most European countries from 1994 to 2022 in both sexes, with an overall increase from 10.85 (95% CI, 9.62-12.07) per 100,000 person-years from 1994 to 2003 to 20.96 (95% CI, 19.26-22.66) per 100,000 person-years from 2013 to 2022.

There are substantial between-country differences in the current levels and trends of IR in type 1 diabetes in European children and adolescents. Our data suggest a worrying upward trend in most European countries.

Emerging evidence indicates that the relationship between coronavirus disease 2019 (COVID-19) and diabetes is 2-fold: 1) it is known that the presence of diabetes and other metabolic alterations poses a considerably high risk to develop a severe COVID-19; 2) patients who survived a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have an increased risk of developing new-onset diabetes. However, the mechanisms underlying this association are mostly unknown, and there are no reliable biomarkers to predict the development of new-onset diabetes. In the present study, we demonstrate that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells reliably predicts the risk of developing new-onset diabetes in COVID-19. This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. SIGNIFICANCE STATEMENT: We demonstrate for the first time that a specific microRNA (miR-34a) contained in circulating extracellular vesicles released by endothelial cells is able to reliably predict the risk of developing diabetes after having contracted coronavirus disease 2019 (COVID-19). This association was independent of age, sex, body mass index (BMI), hypertension, dyslipidemia, smoking status, and D-dimer. Our findings are also relevant when considering the emerging importance of post-acute sequelae of COVID-19, with systemic manifestations observed even months after viral negativization (long COVID).

The COVID-19 pandemic has had a significant impact on both the United Arab Emirates (UAE) and Malaysia, emphasizing the importance of developing accurate and reliable forecasting mechanisms to guide public health responses and policies. In this study, we compared several cutting-edge deep learning models, including Long Short-Term Memory (LSTM), bidirectional LSTM, Convolutional Neural Networks (CNN), hybrid CNN-LSTM, Multilayer Perceptron's, and Recurrent Neural Networks (RNN), to project COVID-19 cases in the aforementioned regions. These models were calibrated and evaluated using a comprehensive dataset that includes confirmed case counts, demographic data, and relevant socioeconomic factors. To enhance the performance of these models, Bayesian optimization techniques were employed. Subsequently, the models were re-evaluated to compare their effectiveness. Analytic approaches, both predictive and retrospective in nature, were used to interpret the data. Our primary objective was to determine the most effective model for predicting COVID-19 cases in the United Arab Emirates (UAE) and Malaysia. The findings indicate that the selected deep learning algorithms were proficient in forecasting COVID-19 cases, although their efficacy varied across different models. After a thorough evaluation, the model architectures most suitable for the specific conditions in the UAE and Malaysia were identified. Our study contributes significantly to the ongoing efforts to combat the COVID-19 pandemic, providing crucial insights into the application of sophisticated deep learning algorithms for the precise and timely forecasting of COVID-19 cases. These insights hold substantial value for shaping public health strategies, enabling authorities to develop targeted and evidence-based interventions to manage the virus spread and its impact on the populations of the UAE and Malaysia. The study confirms the usefulness of deep learning methodologies in efficiently processing complex datasets and generating reliable projections, a skill of great importance in healthcare and professional settings.

Experiences during childhood and adolescence have enduring impacts on physical and mental well-being, overall quality of life, and socioeconomic status throughout one's lifetime. This underscores the importance of prioritizing the health of children and adolescents to establish an impactful healthcare system that benefits both individuals and society. It is crucial for healthcare providers and policymakers to examine the relationship between COVID-19 and the health of children and adolescents, as this understanding will guide the creation of interventions and policies for the long-term management of the virus.

In this umbrella review (PROSPERO ID: CRD42023401106), systematic reviews were identified from the Cochrane Database of Systematic Reviews; EMBASE (OvidSP); and MEDLINE (OvidSP) from December 2019 to February 2023. Pairwise and single-arm meta-analyses were extracted from the included systematic reviews. The methodological quality appraisal was completed using the AMSTAR-2 tool. Single-arm meta-analyses were re-presented under six domains associated with COVID-19 condition. Pairwise meta-analyses were classified into five domains according to the evidence classification criteria. Rosenberg's FSN was calculated for both binary and continuous measures.

We identified 1551 single-arm and 301 pairwise meta-analyses from 124 systematic reviews that met our predefined criteria for inclusion. The focus of the meta-analytical evidence was predominantly on the physical outcomes of COVID-19, encompassing both single-arm and pairwise study designs. However, the quality of evidence and methodological rigor were suboptimal. Based on the evidence gathered from single-arm meta-analyses, we constructed an illustrative representation of the disease severity, clinical manifestations, laboratory and radiological findings, treatments, and outcomes from 2020 to 2022. Additionally, we discovered 17 instances of strong or highly suggestive pairwise meta-analytical evidence concerning long-COVID, pediatric comorbidity, COVID-19 vaccines, mental health, and depression.

The findings of our study advocate for the implementation of surveillance systems to track health consequences associated with COVID-19 and the establishment of multidisciplinary collaborative rehabilitation programs for affected younger populations. In future research endeavors, it is important to prioritize the investigation of non-physical outcomes to bridge the gap between research findings and clinical application in this field.

Diabetes-induced cognitive impairment is a major challenge in patients with uncontrolled diabetes mellitus. It has a complicated pathophysiology, but the role of oxidative stress is central. Therefore, the use of antidiabetic drugs with extra-glycemic effects that reduce oxidative damage may be a promising treatment option.

Male Wistar rats were randomly divided into four groups as normal, normal treated, diabetic and diabetic treated (n = 8 per group). Type 1 diabetes was induced by a single intraperitoneal dose of streptozotocin (STZ) (40 mg/kg). Two treatment groups received empagliflozin for 5 weeks (20 mg/kg/po). Cognitive ability was evaluated using open field, Elevated Plus Maze (EPM) and the Morris Water Maze (MWM) tests at study completion. Blood and brain tissue samples were collected - and analysis for malondialdehyde (MDA) and glutathione (GLT) content and catalase (CAT) and superoxide dismutase (SOD) enzyme activity were performed. Additionally, expression of nicotinamide adenine dinucleotide phosphate oxidase-4 (Nox-4) enzyme in brain tissue was analyzed using RT-PCR.

STZ increased blood glucose and induced diabetes with oxidative stress by lowering the antioxidant system potency and increasing Nox-4 expression after 5-weeks in brain tissue accompanied by reduction in cognitive performance. Also, diabetes induced anxiety-like behavior and impaired spatial memory in MWM, EPM and open field tests. However, empagliflozin reversed these changes, improving SOD and CAT activity, GLT content and reducing Nox-4 expression and MDA concentration in brain tissue while improving cognitive ability. It reduced anxiety and depression-related activities. It also improved spatial memory in MWM test.

Uncontrolled diabetes negatively impacts mental function and impairs learning and cognitive performance via oxidative stress induction, the Nox-4 enzyme playing a central role. Empagliflozin reverses these effects, improving cognitive ability via promoting the anti-oxidative system and damping Nox-4 free radical generator enzyme expression. Therefore, empagliflozin is a promising treatment, providing both antidiabetic and extra-glycemic benefits for improving brain function in the diabetic milieu.

The aim of this study was to determine the global incidence of type 1 diabetes mellitus (T1DM) in children and adolescents under 20 years of age from 2000 to 2022.

Two reviewers searched three electronic databases (PubMed, Web of Science, and CINAHL) for studies published between January 2000 and November 2022. Pooled estimates of T1DM incidence with a 95% confidence interval (CI) per 100,000 person-years were calculated by country/region, sex, age, and COVID-19 pandemic period (pre-COVID-19 and pandemic).

The study included 126 studies from 55 countries and 18 regions. The incidence rate (IR) of T1DM from 2000 to 2022 was 14.07 (95%CI, 12.15-16.29) per 100,000 person-years. Finland and high-income North America had the highest IR, with 56.81 (95%CI, 55.91-57.73) and 28.77 (95%CI, 26.59-31.13) per 100,000 person-years, respectively. The IR was 13.37 (95%CI, 10.60-16.88) per 100,000 person-years in boys and 13.87 (95%CI, 11.51-16.70) per 100,000 person-years in girls. There were statistically significant differences among different age ranges: 0-4 versus 5-9 and 10-14 years old (p < 0.001); 5-9 versus 15-19 (p < 0.001) and 10-14 versus 15-19 years old (p = 0.003). Finally, during the pandemic period (2020-2022), the IR was 24.84 (95%CI, 17.16-35.96) per 100,000 person-years, which was higher but not significant compared with the prepandemic period (2017-2019) of 13.56 (95%CI, 7.49-24.56) per 100,000 person-years (p = 0.090).

The IR of T1DM in children and adolescents under 20 years of age is substantial, especially during the pandemic period, although it varies across regions. More reliable data from additional countries are needed to determine the worldwide incidence of T1DM.

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.