High Prevalence of A-ß+ Ketosis-Prone Diabetes in Children with Type 2 Diabetes and Diabetic Ketoacidosis at Diagnosis: Evidence from the Rare and Atypical Diabetes Network (RADIANT).

Background: A-ß+ ketosis-prone diabetes (KPD) in adults is characterized by presentation with diabetic ketoacidosis (DKA), negative islet autoantibodies, and preserved ß-cell function in persons with a phenotype of obesity-associated type 2 diabetes (T2D). The prevalence of KPD has not been evaluated in children. We investigated children with DKA at "T2D" onset and determined the prevalence and characteristics of pediatric A-ß+ KPD within this cohort. Methods: We reviewed the records of 716 children with T2D at a large academic hospital and compared clinical characteristics of those with and without DKA at onset. In the latter group, we identified patients with A-ß+ KPD using criteria of the Rare and Atypical Diabetes Network (RADIANT) and defined its prevalence and characteristics. Results: Mean age at diagnosis was 13.7 ± 2.4 years: 63% female; 59% Hispanic, 29% African American, 9% non-Hispanic White, and 3% other. Fifty-six (7.8%) presented with DKA at diagnosis and lacked islet autoantibodies. Children presenting with DKA were older and had lower C-peptide and higher glucose concentrations than those without DKA. Twenty-five children with DKA (45%) met RADIANT A-ß+ KPD criteria. They were predominantly male (64%), African American or Hispanic (96%), with substantial C-peptide (1.3 ± 0.7 ng/mL) at presentation with DKA and excellent long-term glycemic control (HbA1c 6.6% ± 1.9% at follow-up (median 1.3 years postdiagnosis)). Conclusions: In children with a clinical phenotype of T2D and DKA at diagnosis, approximately half meet criteria for A-ß+ KPD. They manifest the key characteristics of obesity, preserved ß-cell function, male predominance, and potential to discontinue insulin therapy, similar to adults with A-ß+ KPD.

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

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

Feature selection and risk prediction for diabetic patients with ketoacidosis based on MIMIC-IV.

Background: Diabetic ketoacidosis (DKA) is a frequent acute complication of diabetes mellitus (DM). It develops quickly, produces severe symptoms, and greatly affects the lives and health of individuals with DM.This article utilizes machine learning methods to examine the baseline characteristics that significantly contribute to the development of DKA. Its goal is to identify and prevent DKA in a targeted and early manner. Methods: This study selected 2382 eligible diabetic patients from the MIMIC-IV dataset, including 1193 DM patients with ketoacidosis and 1186 DM patients without ketoacidosis. A total of 42 baseline characteristics were included in this research. The research process was as follows: Firstly, important features were selected through Pearson correlation analysis and random forest to identify the relevant physiological indicators associated with DKA. Next, logistic regression was used to individually predict DKA based on the 42 baseline characteristics, analyzing the impact of different physiological indicators on the experimental results. Finally, the prediction of ketoacidosis was performed by combining feature selection with machine learning models include logistic regression, XGBoost, decision tree, random forest, support vector machine, and k-nearest neighbors classifier. Results: Based on the importance analysis conducted using different feature selection methods, the top five features in terms of importance were identified as mean hematocrit (haematocrit_mean), mean hemoglobin (haemoglobin_mean), mean anion gap (aniongap_mean), age, and Charlson comorbidity index (charlson_comorbidity_index). These features were found to have significant relevance in predicting DKA. In the individual prediction using logistic regression, these five features have been proven to be effective, with F1 scores of 1.000 for hematocrit mean, 0.978 for haemoglobin_mean, 0.747 for age, 0.692 for aniongap_mean and 0.666 for charlson_comorbidity_index. These F1 scores indicate the effectiveness of each feature in predicting DKA, with the highest score achieved by mean hematocrit. In the prediction of DKA using machine learning models, including logistic regression, XGBoost, decision tree, and random forest demonstrated excellent results, achieving an F1 score of 1.000. Additionally, by applying feature selection techniques, noticeable improvements were observed in the experimental performance of the support vector machine and k-nearest neighbors classifier. Conclusion: The study found that hematocrit, hemoglobin, anion gap, age, and Charlson comorbidity index are closely associated with ketoacidosis. In clinical practice, these five baseline characteristics should be given with the special attention to achieve early detection and treatment, thus reducing the incidence of the disease.

Fulminant type 1 diabetes, an underrecognized and unique subtype of type 1 diabetes: A case series from Singapore.

Fulminant type 1 diabetes (FT1D) is a unique subtype of type 1 diabetes, characterized by acute absolute insulin deficiency, severe ketosis, and increased risk of hypoglycemia, glycemic variability and microvascular complications. Seven people with FT1D were identified from two tertiary centers in Singapore. Six were Chinese, the mean age was 35 years and all were lean (mean body mass index 20.3 kg/m2). All presented with diabetes ketosis or ketoacidosis and low C-peptide. All but one had low glutamic acid decarboxylase antibodies. Nearly half had a missed/delayed diagnosis of FT1D. Three had frequent hypoglycemia, which improved after transition to continuous subcutaneous insulin infusion therapy. Individuals with FT1D experience unique diagnostic and management challenges associated with rapid absolute insulin deficiency. Greater awareness about this clinical entity is required.

Increased Severity of Presentation Signs in Children with Newly Diagnosed Type 1 Diabetes during the COVID-19 Pandemic: A Tertiary Center Experience.

INTRODUCTION: Diabetic ketoacidosis (DKA) is an important complication of type 1 diabetes mellitus (T1DM) which is worsened when the diagnosis of T1DM is delayed. The aim of this study was to evaluate the presentation patterns, severity, autoantibody status, and seasonal variability of newly diagnosed T1DM patients during the pandemic period of 2 years compared to those in the pre-pandemic period. METHODS: In this single tertiary center retrospective cohort study, newly diagnosed T1DM patients were grouped as pre-pandemic and pandemic period. Age, gender, the month of diagnosis, hemoglobin A1c, venous blood gas parameters, duration of symptoms, glutamic-acid-decarboxylase-antibody (anti-GAD), islet-cell antibody (ICA), and insulin autoantibody levels were recorded. The data obtained were compared between the groups. RESULTS: Number of patients presenting with DKA was significantly higher during the pandemic period (92 [65.7%] vs. 62 [40.8%] patients, p < 0.001). In terms of clinical severity of DKA, pH, and HCO3 levels were lower during the pandemic period (p < 0.001), while the number of patients presenting with severe DKA was significantly higher during the pandemic period (41 [44.6%] vs. 17 [27.4%] patients, p = 0.031). ICA positivity was significantly higher in patients admitted during the pandemic period (47 [36.4%] vs. 21 patients [16.9%], p < 0.001), especially in the second year of the pandemic (p < 0.001). Anti-GAD-ICA co-positivity was significantly higher in patients admitted during the pandemic period and also in second year of the pandemic (p < 0.001). CONCLUSION: DKA rates increased in newly diagnosed T1DM cases during the pandemic. Despite the relaxation of bans, the second year of the pandemic also saw increased rates of DKA and severe DKA compared to the pre-pandemic period. The significantly increased ICA positivity in the pandemic may support the effects of COVID-19 on autoimmune T1DM.

Development of Machine Learning Models for the Identification of Elevated Ketone Bodies During Hyperglycemia in Patients with Type 1 Diabetes.

Aims: Diabetic ketoacidosis (DKA) is a serious life-threatening condition caused by a lack of insulin, which leads to elevated plasma glucose and metabolic acidosis. Early identification of developing DKA is important to start treatment and minimize complications and risk of death. The aim of the present study is to develop and test prediction model(s) that gives an alarm about their risk of developing elevated ketone bodies during hyperglycemia. Methods: We analyzed data from 138 type 1 diabetes patients with measurements of ketone bodies and continuous glucose monitoring (CGM) data from over 30,000 days of wear time. We utilized a supervised binary classification machine learning approach to identify elevated levels of ketone bodies (≥0.6 mmol/L). Data material was randomly divided at patient level in 70%/30% (training/test) dataset. Logistic regression (LR) and random forest (RF) classifier were compared. Results: Among included patients, 913 ketone samples were eligible for modeling, including 273 event samples with ketone levels ≥0.6 mmol/L. An area under the receiver operating characteristic curve from the RF classifier was 0.836 (confidence interval [CI] 90%, 0.783-0.886) and 0.710 (CI 90%, 0.646-0.77) for the LR classifier. Conclusions: The novel approach for identifying elevated ketone levels in patients with type 1 diabetes utilized in this study indicates that CGM could be a valuable resource for the early prediction of patients at risk of developing DKA. Future studies are needed to validate the results.

Incidence and determinants of diabetic ketoacidosis among people with diabetes in Woldiya comprehensive specialized hospital, Ethiopia: a retrospective cohort study.

INTRODUCTION: Diabetic ketoacidosis is an acute complication of diabetes mellitus that is characterised by hyperglycemia, acidosis, and ketonuria. Diabetes is the most challenging public health problem in the twenty-first century for both developed and developing countries. OBJECTIVE: To assess the incidence of Diabetic ketoacidosis and its determinants among adult people with diabetes at an Ethiopian Hospital. METHOD: An institution-based retrospective cohort study was conducted among 390 adult people with diabetes attending services at Wolida Comprehensive Specialized Hospital. The consecutive sampling method was used to select study participant charts. Data were collected using a checklist prepared from different literature. The data were entered into EPI data version 4.6.0.5 and exported to STATA version 14.0 for further analysis. The Wiebull model was the best fitted model that was selected using the log-likelihood ratio method and the Akakian information criterion. Hazard ratios with their 95% confidence interval and p-value were computed. RESULT: From the total 405 charts reviewed, 390 adult charts were included for analysis. A total of 121 DKA occurred from 5471 person-months of observation. The overall incidence rate of diabetic ketoacidosis was found to be 2.2 per 100 person-months (95% CI: 1.8- 2.6). Being urban dweller (AHR: 0.59, 95% CI: 0.36-0.99), having no family history of DM (AHR: 0.55, 95%CI: 0.31-0.97), presence of infection (AHR: 2.60, 95%CI = 1.06-6.39), having of any comorbidities (AHR: 4.31, 95% CI: 1.70-10.90), and having poor glycemic control (AHR: 7.45, 95% CI: 3.84-14.47) were significant determinants. CONCLUSION AND RECOMMENDATIONS: The overall incidence of diabetic ketoacidosis in study area was relatively high. Poor glycemic control, the presence of infection, and comorbidity were determinants of diabetic ketoacidosis. There is a need to have close follow-up of people with diabetes who have comorbidity, infection, and poor glycemic control.

Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Glycemic Outcomes with Closed-Loop Insulin Delivery.

The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9-10.0 mmol/L (70-180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis.

Effects of ADHD and ADHD treatment on glycemic management in type 1 diabetes: A systematic review and meta-analysis of observational studies.

AIMS: Studies suggested a higher prevalence of Attention-deficit/hyperactivity disorder (ADHD) in individuals with Type 1 Diabetes Mellitus (T1D). However, it is unclear how ADHD impacts glycemia and diabetes-related complications. This systematic review and meta-analysis aimed to investigate the effect of ADHD and ADHD medications on HbA1c and acute complications in T1D. METHODS: A literature search was conducted in PubMed, EMBASE, CINAHL, Scopus, PsycINFO, CENTRAL, and Web of Science collections up to November 22, 2023. Seventeen studies were selected for the systematic review by independent reviewers, with twelve included in the meta-analysis. RESULTS: Mean HbA1c levels were significantly higher in T1D individuals with ADHD compared to those without ADHD (MD = 0.60; 95 % CI: 0.41, 0.79; I2 = 90.1 %; p-value < 0.001). The rates of suboptimal HbA1c levels, hospitalization, diabetic ketoacidosis, and hypoglycemia were all substantially higher in T1D individuals with ADHD than those without ADHD. No difference was found in mean HbA1c between those who received ADHD treatment and those who did not (mean difference = -0.52; 95 % confidence interval: -1.16, 0.13; I2 = 78.6 %; p-value = 0.12). CONCLUSIONS: ADHD is associated with higher HbA1c and increased acute diabetes-related complications. More research is needed to assess the effects of ADHD treatments on T1D management.

Eu- or hypoglycemic ketosis and ketoacidosis in children: a review.

The last decade has been characterized by exciting findings on eu- or hypoglycemic ketosis and ketoacidosis. This review emphasizes the following five key points: 1. Since the traditional nitroprusside-glycine dipstick test for urinary ketones is often falsely negative, the blood determination of ß-hydroxybutyrate, the predominant ketone body, is currently advised for a comprehensive assessment of ketone body status; 2. Fasting and infections predispose to relevant ketosis and ketoacidosis especially in newborns, infants, children 7 years or less of age, and pregnant, parturient, or lactating women; 3. Several forms of carbohydrate restriction (typically less than 20% of the daily caloric intake) are employed to induce ketosis. These ketogenic diets have achieved great interest as antiepileptic treatment, in the management of excessive body weight, diabetes mellitus, and in sport training; 4. Intermittent fasting is more and more popular because it might benefit against cardiovascular diseases, cancers, neurologic disorders, and aging; 5. Gliflozins, a new group of oral antidiabetics inhibiting the renal sodium-glucose transporter 2, are an emerging cause of eu- or hypoglycemic ketosis and ketoacidosis. In conclusion, the role of ketone bodies is increasingly recognized in several clinical conditions. In the context of acid-base balance evaluation, it is advisable to routinely integrate both the assessment of lactic acid and ß-hydroxybutyrate.

Impact of COVID-19 Lockdown on Occurrence of Acute Complications of Type 1 and Type 2 Diabetes and Overall Glycemic Management.

OBJECTIVES: The association of diabetes, and COVID-19 infection has been studied extensively; however, the occurrence of diabetic ketoacidosis (DKA) or hyperglycemic/hyperosmolar states (HHS) in adults during the lockdown has not been well characterized. In this study, we aimed to identify the impact of the lockdown on occurrence and severity of DKA/HHS admissions and glycemic management. METHODS: A retrospective chart review was conducted of patients admitted to Hamilton Health Sciences with a diagnosis of DKA or HHS from April to September 2019 (pre-lockdown) and from April to September 2020 (lockdown). Adult (≥18 years old) nonpregnant patients with a single admission in the study period were included for study. RESULTS: There were 229 admissions related to diabetes, with 171 admissions meeting the inclusion criteria (n=92 pre-lockdown, n=79 lockdown). In the lockdown group, 51.8% of the patients had type 2 diabetes mellitus, with 96.2% of admissions secondary to DKA. When comparing the 2 periods, the lockdown group trended toward higher rates of death (5.4% vs 10.1%, p=0.247) and euglycemic DKA (17.6% vs 24.4%, p=0.403). There were more new diagnoses of type 1 diabetes mellitus in the lockdown group compared with the pre-lockdown group (7.3% vs 16.7%, p=0.230). The average glycated hemoglobin was lower in the lockdown group compared with the pre-lockdown group (11.8% vs 10.4%, p=0.032). CONCLUSIONS: Overall, this study is among the first in Canada to assess the impact of the COVID-19 lockdown on admissions due to DKA and HHS. Although no significant differences were noted in severity of admissions, there was a trend toward more new diagnoses of type 1 diabetes mellitus presenting in DKA during the lockdown period.

Diabetic Ketoacidosis at Diagnosis in Youth with Type 1 Diabetes Is Associated with a Higher Hemoglobin A1c Even with Intensive Insulin Management.

Introduction: Diabetic ketoacidosis (DKA) at diagnosis is associated with short- and long-term complications. We assessed the relationship between DKA status and hemoglobin A1c (A1c) levels in the first year following type 1 diabetes (T1D) diagnosis. Research Design and Methods: The Pilot Teamwork, Targets, Technology, and Tight Control (4T) study offered continuous glucose monitoring to youth with T1D within 1 month of diagnosis. A1c levels were compared between historical (n = 271) and Pilot 4T (n = 135) cohorts stratified by DKA status at diagnosis (DKA: historical = 94, 4T = 67 versus without DKA: historical = 177, 4T = 68). A1c was evaluated using locally estimated scatter plot smoothing. Change in A1c from 4 to 12 months postdiagnosis was evaluated using a linear mixed model. Results: Median age was 9.7 (interquartile range [IQR]: 6.6, 12.7) versus 9.7 (IQR: 6.8, 12.7) years, 49% versus 47% female, 44% versus 39% non-Hispanic White in historical versus Pilot 4T. In historical and 4T cohorts, DKA at diagnosis demonstrated higher A1c at 6 (0.5% [95% confidence interval (CI): 0.21-0.79; P < 0.01] and 0.38% [95% CI: 0.02-0.74; P = 0.04], respectively), and 12 months (0.62% [95% CI: -0.06 to 1.29; P = 0.07] and 0.39% [95% CI: -0.32 to 1.10; P = 0.29], respectively). The highest % time in range (TIR; 70-180 mg/dL) was seen between weeks 15-20 (69%) versus 25-30 (75%) postdiagnosis for youth with versus without DKA in Pilot 4T, respectively. Conclusions: Pilot 4T improved A1c outcomes versus the historical cohort, but those with DKA at diagnosis had persistently elevated A1c throughout the study and intensive diabetes management did not mitigate this difference. DKA prevention at diagnosis may translate into better glycemic outcomes in the first-year postdiagnosis. Clinical Trial Registration: clinicaltrials.gov: NCT04336969.

One third of cases of new-onset diabetic ketosis in adults are associated with ketosis-prone type 2 diabetes-A systematic review and meta-analysis.

AIMS: Ketosis-prone type 2 diabetes was defined by the World Health Organization in 2019. According to the literature, the diagnosis is based on the presence of ketosis, islet autoantibody negativity and preserved insulin secretion. Our meta-analysis assessed the prevalence and clinical characteristics of ketosis-prone type 2 diabetes among patients hospitalised with diabetic ketoacidosis (DKA) or ketosis. METHODS: The systematic search was performed in five main databases as of 15 October 2021 without restrictions. We calculated the pooled prevalence of ketosis-prone type 2 diabetes (exposed group) within the diabetic population under examination, patients with ketoacidosis or ketosis, to identify the clinical characteristics, and we compared it to type 1 diabetes (the comparator group). The random effects model provided pooled estimates as prevalence, odds ratio and mean difference (MD) with 95% confidence intervals. RESULTS: Eleven articles were eligible for meta-analysis, thus incorporating 2010 patients of various ethnic backgrounds. Among patients presenting with DKA or ketosis at the onset of diabetes, 35% (95% CI: 24%-49%) had ketosis-prone type 2 diabetes. These patients were older (MD = 11.55 years; 95% CI: 5.5-17.6) and had a significantly higher body mass index (BMI) (MD = 5.48 kg/m2 ; 95% CI: 3.25-7.72) than those with type 1 diabetes. CONCLUSIONS: Ketosis-prone type 2 diabetes accounts for one third of DKA or ketosis at the onset of diabetes in adults. These patients are characterised by islet autoantibody negativity and preserved insulin secretion. They are older and have a higher BMI compared with type 1 diabetes. C-peptide and diabetes-related autoantibody measurement is essential to identify this subgroup among patients with ketosis at the onset of diabetes.

Paediatric diabetes-related presentations to emergency departments in Victoria, Australia from 2008 to 2018.

OBJECTIVES: Despite significant treatment advances in paediatric diabetes management, ED presentations for potentially preventable (PP) complications such as diabetic ketoacidosis (DKA) remains a major issue. We aimed to examine the characteristics, rates and trends of diabetes-related ED presentations and subsequent admissions in youth aged 0-19 years from 2008 to 2018. METHODS: Data were obtained from the Victorian Emergency Minimum Dataset and the National Diabetes Register. A diabetes-related ED presentation is defined using the International Statistical Classification of Diseases and Related Health Problems, Tenth Revision, Australian Modification diagnosis codes. 'Non-preventable' presentations were the number of youths with newly diagnosed diabetes, and the remaining are classified as PP diabetes-related presentations. Poisson regression model was used to examine the trends in incidence rate and prevalence. RESULTS: Four thousand eight hundred and seventy-two (59%) of 8220 presentations were PP, 4683 (57%) were for DKA whereas 6200 (82%) required hospital admission. Diabetes-related ED presentations decreased from 38.4 to 27.5 per 100 youth with diabetes per year between 2008 and 2018 (ß = -0.04; confidence interval [CI] -0.04 to -0.03; P < 0.001). Females, those aged 0-4 years and rural youth had higher rates of ED presentations than males, older age groups and metropolitan youth. DKA presentations decreased from 20.1 presentations per 100 youth with diabetes in 2008-2009 to 14.9 presentations per 100 youth with diabetes in 2017-2018. The rate of DKA presentations was 68% higher in rural areas compared to metropolitan areas (incidence rate ratio 1.68; CI 1.59-1.78; P < 0.001). CONCLUSIONS: Although the rates of diabetes-related ED presentations declined, PP diabetes-related presentations and subsequent hospitalisation remain high. Patient level research is required to understand the increased DKA presentations in rural youth.

Clinical profile of patients with diabetic ketoacidosis and hyperglycemic hyperosmolar syndrome in Japan: a multicenter retrospective cohort study.

INTRODUCTION: Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated. METHODS: A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes. RESULTS: A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups. CONCLUSIONS: The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population. TRIAL REGISTRATION: This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016).

Fulminant type 1 diabetes: Focusing on triggering factors.

Fulminant type 1 diabetes (FT1D) is a novel type of type 1 diabetes that is caused by extremely rapid destruction of the pancreatic ß cells. Early diagnosis or prediction of FT1D is critical for the prevention or timely treatment of diabetes ketoacidosis, which can be life-threatening. Understanding its triggers or promoting factors plays an important role in the prevention and treatment of FT1D. In this review, we summarised the various triggering factors of FT1D, including susceptibility genes, immunological factors (cellular and humoural immunity), immune checkpoint inhibitor therapies, drug reactions with eosinophilia and systemic symptoms or drug-induced hypersensitivity syndrome, pregnancy, viral infections, and vaccine inoculation. This review provides the basis for future research into the pathogenetic mechanisms that regulate FT1D development and progression to further improve the prognosis and clinical management of patients with FT1D.

Association of Diabetic Ketoacidosis in Childhood New-Onset Type 1 Diabetes With Day of Presentation in Germany.

OBJECTIVE: Whether the day of the week on which the child presents affects timely diagnosis and risk of diabetic ketoacidosis (DKA) in children with new-onset type 1 diabetes (T1D) is not known. RESEARCH DESIGN AND METHODS: We used data of 30,717 children with new-onset T1D during the last 10 years from the German Prospective Diabetes Registry. We determined the odds ratios of T1D diagnosis and DKA on a weekday, public holiday, and school vacation. RESULTS: Compared with workdays, the odds ratios of being diagnosed with T1D were lower on weekends (0.39 [95% CI, 0.38-0.41]), public holidays (0.57 [0.53-0.63]), and school vacations (0.83 [0.80-0.85]). The odds of DKA diagnosis were also reduced on weekends (0.55 [0.52-0.59]), public holidays (0.73 [0.63-0.84]), and school vacations (0.85 [0.80-0.90]). Results did not change during the coronavirus 2019 pandemic. CONCLUSIONS: New-onset T1D and DKA in children are more often diagnosed during weekdays than weekends and holidays.

Pediatric diabetes mellitus hospitalizations and COVID-19 pandemic response measures.

AIMS: In the United States, evidence suggests that during the COVID-19 pandemic, admissions of patients with diabetes mellitus (DM) have increased. This study assessed hospital admission rates for pediatric type 1 (T1DM) and type 2 (T2DM) diabetes mellitus during 2019-2021, and the potential influence of the timing of various pandemic response measures. METHODS: Retrospective chart reviews were conducted of 854 T1DM and 135 T2DM hospital admissions between January 2019 and December 2021 in patients < 20 years old to collect demographic data, admission type, body mass index (BMI), and area deprivation index (ADI, a measure of socioeconomic vulnerability). Patients were divided into three cohorts based on their admission year: 2019 (Pre-pandemic), 2020 (Pandemic, Pre-vaccine), and 2021 (Pandemic, Post-vaccine). Admissions were categorized within each cohort by diagnosis (T1DM or T2DM) and clinical presentation (new onset, diabetic ketoacidosis: DKA). Cohorts were compared using an independent samples t-test for continuous variables or a chi-square test for categorical variables. RESULTS: The incidence of T2DM hospitalizations tripled during the pandemic, increasing from 18 in 2019 (Pre-pandemic), to 55 in 2020 (Pandemic, Pre-vaccine), and 62 in 2021 (Pandemic, Post-vaccine). The rate of patients presenting with DKA was 15.4 % (95 % CI: 4 %-26.9 %) higher in 2020 (Pandemic, Pre-vaccine) among patients with new-onset T1DM (72/139 vs. 52/143), and 22.5 % (95 % CI: 9.6 %-35.4 %) higher in 2020 (Pandemic, Pre-vaccine) among T2DM patients (9/40 vs. 0/14). This increased rate of new onset T2DM significantly correlated with younger age (P = 0.046) and higher ADI score (P = 0.017), but not with BMI. CONCLUSION: The incidence of T1DM hospitalizations did not increase during the pandemic; however, they tripled for T2DM patients. All new onset DM pediatric patients during the pandemic were more likely to present in DKA. Patients admitted with new onset T2DM were socioeconomically more vulnerable. For T1DM, the peak of local pediatric diabetes admissions in 2020 occurred slightly later coinciding with the reopening of primary care physicians (PCP) offices and schools.

Increased Use of Hyperosmolar Therapy for Suspected Clinically Apparent Brain Injury in Pediatric Patients with Diabetic Ketoacidosis during the Peak of the COVID-19 Pandemic.

The incidence of pediatric diabetic ketoacidosis (DKA) increased during the peak of the COVID-19 pandemic. The objective of this study was to investigate whether rates of hyperosmolar therapy administration for suspected clinically apparent brain injury (CABI) complicating DKA also increased during this period as compared to the three years immediately preceding the pandemic and to compare the characteristics of patients with suspected CABI before the pandemic, patients with suspected CABI during the peak of the pandemic, and those with DKA but without suspected CABI during the pandemic. Patients aged ≤18 years presenting with DKA before (March 11, 2017-March 10, 2020) and during the peak of the pandemic (March 11, 2020-March 10, 2021) were identified through a rigorous search of two databases. Predefined criteria were used to diagnose suspected CABI. Biochemical, clinical, and sociodemographic data were collected from a comprehensive review of the electronic medical record. The proportion of patients with DKA who received hyperosmolar therapy was significantly higher (P = 0.014) during the pandemic compared to the prepandemic period; however, this was only significant among patients with newly diagnosed diabetes. Both groups with suspected CABI had more severe acidosis, lower Glasgow Coma Scale scores, and longer hospital admissions (P< 0.001 for all) than cases without suspected CABI. During the pandemic, the blood urea nitrogen concentration was significantly higher in patients with suspected CABI than those without suspected CABI, suggesting they were more severely dehydrated. The clinical, biochemical, and sociodemographic characteristics of patients with suspected CABI were indistinguishable before and during the pandemic. In conclusion, administration of hyperosmolar therapy for suspected CABI was more common during the peak of the COVID-19 pandemic, possibly a result of delayed presentation, highlighting the need for increased awareness and early recognition of the signs and symptoms of diabetes and DKA, especially during future surges of highly transmissible infections.