Search

Elevated blood ketone levels (ketosis) in inpatients with diabetes can herald diabetic ketoacidosis (DKA). However, ketosis can also occur in individuals without diabetes in certain settings. It is unclear what proportion of inpatients with ketosis are in DKA and which patients are at the highest risk of DKA. This study determined that many ketone tests are performed in individuals at low risk of DKA, and a β-hydroxybutyrate <1.0 mmol/L had a low incidence of DKA and less need for escalation in their management., (© 2024 Royal Australasian College of Physicians.)

The aim of the study was to investigate whether the biomarkers for bone turnover could rapidly recover during the period of diabetic ketoacidosis (DKA). Bone turnover biomarkers, including 25-hydroxyvitamin D3, N-terminal middle molecular fragment of osteocalcin (NMID), and β-C terminal cross-linking telopeptide of type 1 collagen were evaluated using in-patient data (n=627) from Shanghai Pudong Hospital from 2018-2022. The comparison was performed between type 2 diabetes (T2D only) (n=602) and DKA (n=25), in which we checked the bone turnover markers at pre-treatment and recovery. After matching by body mass index (BMI), we found that except for 25-OH-VitD3, the age difference, indices of glucose metabolism, and bone turnover were significant between the 2 groups (p<0.05). We found only a significant restoration of NMID (p<0.001). NMID and β-CTX, when compared with T2D, showed overt distinction between recovery and T2D (p<0.05). In addition, the investigations demonstrated a substantial difference between 25-OH-VitD3 in males and NMID in females, regardless of age (p<0.05). Multilinear regression analysis revealed that 2 hours postprandial plasma C-peptide was an independent predictor of the NMID in both pre-treatment (β=0.58, p=0.003) and recovery (β=0.447, p=0.025), although sex was significant in pre-treatment (β=-0.444, p=0.020). Finally, we found that only age variation affected DKA's fasting plasma glucose level (p<0.05). The study revealed that the bone turnover of DKA is significantly different in pre-treatment and recovery; however, NMID might recover quickly if the patients received appropriate treatment. Importantly, pancreatic function plays a critical role in changing bone turnover biomarkers., Competing Interests: The authors declare that they have no conflict of interest., (Thieme. All rights reserved.)

Objective: Continuous glucose monitoring (CGM) devices are integral in the outpatient care of people with type 1 diabetes, although they lack inpatient labeling. Food and Drug Administration began allowing inpatient use during the coronavirus disease 2019 (COVID-19) pandemic, with some accuracy data now available, primarily from adult hospitals. Pediatric inpatient data remain limited, particularly during diabetic ketoacidosis (DKA) admissions and for patients receiving intravenous (IV) insulin. Design and Methods: This retrospective chart review compared point-of-care glucose values to personal Dexcom G6 sensor data during pediatric hospitalizations. Accuracy was assessed using mean absolute relative difference (MARD), Clarke Error Grids, and the percentage of values within 15/20/30% if glucose value >100 mg/dL and 15/20/30 mg/dL if glucose value ≤100 mg/dL. Results: Matched paired glucose values ( N  = 612) from 36 patients (median age 14 years, 58.3% non-Hispanic White, 47.2% male) and 42 inpatient encounters were included in this subanalysis of DKA admissions. The MARDs for DKA and non-DKA admissions ( N  = 503) were 11.8% and 11.7%, with 97.6% and 98.6% of pairs falling within A and B zones of the Clarke Error Grid, respectively. Severe DKA admissions (pH <7.15 and/or bicarbonate <5 mmol/L) had a MARD of 8.9% compared to 14.3% for nonsevere DKA admissions. The MARD during administration of IV insulin ( N  = 266) was 13.4%. Conclusions: CGM accuracy is similar between DKA and non-DKA admissions and is maintained in severe DKA and during IV insulin administration, suggesting potential usability in pediatric hospitalizations. Further study on the feasibility of implementation of CGM in the hospital is needed.

Aim: To determine whether it was feasible, safe and acceptable for ambulance clinicians to use capillary blood ketone meters for 'high-risk' diabetic ketoacidosis (DKA) recognition and fluid initiation, to inform the need for a full-powered, multi-centre trial., Methods: Adopting a stepped-wedge controlled design, participants with hyperglycaemia (capillary blood glucose >11.0 mmol/L) or diabetes and unwell were recruited. 'High-risk' DKA intervention participants (capillary blood ketones ≥3.0 mmol/L) received paramedic-led fluid therapy. Participant demographic and clinical data were collated from ambulance and hospital care records. Twenty ambulance and Emergency Department clinicians were interviewed to understand their hyperglycaemia and DKA care experiences., Results: In this study, 388 participants were recruited (Control: n = 203; Intervention: n = 185). Most presented with hyperglycaemia, and incidence of type 1 and type 2 diabetes was 18.5% and 74.3%, respectively. Ketone meter use facilitated 'high-risk' DKA identification (control: 2.5%, n = 5; intervention: 6.5%, n = 12) and was associated with improved hospital pre-alerting. Ambulance clinicians appeared to have a high index of suspicion for hospital-diagnosed DKA participants. One third (33.3%; n = 3) of Control and almost half (45.5%; n = 5) of Intervention DKA participants received pre-hospital fluid therapy. Key interview themes included clinical assessment, ambulance DKA fluid therapy, clinical handovers; decision support tool; hospital DKA management; barriers to hospital DKA care., Conclusions: Ambulance capillary blood ketone meter use was deemed feasible, safe and acceptable. Opportunities for improved clinical decision making, support and safety-netting, as well as in-hospital DKA care, were recognised. As participant recruitment was below progression threshold, it is recommended that future-related research considers alternative trial designs., Clinicaltrials: gov: NCT04940897., (© 2024 The Author(s). Diabetic Medicine published by John Wiley & Sons Ltd on behalf of Diabetes UK.)

Introduction: There is little published information on type 1 diabetes (T1D) in children in Yemen. We aimed to identify the clinical characteristics, biomarkers and diabetic ketoacidosis (DKA) at diagnosis of T1D among children and adolescents in a diabetes centre in Sana'a, Yemen., Methods: A total of 485 children and adolescents aged ≤18 years diagnosed with T1D during the period 2010-2020 were included in the study. The variables investigated were demographic and clinical characteristics, biomarkers, subtypes of T1D, and the risk factors for severe DKA at diagnosis., Results: At diagnosis, children aged <10 years compared with those aged ≥10 years had higher mean plasma glucose (p<0.001) and mean HbA1c (p=0.026), and lower mean C-peptide (pmol/L) (p=0.019), and a higher frequency of DKA at diagnosis than older children (p<0.001). A majority of the study population (383, 79%) presented in DKA . Children aged <10 years presenting with DKA had significantly longer median appraisal interval (p=0.009) and median total diagnosis interval (p=0.025), and significantly lower mean C-peptide (p=0.001) as compared with their peers without DKA. The prevalence of autoantibody-negative 'idiopathic' T1D was 36 (32%) of the total number tested for autoantibody and familial T1D 61 (12.6%) of all the study population., Conclusion: In Yemen children aged <10 years with new-onset T1D frequently faced the challenge of a delay in diagnosis and treatment initiation, with severe hyperglycaemia and a higher risk of DKA at diagnosis., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The aim of this study was to determine whether diabetes mellitus has a high risk of diabetic ketoacidosis-related complications. Biochemical parameters affect the resolution time of diabetic ketoacidosis., Methods: The present study is based on a retrospective evaluation of the records of patients who presented to the Pediatrics Clinic of Adiyaman University Hospital between January 1, 2017, and October 1, 2022, with a diagnosis ofdiabetic ketoacidosis. The demographic characteristics, serum biochemical parameters, blood gas results, and time to transition to subcutaneous insulin therapy were all recorded., Results: This study included 49 (49%) female and 51 (51%) male patients aged 1-17 years (mean age: 9.05±4.33 years). The average time to clinical improvement of the sample, that is, transition to subcutaneous insulin therapy, was 21.04±7.8 h. An evaluation of the presence of acute kidney injury based on serum urea and creatinine levels and eGFR values revealed no significant effect on the rate of clinical recovery (respective p-values: p=0.076, p=0.494, and p=0.884). A univariate analysis identified blood glucose (p=0.025), blood gas pH (p<0.001), and blood bicarbonate (p=0.004) values as prognostic factors, while a multivariate analysis revealed pH values had an independent and significant effect on the resolution time of diabetic ketoacidosis., Conclusion: Serum glucose, pH, and bicarbonate levels are the most important determinants of clinical prognosis in patients with diabetic ketoacidosis. These findings can serve as a guide for clinicians in the follow-up and treatment of such patients.

Aim: This study aimed to develop and validate a nomogram to predict prolonged diabetes ketoacidosis (DKA) resolution time (DRT)., Methods: We retrospectively extracted sociodemographic, clinical, and laboratory data from the electronic medical records of 394 adult patients with DKA admitted to Tawam Hospital between January 2017 and October 2022. Logistic regression stepwise model was developed to predict DRT ≥ 24 h. Model discrimination was evaluated using C-index and calibration was determined using calibration plot and Brier score., Results: The patients' average age was 34 years; 54 % were female. Using the stepwise model, the final variables including sex, diabetes mellitus type, loss of consciousness at presentation, presence of infection at presentation, body mass index, heart rate, and venous blood gas pH at presentation were used to generate a nomogram to predict DRT ≥ 24 h. The C-index was 0.76 in the stepwise model, indicating good discrimination. Despite the calibration curve of the stepwise model showing a slight overestimation of risk at higher predicted risk levels, the Brier score for the model was 0.17, indicating both good calibration and predictive accuracy., Conclusion: An effective nomogram was established for estimating the likelihood of DRT ≥ 24 h, facilitating better resource allocation and personalized treatment strategy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Use of real-time continuous glucose monitoring (rtCGM) in ambulatory settings improves overall glycemic control and reduces the incidence of diabetic ketoacidosis (DKA) in adults and children/adolescents with type 1 diabetes (T1D). However, the use of rtCGM in children with DKA has not been well studied., Method: This prospective, single-arm, single-center study assessed the accuracy, reliability, and feasibility of a commercially available rtCGM device compared with point-of-care (POC) capillary and serum glucose values in pediatric patients admitted to the pediatric intensive care unit for DKA. The primary outcome was the accuracy of rtCGM glucose values compared with POC capillary and serum glucose values during standard treatment of DKA as assessed by Clarke Error Grid (CEG) analysis. Secondary outcomes were assessment of the relationship between rtCGM readings and degree of acidosis and mean length of hospital stay (LOS)., Results: Data from 35 hospitalized children (mean ± SD age, 11.9 ± 4.1 years) with DKA were included in our analysis. Five hundred twenty-four time-matched glucose values between serum glucose and rtCGM and 91 time-matched glucose values between POC capillary glucose and rtCGM were obtained. The effect of acidosis on accuracy CEG analysis showed 95.4% of the 524 matched CGM/POC pairs and 95.6% of the 91 matched CGM/serum glucose pairs in the clinically acceptable A + B zones. The average LOS was 1.32 ± 0.73 days. Serum bicarbonate level did not appear to affect the accuracy of rtCGM in the setting of DKA., Conclusions: Continuous glucose monitoring use in inpatient pediatric DKA treatment was found to be feasible and reliable., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: This study aimed to investigate the association between blood urea nitrogen to serum albumin ratio (BAR) and the risk of in-hospital mortality in patients with diabetic ketoacidosis., Methods: A total of 3,962 diabetic ketoacidosis patients from the eICU Collaborative Research Database were included in this analysis. The primary outcome was in-hospital death., Results: Over a median length of hospital stay of 3.1 days, 86 in-hospital deaths were identified. One unit increase in LnBAR was positively associated with the risk of in-hospital death (hazard ratio [HR], 1.82 [95% CI, 1.42-2.34]). Furthermore, a nonlinear, consistently increasing correlation between elevated BAR and in-hospital mortality was observed (P for trend =0.005 after multiple-adjusted). When BAR was categorized into quartiles, the higher risk of in-hospital death (multiple-adjusted HR, 1.99 [95% CI, (1.1-3.6)]) was found in participants in quartiles 3 to 4 (BAR≥6.28) compared with those in quartiles 1 to 2 (BAR<6.28). In the subgroup analysis, the LnBAR-hospital death association was significantly stronger in participants without kidney insufficiency (yes versus no, P-interaction=0.023)., Conclusion: There was a significant and positive association between BAR and the risk of in-hospital death in patients with diabetic ketoacidosis. Notably, the strength of this association was intensified among those without kidney insufficiency., 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 © 2024 Chen, Wang, Ji and Li.)

Aims: We investigated the characteristics of infection and the utility of inflammatory markers in diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic syndrome (HHS)., Methods: A multicenter, retrospective observational study in 21 acute-care hospitals was conducted in Japan. This study included adult hospitalized patients with DKA and HHS. We analyzed the diagnostic accuracy of markers including C-reactive protein (CRP) and procalcitonin (PCT) for bacteremia. Multiple regression models were created for estimating bacteremia risk factors., Results: A total of 771 patients, including 545 patients with DKA and 226 patients with HHS, were analyzed. The mean age was 58.2 (SD, 19.3) years. Of these, 70 tested positive for blood culture. The mortality rates of those with and without bacteremia were 14 % and 3.3 % (P-value < 0.001). The area under the curve (AUC) of CRP and PCT for diagnosis of bacteremia was 0.85 (95 %CI, 0.81-0.89) and 0.76 (95 %CI, 0.60-0.92), respectively. Logistic regression models identified older age, altered level of consciousness, hypotension, and higher CRP as risk factors for bacteremia., Conclusions: The mortality rate was higher in patients with bacteremia than patients without it. CRP, rather than PCT, may be valid for diagnosing bacteremia in hyperglycemic emergencies., Trial Registration: This study is registered in the UMIN clinical trial registration system (UMIN000025393, Registered December 23, 2016)., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

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.

Objective: To investigate the predictive value of the blood urea nitrogen to serum albumin ratio for in-hospital and out-of-hospital mortality in critically ill patients with diabetic ketoacidosis., Methods: Data were obtained from the Medical Information Mart for Intensive Care III (MIMIC III) database, and all eligible participants were categorized into two groups based on the BAR cutoff value. Multiple logistic regression analysis was conducted to determine the association between BAR and in-hospital mortality. The Kaplan-Meier (K-M) analysis was performed to evaluate the predictive performance of BAR. Propensity score matching (PSM) was applied to control confounding factors between the low and high BAR groups., Results: A total of 589 critically ill patients with diabetic ketoacidosis were enrolled. Patients with diabetic ketoacidosis with a higher BAR level were associated with higher in- and out-hospital mortality (all p<0.001). A significant 4-year survival difference was observed between the low and high BAR groups (p<0.0001). After PSM analysis, two PSM groups (202 pairs, n=404) were generated, and similar results were observed in the K-M curve (p<0.0001)., Discussion: Elevated BAR levels were associated with an increased risk of in-hospital mortality in critically ill patients with diabetic ketoacidosis, and BAR could serve as an independent prognostic factor in in-hospital and out-of-hospital mortality for patients diagnosed with diabetic ketoacidosis., 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., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial-License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Objectives: The aim of our study was to investigate the changes in thyroid hormone levels during and after acute metabolic disorder in patients with diabetic ketoacidosis (DKA)., Methods: Eighty five patients diagnosed with DKA were included in the study. Patients with control thyroid function test (TFT) values at admission (the first blood sample) and 1 month later were included in the study. Thyroid function tests obtained during diabetic ketoacidosis and at the first month follow-up were compared. Euthyroidism and euthyroid sick syndrome were defined and grouped according to current guidelines. The mild and moderate groups, according to DKA classification, were combined and compared with the severe group., Results: A significant increase was observed between the first admission and the control TFT values 1 month later. However, there was no significant difference found in TFT between mild/moderate and severe groups taken at the time of DKA. Difference between two groups, euthyroid sick syndrome and euthyroid, was examined and the result that was different from the literature was the difference between TSH levels. We found that low FT4 levels were associated with higher HgbA1c, although the correlation was weak., Conclusions: Thyroid hormone levels may not reflect a thyroid disease during severe DKA attack. Therefore, it is unnecessary to check thyroid function tests., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

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 &lt; 0.001). In terms of clinical severity of DKA, pH, and HCO3 levels were lower during the pandemic period (p &lt; 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 &lt; 0.001), especially in the second year of the pandemic (p &lt; 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 &lt; 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., (© 2024 S. Karger AG, Basel.)

Sodium-glucose cotransporter-2 inhibitors (SGLT2i) are a class of oral glucose-lowering agents commonly used for the treatment of type 2 diabetes. With increased use, there has been an increase in the incidence of the rare but life-threatening complication of euglycemic diabetic ketoacidosis. A common but underappreciated precipitant is colonoscopy. In this work, we outline the pathophysiology of the interaction between colonoscopy and SGLT2i use, the evidence regarding SGLT2i use in the periprocedural setting and Australian Diabetes Society guidelines., (Copyright © 2022 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.)

Abstract: Glycosylated hemoglobin (HbA1c) reflects how well blood glucose is controlled and is one of the strongest predictors of chronic complications of diabetes mellitus. The degree of acidosis helps determine the severity of diabetic ketoacidosis (DKA) (mild: pH 7.2-7.3; moderate: pH 7.1-7.2; severe: pH <7.1) and guides the level of care and predicts outcome. Many studies have implicated that higher HbA1c levels lead to recurrent DKA. However, there is no description of the association of higher HbA1c with the severity of DKA. One hundred thirty-eight electronic medical records of patients aged 1 to 21 years admitted to the pediatric intensive care unit with DKA between 2011 and 2015 were analyzed. We excluded 50 patients because the HbA1c level was not available. Spearman correlation analyzed the data for 88 patients included in the study. The mean HbA1c was 13.3, with female patients having more admissions compared with male patients (58% vs 42%). The age group from 13 to 21 years accounted for 77.3% of the patients. The duration of type 1 diabetes mellitus did not affect the HbA1c level. Likewise, the blood glucose and serum creatinine level did not show a statistical correlation with blood pH levels. Mean HbA1c for mild, moderate, and severe DKA groups were 11.4%, 12.2%, and 14.8%, respectively. Blood pH and HbA1c returned a negative correlation (correlation coefficient, -0.557; P = 0.005). The HbA1c level correlated positively with the 3 groups of DKA (correlation coefficient, 0.595; P = 0.01). A higher A 1c was associated with more severe DKA., Competing Interests: Disclosure: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The aim of this study was to determine the differences in biochemical parameters and diabetic ketoacidosis (DKA) severity in adult patients with type 1 and type 2 diabetes and utilization of serum BHB as a biomarker for DKA resolution was also evaluated., Materials and Methods: This prospective observational study of type 1 or type 2 diabetes mellitus who were diagnosed with DKA between 01 October 2018 and 30 September 2020. The correlations between serum BHB, measured by the Ranbut assay, and pH, bicarbonate, and anion gap were examined., Results: A total of 99 diabetes patients were diagnosed with DKA (mean age 39.4 years, 63.4% female, 53.6% T2DM). while infection was the most common precipitating factor in T2DM (43.4%), non-compliance with treatment was the most common precipitating factor in T1DM (43.5%). T1DM patients had more severe DKA more hypokalemia during treatment. However, there was no significant difference in mortality between type1 and type2 diabetes. The initial laboratories evaluation of patients did not significant differ between type1 and type2 diabetes. Serum BHB during treatment of DKA was significantly correlated with changes in serum bicarbonate (r = - 0.64), serum anion gap (r = 0.84), and venous pH (r = - 0.6). The serum BHB levels corresponding to HCO 3 levels for DKA severity were 4.5, 5.7, and 5.9 mmol/L in mild, moderate, and severe DKA, respectively. The serum BHB level of < 1 mmol/L had 73.7% sensitivity and 100% specificity to predict DKA resolution. Median time to resolution of DKA was 12 h with an optimized BHB cut-off value of < 1 mmol/L. There were no significant difference in time to resolution of DKA in the patients with type 1 and type 2 diabetes., Conclusions: There are no differences in DKA-related biochemical parameters between type 1 and type 2 diabetes patients. The present findings suggest that DKA should be assessed and treated similarly, regardless of its occurrence in type 1 or type 2 diabetes patients., (© 2021. The Author(s).)

Abstract: To explore the effects of nutritional support combined with insulin therapy on serum protein, procalcitonin (PCT), C-reactive protein (CRP), tumor necrosis factor-α (TNF-α), pentraxin-3 (PTX-3), and serum amylase (AMS) levels in patients with diabetic ketoacidosis complicated with acute pancreatitis.A total of 64 patients with diabetic ketoacidosis complicated with acute pancreatitis admitted to our hospital from January 2018 to February 2019 were enrolled in this prospective study. They were divided into the study group and the control group according to the random number table method, with 32 patients in each group. Patients in the study group were given nutritional support combined with insulin therapy, and patients in the control group were given insulin therapy.There were no significant differences in general data including age, gender, body mass index, course and type of diabetes, acute physiology and chronic health evaluation II, RANSON, CT grades between the 2 groups before treatment (all P > .05). After 7 days of treatment, the clinical efficacy of the study group was significantly higher than that of the control group (study group vs control group, 94.44% vs 75.00%, P < .05). After 7 days of treatment, the levels of prealbumin and albumin in the study group were significantly higher than those in the control group (P < .05). After 7 days of treatment, the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the 2 groups were significantly lower than those before treatment (P < .05), and the levels of PCT, CRP, TNF-α, PTX-3, and AMS in the study group were significantly lower than those in the control group. After 7 days of treatment, the levels of IgG, IgM, and IgA in the 2 groups were significantly higher than those before treatment, and the levels of IgG, IgM, and IgA in the study group were significantly higher than those in the control group (P < .05).Nutritional support combined with insulin is obviously effective in the treatment of diabetic ketoacidosis complicated with acute pancreatitis, which can improve serum protein levels, reduce inflammatory response, improve immune function, and is worthy of clinical application., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To compare patients with DKA, hyperglycaemic hyperosmolar syndrome (HHS), or mixed DKA-HHS and COVID-19 [COVID (+)] to COVID-19-negative (-) [COVID (-)] patients with DKA/HHS from a low-income, racially/ethnically diverse catchment area., Methods: A cross-sectional study was conducted with patients admitted to an urban academic medical center between 1 March and 30 July 2020. Eligible patients met lab criteria for either DKA or HHS. Mixed DKA-HHS was defined as meeting all criteria for either DKA or HHS with at least 1 criterion for the other diagnosis., Results: A total of 82 participants were stratified by COVID-19 status and type of hyperglycaemic crisis [26 COVID (+) and 56 COVID (-)]. A majority were either Black or Hispanic. Compared with COVID (-) patients, COVID (+) patients were older, more Hispanic and more likely to have type 2 diabetes (T2D, 73% vs 48%, p  < .01). COVID(+) patients had a higher mean pH (7.25 ± 0.10 vs 7.16 ± 0.16, p  < .01) and lower anion gap (18.7 ± 5.7 vs 22.7 ± 6.9, p  = .01) than COVID (-) patients. COVID (+) patients were given less intravenous fluids in the first 24 h (2.8 ± 1.9 vs 4.2 ± 2.4 L, p  = .01) and were more likely to receive glucocorticoids (95% vs. 11%, p  < .01). COVID (+) patients may have taken longer to resolve their hyperglycaemic crisis (53.3 ± 64.8 vs 28.8 ± 27.5 h, p  = .09) and may have experienced more hypoglycaemia <3.9 mmol/L (35% vs 19%, p  = .09). COVID (+) patients had a higher length of hospital stay (LOS, 14.8 ± 14.9 vs 6.5 ± 6.0 days, p  = .01) and in-hospital mortality (27% vs 7%, p  = .02)., Discussion: Compared with COVID (-) patients, COVID (+) patients with DKA/HHS are more likely to have T2D. Despite less severe metabolic acidosis, COVID (+) patients may require more time to resolve the hyperglycaemic crisis and experience more hypoglycaemia while suffering greater LOS and risk of mortality. Larger studies are needed to examine whether differences in management between COVID (+) and (-) patients affect outcomes with DKA/HHS.

Background: Hyperosmolar diabetic ketoacidosis (H-DKA), a distinct clinical entity, is the overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS)., Aim: We describe the clinical presentation, metabolic aberrations, and associated morbidity/mortality of these cases with H-DKA. We highlight the problem areas of medical care which require particular attention when caring for pediatric diabetes patients presenting with H-DKA., Methods: In our study we reviewed the literature back to 1963 and retrieved twenty-four cases meeting the criteria of H-DKA: glucose >600 mg/dL, pH < 7.3, bicarbonate <15 mEq/L, and serum osmolality >320 mOsm/kg, while adding three cases from our institution., Results: Average age of presentation of H-DKA was 10.2 years ± 4.5 years in females and 13.3 years ± 4 years in males, HbA1c was 13%. Biochemical parameters were consistent with severe dehydration: serum osmolality = 394.8±55 mOsm/kg, BUN = 48±22 mg/dL, creatinine = 2.81±1.03 mg/dL. Acute kidney injury, present in 12 cases, was the most frequent end-organ complication., Conclusion: Multi-organ involvement with AKI, rhabdomyolysis, pancreatitis, neurological and cardiac issues such as arrhythmias, are common in H-DKA. Aggressive fluid management, insulin therapy and supportive care can prevent acute and long term adverse outcomes in children and adolescents., Competing Interests: Declaration of competing interest There was no potential conflict of interest, real or perceived in the [1] study design [2]; the collection, analysis, and interpretation of data [3]; the writing of the report; and [4] the decision to submit the paper for publication. There was for no study sponsor involved in this study. The authors have no financial disclosures pertaining to this manuscript., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Objectives: Diabetic ketoacidosis (DKA) is typically characterized by low or low-normal serum sodium concentrations, which rise as hyperglycemia resolves. In retrospective studies, researchers found associations between declines in sodium concentrations during DKA and cerebral injury. We prospectively investigated determinants of sodium concentration changes and associations with mental status alterations during DKA., Methods: Using data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis Trial, we compared children who had declines in glucose-corrected sodium concentrations with those who had rising or stable concentrations. Children were randomly assigned to 1 of 4 intravenous fluid protocols that differed in infusion rate and sodium content. Data from the first 4, 8, and 12 hours of treatment were analyzed for 1251, 1086, and 877 episodes, respectively., Results: In multivariable analyses, declines in glucose-corrected sodium concentrations were associated with higher sodium and chloride concentrations at presentation and with previously diagnosed diabetes. Treatment with 0.45% (vs 0.9%) sodium chloride fluids was also associated with declines in sodium concentration; however, higher rates of fluid infusion were associated with declines in sodium concentration only at 12 hours. Frequencies of abnormal Glasgow Coma Scale scores and clinical diagnoses of cerebral injury were similar in patients with and without declines in glucose-corrected sodium concentrations., Conclusions: Changes in glucose-corrected sodium concentrations during DKA treatment are influenced by the balance of free-water loss versus sodium loss at presentation and the sodium content of intravenous fluids. Declines in glucose-corrected sodium concentrations are not associated with mental status changes during treatment., Competing Interests: POTENTIAL CONFLICTS OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose., (Copyright © 2021 by the American Academy of Pediatrics.)

Objective: Delayed treatment for new-onset diabetes Type 1 (T1D) can lead to diabetic ketoacidosis (DKA) with potentially devastating consequences. This prospective observational study aimed to characterize pediatric patients with DKA at hospital admission, regarding parental awareness of diabetes-related symptoms and delayed referrals from primary health care providers to pediatric emergency wards., Research Design and Methods: Patients 0-18 years admitted to hospital with new-onset T1D and DKA between 2015 and 2017 were invited to participate. Questionnaires were filled out separately by the caregivers and by the attending hospital staff. Data from the Swedish National Diabetes Registry (SWEDIABKIDS) were used for comparison. Delayed referral was defined as a primary healthcare contact due to diabetes-related symptoms 0-4 weeks before hospital admission without immediate referral, or registered elevated glucose levels at primary healthcare centers without immediate referral., Results: The study included 237 patients, among which parental suspicion of new-onset diabetes before healthcare contacts was reported in 39%. Parental suspicion of diabetes was associated with higher pH values at diagnosis. Patients in contact with primary health care providers before hospital admission had a delayed referral in 43% of the cases. Delayed referral was associated with lower pH values at hospital admission. Symptoms leading to primary healthcare contacts were similar regardless of whether delay occurred or not., Conclusions: Parental suspicion of diabetes was associated with milder DKA at hospital admission. Delayed referral was seen in a considerable proportion of children with primary healthcare contacts for symptoms associated with diabetes. Increased awareness of diabetes symptoms is of paramount importance., (© 2021 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Aims: To identify risk factors for recurrent episodes of DKA that may allow the development of an effective prevention strategies., Methods: Retrospective analysis of admissions for DKA in adult patients between 2004, and 2017 in a tertiary hospital. The clinical characteristics and outcomes of DKA of patients were stratified into an isolated episode of DKA (group 1) and recurrent episodes (group 2)., Results: 385 patients were included in the study, 281 had a single admission of DKA, and 104 had recurrent admissions. There were no statistically significant differences between the two groups in demographic or clinical variables. Patients in the recurrent DKA group had a younger age at diabetes diagnosis, 32.1 ± 17.08 vs. 36.13 ± 19.52 (p = 0.05). Patients with A1C greater than 9.0% were associated with recurrent DKA in cox regression analysis (HR 2.023; 95% Cl 1.112-3.679; p = 0.021). Recurrent DKA was a significant predictor of one-year mortality in cox regression analysis (HR 0.172; 95% CI 0.04-0.742; p = 0.018)., Conclusion: High A1C levels, which account for poorly controlled diabetes, was identified as the strongest predictor of recurrent DKA. This patient population warrants particular attention and the development of intervention strategies in further studies., Competing Interests: Declaration of competing interest All the authors declare that there is no potential duality of interest associated with this manuscript. No financial support, political or academic pressures affected this study., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

When stable and near-normoglycemic, patients with "A-β+" ketosis-prone diabetes (KPD) manifest accelerated leucine catabolism and blunted ketone oxidation, which may underlie their proclivity to develop diabetic ketoacidosis (DKA). To understand metabolic derangements in A-β+ KPD patients during DKA, we compared serum metabolomics profiles of adults during acute hyperglycemic crises, without ( n = 21) or with ( n = 74) DKA, and healthy control subjects (n = 17). Based on 65 kDa GAD islet autoantibody status, C-peptide, and clinical features, 53 DKA patients were categorized as having KPD and 21 type 1 diabetes (T1D); 21 nonketotic patients were categorized as having type 2 diabetes (T2D). Patients with KPD and patients with T1D had higher counterregulatory hormones and lower insulin-to-glucagon ratio than patients with T2D and control subjects. Compared with patients withT2D and control subjects, patients with KPD and patients with T1D had lower free carnitine and higher long-chain acylcarnitines and acetylcarnitine (C2) but lower palmitoylcarnitine (C16)-to-C2 ratio; a positive relationship between C16 and C2 but negative relationship between carnitine and β-hydroxybutyrate (BOHB); higher branched-chain amino acids (BCAAs) and their ketoacids but lower ketoisocaproate (KIC)-to-Leu, ketomethylvalerate (KMV)-to-Ile, ketoisovalerate (KIV)-to-Val, isovalerylcarnitine-to-KIC+KMV, propionylcarnitine-to-KIV+KMV, KIC+KMV-to-C2, and KIC-to-BOHB ratios; and lower glutamate and 3-methylhistidine. These data suggest that during DKA, patients with KPD resemble patients with T1D in having impaired BCAA catabolism and accelerated fatty acid flux to ketones-a reversal of their distinctive BCAA metabolic defect when stable. The natural history of A-β+ KPD is marked by chronic but varying dysregulation of BCAA metabolism., (© 2021 by the American Diabetes Association.)

Background: Diabetes is a risk factor for poor COVID-19 outcomes, but pediatric patients with type 1 diabetes are poorly represented in current studies., Methods: T1D Exchange coordinated a US type 1 diabetes COVID-19 registry. Forty-six diabetes centers submitted pediatric cases for patients with laboratory confirmed COVID-19. Associations between clinical factors and hospitalization were tested with Fisher's Exact Test. Logistic regression was used to calculate odds ratios for hospitalization., Results: Data from 266 patients with previously established type 1 diabetes aged <19 years with COVID-19 were reported. Diabetic ketoacidosis (DKA) was the most common adverse outcome (n = 44, 72% of hospitalized patients). There were four hospitalizations for severe hypoglycemia, three hospitalizations requiring respiratory support (one of whom was intubated and mechanically ventilated), one case of multisystem inflammatory syndrome in children, and 10 patients who were hospitalized for reasons unrelated to COVID-19 or diabetes. Hospitalized patients (n = 61) were more likely than nonhospitalized patients (n = 205) to have minority race/ethnicity (67% vs 39%, P < 0.001), public insurance (64% vs 41%, P < 0.001), higher A1c (11% [97 mmol/mol] vs 8.2% [66 mmol/mol], P < 0.001), and lower insulin pump and lower continuous glucose monitoring use (26% vs 54%, P < 0.001; 39% vs 75%, P < 0.001). Age and gender were not associated with risk of hospitalization. Higher A1c was significantly associated with hospitalization, with an odds ratio of 1.56 (1.34-1.84) after adjusting for age, gender, insurance, and race/ethnicity., Conclusions: Higher A1c remained the only predictor for hospitalization with COVID-19. Diabetic ketoacidosis is the primary concern among this group., (© 2021 Ruijin Hospital, Shanghai JiaoTong University School of Medicine and John Wiley & Sons Australia, Ltd.)

Aims: The aim was to systematically review the efficacy and safety of sodium-glucose cotransporter inhibitor (SGLT2i) as an adjunct to insulin at different follow-up durations in randomized, double-blind clinical trials in patients with type 1 diabetes., Methods: We conducted a search on Medline, Embase, and the Cochrane Library for relevant studies published before May 2020. According to the duration of follow-up, the subgroup analysis included four periods: 1-4, 12-18, 24-26, and 52 weeks. In the five trials included both 24-26 and 52 weeks of follow-up, we compared the efficacy by the placebo-subtracted difference and changes in SGLT2i groups., Results: Fifteen trials including 7109 participants were analyzed. The combination of SGLT2i and insulin improved hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), daily insulin dose, body weight, and blood pressure, which varied greatly by different follow-ups. Compared with %HbA1c at 24-26 weeks, placebo-subtracted differences and changes in the SGLT2i groups slightly increased. SGLT2i plus insulin treatment showed no difference in the occurrence of urinary tract infections (UTIs), hypoglycemia, or severe hypoglycemia but increased the risk of genital tract infections (GTIs) in a duration-dependent manner. SGLT2i treatment was associated with a significantly higher rate of ketone-related SAEs and diabetic ketoacidosis (DKA) at 52 weeks., Conclusion: SGLT2i as an add-on therapy to insulin improved glycemic control and body weight and decreased the required dose of insulin without increasing the risk of hypoglycemia. However, after 6 months the benefits of SGLT2is on glycemic control may weaken and the risks of GTIs and DKA increased.

Background: This study aims to explore the correlation between procalcitonin (PCT), 25-hydroxyvitamin D3 (25(OH)D), pentraxin-3 (PTX-3), amylase (AMS) levels and severity of diabetic ketoacidosis complicated by pancreatitis., Methods: A retrospective analysis of 198 patients with diabetic ketoacidosis admitted to our hospital from January 2015 to February 2020 were included. According to whether the patients with pancreatitis, subjects were divided into diabetic ketoacidosis with pancreatitis (DKA-AP) group and diabetic ketoacidosis (DKA) group. Healthy controls admitted to the hospital for physical examinations were included as a control group. Clinical outcomes were collected., Results: On the first day after admission, the levels of PCT, PTX-3, and AMS in DKA-AP group were significantly higher than those in DKA group and control group, and 25(OH)D levels in DKA-AP group were lower than those in DKA group and control group. PCT, PTX-3, and AMS levels were significantly increased, and 25(OH)D levels were decreased in the DKA group compared with the control group. Furthermore, the levels of PCT, 25(OH)D, PTX-3, and AMS in the DKA-AP group were correlated with the disease severity of of diabetic ketoacidosis complicated by pancreatitis. The levels of PCT, PTX-3, and AMS in the DKA-AP group on day 1 were significantly higher and 25(OH)D levels were significantly lower than those on days 3-7 after admission. The levels of PCT, PTX-3, and AMS in the DKA group on day 1 were significantly higher and 25(OH)D levels were significantly lower than those on days 2-7 after admission. The levels of these indicators returned to normal levels on day 3 or day 7 in DKA or DKA-AP group, respectively. PCT, PTX-3, and AMS levels in the DKA-AP group were significantly increased, while 25(OH)D levels in the DKA-AP group were decreased compared with DKA group on days 1-6 after admission. The duration of hospital stay, patients of ICU care, duration of ICU stay, and cost in DKA-AP group were all higher than those in the DKA group., Conclusion: Blood levels of PCT, 25(OH)D, PTX-3, and AMS were correlated with diabetic ketoacidosis complicated by pancreatitis, and have certain application value in assessment of the disease severity.

Background: The hallmark of type 1 diabetes (T1D) is an absolute lack of insulin. However, many studies showed a tendency to heterogeneity in TID. We aimed to investigate the demographic and clinical characteristics in T1D and the differences in young-onset and adult-onset patients., Methods: This retrospective study was conducted among 1943 patients with clinically diagnosed T1D. Medical records on patients' demographics, anthropometric measurements, and clinical manifestation were collected. According to the age at onset, the newly diagnosed patients were divided into the young-onset group (< 18 years, 234 patients, mean age 11 years) and adult-onset group (≥ 18 years, 219 patients, mean age 27 years). Pancreatic β-cell function was assessed by fasting C-peptide (FCP) and 2-h C-peptide (2-h CP)., Results: The median age of patients at disease onset was 22 years. The median duration of patients was 3 years. The overall median glycated hemoglobin (HbA1c) value was 10.3 % [89(mmol/mol)]. The prevalence of diabetic retinopathy was 25.1 %. The overall rate of DKA at onset in the new-onset patients was 59.6 %. The frequency of overall dyslipidemia was 37.8 %. The most frequent dyslipidemia was low high-density lipoprotein-cholesterol (HDL) (29 %). The proportion of patients with anti-glutamic acid decarboxylase (GADA), insulin antibody (IAA) and islet cell antibody (ICA) were 28.1 %, 6.4 % and 21.6 %, respectively. The mean HbA1c showed a downward trend with age. Increasing or decreasing trends of overweight and obesity in this population during the period 2012 to 2018 was not found. Compared with young-onset T1D, adult-onset patients comprised better islet function (FCP: 0.4 vs. 0.3 ng/ml, P < 0.001; 2-h CP: 0.9 vs. 0.7 ng/ml P < 0.001, respectively) and glycemic control [12.9 % (117mmol/mol) vs. 11.7 % (104mmol/mol), P < 0.001], higher prevalence of diabetes condition in the male gender (64.4 % vs. 51.3 %, P = 0.006), higher proportion of obesity or overweight (24.6 % vs. 9.5 %, P = 0.002), higher frequency of GADA (33.7 % vs. 23.3 %, P = 0.025), and lower frequency of diabetic ketoacidosis at disease onset (64.5 % vs. 43.5 %, P < 0.001)., Conclusions: This population was characterized by poor overall blood glucose control, high prevalence of DKA, dyslipidemia and diabetic retinopathy, and low prevalence of islet-related antibodies, and overweight or obesity. Adult-onset patients with T1D were not uncommon and had better clinical manifestations than young-onset patients. Any findings related to body mass index (BMI) and autoantibodies should be considered strictly exploratory due to excessive missing data.

Introduction: Differences in biochemical parameters of diabetic ketoacidosis in patients with end-stage kidney disease (ESKD) has not been established. Accordingly, we assessed the relationship between degree of metabolic acidosis and ß-hydroxybutyrate in patients with ESKD (eGFR < 15 mL/min/1.73 m2), moderate renal failure (eGFR 15-60), or preserved renal function (eGFR > 60)., Methods: This observational study included adults (18-80 years) with diabetes ketoacidosis (DKA), admitted to Emory University Hospitals between January 1, 2006 to December 31, 2016. DKA and renal stages were confirmed on admission laboratory values., Results: Admission bicarbonate levels (13.9 ± 5 vs 13.4 ± 5.3 vs 13.8 ± 4.2 mmol/L, P = 0.7), and pH levels (7.2 ± 0.3 vs 7.2 ± 0.2 vs 7.2 ± 0.2, P = 0.8) were similar among groups. Patients with ESKD had lower mean ß-hydroxybutyrate level (4.3 ± 3.3 vs 5.6 ± 2.9 vs 5.9 ± 2.5 mmol/L, P = 0.01), but higher admission glucose (852 ± 340.4 vs 714.6 ± 253.3 mg/dL vs 518 ± 185.7 mg/dL, P < 0.01), anion gap (23.4 ± 7.6 vs 23 ± 6.9 vs 19.5 ± 4.7 mmol/L, P < 0.01), and osmolality (306 ± 20.6 vs 303.5 ± vs 293.1 ± 3.1mOsm/kg, P < 0.01) compared with patients with moderate renal failure and preserved renal function, respectively. The sensitivity of ß-hydroxybutyrate > 3 mmol/L for diagnosing DKA by bicarbonate level < 15 and <18 mmol/L was 86.9% and 72% in ESKD, 89.3% and 83.7% in moderate renal failure, and 96.2% and 88.3% in preserved renal function. In patients with ESKD, the corresponding ß-hydroxybutyrate with bicarbonate levels < 10, 10-15, <18 mmol/L were 5.5, 3.9, 3.0 mmol/L, respectively., Conclusions: Significant metabolic differences were found among DKA patients with different levels of renal function. In patients with ESKD, a ß-hydroxybutyrate level > 3 mmol/L may assist with confirmation of DKA diagnosis., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Purpose: To investigate the features and treatment status of children with type 1 diabetes mellitus (T1DM) in China., Methods: We recruited patients <14 years of age with T1DM from 33 medical centers in 25 major cities of China between January 2012 and March 2015. All patients completed a questionnaire that was conducted by their pediatric endocrinologists at all centers., Results: A total of 1,603 children (755 males and 848 females) with T1DM participated in this survey. Of these, 834 (52.03%) of the patients exhibited diabetic ketoacidosis (DKA) at onset, while 769 patients (47.97%) did not exhibit DKA (non-DKA) at onset. There was a higher proportion of females (55.71%) in the cohort of patients exhibiting DKA at onset than in the non-DKA cohort (49.33%). The mean age of patients exhibiting DKA at presentation was 7.12 ± 0.14 years; this was significantly younger than that in non-DKA group (7.79 ± 0.15 years; P < 0.005). The frequency of DKA in 3 years old, 3-7 years old, and 7 years old or more was 77.21%, 26.17%, and 37.62%, respectively. Upon initial diagnosis, 29.4%, 15.2% and 11.8% of patients showed positivity for glutamic acid decarboxylase antibody (GADA), Insulin autoantibodies (IAA), or islet cell antibody (ICA), respectively. During six months follow-up, 244 patients (15.21%) reported receiving insulin pump therapy, and more than 60% of patients monitored their blood glucose levels less than 35 times per week. Although the majority of patients had no problems with obtaining insulin, 4.74% of the children surveyed were not able to receive insulin due to financial reasons, a shortage of insulin preparations, or the failure of the parents or guardians to acquire the appropriate medicine., Conclusion: DKA is more common in very young children. Treatment and follow-up of T1DM in China still face very serious challenges., 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 © 2021 Hou, Li, Liu, Wei, Xiong, Du, Yang, Zhang, Zhang, Yao, Fu, Yan, Cui, Liu, Li, Chen, Li, Xin, Liang, Yu, Dong, Chen, Ma, Cheng, Luo, Gong, Song, Chen, Zhang, Peng, Li, Liang, Maimaiti, Cheung and Luo.)

Background: Diabetic ketoacidosis (DKA) is a major acute metabolic complication of type I diabetes mellitus but may occur in type II diabetes during severe stressful conditions., Aim: The aim of this study was to describe the clinical profile of DKA patients admitted to the National Diabetes and Endocrine Center in Tripoli, Libya, during 2015., Patients and Methods: The profiles of 490 patients admitted with DKA were retrospectively studied. All the data was collected from the patient files., Results: Most of the patients (91.6%) were admitted to the intensive care unit. The mean age was 35.9 years. DKA was more common among young males with type I diabetes. The average duration of diabetes disease of the patient when admitted with DKA was 16.8 ± 8.2 years. The frequencies of patients admitted with mild, moderate or severe diabetic ketoacidosis were 49.8%, 32.7% and 17.8%, respectively. The most frequent causes of admission were insulin omission (21.8%), infection (20.2%), and wrong dose (11%). The cause of DKA was not known for 29.8% of the patients. DKA was more common among young males, and the rate increased with longer duration of the condition. Most of the patients (93.1%) were discharged in good health, and mortality was 0.6%., Conclusion: Males and patients with a long duration of diabetes disease are more prone to develop DKA. The common causes of DKA were unknown in our study; however, admission of individuals with less serious illness, insulin omission, and infection may contribute to the development of DKA., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Rationale: Diabetic ketoacidosis (DKA) can cause several complications. Among them, cardiac complications are the most fatal and difficult to detect. Cardiac markers are prognostic factors for morbidity and mortality in adult patients with DKA. But, there have been very few discussed cases in pediatrics. We report a case of severe DKA in child with elevated cardiac enzymes and prolonged QT interval., Patient Concerns: A 12-year-old girl admitted by nausea, vomiting, and lethargy for 1 day., Diagnoses: Her blood sugar level was initially undetectable by the capillary blood glucose meter, and blood gas analysis showed severe DKA with elevated cardiac enzymes and prolonged QT interval., Interventions: The patient was admitted to hospital and intensive intravenous fluid and regular insulin infusion were administered., Outcomes: After 5 days of supportive care, the patient was fully recovered, discharged, and followed up in an outpatient clinic., Lessons: Since the relationship between DKA and myocardial injury has not been clearly elucidated, pediatricians and emergency physicians should remain careful throughout the recovery time as it can lead to life-threatening conditions in various courses., Competing Interests: The authors have no funding and conflicts of interests to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Background and Aims: Diabetic ketoacidosis (DKA) treatment guidelines recommend to initiate potassium-replacement when serum potassium (S K ) drops within normal range, and to withhold insulin if S K is below normal. Despite strict recommendations, hypokalemia is frequently observed in DKA., Methods: Scientific literature was thoroughly searched to find 1) DKA treatment guidelines, 2) studies reporting hypokalemia in DKA, 3) and literature elaborating mechanisms involved in hypokalemia., Results: Acidosis affects S K and its regulators including insulin, catecholamines and aldosterone. Current conceptual framework is an argument to gauge the degree of hypokalemia before it strikes DKA patients utilizing S K level after adjusting it with pH. Suggested approach will reduce hypokalemia risk and its associated complications. The nomogram calculates pH-adjusted potassium and expected potassium loss. It also ranks hypokalemia associated risk, and proposes the potassium-replacement rate over given time period. The differences between current DKA treatment guidelines and proposed strategy are also discussed. Moreover, reasons and risk of hyperkalemia due to early initiation of potassium replacement and remedial actions are debated., Conclusion: In light of proposed strategy, utilizing the nomogram ensures reduced incidence of hypokalemia in DKA resulting in improved clinical and patient outcomes. Pharmacoeconomic benefits can also be expected when avoiding hypokalemia ensures early discharge., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Background: Diabetes Mellitus (DM) is a metabolic disorder associated with acute and chronic complications. Diabetic ketoacidosis (DKA) is the most serious diabetic emergency in patients with type one and type two diabetes mellitus. It is the leading cause of mortality in children and young adults. Even though the burden of DKA has increased, no research has been conducted on the determinants of Diabetes ketoacidosis in Ethiopia, particularly in the Amhara region. Thus, this study aimed to identify the determinants of diabetes Ketoacidosis among Diabetes Mellitus patients at North Wollo and Waghimra Zone public Hospitals., Methods: An institution-based unmatched case-control study design was employed among 408 patients at North Wollo and Waghimra Zone Public Hospitals from March 1st to April 30th, 2020. A consecutive sampling method was used to select study participants. The data were collected using structured interviewer-administered questioners and reviewing of patient charts. The analysis was done using a binary logistic regression model. Then, P-value < 0.05 was considered statistically significant., Result: The mean (±SD) age of the study participants was 46.96 (± 15.175 SD) years. Irregular follow-up in diabetes clinic (AOR:4.19, 95% CI: 2.28-7.71), not received diabetic education (AOR: 2.87, 95% CI:1.44-5.72), alcohol drinking (AOR:2.99, 95% CI: 1.46-6.12), discontinuation of medications (AOR: 4.31, 95% CI:1.92-9.68), presence of comorbidity (AOR:2.57, 95% CI: 1.37-4.84), and being type one of diabetes mellitus (AOR: 2.01, 95% CI:1.11-3.63) were determinant factors of diabetic ketoacidosis ., Conclusions: This study showed that the behavioral and clinical characteristics of diabetic patients were determinant factors of DKA. Follow-up in the diabetic clinic, diabetic education, discontinuation of medications, alcohol drinking, presence of comorbidities, and type of diabetes mellitus were independent determinants of diabetic ketoacidosis.

Objective: We conducted this study to investigate whether the COVID-19 pandemic impacted the rate of DKA and previously identified risk factors in children presenting with T1D., Methods: We performed an extension of a retrospective analysis of all paediatric patients (age ≤ 18) newly diagnosed with T1D within a tertiary care referral centre between 01/01/2017 and 09/14/2020. Demographics, insurance coverage and clinical documents 30 days before their T1D diagnosis were abstracted to assess for symptoms at diagnosis, laboratory values (blood glucose, HbA 1c , venous pH and bicarbonate) and any healthcare encounters within 30 days of their diagnosis of T1D., Results: 412 patients with T1D [171 F:241 M; 370 pre-COVID era:42 post-COVID era] were included. The percentages of DKA diagnoses at admission were very similar between the pre-COVID and post-COVID groups (47% vs. 48%), as were the severity (13% vs. 14% mild DKA; 33% vs. 31% moderate or severe DKA)., Conclusion: There were no fluctuations in the rate of DKA among paediatric patients newly diagnosed with T1D throughout the coronavirus pandemic in central Pennsylvania., Competing Interests: No authors report a conflict of interest., (© 2021 The Authors. Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background: Diabetic ketoacidosis (DKA) is a medical emergency with a high mortality rate and is associated with severe metabolic acidosis and dehydration. DKA patients have an increased risk of arterial and venous thromboembolism, however little is known about this metabolic derangement in the first 24 hours of admission and to assess its effect on coagulation. We therefore utilised a novel functional marker of clot microstructure (fractal dimension - df) to assess these changes within the first 24 hours., Methods: Prospective single centre observational study to demonstrate whether the tendency of blood clot formation differs in DKA patients., Results: 15 DKA patients and 15 healthy matched controls were recruited. Mean df in the healthy control group was 1.74±0.03. An elevated df of 1.78±0.07 was observed in patients with DKA on admission. The mean pH on admission was 7.14±0.13 and the lactate was 3.6±2.0. df changed significantly in response to standard treatment and was significantly reduced to 1.68±0.09 (2-6& h) and to 1.66±0.08 at 24& h (p < 0.01 One-way ANOVA). df also correlated significantly with lactate and pH (Pearson correlation coefficient 0.479 and -0.675 respectively, p < 0.05)., Conclusions: DKA patients at presentation have a densely organising less permeable thrombogenic clot microstructure as evidenced by high df. These structural changes are due to a combination of dehydration and a profound metabolic acidosis, which was reversed with treatment. These changes were not mirrored in standard clinical markers of thromboge-nicity.

Competing Interests: Declaration of competing interest No potential conflict of interest relevant to this article was reported.

Background: Diabetic ketoacidosis (DKA) is potentially a lethal complication of uncontrolled, especially type 1, diabetes. Understanding the mechanisms underlying adipokine involvement in the regulation of glucose metabolism is important to prevent complications of hyperglycemia. The role of novel adipokines during DKA in human remains unclear., Method: The method is to determine the changes in the circulating levels of adiponectin, visfatin, and omentin after treating DKA in the patients referred to Shohadaye Khalij-e-Fars hospital at the Bushehr University of Medical Sciences. Measuring adipokines (adiponectin, visfatin, and omentin) in 31 patients with DKA who are admitted in Shohadaye Khalij-e-Fars hospital at the Bushehr University of Medical Sciences. Adipokines are measured at the time of admission and after recovery from DKA, using ELISA method., Results: After recovery from DKA, omentin-1 serum concentration decreased significantly (from 183 to 165), but adiponectin and visfatin did not change significantly., Conclusion: Omentin-1 may play a significant role in insulin resistance during the DKA and could be potentially recommended as a marker of recovery in DKA.

Aim: Diabetic ketoacidosis is a hyperglycaemic emergency that is often treated in intensive care units (ICUs) despite having a low mortality and good prognosis. Current risk stratification is based primarily on acidosis, but it has been suggested that hyperosmolarity may also be an important marker of increased severity. Our aim was to evaluate the relationship between raised serum osmolarity and adverse clinical outcomes in ICU admissions for ketoacidosis., Methods: Retrospective review of prospectively collected data for adult admissions with ketoacidosis in the Australian and New Zealand Intensive Care Society Adult Patient Database over a 15-year period (2004-2018). Exclusions were readmissions and records with critical missing data. Serum hyperosmolarity was defined as > 320 mosm/l. The primary outcome was hospital mortality; secondary outcomes were ICU mortality and other adverse clinical events., Results: Some 17 379 admissions were included in the study population. People with hyperosmolarity had fourfold increased mortality, a higher incidence of renal failure and need for mechanical ventilation, and prolonged ICU and hospital length of stay. The relationship with mortality remained highly significant even after adjusting for severity of acidosis, hospital type, year of admission, time to ICU, and a modified Australia and New Zealand Risk of Death propensity score., Conclusions: Although adults with ketoacidosis have a good prognosis overall, hyperosmolarity was independently associated with a significantly higher incidence of multiple adverse outcomes including mortality. Whether or not this is directly causal, it may have practical applications to improve risk stratification and identify individuals at risk of adverse outcomes., (© 2020 Diabetes UK.)

We aimed to collect data on all paediatric patients who were diagnosed with type 1 diabetes mellitus (T1DM) between the years 2000 and 2019 in Serbia and estimate for the first time its prevalence. Also, the trends of diabetes ketoacidosis (DKA) occurrence at the time of diagnosis are monitored. We collected and retrospectively analysed the data of patients <19 years with newly diagnosed T1DM. T1DM was diagnosed in 3134 patients (53.2% male). Total number of youth <19 years with T1DM was 1735 with prevalence of 135.25/100000 at the end of study period. T1DM was diagnosed most frequently between the ages of 5 and 11 years (42.1%). At the time of diagnosis, 35.7% presented in DKA. The incidence and severity of DKA were more significant at the youngest age (p<0.001). There were significant annual percentage increase (2.2%) in the number of new cases of DKA (p=0.007). Conclusion: This first report of nationwide prevalence of T1DM in youth shows that Serbia is among countries with high prevalence of T1DM in youth. System changes are needed in order to provide better quality of health care to these patients., (© 2020 Walter de Gruyter GmbH, Berlin/Boston.)

Importance: Saline (0.9% sodium chloride), the fluid most commonly used to treat diabetic ketoacidosis (DKA), can cause hyperchloremic metabolic acidosis. Balanced crystalloids, an alternative class of fluids for volume expansion, do not cause acidosis and, therefore, may lead to faster resolution of DKA than saline., Objective: To compare the clinical effects of balanced crystalloids with the clinical effects of saline for the acute treatment of adults with DKA., Design, Setting, and Participants: This study was a subgroup analysis of adults with DKA in 2 previously reported companion trials-Saline Against Lactated Ringer's or Plasma-Lyte in the Emergency Department (SALT-ED) and the Isotonic Solutions and Major Adverse Renal Events Trial (SMART). These trials, conducted between January 2016 and March 2017 in an academic medical center in the US, were pragmatic, multiple-crossover, cluster, randomized clinical trials comparing balanced crystalloids vs saline in emergency department (ED) and intensive care unit (ICU) patients. This study included adults who presented to the ED with DKA, defined as a clinical diagnosis of DKA, plasma glucose greater than 250 mg/dL, plasma bicarbonate less than or equal to 18 mmol/L, and anion gap greater than 10 mmol/L. Data analysis was performed from January to April 2020., Interventions: Balanced crystalloids (clinician's choice of Ringer lactate solution or Plasma-Lyte A solution) vs saline for fluid administration in the ED and ICU according to the same cluster-randomized multiple-crossover schedule., Main Outcomes and Measures: The primary outcome was time between ED presentation and DKA resolution, as defined by American Diabetes Association criteria. The secondary outcome was time between initiation and discontinuation of continuous insulin infusion., Results: Among 172 adults included in this secondary analysis of cluster trials, 94 were assigned to balanced crystalloids and 78 to saline. The median (interquartile range [IQR]) age was 29 (24-45) years, and 90 (52.3%) were women. The median (IQR) volume of isotonic fluid administered in the ED and ICU was 4478 (3000-6372) mL. Cumulative incidence analysis revealed shorter time to DKA resolution in the balanced crystalloids group (median time to resolution: 13.0 hours; IQR: 9.5-18.8 hours) than the saline group (median: 16.9 hours; IQR: 11.9-34.5 hours) (adjusted hazard ratio [aHR] = 1.68; 95% CI, 1.18-2.38; P = .004). Cumulative incidence analysis also revealed shorter time to insulin infusion discontinuation in the balanced crystalloids group (median: 9.8 hours; IQR: 5.1-17.0 hours) than the saline group (median: 13.4 hours; IQR: 11.0-17.9 hours) (aHR = 1.45; 95% CI, 1.03-2.03; P = .03)., Conclusions and Relevance: In this secondary analysis of 2 cluster randomized clinical trials, compared with saline, treatment with balanced crystalloids resulted in more rapid resolution of DKA, suggesting that balanced crystalloids may be preferred over saline for acute management of adults with DKA., Trial Registration: ClinicalTrials.gov Identifiers: NCT02614040; NCT02444988.

Background and Aims: Acute onset diabetes and diabetic ketoacidosis (DKA) can be precipitated by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection in individuals with no history of diabetes. However, data regarding the follow-up of these individuals are scarce., Methods: Three patients (data of two patients already published) with acute onset diabetes and DKA, precipitated by coronavirus disease 2019 (COVID-19), were followed for 14 weeks to assess the behavior of the diabetes. Detailed history, anthropometry, laboratory investigations, imaging studies, clinical course and outcomes were documented., Results: Three individuals developed symptoms suggestive of SARS CoV-2 infection. After a few days, they were detected to have COVID-19 pneumonia, based on reverse transcription-polymerase chain reaction (RT-PCR) assay and chest imaging. In the meantime, they also developed acute onset diabetes and DKA, which were precipitated by COVID-19. They responded well to treatment, including intravenous fluids and insulin. After around one week, they were transitioned to multiple shots of subcutaneous insulin. After about 4-6 weeks, their insulin requirement diminished and oral antihyperglycemic drugs were initiated. At the last follow-up (14 months), they had controlled glycemia with oral antihyperglycemic medicines., Conclusions: COVID-19 can induce acute onset diabetes and DKA in some individuals with no history of diabetes. These features resemble type 1 diabetes. However, after 4-6 weeks, their requirement for exogenous insulin diminishes and respond to oral antihyperglycemic medications. Long term follow up is required to further understand the type of diabetes induced by SARS CoV-2 infection in these individuals., Competing Interests: Declaration of competing interest There are no conflicts of interest relevant to this article., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)

Context: Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA)., Objective: The objective of this work is to characterize kinetics of copeptin and osmolality, and their dynamic relationship during rehydration and insulin therapy in children with type 1 diabetes (T1D) and DKA., Design and Setting: A prospective, observational, multicenter study was conducted., Patients and Intervention: Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours., Main Outcome Measures: Measurements included temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), and association between-subject variability (BSV) (coefficient of variation, CV%)., Results: Twenty-eight children (20 newly diagnosed T1D) aged 1 to 16 years were included. Copeptin decreased from 95 pmol/L (95% CI, 55-136 pmol/L) (CV%, 158%) to 9.7 pmol/L (95% CI, 8.1-11.4 pmol/L) (CV%, 31%) with a 50% recovery time (t1/2) of 7.1 hours (range, 5.1-11.5 hours) (114%). Serum osmolality decreased from 321 mOsm/kg (range, 315-327 mOsm/kg) (4%) to 294 mOsm/kg (range, 292-296 mOsm/kg) (1%) with a t1/2 of 4.3 hours (range, 3.0-5.6 hours) (64%). Copeptin levels doubled with each osmolality increase by 15 mOsm/kg (range, 10-21 mOsm/kg) (59%), from 9.8 pmol/L (range, 7.3-12.3 pmol/L) (48%) to 280 mOsm/kg. Copeptin kinetics differed between newly diagnosed and known T1D patients (P = .001), and less between mild vs moderate-severe DKA (P = .04)., Conclusions: First, this study characterized for the first time copeptin kinetics and dynamics in the high hyperosmolar range in children with DKA. Second, it revealed significant differences in copeptin kinetics between newly diagnosed and known T1D patients that may be explained by changes at the osmoreceptor and renal AVP receptor level due to longstanding osmotic diuresis and DKA., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Objective: To evaluate the incidence and risk factors for diabetic ketoacidosis (DKA) and related adverse events (AEs) in adults with type 1 diabetes treated with sotagliflozin adjunctive to insulin., Research Design and Methods: Data from two identically designed, 52-week, randomized studies were pooled and analyzed for DKA, changes in β-hydroxybutyrate (BHB), and percentage of patients with BHB >0.6 and >1.5 mmol/L. The patients were administered placebo, sotagliflozin 200 mg, or sotagliflozin 400 mg once daily., Results: A total of 191 ketosis-related AEs were reported, and 98 underwent adjudication. Of these, 37 events (36 patients) were adjudicated as DKA, with an exposure-adjusted incidence rate of 0.2, 3.1, and 4.2 events per 100 patient-years for placebo, sotagliflozin 200 mg, and sotagliflozin 400 mg, respectively. No patient died of a DKA event. From a baseline BHB of ∼0.13 mmol/L, sotagliflozin treatment led to a small median increase over 52 weeks (≤0.05 mmol/L at all time points). Of sotagliflozin-treated patients, approximately 47% and 7% had ≥1 BHB measurement >0.6 mmol/L and >1.5 mmol/L, respectively (vs. 20% and 2%, respectively, of placebo-treated patients). Subsequent to the implementation of a risk mitigation plan, annualized DKA incidence was lower versus preimplementation in both the sotagliflozin 200 and 400 mg groups., Conclusions: In patients with type 1 diabetes, confirmed DKA incidence increased when sotagliflozin was added to insulin compared with insulin alone. A lower incidence of DKA was observed following the implementation of an enhanced risk mitigation plan, suggesting that this risk can be managed with patient education., (© 2020 by the American Diabetes Association.)

Background and Aim: To conduct a systematic literature review and analyze the demographic/biochemical parameters and clinical outcomes of COVID-19 patients with diabetic ketoacidosis (DKA) and combined DKA/HHS (hyperglycemic hyperosmolar syndrome)., Methods: PubMed, Scopus, Embase, and Google Scholar databases were systematically searched till August 3, 2020 to identify studies reporting COVID-19 patients with DKA and combined DKA/HHS. A total of 19 articles reporting 110 patients met the eligibility criteria., Results: Of the 110 patients, 91 (83%) patients had isolated DKA while 19 (17%) had DKA/HHS. The majority of the patients were male (63%) and belonged to black ethnicity (36%). The median age at presentation ranged from 45.5 to 59.0 years. Most of the patients (77%) had pre-existing type 2 diabetes mellitus. Only 10% of the patients had newly diagnosed diabetes mellitus. The median blood glucose at presentation ranged from 486.0 to 568.5 mg/dl, being higher in patients with DKA/HHS compared to isolated DKA. The volume of fluid replaced in the first 24 h was higher in patients with DKA/HHS in contrast to patients with DKA alone. The in-hospital mortality rate was 45%, with higher mortality in the DKA/HHS group than in the isolated DKA group (67% vs. 29%). pH was lower in patients who had died compared to those who were discharged., Conclusion: DKA in COVID-19 patients portends a poor prognosis with a mortality rate approaching 50%. Differentiating isolated DKA from combined DKA/HHS is essential as the latter represents nearly one-fifth of the DKA cases and tends to have higher mortality than DKA alone., Competing Interests: Declaration of competing interest None., (Copyright © 2020 Diabetes India. Published by Elsevier Ltd. All rights reserved.)