Hyperglycemic crisis is one of the most common and severe complications of diabetes mellitus, associated with a high motarlity rate. Emergency admissions due to hyperglycemic crisis remain prevalent and challenging. This study aimed to develop and validate predictive models for in-hospital mortality risk among patients with hyperglycemic crisis admitted to the emergency department using various machine learning (ML) methods.

A multi-center retrospective study was conducted across six large general adult hospitals in Chongqing, western China. Patients diagnosed with hyperglycemic crisis were identified using an electronic medical record (EMR) database. Demographics, comorbidities, clinical characteristics, laboratory results, complications, and therapeutic interventions were extracted from the medical records to construct the prognostic prediction model. Seven machine learning algorithms, including support vector machines (SVM), random forest (RF), recursive partitioning and regression trees (RPART), extreme gradient boosting with dart booster (XGBoost), multivariate adaptive regression splines (MARS), neural network (NNET), and adaptive boost (AdaBoost) were compared with logistic regression (LR) for predicting the risk of in-hospital mortality in patients with hyperglycemic crisis. Stratified random sampling was used to split the data into training (80%) and validation (20%) sets. Ten-fold cross validation was performed on the training set to optimize model hyperparameters. The sensitivity, specificity, positive and negative predictive values, area under the curve (AUC) and accuracy of all models were computed for comparative analysis.

A total of 1668 patients were eligible for the present study. The in-hospital mortality rate was 7.3% (121/1668). In the training set, feature importance scores were calculated for each of the eight models, and the top 10 significant features were identified. In the validation set, all models demonstrated good predictive capability, with areas under the curve value exceeding 0.9 with a F1 score between 0.632 and 0.81, except the MARS model. Six machine learning algorithm models outperformed the referred logistic regression algorithm except the MARS model. Among the selected models, RPART, RF, and SVM achieved the best performance in the selected models (AUC values were 0.970, 0.968 and 0.968, F1 score were 0.652, 0.762, 0.762 respectively). Feature importance analysis identified novel predictors including mechanical ventilation, age, Charlson Comorbidity Index, blood gas index, first 24-hour insulin dosage, and first 24-hour fluid intake.

Most machine learning algorithms exhibited excellent performance predicting in-hospital mortality among patients with hyperglycemic crisis except the MARS model, and the best one was RPART model. These algorithms identified overlapping but different, up to 10 predictors. Early identification of high-risk patients using these models could support clinical decision-making and potentially improve the prognosis of hyperglycemic crisis patients.

Not applicable.

SGLT-2 inhibitors (SGLT-2i) are linked to a higher risk of diabetic ketoacidosis (DKA). However, it is still unclear whether the severity of SGLT-2i associated DKA is higher. This is a retrospective cohort study with patients admitted for DKA at a tertiary hospital (2013-2024). Patients were matched by propensity score for age, sex, diabetes duration, type, and ischemic heart disease. ICU admission risk and clinical severity were compared between SGLT-2i users and controls. The matched sample included 105 subjects (35 SGLT-2i users, 70 controls). The average age was 63.1 ± 15.4 years, and 40 (38.1%) patients were women. ICU admission was higher in the treatment group (65.7% versus 24.6%, p < 0.001). A conditional logistic regression showed higher risk of ICU admission in the treatment group (odds ratio 12.7, 95% confidence interval 1.9-84.3, p = 0.009) after adjusting for confounding factors. The treatment group exhibited less favorable blood gas results (pH 7.10 ± 0.17 vs 7.18 ± 0.16, p = 0.024) and shorter symptom duration (2 [1-3] vs 3 [2-7] days, p < 0.002). No significant differences were found in diabetes type, ketonemia, creatinine, or DKA precipitating factors. DKA in patients with diabetes treated with SGLT-2i is associated with more severe acidosis with quicker onset, leading to higher risk of ICU admission compared to patients not receiving this treatment. We recommend temporary discontinuation of SGLT-2i during any acute event until resolution, regardless of diabetes type or the patient's glycemic control.

Fluid therapy with normal saline (NS) in diabetic ketoacidosis (DKA) can cause hyperchloremic acidosis and delay DKA resolution. Balanced crystalloids may address this concern, though results with Ringer lactate and Plasma-Lyte have been mixed.

This study aimed to compare the effectiveness of Sterofundin (SF) vs. NS in the management of DKA.

A prospective, intervention trial with historical controls was conducted at the Postgraduate Institute of Medical Education and Research, Chandigarh, India. Patients aged 13 years or older with DKA were enrolled. The primary outcome was the time taken to DKA resolution, with a predefined superiority margin of a one-fourth reduction in resolution time. Secondary outcomes included total intravenous fluid and short-acting regular insulin requirements, the need for 0.45% saline, hospital stay duration and in-hospital mortality.

A total of 150 patients (mean age 36.8 years, 56.7% males) were included, with 75 receiving SF (intervention group) and 75 receiving NS (historical control group). The SF group showed a significantly shorter mean time to DKA resolution (13.8 ± 6.0 h) compared to the NS group (18.1 ± 5.5 h; P < 0.001). SF patients required less total intravenous fluid (4500 vs. 6000 ml; P = 0.004), less insulin (98 units vs. 112 units; P = 0.017) and had a lower need for 0.45% saline (8% vs. 74.3%; P < 0.001). Patients receiving SF had shorter hospital stays (4 [interquartile range, IQR 3-5] days vs. 4 [IQR 4-6] days; P = 0.020). Mortality rates were similar between the groups (SF: 9.3%, NS: 8.1%; P = 0.791).

SF may be a superior alternative to NS for fluid therapy in DKA.

Background/Objectives: Hyperglycemic emergencies cause significant losses of body water, sodium, and potassium. This report presents a method for computing the actual losses of water and monovalent cations in these emergencies. Methods: We developed formulas for computing the losses of water and monovalent cations as a function of the presenting serum sodium and glucose levels, the sum of the concentrations of sodium plus potassium in the lost fluids, and body water at the time of hyperglycemia presentation as measured by bioimpedance or in the initial euglycemic state as estimated by anthropometric formulas. The formulas for computing the losses from hyperglycemia were tested in examples of hyperglycemic episodes. Results: The formulas were tested in two patient groups, those with or without known weight loss during the development of hyperglycemia. In the first group, these formulas were applied to estimate the losses of body water and monovalent cations in (a) a previously published case of a boy with diabetic ketoacidosis and known weight loss who, during treatment not addressing his water deficit, developed severe hypernatremia and (b) a comparison of water loss computed by this new method with the reported average fluid gained during treatment of the hyperglycemic hyperosmolar state in a published study. In the second group, the formulas were applied in hypothetical subjects with varying levels of initial body water, serum sodium, and glucose at the time of hyperglycemia and sums of sodium and potassium concentrations in the lost fluids. Conclusions: Losses of body water and monovalent cations, which determine the severity of dehydration and hypovolemia, vary significantly between patients with hyperglycemic emergencies presenting with the same serum glucose and sodium concentrations. These losses can be calculated using estimated or measured body water values. Prospective studies are needed to test this proof-of-concept report.

The objective of this study was to develop a predictive model capable of determining the need for intensive care unit (ICU) admission of patients with diabetic ketoacidosis (DKA) during their assessment in the Emergency Department.

This is an observational study of consecutive cases including all adult patients diagnosed with DKA at a tertiary hospital between 2010 and 2024. Variables from medical history, physical examination, and laboratory tests at admission were collected and studied for their association with ICU admission. The sample was divided into two randomized parts: one to build a logistic regression model and another to validate it.

Two hundred and thirty-one DKA events were included. Individuals had a mean age of 49.6 ± 19.9 years and 50.2% were male. Forty-eight point five percent of cases required ICU admission, and 30-day mortality was 4.8%. The best model to predict ICU admission included Glasgow Coma Scale (odds ratio [OR] = 0.64, p = 0.003), pH (OR = 0.0088, p = 0.005), bilirubin (OR = 0.13, p = 0.036), bicarbonate (OR = 0.0091, p = 0.013), and pH-bicarbonate interaction (OR = 3.78, p = 0.015). The model had an R2 of 0.561, and the area under the curve (AUC) in the validation cohort was 0.842. Internal validation by bootstrap resampling showed an AUC = 0.871.

Variables associated with the severity of acidosis in patients with DKA predict the need for ICU admission better and earlier than other clinical variables.

Hyperglycemic emergencies (HGEs) are the major deadliest acute complications of diabetes. HGEs have reached an alarming stage and increased year-to-year leading to increased morbidity, hospitalization, and mortality. Despite HGEs causing this increased healthcare, psychological, social, and economic burden, studies conducted to address this burden and its predictive factors remain limited. Thus, this study aimed to investigate the incidence and predictors of HGEs among adult diabetic patients.

An institution-based retrospective follow-up study was employed on 538 systematically selected adult diabetic patients who had diabetic follow-up in Sidama region and Gedeo zone public hospitals from September 1, 2018, to September 1, 2022. The sample size was determined using STATA V-14. Data were collected using an extraction checklist, entered into EPI data version 4.4.2.2, and analyzed using STATA version 14. The Kaplan-Meier curve and log-rank test were used to determine the survival probabilities and to compare the survival status. The Cox proportional hazard regression model was used to determine the association and identify the predictor variables. A statistical significance was declared at a p-value of <0.05 in line with a 95% confidence interval (CI) and hazard ratios.

The study was conducted on 538 diabetic adult patients with a response rate of 100%. The mean age of study participants was 44.5 years, and more than 66.7% were males. The incidence rate of HGEs was found to be 29 (95% CI: 25.3-33.2) per 1000 person-months with a total of 7176.5 person-month observations. Being farmer (adjusted hazard ratio (AHR) = 6.47; 95% CI: 2.61-16.04), poor glycemic control (AHR = 6.84; 95% CI: 3.47-13.49), less frequent diabetic follow-up (AHR = 4.00; 95% CI: 1.02-15.57), and having hypertension (HTN) (AHR = 2.94; 95% CI: 1.62-5.34) were significantly associated with increased hazard of acquiring HGEs among adult diabetic patients. Conversely, the hazard of experiencing HGE was 63% lower among patients who had diabetic nephropathy relative to those without diabetic nephropathy (AHR = 0.35; 95% CI: 0.15-0.83). Hence, setting and strengthening specific diabetic management strategies focused on the identified predictors could be paramount to reducing HGEs and their unwanted effects. Moreover, it's better to consider more frequent diabetic follow-up visits for all patients regardless of other complications.

Diabetic ketoacidosis (DKA) is typically but not exclusively seen in patients with a history of diabetes mellitus.

This is a case of 39 year-old male who was diagnosed with acute pancreatitis based on characteristic symptoms and positive CT findings on presentation. Laboratory testing revealed elevated serum glucose 251 mg/dL, low serum bicarbonate 8 mmol/L, increased anion gap 21, and elevated serum beta-hydroxybutyrate 9.62 mmol/L. Diagnosis of DKA was made, however patient did not carry a diagnosis of diabetes mellitus. His hemoglobin A1c in hospital was normal at 5.4%. Additionally, follow-up hemoglobin A1c at 4 months and 10 months postdischarge did not imply diabetes mellitus, 5.8% at both time points. The patient who was initially managed with intravenous insulin required no insulin or oral diabetic medication on discharge. All these findings argued against new onset diabetes mellitus.

This case explores the potential pathophysiology that underlies this phenomenon including possible transient insulin insufficiency due to beta cell dysfunction from pancreatic inflammation. It also highlights the reversibility and transiency of possible beta cell dysfunction during acute pancreatitis and emphasizes the importance of closely assessing the patients' insulin requirements upon discharge, especially when a prior history of diabetes mellitus is absent.

DKA can occur as a rare complication of acute pancreatitis in a nondiabetic patient. Hyperglycemia associated with acute pancreatitis-induced DKA can be temporary and these patients might not necessarily require insulin upon discharge. Therefore, careful discharge planning is very important in such patients.

The ketogenic diet or exogenous supplementation with 3-hydroxybutyrate (3HB) is progressively gaining recognition as a valuable therapeutic or health intervention strategy. However, the effects of 3HB on cancers have been inconsistent in previous studies. This study aimed to comprehensively investigate the causal effects of circulating 3HB levels on 120 cancer phenotypes, and explore the 3HB mediation effect between liver fat accumulation and cancers.

Univariate Mendelian randomization (UVMR) was used in this study to investigate the causal impact of circulating 3HB levels on cancers. We conducted meta-analyses for 3HB-cancer associations sourced from different exposure data. In multivariate MR(MVMR), the body mass index, alcohol frequency and diabetes were included as covariates to investigate the independent effect of 3HB on cancer risk. Additionally, utilizing mediation MR analysis, we checked the potential mediating role of 3HB in the association between liver fat and cancer.

Integrating findings from UVMR and MVMR, we observed that elevated circulating 3HB levels were associated with reduced risk of developing diffuse large B-cell lymphoma(DLBCL) (OR[95%CI] = 0.28[0.14-0.57] p = 3.92e-04), biliary malignancies (OR[95%CI] = 0.30[0.15-0.60], p = 7.67e-04), hepatocellular carcinoma(HCC) (OR[95%CI] = 0.25[0.09-0.71], p = 9.33e-03), primary lymphoid and hematopoietic malignancies (OR[95%CI] = 0.76[0.58-0.99], p = 0.045). Further UVMR analysis revealed that an increase in the percent liver fat was associated with reduced 3HB levels (Beta[95%CI] = -0.073[-0.122∼-0.024], p = 0.0034) and enhanced susceptibility to HCC (OR[95%CI] = 13.9[9.76-19.79], p = 3.14e-48), biliary malignancies (OR[95%CI] = 4.04[3.22-5.07], p = 1.64e-33), nasopharyngeal cancer (OR[95%CI] = 3.26[1.10-9.67], p = 0.03), and primary lymphoid and hematopoietic malignancies (OR[95%CI] = 1.27[1.13-1.44], p = 1.04e-4). Furthermore, 3HB fully mediated the effect of liver fat on susceptibility to DLBCL (OR[95%CI] = 1.076[1.01-1.15], p = 0.034).

Circulating 3HB is associated with a reduced susceptibility to developing DLBCL, HCC, biliary malignancies, and primary lymphoid and hematopoietic malignancies. The impaired ketogenesis induced by metabolic-dysfunction associated fatty liver disease (MAFLD) contributes to risk of DLBCL.

This review discusses the challenges and controversies in the treatment of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemic state (HHS). Key areas include the selection of intravenous (IV) fluids, insulin therapy, strategies for preventing and monitoring cerebral edema (CE) by managing hyperglycemia overcorrection, electrolyte replacement, timing of nutrition, use of IV sodium bicarbonate, and airway management in critically ill DKA patients. Isotonic normal saline remains the standard for initial fluid resuscitation, though balanced solutions have been shown to have faster DKA resolution. Current guidelines recommend using continuous IV insulin for DKA management after fluid status has been restored potassium levels have been achieved and subcutaneous (SQ) insulin is started only after the resolution of metabolic acidosis. In comparison, the British guidelines recommend using SQ insulin glargine along with continuous regular IV insulin, which has shown faster DKA resolution and shorter hospital stays compared to continuous IV insulin alone. Although rare, rapid overcorrection of hyperglycemia with fluids and insulin can lead to CE, seizures, and death. Clinicians should be aware of risk factors and preventive strategies for CE. DKA frequently involves multiple electrolyte abnormalities, such as hypokalemia, hypophosphatemia, and hypomagnesemia and regular monitoring is essential for DKA management. Early initiation of oral nutrition has been shown to reduce intensive care unit and overall hospital length of stay. For impending respiratory failure, Bilevel positive airway pressure is not recommended due to aspiration risks. Instead, intubation and mechanical ventilation, with monitoring and management of acid-base and fluid status, are recommended. The use of sodium bicarbonate is discouraged due to the potential for worsening ketosis, hypokalemia, and risk of CE. However, IV sodium bicarbonate can be considered if the serum pH falls below 6.9, or when serum pH is less than 7.2 and/or serum bicarbonate levels are below 10 mEq/L, pre-and post-intubation, to prevent metabolic acidosis and hemodynamic collapse that occurs from apnea during intubation. Managing DKA and HHS in critically ill patients includes using balanced IV fluid solutions to restore volume status, followed by continuous IV insulin, early use of SQ glargine insulin, electrolyte replacement, and monitoring, CE preventive strategies by avoiding hyperglycemia overcorrection, early nutritional support, and appropriate airway management.

Rebound hyperglycemia following the resolution of diabetic ketoacidosis (DKA) is common in pediatric patients with type 1 diabetes, increasing the risk of recurrent DKA and complicating the transition to subcutaneous insulin. Multiple studies suggest that early administration of long-acting insulin analogs during DKA management safely improves this transition.

This study aimed to determine whether early insulin glargine administration in children with DKA prevents rebound hyperglycemia and recurrent ketosis without increasing the rate of hypoglycemia or hypokalemia.

Patients aged <21 years presenting with DKA to Children's Mercy Kansas City between October 2012 and October 2016 were reviewed. They were categorized as Early (>4 h of overlap with intravenous [IV] insulin) and Late (<2 h of overlap) cohorts.

We reviewed 546 DKA admissions (365 Early and 181 Late). Rebound hyperglycemia (>180 mg/dL) was lower in the Early group (66% vs. 85%, p ≤ 0.0001). Hypoglycemia (<70 mg/dL) during IV insulin administration was higher in the Early group than in the Late group (27% vs. 19%, p = 0.042). Hypoglycemia within 12 h of IV insulin discontinuation was lower in the Early group (16% vs. 26%, p = 0.012). Recurrent ketosis, hypokalemia, and cerebral edema were not different between the groups.

Early glargine administration in pediatric DKA management is safe, decreases the rate of rebound hyperglycemia, and improves the transition to subcutaneous insulin. Hypoglycemia is less frequent following IV insulin discontinuation with early glargine, but the IV insulin rate may need to be reduced to minimize hypoglycemia during IV insulin infusion.

Diabetic ketoacidosis (DKA), a severe complication of type 1 diabetes (T1D), is triggered by production of large quantities of ketone bodies, requiring patients with T1D to constantly monitor their ketone levels. Here, a skin-compatible hydrogel microneedle (HMN)-continuous ketone monitoring (HMN-CKM) device is reported. The sensing mechanism relies on the catechol-quinone chemistry inherent to the dopamine (DA) molecules that are covalently linked to the polymer structure of the HMN patch. The DA serves the dual-purpose of acting as a redox mediator for measuring the byproduct of oxidation of 3-beta-hydroxybutyrate (β-HB), the primary ketone bodies; while, also facilitating the formation of a crosslinked HMN patch. A universal approach involving pre-oxidation and detection of the generated catechol compounds is introduced to correlate the sensor response to the β-HB concentrations. It is further shown that real-time tracking of a decrease in ketone levels of T1D rat model is possible using the HMN-CKM device, in conjunction with a data-driven machine learning model that considers potential time delays.

Limited data exist on long-term renal outcomes in patients with hyperglycemic crisis (HC) as initial type 2 diabetes presentation. We evaluated the risk of chronic kidney disease (CKD) development in those with concurrent HC at diagnosis. Utilizing Taiwan's insurance claims from adults newly diagnosed with type 2 diabetes during 2006-2015, we created HC and matched non-HC cohorts. We assessed incident CKD/diabetic kidney disease (DKD) by 2018's end, calculating the hazard ratio (HR) with the Cox model. Each cohort comprised 13,242 patients. The combined CKD and DKD incidence was two-fold higher in the HC cohort than in the non-HC cohort (56.47 versus 28.49 per 1000 person-years) with an adjusted HR (aHR) of 2.00 (95% confidence interval [CI] 1.91-2.10]). Risk increased from diabetic ketoacidosis (DKA) (aHR:1.69 [95% CI 1.59-1.79]) to hyperglycemic hyperosmolar state (HHS) (aHR:2.47 [95% CI 2.33-2.63]) and further to combined DKA-HHS (aHR:2.60 [95% CI 2.29-2.95]). Subgroup analysis in individuals aged ≥ 40 years revealed a similar trend with slightly reduced incidences and HRs. Patients with HC as their initial type 2 diabetes presentation face a higher CKD risk than do those without HC. Enhanced medical attention and customized interventions are crucial to reduce this risk.

The optimal resuscitative fluid for patients with diabetic ketoacidosis (DKA) remains controversial. Therefore, our objective was to assess the effect of balanced crystalloids in contrast to normal saline on clinical outcomes among patients with DKA.

We searched electronic databases for randomized controlled trials comparing balanced crystalloids versus normal saline in patients with DKA, the search period was from inception through October 20th, 2023. The outcomes were the time to resolution of DKA, major adverse kidney events, post-resuscitation chloride, and incidence of hypokalemia.

Our meta-analysis encompassed 11 trials, incorporating a total of 753 patients with DKA. There was no significant difference between balanced crystalloids and normal saline group for the time to resolution of DKA (MD -1.49, 95%CI -4.29 to 1.31, P=0.30, I2 = 65%), major adverse kidney events (RR 0.88, 95%CI 0.58 to 1.34, P=0.56, I2 = 0%), and incidence of hypokalemia (RR 0.80, 95%CI 0.43 to 1.46, P=0.46, I2 = 56%). However, there was a significant reduction in the post-resuscitation chloride (MD -3.16, 95%CI -5.82 to -0.49, P=0.02, I2 = 73%) among patients received balanced crystalloids.

Among patients with DKA, the use of balanced crystalloids as compared to normal saline has no effect on the time to resolution of DKA, major adverse kidney events, and incidence of hypokalemia. However, the use of balanced crystalloids could reduce the post-resuscitation chloride.

https://osf.io, identifier c8f3d.

Diabetic ketoacidosis (DKA) is a life-threatening condition affecting individuals with diabetes characterised by hyperglycaemia, metabolic acidosis and ketonemia. The incidence and financial burden of DKA is still high. Thiamine deficiency is well documented in patients with DKA and could be associated with cardiac dysfunction in those patients. Thiamine deficiency leads to cardiac dysfunction, neuronal death and worsens the prognosis of DKA. There is an existing metabolic relationship between thiamine deficiency in diabetes, obesity and bariatric surgery. Careful monitoring of thiamine, along with other vitamins, is essential for diabetic patients, obese individuals and postbariatric surgery. Further research and clinical studies are urgently needed to assess the following: (1) Whether diabetes, obesity and bariatric surgery make individuals more prone to have DKA related to thiamine deficiency and (2) Whether supplementation of thiamine can protect diabetic patients, obese subjects and individuals undergoing bariatric surgery from DKA. This review summarises the biochemistry of thiamine and the existing metabolic relationships between thiamine deficiency in DKA, diabetes, obesity and bariatric surgery. Primary and family physicians have an important role in ensuring adequate replacement of thiamine in individuals with diabetes, obesity and bariatric surgery.

Background Diabetes mellitus remains a pressing global health issue, characterized by chronic metabolic dysfunction and the potential for life-threatening acute hyperglycemic emergencies. These emergencies, known as diabetic ketoacidosis and hyperosmolar hyperglycemic states, trigger a series of physiological disruptions. This article delves deeply into how the type and duration of diabetes mellitus affect the occurrence of hyperglycemic emergencies and mortality rates. Methods The study was conducted at the Institute of Internal Medicine, Rajiv Gandhi General Hospital, affiliated with Madras Medical College, spanning from July 2021 to December 2021. It encompassed both individuals newly diagnosed with diabetic ketoacidosis and patients already undergoing diabetic treatment who developed diabetic ketoacidosis and hyperosmolar hyperglycemic states. Results Within the study cohort of 110 patients, 37.27% were diagnosed with Type 1 diabetes mellitus, while 62.73% were classified as Type 2 diabetes mellitus patients. Among these individuals, 23.60% were newly diagnosed with diabetes, 22.70% had been diabetic for less than one year, 47.30% had a diabetic history of two to five years, and 6.40% had been diabetic for over six years. However, upon investigating the relationship between diabetes duration and mortality rate, no statistically significant findings were observed. Conclusion Hyperglycemic emergencies represent multifaceted clinical challenges influenced by the interplay of various factors, including the type and duration of the disease. By maintaining effective management of hyperglycemia from the outset and sustaining it throughout their lives, people with diabetes can improve their physical and mental health and reduce the likelihood of developing long-term complications that may negatively impact their overall well-being.

In hyperglycemia, the serum sodium concentration ([Na]S) receives influences from (a) the fluid exit from the intracellular compartment and thirst, which cause [Na]S decreases; (b) osmotic diuresis with sums of the urinary sodium plus potassium concentration lower than the baseline euglycemic [Na]S, which results in a [Na]S increase; and (c), in some cases, gains or losses of fluid, sodium, and potassium through the gastrointestinal tract, the respiratory tract, and the skin. Hyperglycemic patients with hypernatremia have large deficits of body water and usually hypovolemia and develop severe clinical manifestations and significant mortality. To assist with the correction of both the severe dehydration and the hypovolemia, we developed formulas computing the fractional losses of the body water and monovalent cations in hyperglycemia. The formulas estimate varying losses between patients with the same serum glucose concentration ([Glu]S) and [Na]S but with different sums of monovalent cation concentrations in the lost fluids. Among subjects with the same [Glu]S and [Na]S, those with higher monovalent cation concentrations in the fluids lost have higher fractional losses of body water. The sum of the monovalent cation concentrations in the lost fluids should be considered when computing the volume and composition of the fluid replacement for hyperglycemic syndromes.

Diabetic ketoacidosis (DKA) is regarded to be a communal complication of both type 1 and type 2 diabetes mellitus in children and adolescents. Successful therapy of DKA in children requires prompt diagnosis, strict monitoring of medical indicators, and prompt action. Thymoquinone (Tq) from black cumin loaded chitosan nanoparticles (ChNPs) intend to assess an effective agent to overcome this problem. XRD, FTIR, SEM, and TEM were used in the physicochemical analysis. Enzymatic activity of α-amylase and α-glucosidase was used in in vitro tests of anti-diabetic efficacy. Protecting insulin against enzyme breakdown is a crucial part of the insulin delivery mechanism. In the STZ-induced diabetes RIN-5F cell line, the anti-apoptotic capability of Tq-ChNPs was demonstrated through the NF-κB mediated apoptotic pathway. The combination of thymoquinone and chitosan NPs demonstrated that a wide variety of incredibly effective substances to elevate their curative effects, thus contributing to the growth of clinical and pharmaceutical fields.

Non-ketotic hyperglycaemic (NKH) seizures are a rare neurological complication of diabetes caused by hyperglycaemia in non-ketotic and non-hyperosmotic states. The clinical characteristics of NKH seizures are atypical and lack unified diagnostic criteria, leading to potential misdiagnoses in the early stages of the disease.

This report presents a rare case of NKH seizures in a 52-year-old male patient with a history of type 2 diabetes mellitus. We performed comprehensive magnetic resonance imaging (MRI) studies at admission, 12 d post-admission, and 20 d post-discharge. The imaging techniques included contrast-enhanced head MRI, T2-weighted imaging (T2WI), fluid-attenuated inversion recovery (FLAIR), diffusion-weighted imaging, susceptibility-weighted imaging, magnetic resonance spectroscopy (MRS), and magnetic resonance venography. At the time of admission, T2WI and FLAIR of the cranial MRI showed that the left parieto-occipital cortex had gyrus-like swelling and high signal, and subcortical stripes had low signal. MRS showed a reduced N-acetylaspartate peak and increased creatine and choline peaks in the affected areas. A follow-up MRI 20 d later showed that the swelling and high signal of the left parieto-occipital cortex had disappeared, and the low signal of the subcortex had disappeared.

This case study provides valuable insights into the potential pathogenesis, diagnosis, and treatment of NKH seizures. The comprehensive MRI findings highlight the potential utility of various MRI sequences in diagnosing and characterizing NKH seizures.

This study is aimed at examining which factors are useful for the diagnosis and distinction of ketoacidosis. We recruited 21 diabetic ketoacidosis (DKA) and alcoholic ketoacidosis (AKA) patients hospitalized in Kawasaki Medical School General Medical Center from April 2015 to March 2021. Almost all patients in this study were brought to the emergency room in a coma and hospitalized. All patients underwent blood gas aspiration and laboratory tests. We evaluated the difference in diagnosis markers in emergencies between DKA and alcoholic ketoacidosis AKA. Compared to AKA patients, DKA patients had statistically higher values of serum acetoacetic acid and lower values of serum lactate, arterial blood pH, and base excess. In contrast, total ketone bodies, β-hydroxybutyric acid, and β-hydroxybutyric acid/acetoacetic acid ratio in serum did not differ between the two patient groups. It was shown that evaluation of each pathology such as low body weight, diabetes, liver dysfunction, and dehydration was important. It is important to perform differential diagnosis for taking medical histories such as insulin deficiency, alcohol abuse, or starvation as the etiology in Japanese subjects with DKA or AKA. Moreover, it is important to precisely comprehend the pathology of dehydration and alcoholic metabolism which would lead to appropriate treatment for DKA and AKA.

Diabetic ketoacidosis (DKA) and hyperglycemic hyperosmolar syndrome (HHS) are life-threatening complications of diabetes mellitus. Their clinical profiles have not been fully investigated.

A multicenter retrospective cohort study was conducted in 21 acute care hospitals in Japan. Patients included were adults aged 18 or older who had been hospitalized from January 1, 2012, to December 31, 2016 due to DKA or HHS. The data were extracted from patient medical records. A four-group comparison (mild DKA, moderate DKA, severe DKA, and HHS) was performed to evaluate outcomes.

A total of 771 patients including 545 patients with DKA and 226 patients with HHS were identified during the study period. The major precipitating factors of disease episodes were poor medication compliance, infectious diseases, and excessive drinking of sugar-sweetened beverages. The median hospital stay was 16 days [IQR 10-26 days]. The intensive care unit (ICU) admission rate was 44.4% (mean) and the rate at each hospital ranged from 0 to 100%. The in-hospital mortality rate was 2.8% in patients with DKA and 7.1% in the HHS group. No significant difference in mortality was seen among the three DKA groups.

The mortality rate of patients with DKA in Japan is similar to other studies, while that of HHS was lower. The ICU admission rate varied among institutions. There was no significant association between the severity of DKA and mortality in the study population.

This study is registered in the UMIN clinical Trial Registration System (UMIN000025393, Registered 23th December 2016).

Despite an increasing prevalence of the aged population with diabetes in low-middle-income countries, there is limited literature on geriatric hyperglycemic emergencies. The present study aimed to compare the spectrum and outcomes of diabetic ketoacidosis (DKA) between elderly and non-elderly adult patients in India.

Seventy-seven elderly patients (≥60 years) were compared to 477 non-elderly patients (13-59 years) with DKA admitted to the medical emergency, Postgraduate Institute of Medical Education and Research, Chandigarh, India, between January 2014 and December 2022. Clinical features, laboratory parameters, precipitating factors, and in-hospital outcomes were reviewed.

Elderly patients less commonly had vomiting and abdominal pain than non-elderly patients (31.3 % vs. 66.2 %, 27.3 % vs. 60.1 %, respectively) and typically presented with dyspnea (48.5 %), altered mental status (47.8 %), and fever (46.3 %). Ketonemia and metabolic acidosis were significantly more marked in non-elderly patients, whereas elderly patients frequently had anemia, hypoalbuminemia, and renal dysfunction. The most common precipitations of geriatric DKA were infections (70.1 %), followed by treatment non-adherence (66.2 %) and non-infectious disorders (35.1 %). Infections and non-infectious disorders were significantly more frequent in elderly patients than in non-elderly patients. Respiratory and urinary tract infections were prevalent in both age groups. In-hospital survival was 74.9 % (n = 415) and remained lower in older patients (48.1 % vs. 79.2 %, P-value <0.001). The independent prognostic factors were age (OR 1.030, 95 % CI 1.006-1.054, P = 0.014), Glasgow coma scale (OR 0.789, 95 % CI 0.717-0.869, P <0.001), and infection trigger (OR 6.635, 95 % CI 2.852-15.441, P <0.001).

Older patients with DKA present atypically, frequently have precipitation with infections and noninfectious disorders, and have poor outcomes.

Procalcitonin is a widely used infection biomarker; however, its utility in identifying bacterial infection in diabetic ketoacidosis (DKA) is unclear. We aimed to evaluate its diagnostic performance for detecting DKA cases triggered by bacterial infections. We reviewed 303 case records of patients aged ≥ 13 years with DKA admitted to the emergency department, PGIMER (Chandigarh), between 2017 and 2022. Baseline procalcitonin was measured by electrochemiluminescence immunoassay, and a value > 0.5 ng/mL was considered elevated. Both microbiological reference standard (MRS) and composite reference standard (CRS) were used to evaluate the diagnostic performance of procalcitonin. 151/303 (49.8%) DKA cases had infection precipitations. Bacterial infections were present in 98 patients (53 microbiologically confirmed), of which urinary tract infection (n = 42), pneumonia (n = 19), skin and soft-tissue infection (n = 13), and bacteremia (n = 11) were common. The median value of procalcitonin was higher with bacterial infections than in patients without (3.68 vs. 1.00, P-value < 0.001). An elevated procalcitonin to detect bacterial infections in DKA had sensitivity 84.69%, specificity 34.15%, positive likelihood ratio (LR +) 1.29, and negative likelihood ratio (LR -) 2.44, against CRS. Against MRS, both LR + and LR - further decreased to 1.23 and 1.81, respectively. Using the receiver-operating-characteristic curve, an optimal cut-off of procalcitonin was calculated at 1.775 ng/ml against both CRS (area under curve 0.655, sensitivity 68.37%, specificity 59.02%, LR + 1.67, LR - 1.86, Yoden's index 0.274) and MRS (area under curve 0.616, sensitivity 67.92%, specificity 59.02%, LR + 1.66, LR - 1.84, Yoden's index 0.269). Procalcitonin does not help detect bacterial infections in patients with DKA at admission.

Euglycemic diabetic ketoacidosis (euDKA) is a life-threatening metabolic complication typically associated with type 1 diabetes mellitus (T1DM). However, its occurrence in type 2 diabetes mellitus (T2DM) remains exceptionally rare. We present a case report detailing the unusual manifestation of euDKA in a patient with T2DM following the initiation of treatment with a sodium-glucose cotransporter-2 (SGLT-2) inhibitor. The patient, a 67-year-old female with a history of T2DM and well-controlled blood glucose levels, was commenced on an SGLT-2 inhibitor as part of her antidiabetic regimen just two weeks prior. Subsequently, the patient developed euDKA despite maintaining near-normal glycemic levels. This paradoxical presentation challenges the conventional understanding of DKA in T2DM and underscores the need for heightened clinical awareness. EuDKA associated with SGLT-2 inhibitors is an infrequently reported phenomenon, further complicating the clinical landscape. This case contributes to the growing evidence suggesting an association between SGLT-2 inhibitors and the development of euDKA in patients with T2DM. The rarity of this occurrence necessitates a thorough exploration of potential risk factors and underlying mechanisms.

Background: An early prediction of infection is challenging in diabetic ketoacidosis (DKA). Methods: This prospective cohort study aimed to assess effectiveness of various sepsis screening tools in predicting infections and prognosis in DKA. Results: Among 141 cases, infection (44.0%) was the commonest precipitating factor. A Sequential Organ Failure Assessment score ≥4 showed high specificity (82.28%) and high positive likelihood ratio (2.64) but limited sensitivity (46.77%). Conversely, Systemic Inflammatory Response Syndrome ≥2 exhibited good sensitivity (95.16%) but a high false-positive rate (84.28%). National Early Warning Score ≥7 and Quick Sequential Organ Failure Assessment ≥2 had low sensitivity and specificity. These sepsis tools also demonstrated low prognostic accuracy for mortality. Conclusion: Sepsis screening tools have limited predictive accuracy for infections and mortality in DKA.

Euglycemic diabetic ketoacidosis (EDKA) is an emerging complication of diabetes associated with an increasing use of sodium-glucose transporter type 2 (SGLT-2) inhibitor drugs. This review highlights the growing incidence of EDKA and its diagnostic challenges due to the absence of hallmark hyperglycemia seen in diabetic ketoacidosis (DKA). The paper presents a classification system for the severity of EDKA, categorizing it into mild, moderate, and severe based on serum pH and bicarbonate levels. Another classification system is proposed to define stages of EDKA based on anion gap and ketones at the time of diagnosis and during the treatment period. A treatment algorithm is proposed to guide clinicians in managing EDKA. This treatment algorithm includes monitoring anion gap and ketones to guide insulin and fluid management, and slower transition to subcutaneous insulin to prevent a relapse. Increased awareness of EDKA is essential for a timely diagnosis because an early diagnosis and treatment can improve clinical outcomes.

Hyperglycemic hyperosmolar syndrome (HHS) is an indolent process characterized by significantly increased levels of serum glucose, high osmolality, and electrolyte abnormalities. The incidence of HHS has steadily risen in the pediatric population over the past several years. Patients with HHS often present with profound dehydration, fatigue, and early mental status changes. Primary emergency management of HHS involves fluid replacement, hemodynamic support, correcting electrolyte derangements, and addressing complications and underlying illnesses. Insulin is not an initial therapy in HHS and should be considered only after the patient's fluids and electrolytes have been repleted. Unlike in diabetic ketoacidosis, HHS patients are not acidotic, although children may present with mixed HHS/diabetic ketoacidosis syndromes. Complications of HHS include thrombosis, rhabdomyolysis, and, rarely, malignant hyperthermia.

Diabetic ketoacidosis (DKA) is an endocrine emergency that can occur in people with diabetes. Its incidence is estimated to be 220,340 hospital admissions each year. Treatment algorithms include fluid resuscitation, intravenous (IV) insulin infusion, and scheduled electrolyte and glucose monitoring. The misdiagnosis of DKA in the setting of hyperglycemic emergencies results in overtreatment and unnecessary increases in healthcare utilization and costs.

The aims of this study were to determine how often DKA is overdiagnosed in the context of other acute hyperglycemic emergencies, to describe the baseline characteristics of patients, to determine the hospital treatments for DKA, and to identify the frequency of endocrinology or diabetology consultation in the hospital setting.

A retrospective chart review was conducted utilizing charts from three different hospitals within a hospital system. Charts were identified utilizing ICD-10 codes for admissions to the hospital for DKA. If the patient was over 18 and had one of the diagnostic codes of interest, the chart was reviewed for further details regarding the criteria for DKA diagnosis as well as admission and treatment details.

A total of 520 hospital admissions were included for review. DKA was incorrectly diagnosed in 28.4 % of the hospital admissions reviewed, based on a review of the labs and DKA diagnostic criteria. Most patients were admitted to the intensive care unit (ICU) and treated with IV insulin infusion (n=288). Consultation of endocrinology or diabetology occurred in 40.2 % (n=209) of all hospital admissions, and 128 of those consults occurred in ICU admissions. The diagnosis of DKA was incorrect in 92 of the patients admitted to the medical surgical unit (MSU) and in 49 of patients admitted to the ICU.

Almost one third of hospital admissions for hyperglycemic emergencies were misdiagnosed and managed as DKA. DKA diagnostic criteria are specific; however, other diagnoses like hyperosmolar hyperglycemic syndrome (HHS), hyperglycemia, and euglycemic DKA can make an accurate diagnosis more complicated. Education directed at improving the diagnostic accuracy of DKA among healthcare providers is needed to improve diagnostic accuracy, ensure the appropriate use of hospital resources, and potentially reduce costs to the healthcare system.

Diabetic ketoacidosis (DKA) is a common, severe and often fatal complication of diabetes. This study aimed to investigate the clinical characteristics and precipitants of DKA, as well as factors associated with DKA severity in Ghanaian patients.

Cross-sectional study of the medical records of all 70 adult patients >18 years managed for DKA in the adult emergency room of Korle-Bu Teaching Hospital in Ghana from March 2019 to July 2019. DKA diagnosis was based on hyperglycaemia >11.0 mmol/L, ketonuria (more than 2+) plus acidaemia of (pH < 7.3) or bicarbonate (HCO3 - ) <15.0 mmol/L. However, when serum bicarbonate and pH were not available, clinical signs of acidosis, for example, Kussmaul breathing aided in the diagnosis. DKA severity was assessed based on the Joint British Diabetes Societies (JBDS) guidelines of factors suggestive of severe DKA. Multivariable logistic regression was used to determine the factors associated with DKA severity. Odds ratio and 95% confidence interval for factors associated with DKA severity were determined.

The mean (±standard deviation) age, diabetes duration and blood sugar at admission were 44.06 (±16.23) years, 7.19 (±6.04) years and 26.37 (±6.70) mmol/L, respectively. Females comprised 51.4% of the study population. The most common presenting symptoms were generalised weakness (30.0%) and fever (14.3%). The major precipitants were infection (70.0%) and non-compliance (22.9%). Overall, 71.4% of participants had features suggestive of severe DKA. In a multivariable regression model, Type 2 diabetes was associated with over fourfold decreased odds of severe DKA (OR 0.23, 95% CI [0.07-0.76], p = 0.016). Patient education on prevention of DKA was documented for only 18.6% of patients before being discharged.

In this study, more than 70% of the study participants had features suggestive of severe DKA, with infection being the most common precipitant of DKA. 51.4% of patients had Type 2 diabetes which was associated with a statistically lower risk of severe DKA. Female sex tended to be positively associated with DKA severity. In a setting where the venous/arterial pH and bicarbonate levels may be inaccessible and/or unaffordable, using clinical features as found in the JBDS guidelines may help categorise patients and escalate care when needed. Indeed it may be useful to validate the use of the JBDS criteria for use in such settings.

The use of sodium bicarbonate to treat metabolic acidosis is intuitive, yet data suggest that not all patients benefit from this therapy.

In this narrative review, we describe the physiology behind commonly encountered nontoxicologic causes of metabolic acidosis, highlight potential harm from the indiscriminate administration of sodium bicarbonate in certain scenarios, and provide evidence-based recommendations to assist emergency physicians in the rational use of sodium bicarbonate.

Sodium bicarbonate can be administered as a hypertonic push, as a resuscitation fluid, or as an infusion. Lactic acidosis and cardiac arrest are two common scenarios where there is limited benefit to routine use of sodium bicarbonate, although certain circumstances, such as patients with concomitant acute kidney injury and lactic acidosis may benefit from sodium bicarbonate. Patients with cardiac arrest secondary to sodium channel blockade or hyperkalemia also benefit from sodium bicarbonate therapy. Recent data suggest that the use of sodium bicarbonate in diabetic ketoacidosis does not confer improved patient outcomes and may cause harm in pediatric patients. Available evidence suggests that alkalinization of urine in rhabdomyolysis does not improve patient-centered outcomes. Finally, patients with a nongap acidosis benefit from sodium bicarbonate supplementation.

Empiric use of sodium bicarbonate in patients with nontoxicologic causes of metabolic acidosis is not warranted and likely does not improve patient-centered outcomes, except in select scenarios. Emergency physicians should reserve use of this medication to conditions with clear benefit to patients.

Diabetic ketoacidosis (DKA) is a life-threatening acute complication of diabetes mellitus and can lead to patient demise if not immediately treated. From the recent literature, the diabetic ketoacidosis mortality rate, depending on age, is 2-5%. Insulin discontinuation and infection remain the two most common triggers for diabetic ketoacidosis. About 50% of cases of ketoacidosis result from bacterial infections like urinary tract infections and pneumonia. It is also important to diagnose the presence of infection in diabetic ketoacidosis patients to prevent the excessive use of antibiotics, which may lead to antibiotic resistance. Although performing bacterial culture is confirmatory for the presence or absence of bacterial infection, the time required to obtain the result is long. At the same time, emergency treatment needs to be started as early as possible.

This narrative review examines various septic markers to identify the appropriate tools for diagnosis and to distinguish between diabetic ketoacidosis with and without infection. Electronic databases were searched using the Google engine with the keywords "Diabetes Mellitus", "Diabetic Ketoacidosis", "Infection with Diabetic Ketoacidosis", "biomarkers for infection in Diabetic Ketoacidosis", "Procalcitonin", "Inflammatory cytokines in DKA", "Lactic acidosis in DKA", and "White blood cell in infection in DKA".

This narrative review article presents the options for diagnosis and also aims to create awareness regarding the gravity of diabetic ketoacidosis with infection and emphasizes the importance of early diagnosis for appropriate management. Diabetes mellitus is a clinical condition that may lead to several acute and chronic complications. Acute diabetic ketoacidosis is a life-threatening condition in which an excess production of ketone bodies results in acidosis and hypovolemia. Infection is one of the most common triggers of diabetic ketoacidosis. When bacterial infection is present along with diabetic ketoacidosis, the mortality rate is even higher than for patients with diabetic ketoacidosis without infection. The symptoms and biomarkers of diabetic ketoacidosis are similar to that of infection, like fever, C reactive protein, and white blood cell count, since both create an environment of systemic inflammation. It is also essential to distinguish between the presence and absence of bacterial infection to ensure the appropriate use of antibiotics and prevent antimicrobial resistance. A bacterial culture report is confirmatory for the existence of bacterial infection, but this may take up to 24 h. Diagnosis needs to be performed approximately in the emergency room upon admission since there is a need for immediate management. Therefore, researching the possible diagnostic tools for the presence of infection in diabetic ketoacidosis patients is of great importance. Several of such biomarkers have been discussed in this research work.

Reports have suggested that COVID-19 vaccination may cause Type 1 diabetes (T1D), particularly fulminant T1D (FT1D). This study aimed to investigate the incidence of T1D in a general population of China, where more than 90% of the people have received three injections of inactivated SARS-Cov-2 vaccines in 2021.

A population-based registry of T1D was performed using data from the Beijing Municipal Health Commission Information Center. Annual incidence rates were calculated by age group and gender, and annual percentage changes were assessed using Joinpoint regression.

The study included 14.14 million registered residents, and 7,697 people with newly diagnosed T1D were identified from 2007 to 2021. T1D incidence increased from 2.77 in 2007 to 3.84 per 100,000 persons in 2021. However, T1D incidence was stable from 2019 to 2021, and the incidence rate did not increase when people were vaccinated in January-December 2021. The incidence of FT1D did not increase from 2015 to 2021.

The findings suggest that COVID-19 vaccination did not increase the onset of T1D or have a significant impact on T1D pathogenesis, at least not on a large scale.

To determine the effectiveness and safety of early combination of insulin glargine with intravenous (IV) insulin infusion compared with IV insulin infusion alone in the management of diabetic ketoacidosis (DKA).

This was a single-centre, open-label, randomized controlled trial of adults aged 18 years or older diagnosed with DKA. The 'early glargine' group was given subcutaneous insulin glargine 0.3 units/kg within the first 3 hours of DKA diagnosis, in addition to the standard IV insulin infusion. The control group received standard IV insulin treatment only. The primary outcome was the time to DKA resolution. The other outcomes included rebound hyperglycaemia, mortality, hypoglycaemia and hypokalaemia, as well as the length of hospital stay (LOS).

A total of 60 patients (30 patients per group) were enrolled. Most patients (76.7%) had type 2 diabetes. Both groups were similar in baseline characteristics, except for higher serum beta-hydroxybutyrate and lower pH levels in the early glargine group. The mean ± standard deviation time to DKA resolution in the early glargine group was significantly faster than the control group (9.89 ± 3.81 vs. 12.73 ± 5.37 hours; P = .022). The median (interquartile range) LOS was significantly shorter in the early glargine group than in the control group (4.75 [3.53-8.96] vs. 15.25 [5.71-26.38] days; P = .024). The incidence of rebound hyperglycaemia, all-cause mortality, hypoglycaemia and hypokalaemia was similar between the groups.

Early combination of insulin glargine with IV insulin infusion led to a faster DKA resolution and a shorter LOS, without increasing hypoglycaemia and hypokalaemia.

Diabetic muscle infarction (DMI), which is also referred to as diabetic myonecrosis, is a rare and long-term complication of poorly controlled diabetes mellitus, while we found that acute diabetes decompensation, such as diabetic ketoacidosis (DKA), could also stimulate the occurrence and development of DMI.

A 23-year-old woman with type 1 diabetes presented with a 10-day history of nausea, vomiting, pain, and swelling of her left leg. Her urine ketone test was positive. The 3-beta-hydroxybutyrate and leukocyte counts and creatine kinase levels were elevated. Magnetic resonance imaging of the left thigh revealed extensive deep tissue oedema and an increase in the T2 signal in the involved muscles. Once the diagnosis of DMI was made, she was managed with rest, celecoxib, clopidogrel and aggressive insulin therapy. Three months after treatment, the patient reported complete resolution of symptoms.

DMI is a rare DM complication with a high recurrence rate, commonly presenting with chronic complications, while our case report shows that acute diabetes decompensation, such as DKA, can stimulate the occurrence and development of DMI. Timely diagnosis and appropriate treatment could shorten the recovery time.

Post-viral new-onset diabetes has been an important feature of the COVID-19 pandemic. It is not always clear if new-onset diabetes is the unmasking of a previously undiagnosed condition, the acceleration of prediabetes, or new-onset diabetes that would not have otherwise occurred. Even asymptomatic cases of COVID-19 have been associated with new-onset diabetes. Diabetes that emerges during acute COVID-19 infection tends to have an atypical presentation, characterized by hyperglycemia and potentially life-threatening diabetic ketoacidosis. It is not always clear if new-onset diabetes is type 1 or type 2 diabetes mellitus. Many cases of COVID-associated diabetes appear to be type 1 diabetes, which is actually an autoimmune disorder. The clinical course varies temporally and with respect to outcomes; in some cases, diabetes resolves completely or improves incrementally after recovery from COVID-19. Disruptions in macrophagy caused by COVID-19 infection along with an exaggerated inflammatory response that can occur in COVID-19 also play a role. Those who survive COVID-19 remain at a 40% elevated risk for diabetes in the first year, even if their case of COVID-19 was not particularly severe. A subsequent post-pandemic wave of new diabetes patients may be expected.

Diabetic ketoacidosis (DKA), a frequent complication of type 1 diabetes (T1D), is characterized by hyperosmolar hypovolemia. The response of water-regulating hormones arginine vasopressin (AVP; antidiuretic hormone) and aldosterone to DKA treatment in children is not well understood, although they may have potential as future diagnostic, prognostic, and/or treatment monitoring markers in diabetic patients. We aimed to characterize the dynamics of the response in copeptin (marker for AVP) and aldosterone secretion to rehydration treatment in pediatric patients with DKA. Data originated from a prospective, observational, multicenter study including 28 pediatric T1D patients treated for DKA (median age, 11.5 years; weight, 35 kg). Serial measurements of hormone levels were obtained during 72 h following rehydration start. Semimechanistic pharmacometric modeling was used to analyze the kinetic/dynamic relationship of copeptin and aldosterone secretion in response to the correction of hyperosmolality and hypovolemia, respectively. Modeling revealed different sensitivities for osmolality-dependent copeptin secretion during the first 72 h of rehydration, possibly explained by an osmotic shift introduced by hypovolemia. Response in aldosterone secretion to the correction of hypovolemia seemed to be delayed, which was well described by an extra upstream turnover compartment, possibly representing chronic upregulation of aldosterone synthase (cytochrome P450 11B2). In conclusion, semimechanistic modeling provided novel physiological insights in hormonal water regulation in pediatric patients during DKA treatment, providing rationale to further evaluate the potential of monitoring copeptin, but not aldosterone due to its delayed response, for future optimization of rehydration treatment to reduce the risk of acute complications such as cerebral edema.

Diabetic ketoacidosis (DKA) and hyperosmolar hyperglycemia state (HHS) are two life-threatening metabolic complications of diabetes that significantly increase mortality and morbidity. Despite major advances, reaching a uniform consensus regarding the diagnostic criteria and treatment of both conditions has been challenging. A significant overlap between these two extremes of the hyperglycemic crisis spectrum poses an additional hurdle. It has well been noted that a complete biochemical and clinical patient evaluation with timely diagnosis and treatment is vital for symptom resolution. Worldwide, there is a lack of large-scale studies that help define how hyperglycemic crises should be managed. This article will provide a comprehensive review of the pathophysiology, diagnosis, and management of DKA-HHS overlap.