New-onset Type 1 Diabetes Mellitus Research Articles

Metformin-Insulin Combination Therapy Ameliorates Hyperglycemia in a COVID-19 Type-1 Diabetic Child with Insulin Resistance: A Case Report

Introduction: Recent studies have indicated that COVID-19 may be linked with type 1 diabetes mellitus (T1DM) in children. It has been observed that not only is there a potential risk of new-onset pediatric T1DM associated with COVID-19, but numerous cases also present with insulin resistance, necessitating prompt management. Case Presentation: We report the case of a 9-year-old girl with a history of T1DM who was admitted with hyperglycemia (blood sugar > 750 mg/dL) and subsequently diagnosed with COVID-19. The co-administration of metformin and intravenous insulin successfully resolved subcutaneous insulin resistance, allowing the patient to be discharged in good health. Conclusions: Insulin resistance is a recognized complication of SARS-CoV-2 infection, and metformin combined with intravenous insulin has proven effective in managing hyperglycemia and improving insulin resistance in this context. Further research is necessary to elucidate the underlying mechanisms and develop optimal therapeutic strategies.

Systemic Inflammatory Response Index (SIRI) as a Predictive Marker for Adverse Outcomes in Children with New-Onset Type 1 Diabetes Mellitus.

(1) Background: Although most cases of new-onset type 1 diabetes mellitus (T1DM) are managed without serious events, life-threatening complications do arise in a subset of patients. Our objective was to assess the correlation between elevated SIRI values and adverse events related to the onset of T1DM. (2) Methods: This retrospective study, spanning ten years, included 187 patients with new-onset T1DM divided into three groups based on SIRI tertiles. The primary outcome was the occurrence of acute complications during hospital admission, while the secondary outcome was prolonged Intensive Care Unit (ICU) admission. (3) Results: Patients with high SIRI values were more likely to experience higher disease activity, leading to longer ICU admission times and more frequent complications. Multivariate logistic regression analysis revealed that the SIRI was independently associated with acute complications (p = 0.003) and prolonged ICU length of stay (p = 0.003). Furthermore, receiver operating characteristic analysis demonstrated the SIRI's superior predictive accuracy compared to venous pH (AUC = 0.837 and AUC = 0.811, respectively) and to the individual component cell lineages of the SIRI. (4) Conclusions: These findings emphasize the potential utility of the SIRI as a prognostic marker in identifying patients at increased risk during T1DM hospital admissions.

COVID-19 Vaccination and Its Relation to New-Onset Diabetes: A NarrativeReview.

The COVID-19 vaccination has been effective in preventing a lot of complications caused by SARS-CoV-2 and its variants. Meanwhile, diabetes mellitus, one of the root causes of many co-morbidities, exhibited itself during the COVID-19 pandemic and after COVID-19 vaccination. Diabetes mellitus introduced itself in a new perspective, leading to a variety of presentations and causing a significant number ofemergency admissions. Many of the pre-diabetes patients with no prior history of diabetes developed fulminant type 1 diabetes mellitus (T1DM) after the COVID-19 vaccination. Some cases of conversion of type 2 diabetes mellitus (T2DM) into T1DM were reported. Some prediabetes/diabetes patientspresented with the development of diabetic ketoacidosis after COVID-19 vaccination, whereas some previously healthy people with no relation to diabetes also developed acute exacerbations of new-onset T1DM or T2DM along with lethal ketoacidosis. The purpose of writing this review was to explore what kind of people are more prone to develop new-onset diabetes or diabetic complications, including diabetic ketoacidosis, the typical presentation of these patients, possible mechanisms that lead to these complications occurring after the COVID-19 vaccination, how they can be managed, and whether there is a good prognosis after management or not.

B-147 Evaluation of Laboratory Database: Is there a Causal Relationship between COVID-19 and Type 1 Diabetes

Abstract Background Type 1 diabetes mellitus (T1DM) constitutes about 5% of all diagnosed cases of diabetes. The global incidence is increasing over the past few years. To date, the pathophysiology of the disease is not fully understood. with descriptions of activation of the immune system by some viral agents. SARS-CoV-2 has been suggested as a potential inducer of new-onset type 1 diabetes mellitus (T1DM). DASA has one of the largestData and Analytics areas in Diagnostic Medicine. The use of laboratory data can represent an important tool in broader knowledge of this relationship. This study aimed to evaluate the frequency of new-onset T1DM in the years 2019, 2020 and 2021. Methods This study was done through an observational, retrospective big data laboratory approach with a network that extends over a large part of Brazil to analyze whether there was an increase in T1DM cases. Individuals aged 18 years or younger were evaluated from January 2019 to December 2021. The subjects were characterized with possible new-onset T1DM through the presence of glycated hemoglobin equal to or greater than 6.5% in the presence of at least one disease-related antibody. The antibodies evaluated were: anti-GAD, anti-islet, anti-insulin and anti-zinc transporter type 8. For data evaluation, the means and standard deviations and the chi-square test were used. The results of patients who underwent RT PCR COVID19 were evaluated. Results A total of 431 060 subjects (<18 years) were evaluated, with 229 201 female (53.17%). Table 1 shows the distribution of data over the years evaluated, the number of patients with glycated levels greater than 6.5% and the number of probable new cases of DM1 from the positivity of at least 1 antibody. In the years evaluated, there was no statistical difference in the incidence of the disease between the sexes (2019 - 51.2%; P:0.92, 2020 - 50.3%; P:0.99 and 2021 - 48.9%; P: 0.67). The mean age with standard deviation in the years 2019, 2020 and 2021, respectively, was: 12.4% ± 4.4; 12.6 ± 4.3 and 12.5% ± 4.3. The mean values of glycated hemoglobin of patients with a value ≥6.5% with standard deviation in the years 2019, 2020 and 2021, respectively, were: 9.3% ± 2.1; 9.2 ± 2.5 and 9.3% ± 3.4. When comparing the incidence of the disease between the years, there was a significant increase in cases when comparing the years 2021 with 2020 and 2019 (P: 0.01 and P < 0.01, respectively). Of the total number of patients in 2020, only 5 underwent RT PCR COVID 19, with no positive result, and in 2021 a total of 32, with 7 positive, corresponding to 21.8% of cases. Conclusion The present study, using a large database, seems to demonstrate an increase in the incidence of DM1 among children diagnosed with diabetes. Prospective studies that evaluate the possible relationship of the disease with the SARS-CoV-2 virus may show this agent as a trigger of disease-related automunity.

Impact of the COVID-19 pandemic on diabetic ketoacidosis management in the pediatric intensive care unit.

Diabetic ketoacidosis (DKA) is a common endocrine emergency in pediatric patients. Early presentation to health facilities, diagnosis, and good management in the pediatric intensive care unit (PICU) are crucial for better outcomes in children with DKA. This was a single-center, retrospective cohort study conducted between February 2015 and January 2022. Patients with DKA were divided into two groups according to pandemic status and diabetes diagnosis. The study enrolled 59 patients, and their mean age was 11±5 years. Forty (68%) had newly diagnosed type 1 diabetes mellitus (T1DM), and 61% received follow-up in the pre-pandemic period. Blood glucose, blood ketone, potassium, phosphorus, and creatinine levels were significantly higher in the new-onset T1DM group compared with the previously diagnosed group (P=0.01, P=0.02, P<0.001, P=0.01, and P=0.08, respectively). In patients with newly diagnosed T1DM, length of PICU stays were longer than in those with previously diagnosed T1DM (28.5±8.9 vs. 17.3±6.7 hours, P<0.001). The pandemic group was compared with pre-pandemic group, there was a statistically significant difference in laboratory parameters of pH, HCO3, and lactate and also Pediatric Risk of Mortality (PRISM) III score. All patients survived, and there were no neurologic sequelae. Patients admitted during the pandemic period were admitted with more severe DKA and had higher PRISM III scores. During the pandemic period, there was an increase in the incidence of DKA in the participating center compared to that before the pandemic.

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.

Early weight gain after diagnosis may have an impact on remission status in children with new-onset type 1 diabetes mellitus.

Residual beta-cell function and improvement in insulin sensitivity by reversal of glucose toxicity are two phenomena thought to be related to partial remission (PR). Body fat mass is the major determinant of insulin sensitivity. The aim of this study is to investigate the relationship between the rate of body weight gain after diagnosis of type 1 diabetes mellitus (T1DM) and other clinical factors for the development and duration of PR. Children (2-16 years) with new-onset T1DM (n = 99) were grouped into remitters and non-remitters by using insulin dose-adjusted glycosylated hemoglobin (HbA1c) values. Laboratory and clinical data as well as daily insulin requirement per kilogram of body weight at diagnosis and each visit were recorded, and the duration of PR was determined. Changes in body mass index standard deviation score (BMI-SDS) were calculated by the auxological data collected every 6 months. There were 47 remitters (47.5%) and 52 (52.5%) non-remitters. The mean increase in BMI-SDS at the first 6 months of diagnosis was higher in the non-remitters than in the remitters (p = 0.04). Duration of PR was negatively correlated with the change in BMI-SDS between 6 and 12 months after diagnosis. Male sex, younger age, prepubertal status, and lower HbA1c were predictors of remission, among which male sex had the highest chance by multivariate regression. Early rapid weight gain after diagnosis of T1DM may play a role in the lack of remission and shorter duration of PR. Interventions to prevent early rapid weight gain can maintain the development and prolongation of remission.

New-onset type 1 diabetes in children and adolescents as postacute sequelae of SARS-CoV-2 infection: A systematic review and meta-analysis of cohort studies.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in children and adolescents may increase risk for a variety of post-acute sequelae including new-onset type 1 diabetes mellitus (T1DM). Therefore, this meta-analysis aims to estimate the risk of developing new-onset type 1 diabetes in children and adolescents as post-acute sequelae of SARS-CoV-2 infection.PubMed/MEDLINE, CENTRAL, and EMBASE were systematically searched up to March 20, 2023. A systematic review and subsequent meta-analyses were performed to calculate the pooled effect size, expressed as risk ratio (RR) with corresponding 95% confidence interval (CI) of each outcome based on a one-stage approach and the random-effects estimate of the pooled effect sizes of each outcome were generated with the use of the DerSimonian-Laird method.Eight reports from seven studies involving 11 220 530 participants (2 140 897 patients with a history of diagnosed SARS-CoV-2 infection and 9 079 633 participants in the respective control groups) were included. The included studies reported data from four U.S. medical claims databases covering more than 503 million patients (IQVIA, HealthVerity, TriNetX, and Cerner Real-World Data), and three national health registries for all children and adolescents in Norway, Scotland, and Denmark. It was shown that the risk of new-onset T1DM following SARS-CoV-2 infection in children and adolescents was 42% (95% CI 13%-77%, p = 0.002) higher compared with non-COVID-19 control groups. The risk of developing new-onset T1DM following SARS-CoV-2 infection was significantly higher (67%, 95% CI 32 %-112%, p = 0.0001) in children and adolescents between 0 and 11 years, but not in those between 12 and 17 years (RR = 1.10, 95% CI 0.54-2.23, p = 0.79). We also found that the higher risk for developing new-onset T1DM following SARS-CoV-2 infection only exists in studies from the United States (RR = 1.70, 95% CI 1.37-2.11, p = 0.00001) but not Europe (RR = 1.02, 95% CI 0.67-1.55, p = 0.93). Furthermore, we found that SARS-CoV-2 infection was associated with an elevation in the risk of diabetic ketoacidosis (DKA) in children and adolescents compared with non-COVID-19 control groups (RR = 2.56, 95% CI 1.07-6.11, p = 0.03).Our findings mainly obtained from USmedical claims databases, suggest that SARS-CoV-2 infection is associated with higher risk of developing new-onset T1DM and diabetic ketoacidosis in children and adolescents. These findings highlight the need for targeted measures to raise public health practitioners and physician awareness to provide intervention strategies to reduce the risk of developing T1DM in children and adolescents who have had COVID-19.

Teplizumab: type 1 diabetes mellitus preventable?

Type 1 diabetes mellitus (T1DM) is an autoimmune condition driven by T lymphocytes that specifically declines the function of beta cells of pancreas. Immunological treatments aim to stop this decline in β-cell function thus preventing TIDM. Although TIDM occur at any age, it is one of the most common chronic disorders in children. T1DM accounts for 5 to 10% of all cases of diabetes amounting 21-42 million affected persons. Teplizumab is a novel drug recently approved by the US FDA for the treatment of T1DM. This drug reduces abnormal glucose tolerance who are at high risk for developing T1DM and have antibodies suggesting an immunological attack on their pancreas. A 14-day infusion of the drug prevents T cells' attack of the insulin-producing cells of the pancreas. Adverse events due to teplizumab reported so far mild and of limited duration. This review gives an overview of the preclinical and clinical research on teplizumab for their role in new-onset T1DM.

Epidemiological features of New-Onset Type 1 Diabetes Mellitus in children and adolescent during 2010-2014 in Albania - a unique experience.

Aim: Diabetes mellitus is a major public health problem worldwide. Type 1 diabetes mellitus (T1DM) is the most common metabolic chronic disease in genetically susceptible children and adolescents, due to an autoimmune process characterized by a selective destruction of insulin producing β-cells. The aim is to assess the epidemiological features of new-onset T1DM in children and adolescent at the national level during the period 2010-2014 in Department of Pediatrics, Endocrine Unit, University Hospital Center 'Mother Teresa', Tirana, as the unique center for pediatric endocrinology and diabetology in Albania.&#x0D; Methods: The clinical and laboratory characteristics of 152 patients aged &lt;15 years newly diagnosed with T1D from 1 January 2010 to 31 December 2014 were studied. T1D was diagnosed according to WHO 2006 criteria and DKA was diagnosed based on ISPAD 2014 criteria. Patients were classified into 3 sub-groups (I: 0-4 years, II: 5-9 years, and III; 10-14 years). Statistical analysis was performed using SPSS 26.&#x0D; Results: The incidence of new-onset of T1DM was 5.012/100.000/year. The mean age of children at diagnosis was 8.3 ± 3.6 years. The patients were mostly diagnosed at ages 5-9 years (40.1%), and 10-14 years (39.5%), followed by the 0-4 years age group (20.4%). Mean duration of symptoms was 23.35 ± 17.16 days; longer in the subgroup 5-9 years (P= 0. 0.013). Three quarters (75%) of children with T1DM live in urban areas. Viral infections or other circumstance triggers were in 41.9% of children aged 0-4 years compared to other subgroups (P=0.002). Most of the children were born in the spring−summer months (53.23%) compared to the autumn−winter months (46.77%). Approximately 1/4 of the children were born and diagnosed with type 1 diabetes in each of the seasons of the year and 52.63% of the patients studied were first born. Family history for DMT1 and DMT2 is observed in 15.8% and 17.8% of the children, respectively. Polyuria (99.3%), polydipsia (99.6%) and weight loss (98.1%) were the most common symptoms and 67.8% of patients presented with diabetic ketoacidosis (DKA). Misdiagnosis was in 21 (13.8%) patients. Mean glycosylated hemoglobin A1c (HbA1c) was 11.63%; 11.9 ± 2.0 in DKA positive children and 11.1 ± 2.4 in DKA negative children (p= 0.195).&#x0D; At diagnosis and during follow up of T1DM 25% (38/152) developed associated autoimmune diseases; 68.42% at diagnosis of T1DM and 65.79% (25/38) of patients were female. During follow up children with T1DM developed associated CD and SAT, 2.54, and 2.19 years, respectively.&#x0D; Conclusion: Diabetes mellitus is one of the major public health problems worldwide. Albania is a country with middle incidence of T1DM and the age at onset is decreasing. The symptoms lasted significantly longer and mean HbA1c levels were significantly higher in older children. The incidence

Incidence of new-onset type 1 diabetes during Covid-19 pandemic: A French nationwide population-based study

AimThe association between infection with SARS-CoV-2 and the development of new-onset type 1 diabetes mellitus (T1DM) is unclear. The aim of this study was to examine the impact of the Covid-19 pandemic on the hospitalization rates for new-onset T1DM and diabetic ketoacidosis at diagnosis, in metropolitan France. MethodsThis nationwide retrospective cohort study included hospital data on all patients aged 1 to 35 years old, hospitalized in France due to onset of T1DM, in 2020 and 2021 compared to 2019. ResultsApart from a decrease during the lockdown in 2020, the number of hospitalizations due to new-onset T1DM was not significantly different in 2020 and 2021 than it was in 2019. In the regions most affected by Covid-19 and covering 7,995,449 inhabitants aged from 1 to 35 years old, standardized hospitalization rates were not significantly different in 2020 and in 2021 compared with 2019. The number of hospitalizations for diabetic ketoacidosis at diagnosis was not significantly different after week 14 in 2020 and in 2021 compared with 2019. ConclusionIn this nationwide study, the incidence of hospitalizations for new-onset T1DM and the incidence of diabetic ketoacidosis at diagnosis was not increased during the Covid-19 pandemic in 2020 and 2021. Our results support the fact that infection with SARS-CoV-2 does not promote the development of T1DM.

The association between anti-glutamic acid decarboxylase IgG and hemoglobin A1C among newly diagnosed type 1 diabetes of some Iraqi children in Karbala City

Abstract Background: Type 1 diabetes mellitus (T1DM) is brought on by immune system dysfunction intolerance, invasion of beta cells by autoreactive immunological T cells, degradation of beta cell activity and survival, and extended exogenous insulin treatment. One of the circulation autoantibodies against antigens of pancreatic cell that produce insulin is glutamic acid decarboxylase (GAD IgG antibody) that indicate the stress and/or death of the islet cell in T1D. A blood glucose monitoring test called hemoglobin A1C (HbA1c) is used to determine the average blood sugar level over three months (February, March, and April of 2022). Objective: The purpose of this study is to assess the frequency of anti-GAD IgG and HbA1c in T1DM children, as well as their correlation. Materials and Methods: Seventy individuals with new-onset T1DM (confirmed by clinical signs, including increased urination, intense hunger, intense thirst, and abrupt weight loss, along with a random blood sugar test that is higher than 200 mg/dL and a fasting blood sugar test that is higher than 126 mg/dL) are male and female, ranging in age from 1 to 12 years. Blood was drawn for the biochemical and immunological tests (including HbA1c, fasting blood sugar, C-peptide, anti-islets antibodies, and anti-GAD antibodies). Results: Ninety-four percent of the T1DM patients had positive anti-GAD IgG with a mean concentration of 147 IU/mL, and 6% had negative anti-GAD IgG with a mean value of 9 IU/mL. At the same time, the findings of the current study’s calculation of HbA1c levels revealed that individuals with newly diagnosed T1DM had a total mean average of HbA1c of 10.53. Conclusion: Specifically in T1D that had arisen in extremely young children, autoimmunity was discovered to take part in the glycemic index expressed by glycated hemoglobin average.

Epidemiological features of New-Onset Type 1 Diabetes Mellitus in children and adolescent during 2010-2014 in Albania - a unique experience.

Aim: Diabetes mellitus is a major public health problem worldwide. Type 1 diabetes mellitus (T1DM) is the most common metabolic chronic disease in genetically susceptible children and adolescents, due to an autoimmune process characterized by a selective destruction of insulin producing β-cells. The aim is to assess the epidemiological features of new-onset T1DM in children and adolescent at the national level during the period 2010-2014 in Department of Pediatrics, Endocrine Unit, University Hospital Center 'Mother Teresa', Tirana, as the unique center for pediatric endocrinology and diabetology in Albania.Methods: The clinical and laboratory characteristics of 152 patients aged &lt;15 years newly diagnosed with T1D from 1 January 2010 to 31 December 2014 were studied. T1D was diagnosed according to WHO 2006 criteria and DKA was diagnosed based on ISPAD 2014 criteria. Patients were classified into 3 sub-groups (I: 0-4 years, II: 5-9 years, and III; 10-14 years). Statistical analysis was performed using SPSS 26.&#x0D; Results: The incidence of new-onset of T1DM was 5.012/100.000/year. The mean age of children at diagnosis was 8.3 ± 3.6 years. The patients were mostly diagnosed at ages 5-9 years (40.1%), and 10-14 years (39.5%), followed by the 0-4 years age group (20.4%). Mean duration of symptoms was 23.35 ± 17.16 days; longer in the subgroup 5-9 years (P= 0. 0.013). Three quarters (75%) of children with T1DM live in urban areas. Viral infections or other circumstance triggers were in 41.9% of children aged 0-4 years compared to other subgroups (P=0.002). Most of the children were born in the spring−summer months (53.23%) compared to the autumn−winter months (46.77%). Approximately 1/4 of the children were born and diagnosed with type 1 diabetes in each of the seasons of the year and 52.63% of the patients studied were first born. Family history for DMT1 and DMT2 is observed in 15.8% and 17.8% of the children, respectively. Polyuria (99.3%), polydipsia (99.6%) and weight loss (98.1%) were the most common symptoms and 67.8% of patients presented with diabetic ketoacidosis (DKA). Misdiagnosis was in 21 (13.8%) patients. Mean glycosylated hemoglobin A1c (HbA1c) was 11.63%; 11.9 ± 2.0 in DKA positive children and 11.1 ± 2.4 in DKA negative children (p= 0.195).At diagnosis and during follow up of T1DM 25% (38/152) developed associated autoimmune diseases; 68.42% at diagnosis of T1DM and 65.79% (25/38) of patients were female. During follow up children with T1DM developed associated CD and SAT, 2.54, and 2.19 years, respectively.Conclusion: Diabetes mellitus is one of the major public health problems worldwide. Albania is a country with middle incidence of T1DM and the age at onset is decreasing. The symptoms lasted significantly longer and mean HbA1c levels were significantly higher in older children. The incidence of DKA in children with newly diagnosed T1DM is high.

Incidence of Type 1 Diabetes Mellitus and Characteristics of Diabetic Ketoacidosis in Children and Adolescents during the First Two Years of the COVID-19 Pandemic in Vojvodina.

Background and Objectives: The COVID-19 pandemic has led to significant changes globally, which has also affected patients with type 1 diabetes mellitus (T1DM). This study aimed to determine the incidence of T1DM and the characteristics of diabetic ketoacidosis (DKA) during the pandemic comparing it to pre-pandemic period. Materials and Methods: Data from patients <19 years with newly diagnosed T1DM between 1st January 2017 and 31st December 2021 from four regional centers in Vojvodina were retrospectively collected and analyzed. Results: In 2021, the highest incidence of T1DM in the last five years was recorded, 17.3/100,000. During the pandemic period (2020–2021), there were 99 new-onset T1DM, of which 42.4% presented in DKA, which is significantly higher than in the pre-pandemic period (34.1%). During the pandemic, symptom duration of T1DM lasted significantly longer than before the COVID-19 period. At the age of 10–14 years, the highest incidence of T1DM and COVID-19, the highest frequency rate of DKA, and severe DKA were observed. Conclusions: The pandemic is associated with a high incidence rate of T1DM, longer duration of symptoms of T1DM, a high frequency of DKA, and a severe DKA at diagnosis. Patients aged 10–14 years are a risk group for the occurrence of T1DM with severe clinical presentation. Additional studies are needed with a longer study period and in a wider geographical area, with data on exposure to COVID-19 infection, the permanence of new-onset T1DM, and the psychosocial impact of the pandemic.

COVID-19-Related Multisystem Inflammatory Syndrome in Children Presenting With New-Onset Type 1 Diabetes in Severe Ketoacidosis: A Case Series.

To report and describe cases of children presenting with coronavirus disease 2019 (COVID-19)-related multisystem inflammatory syndrome in children (MIS-C) with new-onset type 1 diabetes mellitus (T1DM) in severe diabetic ketoacidosis (DKA). This prospective observational study was conducted to characterize children with COVID-19-related MIS-C and new-onset T1DM who were in DKA. MIS-C was diagnosed if Centers for Disease Control and Prevention and World Health Organization criteria were fulfilled. Six cases were identified. The patients were critically ill and in nonfluid responsive shock (combined hypovolemic and cardiogenic or distributive shock). All had cardiac involvement. One patient had a Kawasaki shock-like presentation. All needed aggressive treatment with careful monitoring of fluid balance (because of associated cardiac dysfunction), early institution of vasoactive/inotropic supports, and use of methylprednisolone and intravenous immunoglobulins. The latter are better administered after DKA resolution to avoid undue volume overload and fluid shifts while the patients are in DKA. Awareness of MIS-C coexistence with DKA at T1DM onset is crucial for rapid proper management.

Does COVID-19 predispose patients to type 1 diabetes mellitus?

.The novel coronavirus disease (COVID-19) has emerged as a global pandemic. This was a prospective, case-control study conducted in Izmir, Turkey. The aim of this study was to assess the relationship between COVID-19 and new-onset T1DM. We included pediatric patients (aged 6 mo–18 yr) with new-onset type-1 diabetes mellitus (T1DM) diagnosed during the COVID-19 pandemic, between April 2020 and January 2021. Polymerase chain reaction was used to diagnose COVID-19 after hospital admission. An enzyme-linked immunoassay for IgM and IgG against SARS-CoV-2 was performed after the diagnosis was confirmed. In the control group, the blood antibody test was conducted as close as possible to the time of the T1DM patient referral. A total of 118 participants were included in the study, comprising 57 (48%) patients with new-onset T1DM and 61 (52%) healthy controls. Of the 57 patients, 36 (63.2%) presented with DKA, 17 (29.7%) with diabetic ketosis, and four (7%) incidentally. The SARS-CoV-2 antibody test was positive in five (8.7%) patients with T1DM and six (10%) controls. The rate of positivity did not differ between the two groups (p = 0.901). It was not possible to demonstrate a clear association between SARS-CoV-2 infection and new-onset T1DM. Whether SARS-CoV-2 increases susceptibility to diabetes by triggering islet cell autoimmunity and affects the timing of overt diabetes in patients with existing autoimmunity should be studied in large cohorts.

Impact of COVID-19 on new-onset type 1 diabetes mellitus - A one-year prospective study.

A positive relationship between the recently emerged Corona Virus Disease-19 (COVID-19) and diabetes has been inferred, but not confirmed, in children. The aim of the present study was to investigate the possible impact of COVID-19 on new-onset Type-1 Diabetes Mellitus (T1DM) in a pediatric population. This is a prospective study of all children and adolescents diagnosed with T1DM during the first year of the COVID-19 pandemic (March 2020-February 2021) in Western Greece (population coverage ≈1,000,000). The incidence and severity of T1DM, the age and sex of the participants and HbA1c and c-peptide concentrations at diagnosis were recorded and compared to those of the previous year (pre-COVID-19 year). 21 children aged 8.03±0.90 years old were diagnosed with T1DM in the COVID-19 year and 17, aged 9.44±3.72 years old, in the pre-COVID-19 year. A different seasonality pattern of new onsets was observed during the COVID-19 year compared to the previous year, with increasing trend from spring to winter (spring: 9.5% vs. 23.5%, autumn: 23.8% vs. 29.4%, summer: 19% vs. 11.8%, winter: 47.6% vs. 35.3%). Also, compared to the preceding year, HbA1c was significantly higher (p=0.012) and the incidence and severity of diabetic ketoacidosis greater (p=0.045, p=0.013, respectively). This is the first study to report a different seasonality pattern and increased severity of new-onset T1DM during the first year of the COVID-19 pandemic. Future research should further investigate the possible role of SARS-CoV-2 and the different pattern of overall infection incidence during the COVID-19 year.

A high potency multi-strain probiotic improves glycemic control in children with new-onset type 1 diabetes mellitus: A randomized, double-blind, and placebo-controlled pilot study.

Studies in animal models and humans with type 1 diabetes mellitus (T1DM) have shown that probiotic supplementation leads to decreased pro-inflammatory cytokines (responsible for damaging β-cells of the pancreas), improved gut barrier function, and induction of immune tolerance. To study the effect of supplementation of probiotics in children with T1DM on glycemic control, insulin dose, and plasma C-peptide levels. A single-centered, double-blinded, and randomized placebo-controlled pilot trial was conducted in children (2-12 years) with new-onset T1DM. Ninety-six children were randomized and allocated to Placebo or Intervention groups. The intervention included high dose (112.5 billion viable lyophilized bacteria per capsule) multi-strain probiotic De Simone formulation (manufactured by Danisco-Dupont) sold as Visbiome® in India. The probiotic was supplemented for 3 months and HbA1c, fasting C-peptide, blood sugar records, and insulin dose was recorded at baseline and 3 months. A total of 90 patients (45 in each group) were analyzed for outcome parameters. We found a significant decrease in HbA1c (5.1 vs. 3.8; p=0.021) and a significant decline in total and bolus insulin dose (U/kg/day; p=0.037 and 0.018, respectively) in the intervention group when compared with the placebo group. A significantly higher (p=0.023) number of children achieved remission in the treatment group. We did not notice adverse effects in either of the study groups. Children with newly diagnosed T1DM managed with standard treatment along with probiotics showed better glycemic control and a decrease in insulin requirements; however, more extensive studies are further warranted.

Prolonged Honeymoon Period in a Thai Patient With Adult-Onset Type 1 Diabetes Mellitus - Metabolic Flexibility in Autoimmune Diabetes?

Abstract Background: ‘Honeymoon’ period among people with type 1 diabetes mellitus (T1DM) refers to the period of time (mostly less than 1 year) which beta-cell is still able to produce insulin to maintain good glycemic control shortly following the development of diabetes. This phenomenon remained incompletely understood but previous studies showed that absence of diabetic ketoacidosis (DKA) at initial presentation, short duration of symptoms, older age at presentation, and strenuous exercise could be potential factors. Herein, we report a 24-year old Thai patient with T1DM who has been in sustained complete remission for more than 5 years while he is maintaining low carbohydrate intake and regular exercise. Clinical Case: A 24-year-old male presented with a 6-month history of polyuria, polydipsia and weight loss of 15 kilograms (baseline BMI at 27.8 kg/m2). His initial laboratory data showed plasma glucose 398 mg/dL and A1C 9.3%. No ketonemia was found. He was diagnosed with stage 3 of Type 1 DM based on clinical presentation and positive pancreatic auto-antibodies (anti-GAD and anti-IA2). Euthyroid Hashimoto’s thyroiditis was also diagnosed based on his enlarged thyroid gland and positive thyroid auto-antibodies. He was started on basal-bolus insulin regimen for only 2 month and then A1C reversed to 5.9% within 2 months. Insulin was gradually withdrawn and completely stopped. Mixed meal stimulation test (MMST) was firstly evaluated at the second year of his diagnosis. The result revealed stimulated C-peptide at 5.5 ng/dL. Next-generation sequencing panel for monogenic diabetes revealed negative results. The patient maintains healthy lifestyle habit with low carbohydrate intake and regular exercise 5–6 times per week. His body weight was maintained at 60–63 kilograms during the past 4 years. His A1C was maintained between 5.0 to 6.0% without any anti-diabetic medication for more than 5 years. Repeated MMST in every 6–12 months still revealed preserved beta-cell functions and normal stimulated plasma glucose. Interestingly, repeated pancreatic auto-antibodies at 3 years after diagnosis showed negative anti-GAD and anti-IA2, but positive anti-ZnT8. The patient was advised to maintain his bodyweight and healthy behavior together with closely regular OPD follow-up. Conclusion: Restored beta-cell function with completely insulin withdrawal in new-onset T1DM has been reported in very few cases which have some common factors as in our patient (low carbohydrate intake with regular exercise). Delaying autoimmune activity by reducing metabolic load in newly diagnosed T1DM might play a role in maintaining a honeymoon period and could lead to an innovative therapeutic option in new-onset T1DM.

The Impact of COVID-19 Pandemic Lockdown on the Incidence of New-Onset Type 1 Diabetes and Ketoacidosis Among Saudi Children.

BackgroundOverburdened healthcare systems during the coronavirus disease (COVID-19) pandemic led to suboptimal chronic disease management, including that of pediatric type 1 diabetes mellitus (T1DM). The pandemic also caused delayed detection of new-onset diabetes in children; this increased the risk and severity of diabetic ketoacidosis (DKA). We therefore investigated the frequency of new-onset pediatric T1DM and DKA in Saudi Arabia during the COVID-19 pandemic and compared it to the same period in 2019.MethodsWe conducted a multicenter retrospective cohort study, including patients aged 1–14 years admitted with new-onset T1DM or DKA during the COVID-19 pandemic (March–June 2020) and the same period in 2019. We assessed factors including age, sex, anthropometric measures, nationality, duration of diabetes, diabetes management, HbA1c levels, glycemic control, cause of admission, blood gas levels, etiology of DKA, DKA complications, length of hospital stay, and COVID-19 test status.ResultDuring the lockdown, 106 children, compared with 154 in 2019, were admitted to 6 pediatric diabetes centers. Among the admissions, DKA was higher in 2020 than in 2019 (83% vs. 73%; P=0.05; risk ratio=1.15; 95% confidence interval, 1.04–1.26), after adjusting for age and sex. DKA frequency among new-onset T1DM and HbA1c levels at diagnosis were higher in 2020 than in 2019 (26% vs. 13.4% [P=<0.001] and 12.1 ± 0.2 vs. 10.8 ± 0.25 [P<0.001], respectively). Females and older patients had a higher risk of DKA.ConclusionThe lockdown implemented in Saudi Arabia has significantly impacted children with T1DM and led to an increased DKA frequency, including children with new-onset T1DM, potentially owing to delayed presentation.