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Introduction: SGLT2i is a new class of drugs used for type 2 diabetes. SGLT2i are known to cause EuKA in the perioperative period. Euglycemic ketoacidosis (EuKA) can cause life-threatening metabolic acidosis in the perioperative setting. Though the event rate of SGLT2i associated diabetic ketoacidosis in nonoperative setting is low, incidence among peri-operative patients can be very high and remains unknown., Aim: The aim of this study was to find the incidence, analyze outcome, and establish correlation between risk factors and EuKA in cardiac surgical patients on SGLT2i., Materials and Methods: This is a retrospective study analyzing 24 cardiac surgical patients who were on SGLT2i for type 2 diabetes mellitus. Data collection included age, sex, BMI, preoperative HbA1C, albumin, creatinine, type of SGLT2i and timing of stopping before surgery, insulin administration in the immediate pre-operative period; use of CPB, GI infusion and inotropes in the intraoperative period; blood ketone, duration of ventilation, hydration status and length of postoperative stay in postoperative period. Patients were diagnosed to have EuKA if any one of the serially measured postoperative ketone values was more than 0.6 mmol/L (ketone positive). The collected data were used to find an association between the risk factors and the occurrence of EuKA., Results: Of the 24 patients, 17 patients developed EuKA. (70.8.%). 10 of the 17 EuKA in our study required preoperative Insulin for diabetic control whereas none in the ketone negative patients required insulin. This was statistically significant (P = 0.019). Association of other factors to EuKA were not statistically significant., Conclusion: Though the event rate of SGLT2i associated Diabetic ketoacidosis in nonoperative setting is low, (17), the occurrence of EUKA in cardiac surgical patients on SGLT2i in our study was 70.8% (17 out of 24 patients). Patients who require insulin in addition to other oral hypoglycemic drugs for immediate preoperative glycemic control are at risk for the development of SGLT2 inhibitor-induced EuKA postoperatively. Missing the diagnosis of EuKA is fatal in these patients. We couldn't make a diagnosis in our first patient whom we lost. Since it was diagnosed in all our study patients by measuring serial ketone values, there was no mortality and insignificant morbidity. Cessation of SGLT2i before surgery, expectant watch for blood ketones, and treatment with GI infusion reduce morbidity and mortality in cardiac surgical patients.

Purpose of Review: In this review, the authors discuss potential clinical applications for continuous ketone monitoring (CKM) in a broad continuum of clinical settings from pre-hospital care and the emergency department to acute inpatient management and post-discharge follow-up., Recent Findings: Though in its early stages, the concept of a novel continuous ketone sensing technology exerts great potential for use in the detection and hospital management of DKA, namely to overcome diagnostic barriers associated with ketoacidosis in patients with diabetes and obtain real-time BOHB levels, which may be useful in understanding both patients' response to treatment and DKA trajectory. Peri- and intra-operative use of CKM technology can potentially be applied in a number of urgent and elective surgical procedures frequently underwent by patients with diabetes and in the observation of patients during peri-operative fasting. In transitional care management, CKM technology could potentially facilitate patients' safe transition through levels of care, following hospital discharge from a DKA episode. This evaluation of the literature presents the potential advantages of adopting CKM and integrating this technology into the care algorithm of patients at risk for ketoacidosis., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

There is growing evidence to support the use of sodium-glucose cotransporter-2 (SGLT2) inhibitors for type 2 diabetes mellitus (T2DM) and the management of heart failure. As such, more patients undergoing cardiac surgery are on SGLT2-inhibitor therapy. Despite the numerous benefits of SGLT2 inhibitors on cardiac health, they can be associated with an increased risk of diabetic ketoacidosis, often with normal glucose levels (euglycemic diabetic ketoacidosis or EDKA), which potentially can be detrimental in this vulnerable patient population. In this narrative review, the authors discuss 17 papers that described EDKA in perioperative cardiac surgical patients. The authors discuss suggested preventative measures and management options, with a particular emphasis on raising the clinical awareness of the care teams toward this complication. SGLT2 inhibitor-induced EDKA is a medical emergency that can be difficult to identify in the postcardiac surgical patient due to the overlap of signs and symptoms with other frequent scenarios in these patients. A reduction in SGLT2 inhibitor-associated EDKA can be mitigated by the appropriate perioperative discontinuation of the medication, clinical awareness, and early investigation to diagnose the condition, with emphasis on serum β-hydroxybutyrate. Future quality improvement initiatives are needed to assist in reducing EDKA in patients taking SGLT2 inhibitors in the perioperative surgical setting., Competing Interests: Conflict of Interest None., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Diabetic ketoacidosis (DKA) is one of the most serious consequences of diabetes. This serious issue occurs when the body cannot use the glucose as a source of energy because of a lack in the level of insulin which as consequence will lead to an increased level of glucose resulting in DKA., Aim: The goal of this study was to increase diabetic patients' and caregivers' awareness and practice of DKA at the community level in Hail City, Saudi Arabia, in 2022. The assessment of people's awareness and knowledge on DKA is importance to support any subsequent actions. Subjects and Methods . This is a cross-sectional study conducted in Hail City, Saudi Arabia, among diabetic patients and carers. A self-administered questionnaire in Arabic was given to the target demographic via an internet survey. The questionnaire includes basic demographic data (i.e., age, gender, and marital status), clinical characteristics of the diabetic patients, and a set of questionnaires to assess the awareness and practice of the subjects regarding DKA., Results: 348 surveys were received (51.1% males vs. 48.9% females). A total of 29.9% of patients have been diagnosed with DKA. Out of a possible 14 points, the average awareness score was 5.22 (SD 3.39). Poor awareness levels had been found in nearly 70% of the subjects, 23.6% were moderate, and only 8.6% were considered good. Factors associated with increased awareness were being younger, female gender, unmarried, students, type 1 DM, DKA diagnosis, and having good information about DKA., Conclusion: The awareness of diabetic patients and their caregivers toward DKA was unsatisfactory. Younger female patients who were single and who had been diagnosed with DKA tend to be more aware of DKA as compared to other subjects. There is a compelling reason to bridge the gaps in the awareness of DKA among the diabetic population and their caregivers in our region., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Nahlah Fahad Alreshidi et al.)

Background: Coronavirus disease 2019 (COVID-19) is associated with an increased prevalence and mortality from diabetic ketoacidosis (DKA) globally. With limited access to specialised care, most patients with DKA in South Africa are managed at district hospital level. This study describes the profile of patients admitted to a district hospital in South Africa with DKA and COVID-19 and examines associated risk factors encountered., Methods: This was a case series of all patients presenting to a district hospital with DKA and COVID-19 infection between July 2020 and July 2021. Data extracted included patients' demographic profiles, biochemical results, comorbidities and clinical outcomes., Results: The median age of the 10 patients admitted during the study period was 39 years old (±12), six of whom were male. The hemoglobin A1c (HbA1c) values on admission ranged from 9.7 to 13.8. Five of the patients had pre-existing type 2 diabetes mellitus (DM). Four of the known DM patients were on metformin only, and one was on biphasic insulin. Three patients had other pre-existing comorbidities, two patients with hypertension and one with human immunodeficiency virus (HIV). Three patients demised, two of whom were hypoxic on admission., Conclusion: Diabetic ketoacidosis appears more commonly in COVID-19 infected patients with type 2 DM and at a young age. Suboptimal glycaemic control was associated with DKA, and hypoxia was a strong predictor for mortality. Treatment inertia was evident in the known DM group, who were on monotherapy despite persistent hyperglycaemia. Greater vigilance is required to detect ketosis in type 2 DM and intensify therapy to improve glycaemic control.

Introduction: Diabetic ketoacidosis (DKA) is a life-threatening complication characterized by hyperglycemia, metabolic acidosis, and ketonemia. Although the time to resolution of DKA has been estimated at 12 to 18 hours, the factors that could prolong it have not been fully studied., Methods: Retrospective study of medical records of adult patients admitted to the general ward with a diagnosis of DKA. They were classified according to severity as mild, moderate and severe. The time to resolution of crisis (TRC) was defined as that necessary until normalization of metabolic parameters. A logistic regression analysis was performed to evaluate the association between TRC>12 hours and continuous variables. ROC analysis and survival analysis were performed using a Cox regression model., Results: 85 patients were studied. 48.23% presented severe DKA. The TRC was 14 hours, being higher in severe DKA. Patients with TRC>12 hours had a lower pH and HCO3-, and a higher anion gap, white blood cells, and volume of crystalloids used. Logistic regression analysis showed that pH and crystalloid volume correlated with TRC>12 hours. ROC analysis determined a pH cutoff value of 7.13 for TRC>12 hours (sensitivity 77%, specificity 88%). The Cox regression showed that a pH<7.13 on admission is associated with a higher TRC (HR 3.30)., Conclusion: A pH lower than 7.13 at the time of hospital admission identifies patients with DKA who will need a longer time to resolve their metabolic parameters., (Universidad Nacional de Córdoba)

Euglycaemic diabetic ketoacidosis is a serious but rare adverse effect of treatment with sodium-glucose cotransporter-2 (SGLT-2) inhibitors. A man in his 60s with type 2 diabetes mellitus underwent total hip replacement for an intracapsular neck of femur fracture. His SGLT-2 inhibitor was continued perioperatively and blood glucose levels were normal throughout the admission. A diagnosis of severe euglycaemic diabetic ketoacidosis was made in the operating theatre which required treatment in a critical care unit. This resulted in increased morbidity due to decreased postoperative mobilisation and a new requirement for subcutaneous insulin. This case highlights the need for withholding SGLT-2 inhibitors in patients admitted for emergency surgery and a need for regular ketone monitoring in these patients, even in the context of normoglycaemia., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

The physiologic changes and common signs and symptoms of pregnancy can make the early recognition of endocrine emergencies more challenging. Diabetic ketoacidosis (DKA) can occur at only modestly elevated glucose levels (euglycemic DKA), often accompanied by starvation ketosis due to substantial fetal-placental glucose demands and is associated with a high stillbirth rate. Thyroid storm is life threatening with a higher rate of heart failure and both require prompt and aggressive treatment to avoid maternal and fetal morbidity and mortality. Treatment of these disorders and the special considerations for recognition and management in the context of pregnancy are reviewed., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Introduction: Diabetic ketoacidosis (DKA) is a serious acute complication of diabetes mellitus that carries a significant risk of mortality with delayed treatment in low-resource countries. This study aimed to determine the outcome of paediatric DKA patients' managed with a modified DKA treatment protocol using intermittent bolus subcutaneous insulin administration., Methods: A cross-sectional study design with retrospective data collection was conducted among children younger than 14 years of age admitted from January 2013 to February 2017. A modified protocol was prepared based on a reference from the international society for paediatric and adolescent diabetes and other international guidelines. Data were analysed using Statistical package for social science (SPSS) version 22.0. Descriptive statistics were performed. Binary logistic regression was used to identify associations, and significant variables were further considered for multivariate logistic regression to determine the outcome of DKA patients., Result: Among the 190 patients, 55.5% (n = 105) were newly diagnosed. The overall average time required for resolution of DKA was 48 ± 27.8 h. Mental status on presentation (p = .001), shock on presentation (p < .01) and severity of DKA (p < .001) were found to have a significant association with the mean time for clearance of DKA. Hypoglycaemia was the most common treatment-related complication, which occurred in 23.7% of patients (n = 45) followed by hypokalaemia in 4.3% of patients (n = 8), and no patient developed cerebral oedema and death., Conclusion: The time required for clearance of DKA was prolonged, and hypoglyceamia was a common complication for children younger than 5 years of age. The modified protocol of DKA is reasonable management for low-resource settings with further modification., (© 2022 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

French health insurance data showed that the incidence of type 1 diabetes mellitus (T1DM) in children increased over the years to 2015. The objective of our study was to assess the evolution of the number of incident cases of paediatric and adult type 1 diabetes in our institution, and to describe their clinical presentation and its evolution. All patients with T1DM managed at diagnosis at Reims University Hospital between 1997 and 2019 were included. The clinical and biological data were extracted from the Champagne-Ardenne Diabetes Network database. Included were 847 patients with a median age of 10.3 years. Diagnosis was established in 71% of cases before 15 years, 7.4% after 35 years. The number of newly diagnosed cases was 3.6-times higher in 2019 compared to 1997. Ketoacidosis, the frequency of which decreased with age (P < 0.0001), revealed diabetes in a total of 32% of cases and in 46% of children under 5 years. It was more severe in children than in adults (P = 0.03), and its frequency increased over the study period. Hypotrophy was found in 23% of children under 15 years of age, and was more pronounced before 5 years of age, with no improvement over time. We saw an increase in the frequency of obesity or overweight among adults. Our study showed an increase in incident cases of diabetes in our hospital that continued over time for both children and adults. Clinical features at diagnosis deteriorated during this period for those under 15 years of age with an increase in ketoacidosis frequency., (Copyright © 2022 Elsevier Masson SAS. All rights reserved.)

Type 1 diabetes (T1D) is a chronic autoimmune disease of childhood affecting 1:500 children aged under 15 years, with around 25% presenting with life-threatening diabetic ketoacidosis (DKA). While first-degree relatives have the highest risk of T1D, more than 85% of children who develop T1D do not have a family history. Despite public health awareness campaigns, DKA rates have not fallen over the last decade. T1D has a long prodrome, and it is now possible to identify children who go on to develop T1D with a high degree of certainty. The reasons for identifying children presymptomatically include prevention of DKA and related morbidities and mortality, reducing the need for hospitalisation, time to provide emotional support and education to ensure a smooth transition to insulin treatment, and opportunities for new treatments to prevent or delay progression. Research studies of population-based screening strategies include using islet autoantibodies alone or in combination with genetic risk factors, both of which can be measured from a capillary sample. If found during screening, the presence of two or more islet autoantibodies has a high positive predictive value for future T1D in childhood (under 18 years), offering an opportunity for DKA prevention. However, a single time-point test will not identify all children who go on to develop T1D, and so combining with genetic risk factors for T1D may be an alternative approach. Here we discuss the pros and cons of T1D screening in the UK, the different strategies available, the knowledge gaps and why a T1D screening strategy is needed., Competing Interests: Competing interests: REJB reports receiving speaking honoraria from Springer Healthcare and Eli Lilly, and reports sitting on the NovoNordisk UK Foundation Research Selection Committee on a voluntary basis. TR reports receiving consultancy fees from Abbott Diabetes Care (specifically for Libre evidence reviews) and lecture/programme organiser fees from Novo Nordisk. CMD reports having been an advisor giving honorarium lectures to NovoNordisk, Sanofi-genzyme, Janssen, Servier, Lilly, AstraZeneca, Provention Bio, UCB, MSD and Vielo Bio. CMD holds a joint patent with Midatech. JWG chairs the NovoNordisk UK Foundation Research Selection Committee and is a Foundation Trustee. TB reports receiving speaking honoraria from AstraZeneca, Servier and Novo Nordisk, and has received consultancy fees from Novo Nordisk and is an NN Global Expert Panel., (© Author(s) (or their employer(s)) 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Lurasidone has few metabolic adverse effects and is recommended as an alternative when other antipsychotic drugs considerably increase body weight or blood sugar concentrations., Case Presentation: An 81-year-old man with bipolar disorder developed hyperosmolar hyperglycemic syndrome as a side effect of lurasidone. Routine monitoring of blood glucose concentrations led to the early detection and treatment of this disease, preventing life-threatening complications., Discussion and Conclusion: We describe a rare case of lurasidone-induced hyperosmolar hyperglycemic syndrome. The mortality rate of this syndrome is estimated to be up to 20%. This rate is significantly higher than that of diabetic ketoacidosis (currently <2%). Although lurasidone is considered to have a low risk of raising blood glucose concentrations, symptoms of hyperglycemia must be evaluated and blood glucose concentrations should be monitored regularly., (© 2022 The Authors. Neuropsychopharmacology Reports published by John Wiley & Sons Australia, Ltd on behalf of The Japanese Society of Neuropsychopharmacology.)

Objective: The international guidelines for the treatment of diabetic ketoacidosis (DKA) advise against rapid changes in osmolarity and glucose; however, the optimal rates of correction are unknown. We aimed to evaluate the rates of change in tonicity and glucose level in intensive care patients with DKA and their relationship with mortality and altered mental status., Methods: This is an observational cohort study using 2 publicly available databases of U.S. intensive care patients (Medical Information Mart for Intensive Care-IV and Electronic Intensive Care Unit), evaluating adults with DKA and associated hyperosmolarity (baseline Osm ≥300 mOsm/L). The primary outcome was hospital mortality. The secondary neurologic outcome used a composite of diagnosed cerebral edema or Glasgow Coma Scale score of ≤12. Multivariable regression models were used to control for confounding factors., Results: On adjusted analysis, patients who underwent the most rapid correction of up to approximately 3 mmol/L/hour in tonicity had reduced mortality (n = 2307; odds ratio [OR], 0.21; overall P < .001) and adverse neurologic outcomes (OR, 0.44; P < .001). Faster correction of glucose levels up to 5 mmol/L/hour (90 mg/dL/hour) was associated with improvements in mortality (n = 2361; OR, 0.24; P = .020) and adverse neurologic events (OR, 0.52; P = .046). The number of patients corrected significantly faster than these rates was low. A maximal hourly rate of correction between 2 and 5 mmol/L for tonicity was associated with the lowest mortality rate on adjusted analysis., Conclusion: Based on large-volume observational data, relatively rapid correction of tonicity and glucose level was associated with lower mortality and more favorable neurologic outcomes. Avoiding a maximum hourly rate of correction of tonicity >5 mmol/L may be advisable., (Copyright © 2022 AACE. All rights reserved.)

Objective: To identify clinical characteristics and factors associated with the development of euglycemic diabetic ketoacidosis (eDKA), and develop suitable strategies to reduce such events., Methods: Electronic health record (EHR) data were extracted to identify all patients between December 1, 2013, and March 30, 2021, who underwent surgical procedures and had been prescribed a sodium-glucose cotransporter 2 inhibitor (SGLT2i) before these procedures. The resulting list was streamlined to a subset of patients who either had diabetic ketoacidosis (DKA) listed as a hospital diagnosis, postoperative serum bicarbonate ≤ 16 mmol/L, or postoperative serum pH ≤ 7.20. Clinical documentation and laboratory data were reviewed to determine the patients with eDKA., Results: A total of 2183 procedures conducted on 1307 patients, met the inclusion criteria with the majority (1726, 79.1%) being nonemergent patients. Among 1307 patients, 625 (47.8%) were prescribed empagliflozin, 447 (34.2%) canagliflozin, 214 (16.4%) dapagliflozin, and 21 (1.6%) ertugliflozin, respectively. A total of 8 incidences pertaining to eDKA were noted for 8 unique patients; 5 had undergone emergency surgery whereas 3 had undergone nonemergent procedures. In the 3 nonemergent cases, only 1 patient had received counseling to stop the SGLT2i 3 days before the procedure. In perioperative patients who were prescribed an SGLT2i over 6 years, the incidence of eDKA was 0.17% and 1.1% for nonemergent and emergent procedures, respectively., Conclusion: Euglycemic DKA was rare in patients undergoing nonemergent procedures, likely because of preoperative instructions to stop their SGLT2i 3 days before the procedure. Euglycemic DKA was more likely to occur in patients undergoing emergency surgery when the SGLT2i could not be prophylactically stopped., (Copyright © 2022 AACE. Published by Elsevier Inc. All rights reserved.)

Background: The indication for treatment of type 1 diabetes(T1D) with the sodium-glucose cotransporter 2 inhibitor (SGLT2i) dapagliflozin has been withdrawn in Europe likely because of concern for diabetic ketoacidosis (DKA). We calculated the incidence of DKA in people with T1D treated with SGLT2i in Denmark., Methods: Clinical data from adults with T1D in Denmark were collected from nine outpatient clinics. Electronic health records made the search for DKA accurate., Results: From a population of 10.500 we observed 134 people treated with SGLT2i over a total period of 222 patient-years. Of those 72% were female, mean age (SD) was 51.4 (13.6) years and median duration of treatment (median, IQR) with an SGLT2i were 12.0 (6.0-29.0) months. The incidence of DKA was zero%., Conclusion: In 134 people with T1D treated with SGLT2i we found that none of the participants developed DKA during the treatment.

Objective: Before 2016, no child was known to survive type 1 diabetes (T1D) in Laos, a lower-middle income country (LMIC) in South-east Asia. In partnership with the Laos government, a non-government organization (NGO) called Action4Diabetes (A4D) has since been providing insulin, blood glucose monitoring kits, HbA1c testing, and emergency hospital expenses for Laotian children and young people (CYP) with T1D, and education for healthcare professionals. Here, we report the demographics and clinical outcomes of the CYP with T1D enrolled in A4D's Clinic Support Programme., Research Design and Methods: We collated and analyzed data on all known CYP with T1D in Laos, including gender, age and presentation at diagnosis, duration of diabetes, hospital admissions, and glycemic control during follow-up., Results: Fifty-three CYP (30 male; 57%) were diagnosed with T1D at a mean age of 11.3 years. Thirty CYP (57%) presented in diabetic ketoacidosis (DKA) at diagnosis. As at 16 August 2021, mean duration of T1D was 2.3 years. Forty-five CYP (85%) remained on active follow-up. Mean HbA1c for all 53 CYP was 8.7% (72 mmol/mol). Average HbA1c for the CYP in the age ranges of 1-5 years, 6-10 years, 11-15 years, 16-20 years, and 21-25 years, was 7.9% (63 mmol/mol), 8.2% (66), 8.4% (68), 9.4% (79), and 8.4% (68), respectively., Conclusions: This is the first report on the status of T1D care in Laos, achieved through close partnership between the government and an NGO from 2016 to 2021. More global efforts to improve T1D care outcomes in Laos and other LMICs are urgently needed., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

A 31-year-old man presented systemically unwell with diabetic ketoacidosis (DKA). He was using an intermittently scanned continuous glucose monitoring (CGM) device that had been recording low or normal glucose readings for the 48 hours prior to admission. The sensor site had become infected, and we believe this soft tissue infection caused his CGM device to record falsely low glucose readings leading the patient to erroneously lower his insulin doses and take extra carbohydrates, precipitating DKA. CGM devices measure glucose levels in the interstitial fluid. When interstitial glucose readings do not match symptoms or expectations, a capillary blood glucose reading should be taken to correlate and impact treatment decisions. There will be an increase in patients presenting to hospital with CGM devices as the National Institute for Health and Care Excellence guidelines have recently been updated. We use this interesting clinical case to provide context for key learning points about CGM devices for the general physician., (© Royal College of Physicians 2022. All rights reserved.)

Background: Latent autoimmune diabetes in adults is an infrequent form of autoimmune diabetes mellitus, while Hashimoto's thyroiditis, the most common thyroid disease in adults, rarely manifests as thyrotoxicosis. The concurrent initial presentation of these two autoimmune disorders is extremely rare., Case Presentation: A 29-year-old male of Albanian descent presented after being hospitalized owing to diabetic ketoacidosis. The diagnosis of type 1 diabetes mellitus was placed, and intensified insulin therapy was initiated. Medical history was not of significance except a 5 kg weight loss within 2 months. The patient presented with recurrent episodes of hypoglycemia, and the doses of preprandial and basal insulin were reduced. The differential diagnosis included type 1 diabetes mellitus "honeymoon" period or another type of diabetes mellitus. His serological tests only revealed positive autoantibodies against glutamic acid decarboxylase 65 and C-peptide. The diagnosis leaned toward latent autoimmune diabetes in adults, and the therapeutic approach involved cessation of preprandial insulin therapy, regulation, and subsequent discontinuation of basal insulin and introduction of metformin. Two years later, basal insulin was reintroduced along with a glucagon-like peptide-receptor agonist and metformin. Further physical examination during the initial visit disclosed upper limb tremor, lid lag, excessive sweating, increased sensitivity to heat, and tachycardia. Laboratory tests were indicative of hashitoxicosis (suppressed level of thyroid-stimulating hormone, high levels of total and free thyroid hormones, positive anti-thyroglobulin and anti-thyroid peroxidase, and negative anti-thyroid-stimulating hormone receptor). Thyroid-stimulating hormone level was spontaneously restored, but an increase was observed during follow-up. Levothyroxine was administrated for 2 years until the patient had normal thyroid function., Conclusions: The prevalence of thyroid autoantibodies in patients with latent autoimmune diabetes in adults ranges from 20% to 30%. This correlation can be attributed to genetic involvement as well as disorders of immune tolerance to autoantigens. Hence, this report gives prominence to the holistic approach and consideration of comorbidities in patients with diabetes mellitus., (© 2022. The Author(s).)

Objective: Diabetic ketoacidosis (DKA) is the leading cause of mortality in children with type 1 diabetes. Diagnosis of DKA is difficult in resource-limited areas owing to the unavailability of blood gas test, the gold standard for DKA diagnosis. The Simplified Pediatric Diabetes Severity Warning System (SPDSWS) has been developed to identify high-risk DKA patients with limited resources in China. Here we optimized and validated this system., Methods: This study included 835 children admitted between January 2011 and June 2020 with the principal diagnosis of type 1 diabetes. Data were collected based on demographic and clinical characteristics. DKA and its severity were defined according to the criteria of ISPAD. SPDSWS was optimized based on logistic regression analyses and then was validated in a validation cohort., Results: The 20-point optimized SPDSWS included strong positive urine ketone, young age, dehydration, fatigue, anorexia, vomiting, abdominal pain, abnormal pulse, and high blood glucose. The optimized SPDSWS predicted DKA with an AUC value of 0.882 in the derivation cohort. When the cut-point score ≥7 was used, the sensitivity and specificity were 75.5% and 86.0%, respectively, in the derivation cohort and were 90.0% and 85.8%, respectively, in the validation cohort. The optimized SPDSWS also predicted the moderate/severe DKA with an AUC value of 0.911 in the derivation cohort and 0.937 in the validation cohort. A score > 11 was associated with an extremely high incidence of DKA., Conclusions: The optimized SPDSWS could assist health care practitioners in underdeveloped remote areas to identify the children at high risk of DKA as early as on admission., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Mucormycosis is a rare but life-threatening disease with high morbidity and mortality and is difficult to diagnose. Mucormycosis, is a severe but rare fungal infection caused by a group of molds called mucormycetes. Diabetes, use of corticosteroids, metabolic/diabetic acidosis and Covid-19 mediated immunosuppression are reported in more than 70% of cases in mucormycosis patients. Coexisting mucormycosis, Covid-19 along with diabetes mellitus increase the likelihood of mortality. Despite its occurrence since the beginning of the pandemic, there are still unanswered concerns regarding the origin of this fungal infection and mortality rate and/or relation with diabetic patients. In this review, we describe the detailed view of causative pathogens responsible for mucormycosis, diabetes mellitus and Covid-19 association along with the morbidity cases during the latest Covid-19 crisis. In the case of mucormycosis diagnosis, imaging, histopathological confirmation, fungal culture and molecular identification methods should be considered. Once mucormycosis is diagnosed, a combined treating method consisting of antifungals administration like amphotericin B, surgical intervention is needed for the reversal of the underlying condition. Early detection of this potentially life-threatening infection and timely care is needed in lowering mortality rates., Competing Interests: Declaration of Competing Interest Authors declare that the research is free from any potential conflict of interest., (Copyright © 2022 SFMM. Published by Elsevier Masson SAS. All rights reserved.)

Objective: To investigate whether socioeconomic deprivation and urbanization are associated with the frequency of diabetic ketoacidosis (DKA) at diagnosis of pediatric type 1 diabetes., Research Design and Methods: Children and adolescents aged ≤18 years, living in Germany, with newly diagnosed type 1 diabetes documented between 2016 and 2019 in the Diabetes Prospective Follow-up Registry (DPV; Diabetes-Patienten-Verlaufsdokumentation), were assigned to a quintile of regional socioeconomic deprivation (German Index of Socioeconomic Deprivation) and to a degree of urbanization (Eurostat) by using their residence postal code. With multiple logistic regression models, we investigated whether the frequency of DKA at diagnosis was associated with socioeconomic deprivation or urbanization and whether associations differed by age-group, sex, or migration status., Results: In 10,598 children and adolescents with newly diagnosed type 1 diabetes, the frequency of DKA was lowest in the least deprived regions (Q1: 20.6% [95% CI 19.0-22.4], and increased with growing socioeconomic deprivation to 26.9% [25.0-28.8] in the most deprived regions [Q5]; P for trend <0.001). In rural areas, the frequency of DKA at diagnosis was significantly higher than in towns and suburbs (intermediate areas) or in cities (27.6% [95% CI 26.0-29.3] vs. 22.7% [21.4-24.0], P < 0.001, or vs. 24.3% [22.9-25.7], P = 0.007, respectively). The results did not significantly differ by age-group, sex, or migration background or after additional adjustment for socioeconomic deprivation or urbanization., Conclusions: This study provides evidence that prevention of DKA at diagnosis by means of awareness campaigns and screening for presymptomatic type 1 diabetes should particularly target socioeconomically disadvantaged regions and rural areas., (© 2022 by the American Diabetes Association.)

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.

Background: Portable breath ketone sensors may help people with Type 1 Diabetes Mellitus (T1DM) avoid episodes of diabetic ketoacidosis; however, the design features preferred by users have not been studied. We aimed to elucidate breath sensor design preferences of young people with T1DM (age 12 to 16) and their parents to inform the development of a breath ketone sensor prototype that would best suit their diabetes management needs., Research Designs and Methods: To elicit foundational experiences from which design preference ideas could be generated, two commercially available breath ketone sensors, designed for ketogenic diet monitoring, were explored over one week by ten young people with T1DM. Participants interacted with the breath ketone sensing devices, and undertook blood ketone testing, at least twice daily for five days to simulate use within a real life and ambulatory care setting. Semi-structured interviews were conducted post-testing with the ten young participants and their caregivers (n = 10) to elicit preferences related to breath sensor design and use, and to inform the co-design of a breath ketone sensor prototype for use in T1DM self-management. We triangulated our data collection with key informant interviews with two diabetes educators working in pediatric care about their perspectives related to young people using breath ketone sensors., Results: Participants acknowledged the non-invasiveness of breath sensors as compared to blood testing. Affordability, reliability and accuracy were identified as prerequisites for breath ketone sensors used for diabetes management. Design features valued by young people included portability, ease of use, sustainability, readability and suitability for use in public. The time required to use breath sensors was similar to that for blood testing. The requirement to maintain a 10-second breath exhalation posed a challenge for users. Diabetes educators highlighted the ease of use of breath devices especially for young people who tended to under-test using blood ketone strips., Conclusions: Breath ketone sensors for diabetes management have potential that may facilitate ketone testing in young people. Our study affirms features for young people that drive usability of breath sensors among this population, and provides a model of user preference assessment., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Despite the use of technology, recurrent diabetic ketoacidosis (DKA) prevention remains an unmet need in children and adolescents with T1D and may be accompanied by life-threatening acute complications. We present a rare case of non-occlusive mesenteric ischemia (NOMI) with overt manifestation after DKA resolution and a discussion of recent literature addressing DKA-associated NOMI epidemiology and pathogenesis in children and adolescents., Case Presentation: A 13-year-old female with previously diagnosed T1D, was admitted at our emergency department with hypovolemic shock, DKA, hyperosmolar state and acute kidney injury (AKI). Mildly progressive abdominal pain persisted after DKA correction and after repeated ultrasound evaluations ultimately suspect for intestinal perforation, an intraoperative diagnosis of NOMI was made., Conclusion: The diagnosis of DKA-associated NOMI must be suspected in pediatric patients with DKA, persistent abdominal pain, and severe dehydration even after DKA resolution., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Frontino, Di Tonno, Castorani, Rigamonti, Morotti, Sandullo, Scialabba, Arrigoni, Foglino, Dionisi, Ferri, Zirpoli, Barera, Meschi and Bonfanti.)

Objectives: Diabetic ketoacidosis is a common emergency in type 1 diabetes mellitus patients. But rarely, they may present with alkalemia instead of acidosis. Diabetic ketoalkalosis which has been reported in adults can also be present in children with type 1 DM. The usual factors causing alkalemia were not found in our patients. This entity may manifest in both newly diagnosed and treated patients., Case Presentation: The first patient, an 8 year male presented with features of DKA, was diagnosed for the first time as type 1 DM, but was found to have alkalemia. The second patient, a 7 year female was a known case of Type 1 DM on insulin, who presented with dehydration and alkalemia. Both were treated with hydration and insulin and made complete recovery., Conclusions: A normal or alkalotic pH does not essentially eliminate DKA and needs to be evaluated further to identify the underlying acid-base disturbance., (© 2022 Walter de Gruyter GmbH, Berlin/Boston.)

Background: Mucormycosis is a rare but serious opportunistic fungal infection that occurs in immunocompromised individuals, especially those with diabetic ketoacidosis. Presently, early diagnosis of the disease remains a challenge for clinicians., Case Presentation: The patient, a 68-year-old woman with type 2 diabetes mellitus, was admitted with paroxic sharp pain in the left upper abdomen. CT imaging revealed a patchy hypodense shadow of the spleen with wedge-shaped changes. The patient was not considered early for fungal infection. The diagnosis of spleen mucormycosis was not confirmed until pathological biopsy after splenectomy. After surgery, blood glucose level was controlled, acidosis was corrected, and antifungal therapy was effective., Conclusions: We report here, for the first time ever, a case of isolated splenic mucormycosis secondary to diabetic ketoacidosis that was diagnosed and treated with antifungal drugs and splenectomy. Following splenectomy, the presence of splenic mucormycosis was confirmed when characteristic mycelia were observed in a tissue biopsy. As the location of any fungal infection is extremely relevant for treatment options and prognoses, early diagnosis and clinical intervention can greatly affect outcomes and prognoses for patients., (© 2022. The Author(s).)

Atezolizumab is a humanised monoclonal IgG1 antibody that is used in treating many solid malignancies. Endocrinopathies are known but a rare adverse event of these immunotherapeutic drugs. Autoimmune diabetes induced by atezolizumab has been rarely reported in the literature. We report the case of a woman in her eighth decade with no known history of diabetes who developed new-onset autoimmune diabetes and Takotsubo cardiomyopathy due to the adverse effects of atezolizumab therapy for hepatocellular carcinoma. We also review the characteristics and outcomes of cases previously reported in the literature., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Acute metabolic disorders of diabetes mellitus (DM), such as diabetic ketoacidosis, hyperosmolar hyperglycemic state, and hypoglycemia, are life-threatening and difficult to diagnose postmortem owing to lack of macroscopic and microscopic findings, especially when the medical history of the patient is not available before autopsy. Although various biochemical tests, including ketone bodies and hemoglobin A1c, have been used to diagnose diabetes in the postmortem setting, each marker has some limitations. Consequently, it would be helpful in forensic practice to find new biomarkers reflecting the decedent's history of DM irrespective of whether the DM was being treated. Metabolomics enables the non-targeting analysis of biomarkers, and metabolomics was performed on postmortem blood from decedents with and without a DM history to determine whether a marker reflecting DM could be identified. The statistical analysis, including primary component analysis, presented a potent set of metabolites that could be used for the forensic diagnosis of DM. Qualitative analysis revealed significantly lower sphingomyelin and plasmalogen lipid levels and higher lysophospholipid levels in the DM group. Meanwhile, some discrepancies in the levels of some classes of phospholipids were noted between samples from living and deceased persons. This suggests that further metabolomics using postmortem samples rather than living persons' samples is required to identify markers that can be used for forensic diagnosis., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Euglycemic diabetic ketoacidosis is characterised by serum blood glucose <250 mg/dl, arterial blood pH <7.35, and the presence of ketones in urine or blood. Here, we present a 36-year female with type-1 diabetes mellitus, a case of euglycemic diabetic ketoacidosis, who was admitted to the emergency unit with nausea, vomiting, and confusion after using empagliflozin, which was added to her treatment one month ago. She was followed up in the intensive care unit for four days. Empagliflozin was discontinued. Intravenous fluids and insulin infusions were given. The patient, whose metabolic acidosis regressed, was discharged with the necessary recommendations and training. Euglycemic diabetic ketoacidosis should be kept in mind as a differential diagnosis in patients with type-1 diabetes and type-2 diabetes presenting with acidosis. Attention should be paid to the patients' medications and whether there are SGLT-2 inhibitors among these drugs. Key Words: Diabetes mellitus, Sodium-glucose co-transporter-2 inhibitors, Euglycemic diabetic ketoacidosis, Empagliflozin.

Objectives: Transition to adult care is challenging for youth with type 1 diabetes (T1D) and their caregivers. We have developed the diabetes-specific "On TRAck" transition readiness scale, and in this study we assess its reliability and validity compared with TRANSITION-Q, a generic transition readiness questionnaire., Methods: We systematically created 3 versions of On TRAck: adolescent, parent and health-care provider (HCP) versions (for case managers and physicians). Among adolescents 13 to 18 years of age with T1D at a single academic centre, we conducted an exploratory factor analysis and assessed interrater agreement, internal consistency and relationship with age; recent glycated hemoglobin (A1C); and recent diabetic ketoacidosis (DKA) with On TRAck and TRANSITION-Q., Results: One hundred fifteen adolescents (aged 15.8±1.6 years and diabetes duration 6.7±4.1 years), their caregivers and diabetes HCPs participated. The final 24-item adolescent and parent scales (with 3 subscales: "Self-efficacy," "Autonomy" and "Support & maturity") and the 3-item HCP version had a Cronbach's alpha of 0.86 to 0.93. Adolescent scores correlated with parents (r=0.64), case managers (r=0.39) and physicians (r=0.28). Mean adolescent score was 190.3±27.1 points out of 240. Adolescent scores were 3.4 points higher per year of age (p=0.03) and 4.4 points higher for every 1% lower A1C (p=0.01), but were not associated with DKA. TRANSITION-Q was associated with age. On TRAck HCP scores were associated with adolescent's age, A1C and DKA., Conclusions: On TRAck represents a new psychometrically comprehensive diabetes-specific scale that can be used in adolescent diabetes clinics for measuring transition readiness. It is a multidimensional instrument with ease of use and high reliability scores., (Copyright © 2022 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

A 16-year-old child with no medical history was admitted to the hospital emergency for abdominal pain associated with polyuria-polydipsia and weight loss (baseline BMI: 25,4 kg/m2). Diagnosis of severe ketoacidosis was quickly raised regarding major metabolic acidosis, high ketonemia and glycemia. Acute pancreatitis was then diagnosed according to a plasmatic lipase more than tenfold normal values associated with a severe hypertriglyceridemia superior to 100 mmol/L. The triad composed of diabetic ketoacidosis-acute pancreatitis-hypertriglyceridemia is rarely found in childhood and can have deleterious consequences. The etiology of this disease is still enigmatic, as one can be both, cause and consequence of the other. Genetic investigation of familial chylomicronemia legitimated to invalidate the dyslipidemia etiology of this event. On the other hand, the association of a genetic variant of lipoprotein lipase leading to a decrease in its activity, with the insulinopenia of type 1 diabetes most certainly triggered this episode of hypertriglyceridemia.

Sodium glucose cotransporter-2 (SGLT2) inhibitors are glucose-lowering drugs with proven efficacy in treating type 2 diabetes mellitus, and more recently, have been shown to improve heart failure outcomes in patients without diabetes. A rare complication of SGLT2 inhibitor use is the development of euglycaemic diabetic ketoacidosis (EDKA), characterised by euglycaemia (blood glucose level <250 mg/dL), metabolic acidosis (arterial pH <7.3 and serum bicarbonate <18 mEq/L), and ketonaemia. Given patients with EDKA do not present with the typical manifestations of diabetic ketoacidosis, including marked hyperglycaemia and dehydration, the diagnosis of EDKA may be missed and initiation of treatment delayed. We present the case of a man with recent SGLT2 inhibitor use and multiple other risk factors who developed EDKA., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2022. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim/hypothesis: To compare the frequency of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes in Italy during the COVID-19 pandemic in 2020 with the frequency of DKA during 2017-2019., Methods: Forty-seven pediatric diabetes centers caring for >90% of young people with diabetes in Italy recruited 4,237 newly diagnosed children with type 1 diabetes between 2017 and 2020 in a longitudinal study. Four subperiods in 2020 were defined based on government-imposed containment measures for COVID-19, and the frequencies of DKA and severe DKA compared with the same periods in 2017-2019., Results: Overall, the frequency of DKA increased from 35.7% (95%CI, 33.5-36.9) in 2017-2019 to 39.6% (95%CI, 36.7-42.4) in 2020 (p=0.008), while the frequency of severe DKA increased from 10.4% in 2017-2019 (95%CI, 9.4-11.5) to 14.2% in 2020 (95%CI, 12.3-16.4, p<0.001). DKA and severe DKA increased during the early pandemic period by 10.4% (p=0.004) and 8% (p=0.002), respectively, and the increase continued throughout 2020. Immigrant background increased and high household income decreased the probability of presenting with DKA (OR: 1.55; 95%CI, 1.24-1.94; p<0.001 and OR: 0.60; 95 CI, 0.41-0.88; p=0.010, respectively)., Conclusions/interpretation: There was an increase in the frequency of DKA and severe DKA in children newly diagnosed with type 1 diabetes during the COVID-19 pandemic in 2020, with no apparent association with the severity of COVID-19 infection severity or containment measures. There has been a silent outbreak of DKA in children during the pandemic, and preventive action is required to prevent this phenomenon in the event of further generalized lockdowns or future outbreaks., Competing Interests: No author reported any conflict of interest as regards this study. The following conflicts of interest pointed out are referred to a period from January 2020 to the submission of this manuscript. VCh’s institution has received research grants from AstraZeneca, Novonordisk, Eli Lilly, Movi, Dompè, and Menarini, and VCh received honoraria from Eli Lilly, Tandem, and Insulet for participating on speakers’ bureaus and scientific advisory boards. CR, DT, IRa, BPr, BPi, SZ, ST, and AR has received support Eli Lilly. In addition, SZ’s institution has received support from Pfeizer, ST, BPi, and DT have received support from Abbott and Theras. MM and AR have received support from Menarini. BPr and PB received honoraria for participating on speakers’ bureaus and scientific advisory boards for Sandoz. Lastly, RS has received research grants by Sanofi and received honoraria for participating on speakers’ bureaus and scientific advisory boards for Movi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cherubini, Marino, Scaramuzza, Tiberi, Bobbio, Delvecchio, Piccinno, Ortolani, Innaurato, Felappi, Gallo, Ripoli, Ricciardi, Pascarella, Stamati, Citriniti, Arnaldi, Monti, Graziani, De Berardinis, Giannini, Chiarelli, Zampolli, De Marco, Bracciolini, Grosso, De Donno, Piccini, Toni, Coccioli, Cardinale, Bassi, Minuto, D’Annunzio, Maffeis, Marigliano, Zanfardino, Iafusco, Rollato, Piscopo, Curto, Lombardo, Bombaci, Sordelli, Mameli, Macedoni, Rigamonti, Bonfanti, Frontino, Predieri, Bruzzi, Mozzillo, Rosanio, Franzese, Piredda, Cardella, Iovane, Calcaterra, Berioli, Lasagni, Pampanini, Patera, Schiaffini, Rutigliano, Meloni, De Sanctis, Tinti, Trada, Guerraggio, Franceschi, Cauvin, Tornese, Franco, Musolino, Maltoni, Talarico, Iannilli, Lenzi, Matteoli, Pozzi, Moretti, Zucchini, Rabbone and Gesuita.)

Introduction: There are variable complications of hyperthyroidism, including atrial fibrillation, heart failure, osteoporosis, and thyroid storm. One infrequent complication of hyperthyroidism is non-diabetic ketoacidosis (NDKA). To the best of our knowledge, our case is the third report of NDKA related to thyrotoxicosis., Patient Concern: We describe a case of a 41-year-old African lady with no past medical history presented to our hospital with severe abdominal pain and vomiting for three weeks. This was associated with decreased appetite and weight loss., Diagnosis: Laboratory findings were significant for high anion gap metabolic acidosis, positive ketones in the urine, and high serum B-hydroxybutyrate. The blood glucose readings and HbA1c were within normal limits. Also, serum lactic acid and salicylate levels were within the normal range. The diagnosis of NDKA was made. Later, the thyroid functions test (TFT) confirmed the diagnosis of primary hyperthyroidism., Intervention and Outcomes: The patient was managed initially with intravenous fluid and antiemetics. Then, she was started on propranolol and carbimazole. After which, her symptoms improved dramatically, and the metabolic acidosis (with serum ketones) were corrected within a few days of starting anti-thyroid medications., Conclusion: Despite its rarity, NDKA can be associated with severe thyrotoxicosis. Vigorous intravenous hydration and anti-thyroid medication are the mainstay treatment. TFT should be requested in a patient with unexplained NDKA., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2022 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background: Hospital visitation has become challenging during the coronavirus disease 2019 pandemic because of quarantine measures and fear of infection. Consequently, newly diagnosed patients may present with more severe diseases during the pandemic. The present study analyzed the differences in the initial clinical presentations of newly diagnosed patients with type 1 diabetes (T1D) and type 2 diabetes (T2D), comparing pre-pandemic and pandemic periods., Methods: Newly diagnosed patients with T1D or T2D and aged < 18 years during 2018-2020 were included in the study. Data were collected retrospectively from four academic centers in Gyeonggi-do, South Korea. Initial clinical data were compared between the pre-pandemic (2018-2019) and pandemic (2020) periods., Results: In the pre-pandemic and pandemic periods, 99 patients (41 T1D and 58 T2D patients) and 84 patients (51 T1D and 33 T2D patients) were identified, respectively. During the pandemic, the proportion of diabetic ketoacidosis (DKA) cases increased compared to the pre-pandemic period (21.2% during 2018-2019 vs. 38.1% in 2020; P = 0.012). In the pre-pandemic and pandemic periods, initial pH was 7.32 ± 0.14 and 7.27 ± 0.15, respectively ( P = 0.040), and HbA1c values were 11.18 ± 2.46% and 12.42 ± 2.87%, respectively ( P = 0.002). During the pandemic, there was an increased risk of DKA in patients with T1D (odds ratio, 2.42; 95% confidence interval, 1.04-5.62; P = 0.040)., Conclusion: During the pandemic, the proportion of DKA in newly diagnosed patients with T1D increased and clinical parameters showed a deteriorating pattern. Increased awareness of pediatric diabetes, especially DKA, could facilitate visit to the hospital for an early diagnosis; thus, reducing the number of DKA cases during the pandemic era., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Objective: To compare the frequency, severity of presentation and initial presentations of new onset diabetes mellitus (DM) in youth in Rhode Island during the early phase of the COVID-19 pandemic compared to the same time frame in 2018 and 2019., Methods: A retrospective cohort study of youth treated for new onset DM at Hasbro Children's Hospital between March 1 and May 15, 2020, compared to those diagnosed in the same period in 2018 and 2019., Results: Fewer youth were diagnosed with new onset DM in Spring 2020 and the percentage of youth with DKA at time of DM diagnosis was higher in Spring 2020 compared to prior years (p=0.048). Age, gender, and DKA complications did not differ by year., Conclusion: Nearly 50% fewer youth were diagnosed with DM at the start of the COVID-19 pandemic compared to years prior, and those diagnosed with new onset DM in Spring 2020 were more likely to present with DKA. Delays in both initial health care evaluation and the recognition of DM symptoms may have contributed to the decline in overall DM diagnoses and the more severe presentations. Identification of DM symptoms is essential, especially during future surges of COVID-19 or other events that impact the healthcare system, to reduce the risk of DM complications including DKA.

Accurate prediction of severity and mortality in diabetic ketoacidosis (DKA) is important for allocation of resources. The APACHE II and SOFA scores are used to predict mortality in critically ill patients, however neither has been tested exclusively in DKA. We sought to determine if these scoring systems can accurately predict mortality in patients with DKA. This was an observational study of patients presenting to an urban tertiary care center with a diagnosis of DKA. Adult patients (age ≥ 18 years) with glucose > 250 mg/dL, bicarbonate ≤ 20 mEg/L, an anion gap ≥ 16 mEg/L, pH ≤ 7.30, and urine ketones were included. Predicted mortality based upon APACHE II and SOFA scores were compared to observed mortality. A total of 50 patients were included. There was no observed mortality in our population. The median APACHE II score was 10 (IQR: 6, 15) which predicted a mortality of 15% and the median SOFA score was 1 (IQR: 0, 2) which predicted a mortality of 0%. In summary, we found the APACHE II illness severity score does not accurately predict mortality in a population of patients with DKA, while the SOFA score appears to predict mortality in the same population.

Fulminant type 1 diabetes mellitus (FT1DM) is recognised as a novel subtype of type 1 diabetes mellitus characterised by the abrupt onset of insulin-deficient hyperglycaemia and ketoacidosis. Fulminant type 1 diabetes mellitus is known to be associated with pregnancy and had been associated with high fetal mortality. We report a case of a gestational diabetes mellitus (GDM) mother complicated with FT1DM immediately post-delivery. A 29-year-old Malay lady who was diagnosed with GDM at 19 weeks of pregnancy, underwent emergency lower segment caesarean section (EMLSCS) due to fetal distress at 36 weeks of gestation; 18 h post-EMLSCS, she developed abrupt onset Diabetic ketoacidosis (DKA) (blood glucose 33.5 mmol/L, pH 6.99, bicarbonate 3.6 mmol/L, ketone 4.4 mmol/L and HbA1c 6.1%). She received standard DKA treatment and discharged well. Her plasma C-peptide level 3 weeks later showed that she has no insulin reserve (C-peptide <33 pmol/L, fasting blood glucose (FBS) 28 mmol/L). Her pancreatic autoantibodies were negative. This case highlights that FT1DM not only can occur in pregnancy with normal glucose tolerance but can also complicate mother with GDM.

Purpose: The aim was to evaluate the impact of familial autoimmunity on the age and severity of type 1 diabetes (T1D) presentation and on the coexistence of other autoimmune diseases., Methods: We retrospectively evaluated the medical records of 121 children/adolescents (male: 63) followed in our Diabetic Clinic from 2002 to 2016., Results: Seventy-six patients (62.8%) had at least one relative with an autoimmune disease, Hashimoto's thyroiditis (49.5%) and T1D (22.3%) being the commonest. Children with familial autoimmunity were younger at T1D diagnosis (mean age ± SD) (6.766 ± 3.75). Median fasting c-peptide levels at presentation were not related to familial autoimmunity. Patients with familial autoimmunity more often exhibited GADA autoantibody positivity at diagnosis. The larger the number of the patient's relatives diagnosed with an autoimmune disease, the higher were the patient's GADA levels (Spearman's rho test = 0.19, p = 0.049). Children with a first-degree relative with autoimmunity had a coexisting autoimmune disorder at a significantly higher percentage (p = 0.016). Family history of autoimmunity was negatively associated with the presence of diabetic ketoacidosis (DKA) (p = 0.024). Patients with a relative with T1D less frequently exhibited DKA at diagnosis (12.8 vs. 87.2%, p = 0.003). The presence of DKA was associated with younger age (p = 0.05) and lower c-peptide levels (p = 0.033)., Conclusions: Familial autoimmunity was present in 62.8% of children with T1D, autoimmune thyroiditis and T1D being the two most frequent familial autoimmune diseases. Familial autoimmunity reduced the risk of DKA at diagnosis, but these patients were younger and had higher levels of pancreatic autoantibodies and a greater risk of developing additional autoimmune diseases., (© 2022. Hellenic Endocrine Society.)

Background: The presence of ketone bodies (KBs) can interfere with creatinine (Cr) measurement in both enzymatic and Jaffe methods. Since a high proportion of children hospitalized for diabetic ketoacidosis (DKA) develop acute kidney injury (AKI), here we investigate whether KB interferences affect the accuracy of pediatric Cr measurement., Methods: Residual patient plasma samples were pooled to make three Cr levels (~ 50, 100, and 250 μM). KBs (acetone, acetoacetate, and β-hydroxybutyrate) were used to spike the pooled samples. All samples were measured for Cr by two enzymatic methods (E1 and E2), two Jaffe methods (J1 and J2), and LC-MS/MS. LC-MS/MS was considered the gold standard, and the % difference in Cr concentration was calculated for each method., Results: E1 and E2 were unaffected by the presence of all three KBs. J1 and J2 were unaffected by the presence of β-hydroxybutyrate. The presence of acetone resulted in dose-dependent positive interference in both Jaffe methods, whereas the presence of acetoacetate resulted in dose-dependent positive and negative interference in J1 and J2, respectively., Conclusions: Compared to the enzymatic methods, the Jaffe methods were much more susceptible to interference by acetone and acetoacetate, especially at lower Cr values which are commonly seen in pediatrics. Interpretation of changes in Cr concentration between different hospitals when transferring patients can become ambiguous and true kidney function unclear if different methods are used without awareness of method-specific biases. To improve DKA patient care, we recommend standardizing all of the Cr methods to an enzymatic method. A higher resolution version of the Graphical abstract is available as Supplementary information., (© 2021. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Recurrent diabetic ketoacidosis (DKA) has been linked to mental health disorders, but less is known about single DKA episodes. Most studies are retrospective, lacking control groups., Aims: To prospectively examine psychosocial factors in patients presenting with recurrent or single episode DKA and compare with people who have not had DKA., Methods: Case-controlled study (consecutive adult DKA admissions April 2015 to December 2016) at Western Health, Melbourne. Data were prospectively collected regarding diagnosed mental health disorders, likely depression (Patient Health Questionnaire (PHQ-9)), diabetes distress (Problem Areas in Diabetes (PAID) questionnaire) and presence of adverse social factors. A control group without a history of DKA was also recruited., Results: Of 123 patients admitted with DKA (164 consecutive episodes), 70 consented to participate and 73 age-matched Type 1 diabetes controls were recruited. Eleven (61%) of 18 with recurrent DKA had a diagnosed mental health disorder versus 8 (19%) of 42 in the single episode group (P = 0.016). The prevalence of likely depression using PHQ-9 was: recurrent 50%; single 40%; and controls 22% (recurrent vs controls, P = 0.036; single vs controls, P = 0.053). Severe diabetes distress (PAID) was present in 47% of recurrent and 34% of single episode DKA (P = 0.387). As a group, DKA patients had significantly more unemployment, illicit drug use and tobacco smoking, a lower level of formal education and less regular medical contact compared with controls., Conclusions: Mental health disorders and adverse socioeconomic factors appear to be common in patients with DKA. The diagnosis of DKA presents an excellent opportunity to screen for depression and offer appropriate intervention., (© 2021 Royal Australasian College of Physicians.)

Background: An increase in newly diagnosed type 1 diabetes (T1D) has been posited during the COVID-19 pandemic, but data are conflicting. We aimed to determine trends in newly diagnosed T1D and severity of presentation at diagnosis for pediatric and adolescent patients during COVID-19 (2020) as compared to the previous year (2019) in a multi-center analysis across the United States., Methods: This retrospective study from seven centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI) included data on new onset T1D diagnosis and proportion in DKA at diagnosis from January 1 to December 31, 2020, compared to the prior year. Chi-square tests were used to compare differences in patient characteristics during the pandemic period compared to the prior year., Results: Across seven sites, there were 1399 newly diagnosed T1D patients in 2020, compared to 1277 in 2019 (p = 0.007). A greater proportion of newly diagnosed patients presented in DKA in 2020 compared to 2019 (599/1399(42.8%) vs. 493/1277(38.6%), p = 0.02), with a higher proportion presenting with severe DKA (p = 0.01) as characterized by a pH <7.1 and/or bicarbonate of <5 mmol/L. Monthly data trends demonstrated a higher number of new T1D diagnoses over the spring and summer months (March to September) of 2020 compared to 2019 (p < 0.001)., Conclusions: We found an increase in newly diagnosed T1D and a greater proportion presenting in DKA at diagnosis during the COVID-19 pandemic compared to the prior year. Future longitudinal studies are needed to confirm these findings with population level data and determine the long-term impact of COVID-19 on diabetes trends., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Objective: To investigate in a population-based pediatric cohort: prevalence of moderate-severe diabetic ketoacidosis (DKA) at type 1 diabetes (T1D) diagnosis over two decades and its association with long-term glycemic control., Research Design and Methods: Children <16 years diagnosed with T1D in Western Australia 2000-2019 were included and followed up for ≤14 years. Moderate-severe DKA at diagnosis was defined as serum pH < 7.2 or bicarbonate<10 mmol/L with hyperglycemia and ketosis. HbA1c was measured ~3-monthly. Trend in prevalence of moderate-severe DKA at diagnosis was investigated using a logistic regression model adjusting for sex, age, socioeconomic status, and area of residence. Long-term glycemic control associated with DKA at diagnosis was investigated using linear mixed models adjusting for the same variables and also for visit frequency, CGM and pump use., Results: Moderate-severe DKA occurred in 534 of 2111 (25.3%) participants. Odds of presenting with moderate-severe DKA increased by 4.1% (95% CI: 2.3, 5.9; p < 0.001) per year. Patients with moderate-severe DKA at diagnosis had higher HbA1c levels than other patients initially; the groups were similar between 2 and 6 years duration; from 7 years HbA1c levels tracked higher in the group with moderate-severe DKA at diagnosis with significant differences at 8 and 12 years (p < 0.05)., Conclusion: The increasing prevalence of DKA at diagnosis of pediatric T1D is concerning and highlights the need for early detection programs. Unlike a similar US study, this study did not find a consistent, clinically significant relationship between DKA at diagnosis and long-term HbA1c, raising important questions about the influence of other factors on long-term glycemic outcomes., (© 2022 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Non-thyroidal illness (NTI) is a condition in which the hypothalamic-pituitary-thyroid system and thyroid hormone metabolism are abnormal due to non-thyroidal diseases. Although NTI has been reported to occur in hyperglycemic emergencies in children, there have been few studies in adult cases. In this study, we examined adult patients with hyperglycemia regarding the frequency of NTI and its triggers. Adult diabetic patients who were hospitalized for diabetic ketosis (DK), diabetic ketoacidosis (DKA), or hyperglycemic hyperosmolarity syndrome (HHS) were included in the study. Compared with the DK group, the DKA and HHS groups had higher admission blood glucose, Anion Gap, serum osmolality, creatinine, and urea nitrogen, and lower pH and eGFR. The frequency of NTI in the DKA, HHS, and DK groups was 80%, 70%, and 50%, respectively, and thyroid stimulating hormone (TSH) and free thyroxine 3 (FT3) were significantly improved after treatment for hyperglycemia. Multiple regression analysis showed a significant correlation between the decrease in FT3 level and 3-hydroxybutyrate and albumin. Acute metabolic failure associated with hyperglycemia tends to be associated with a high rate of NTI and low FT3 levels at the start of treatment. The data in this study clearly shows that transient NTI is frequently observed in subjects with acute metabolic disorders such as DKA, HHS and DK. In addition, we should bear in mind that thyroid hormone replacement therapy is not necessary in subjects with NTI due to DKA, HHS and DK, especially when overt symptoms of hypothyroidism are not observed., Competing Interests: HK has received honoraria for lectures, received scholarship grants, and received research grant from Novo Nordisk Pharma, Sanofi, Eli Lilly, Boehringer Ingelheim, Taisho Pharma, Sumitomo Dainippon Pharma, Takeda Pharma, Ono Pharma, Daiichi Sankyo, Mitsubishi Tanabe Pharma, Kissei Pharma, MSD, AstraZeneca, Astellas, Novartis, Kowa, Abbott. KK has been an advisor to, received honoraria for lectures from, and received scholarship grants from Novo Nordisk Pharma, Sanwa Kagaku, Takeda, Taisho Pharma, MSD, Kowa, Sumitomo Dainippon Pharma, Novartis, Mitsubishi Tanabe Pharma, AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Iwamoto, Kimura, Tatsumi, Sugisaki, Kubo, Nakao, Dan, Wamata, Iwamoto, Takahashi, Sanada, Fushimi, Katakura, Shimoda, Nakanishi, Mune, Kaku and Kaneto.)

Background and Objectives : The incidence of severe and moderate forms of DKA as the initial presentation of type 1 diabetes mellitus (T1D) is increasing, especially during the COVID-19 pandemic. This poses a higher risk of developing cerebral edema as a complication of diabetic ketoacidosis (DKA), as well as morbidity and mortality rates. The aim of this study was to determine the trend and clinical features of children treated in the last 10 years in the Pediatric Intensive Care Unit (PICU) due to the development of DKA. Materials and Methods : This retrospective study was performed in the PICU, Clinical Hospital Centre Rijeka, in Croatia. All children diagnosed with DKA from 2011-2020 were included in this study. Data were received from hospital medical documentation and patient paper history. The number of new cases and severity of DKA were identified and classified using recent International Society for Pediatric and Adolescent Diabetes (ISPAD) guidelines. Results : In this investigation period, 194 children with newly diagnosed T1D were admitted to our hospital: 58 of them were treated in the PICU due to DKA; 48 had newly diagnosed T1D (48/58); and ten previously diagnosed T1D (10/58). DKA as the initial presentation of T1D was diagnosed in 24.7% (48/194). Moderate or severe dehydration was present in 76% of the children at hospital admission. Polyuria, polydipsia, and Kussmaul breathing were the most common signs. Three patients (5.2%) developed cerebral edema, of whom one died. Conclusions : During the investigation period a rising trend in T1D was noted, especially in 2020. About one quarter of children with T1D presented with DKA at initial diagnosis in western Croatia, most of them with a severe form. Good education of the general population, along with the patients and families of children with diabetes, is crucial to prevent the development of DKA and thus reduce severe complications.

A 34-year-old man visited our Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan, because of dry mouth and weight loss. His plasma glucose level was 32.8 mmol/L and serum levels of ketone bodies were increased, but with metabolic alkalemia. He was also suffering from renal tubular hypomagnesemia and hypokalemia. Abdominal computed tomography showed bilateral renal cysts. These findings were suggestive of maturity-onset diabetes of the young type 5. Genetic testing showed heterozygous hepatocyte nuclear factor 1 beta gene deletion. In the present case, it seemed reasonable to view hepatocyte nuclear factor 1 beta gene deletion as the common cause of maturity-onset diabetes of the young type 5-associated diabetic ketoacidosis and tubular malfunction-induced hypokalemic alkalosis. This case exemplifies the importance of hepatocyte nuclear factor 1 beta gene abnormality as a potential cause of diabetic ketoacidosis with alkalemia., (© 2021 The Authors. Journal of Diabetes Investigation published by Asian Association for the Study of Diabetes (AASD) and John Wiley & Sons Australia, Ltd.)