Diabetic Ketoacidosis In Children Research Articles

Cognitive Function Following Diabetic Ketoacidosis in Children With New-Onset or Previously Diagnosed Type 1 Diabetes.

This study assessed whether a single diabetic ketoacidosis (DKA) episode is associated with cognitive declines in children with newly diagnosed type 1 diabetes and whether the same is true in children who had previously been diagnosed after accounting for variations in glycemic control and other relevant factors. We prospectively enrolled 758 children, 6-18 years old, who presented with DKA in a randomized multisite clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 430 children and mild in 328 children. A total of 392 children with DKA had new onset of type 1 diabetes, and the rest were previously diagnosed. Neurocognitive assessment occurred 2-6 months after the DKA episode. A comparison group of 376 children with type 1 diabetes, but no DKA exposure, was also enrolled. Among all patients, moderate/severe DKA was associated with lower intelligence quotient (IQ) (β = -0.12, P < 0.001), item-color recall (β = -0.08, P = 0.010), and forward digit span (β = -0.06, P = 0.04). Among newly diagnosed patients, moderate/severe DKA was associated with lower item-color recall (β = -0.08, P = 0.04). Among previously diagnosed patients, repeated DKA exposure and higher HbA1c were independently associated with lower IQ (β = -0.10 and β = -0.09, respectively, P < 0.01) and higher HbA1c was associated with lower item-color recall (β = -0.10, P = 0.007) after hypoglycemia, diabetes duration, and socioeconomic status were accounted for. A single DKA episode is associated with subtle memory declines soon after type 1 diabetes diagnosis. Sizable IQ declines are detectable in children with known diabetes, suggesting that DKA effects may be exacerbated in children with chronic exposure to hyperglycemia.

Copeptin Kinetics and Its Relationship to Osmolality During Rehydration for Diabetic Ketoacidosis in Children.

Copeptin is a surrogate marker for arginine vasopressin (AVP) release in response to hyperosmolal stimuli such as diabetic ketoacidosis (DKA). 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. A prospective, observational, multicenter study was conducted. Children with T1D admitted for DKA underwent serial serum copeptin and osmolality measurements from start of rehydration at 14 time points during 72 hours. Measurements included temporal course of copeptin and osmolality (kinetics), relationship between both (dynamics), and association between-subject variability (BSV) (coefficient of variation, CV%). 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). 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.

Efficacy of low-dose insulin combined with electrolyte in the treatment of pediatric diabetic ketoacidosis and its effect on serum inflammatory factors

Diabetic ketoacidosis (DKA) is a very serious disease that can occur in both types of diabetes (type 1 and 2). It is caused by a combination of high blood sugar and low insulin levels, which can cause the body to produce too much ketone. Ketones are toxic to human organs. This research aimed to investigate the clinical efficacy of low-dose insulin combined with electrolyte in the treatment of pediatric DKA and its effect on serum inflammatory factors. For this purpose, a total of 122 children with DKA admitted to our hospital from April 2013 to May 2016 were selected as research objects. They were divided into group A with 60 cases and group B with 62 cases. Group B was treated with supplemental electrolytes, and group A was treated with low-dose insulin based on group B. The serum levels of TNF-α, IL-6, and IL-18 were measured by enzyme-linked immunosorbent assay (ELISA) before and after treatment, and the blood sugar, sodium, and potassium levels were measured by an automatic biochemical analyzer. The time when blood sugar reached the standard level when acidosis was corrected and hospitalization time was compared between the two groups. The total effective rate of group A was significantly higher than that of group B (p&lt; 0.05). There was no significant difference in blood glucose, sodium, potassium, TNF-α, IL-6, and IL-18 levels between the two groups before treatment. (all p &gt; 0.05). But the blood glucose, sodium and potassium levels in group A were significantly better than those in group B (all p&lt; 0.001). The levels of serum TNF-α, IL-6, and IL-18 in group A were significantly lower than those in group B after treatment (all p&lt; 0.001). After treatment, the time when blood sugar reached the standard level when acidosis was corrected and hospitalization time in group A were significantly shorter than those in group B (all p&lt; 0.001). Low-dose insulin combined with electrolyte supplementation is effective in the treatment of DKA in children, which can effectively control blood sugar, sodium, potassium level, and inflammatory factor concentration.

Management of Diabetic Ketoacidosis in Children and Adolescents with Type 1 Diabetes Mellitus.

Diabetic ketoacidosis (DKA) is the end result of insulin deficiency in type 1 diabetes mellitus (T1D). Loss of insulin production leads to profound catabolism with increased gluconeogenesis, glycogenolysis, lipolysis, and muscle proteolysis causing hyperglycemia and osmotic diuresis. High levels of counter-regulatory hormones lead to enhanced ketogenesis and the release of 'ketone bodies' into the circulation, which dissociate to release hydrogen ions and cause an overwhelming acidosis. Dehydration, hyperglycemia, and ketoacidosis are the hallmarks of this condition. Treatment is effective repletion of insulin, fluids and electrolytes. Newer approaches to early diagnosis, treatment, and prevention may diminish the risk of DKA and its childhood complications including cerebral edema. However, the potential for some technical and pharmacologic advances in the management of T1D to increase DKA events must be recognized.

Incidence Trends of Diabetic Ketoacidosis in Children and Adolescents with Type 1 Diabetes in British Columbia, Canada

To estimate the 11-year incidence trend of diabetic ketoacidosis (DKA) at and after the diagnosis of type 1 diabetes. A retrospective cohort study using a population-based administrative cohort diagnosed with type 1 diabetes at <20years of age from 2002 to 2012 in British Columbia, Canada. DKA at (1 episode per individual) andDKA after (multiple episodes per individual) the diagnosis of diabetes were defined as DKA occurring ≤14days or >14days, respectively, from diagnosis, identified using International Classification of Diseases,9th and 10theditions codes. Incidence rate ratios were estimated using Poisson regression and DKA trends using Joinpoint regression analyses. There were 1519 individuals (mean age at first-DKA, 12.6±5.9years; 50% male) with ≥1 DKA episode identified. Of 2615 incident cases of type 1 diabetes, there were 847 (32.4%; mean age, 9.9±4.8years; 52% male) episodes of DKA at the diagnosis of diabetes. Among prevalent cases of type 1 diabetes (1790 cases in 2002 increasing to 2264 in 2012), there were 1886 episodes of DKA after the diagnosis of diabetes (mean age at first DKA, 15.7±5.2years). The rates per 100 person-years of DKA at diabetes diagnosis (ranging from 24.1 in 2008 to 37.3 in 2006) and DKA after diabetes diagnosis (ranging from 4.9 in 2002 to 7.7 in 2008) remained stable. Females showed a 67% higher rate of incidence of DKA after the diagnosis of diabetes compared with their male counterparts (incidence rate ratio, 1.67; 95% CI, 1.50-1.86; P<.001), adjusted for the temporal trend by fiscal year. Younger age at diagnosis (<5years) was associated with a greater risk of DKA at the time of diabetes diagnosis and older children (≥10years) had a greater risk of DKA after the diagnosis of diabetes. The risk of DKA at the time of diagnosis of diabetes was greater with younger age and the risk of DKA after the diagnosis of diabetes was higher in females and older children and youth.

The persistent challenge of diabetic ketoacidosis in children and adolescents with type 1 diabetes

The persistent challenge of diabetic ketoacidosis in children and adolescents with type 1 diabetes

Hypertension during Diabetic Ketoacidosis in Children

To characterize hemodynamic alterations occurring during diabetic ketoacidosis (DKA) in a large cohort of children and to identify clinical and biochemical factors associated with hypertension. This was a planned secondary analysis of data from the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in DKA Study, a randomized clinical trial of fluid resuscitation protocols for children in DKA. Hemodynamic data (heart rate, blood pressure) from children with DKA were assessed in comparison with normal values for age and sex. Multivariable statistical modeling was used to explore clinical and laboratory predictors of hypertension. Among 1258 DKA episodes, hypertension was documented at presentation in 154 (12.2%) and developed during DKA treatment in an additional 196 (15.6%), resulting in a total of 350 DKA episodes (27.8%) in which hypertension occurred at some time. Factors associated with hypertension at presentation included more severe acidosis, (lower pH and lower pCO2), and stage 2 or 3 acute kidney injury. More severe acidosis and lower Glasgow Coma Scale scores were associated with hypertension occurring at any time during DKA treatment. Despite dehydration, hypertension occurs in a substantial number of children with DKA. Factors associated with hypertension include greater severity of acidosis, lower pCO2, and lower Glasgow Coma Scale scores during DKA treatment, suggesting that hypertension might be centrally mediated.

Diabetic ketoacidosis at the onset of disease during a national awareness campaign: a 2-year observational study in children aged 0–18 years

ObjectiveAfter a previous survey on the incidence of diabetic ketoacidosis (DKA) at onset of type 1 diabetes in children in 2013–2014 in Italy, we aimed to verify a possible decline...

Plasma β-Hydroxybutyrate for the Diagnosis of Diabetic Ketoacidosis in the Emergency Department.

Diabetic ketoacidosis (DKA) is a common emergency department presentation of both new-onset and established diabetes mellitus (DM). β-Hydroxybutyrate (BOHB) provides a direct measure of the pathophysiologic derangement in DKA as compared with the nonspecific measurements of blood pH and bicarbonate. Our objective was to characterize the relationship between BOHB and DKA. This is a cross-sectional retrospective study of pediatric patients with DM presenting to an urban pediatric emergency department between January 1, 2016, and September 30, 2018. Analyses were performed on each patient's initial, simultaneous BOHB and pH. Diagnostic test characteristics of BOHB were calculated, and logistic regression was performed to investigate the effects of age and other key clinical factors. Among 594 patients with DM, with median age of 12.3 years (interquartile range, 8.7-15.9 years), 176 (29.6%) presented with DKA. The inclusion of age, transfer status, and new-onset in the statistical model did not improve the prediction of DKA beyond BOHB alone. β-Hydroxybutyrate demonstrated strong discrimination for DKA, with an area under the curve of 0.95 (95% confidence interval, 0.93-0.97). A BOHB value of 5.3 mmol/L predicted DKA with optimal accuracy (90.6% of patients were correctly classified). The sensitivity, specificity, and positive and negative predictive values of this cut point were 76.7% (95% confidence interval, 69.8%-82.7%), 96.4% (94.2%-98.0%), 90.0% (84.0%-94.3%), and 90.8% (87.7%-93.3%), respectively. β-Hydroxybutyrate accurately predicts DKA in children and adolescents. More importantly, because plasma BOHB is the ideal biochemical marker of DKA, BOHB may provide a more optimal definition of DKA for management decisions and treatment targets.

Management of diabetic ketoacidosis in children and spectrum of complications in the pediatric intensive care unit

Management of diabetic ketoacidosis in children and spectrum of complications in the pediatric intensive care unit

Audit on the management of diabetic ketoacidosis in children in 2 District General Hospitals: creation of a DKA pathway

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Improving Emergency Department Management of Diabetic Ketoacidosis in Children.

Diagnostic delays in the pediatric emergency department (ED) can lead to unnecessary interventions and prolonged ED length of stay (LOS), especially in patients with diabetes mellitus evaluated for diabetic ketoacidosis (DKA). At our institution, baseline DKA determination time (arrival to diagnosis) was 86 minutes, and 61% of patients did not meet DKA criteria. Subsequently, intravenous (IV) placement occurred in 85% of patients without DKA. We aimed to use point-of-care (POC) testing to reduce DKA determination time from 86 to 30 minutes and to reduce IV placements in patients without DKA from 85% to 20% over 18 months. Four key interventions (POC tests, order panels, provider guidelines, and nursing guidelines) were tested by using plan-do-study-act cycles. DKA determination time was our primary outcome, and secondary outcomes included the percentage of patients receiving IV placement and ED LOS. Process measures included the rate of use of POC testing and order panels. All measures were analyzed on statistical process control charts. Between January 2015 and July 2018, 783 patients with diabetes mellitus were evaluated for DKA. After all 4 interventions, DKA determination time decreased from 86 to 26 minutes (P < .001). In patients without DKA, IV placement decreased from 85% to 36% (P < .001). ED LOS decreased from 206 to 186 minutes (P = .009) in patients discharged from the hospital after DKA evaluation. POC testing and order panel use increased from 0% to 98% and 90%, respectively. Using quality-improvement methodology, we achieved a meaningful reduction in DKA determination time, the percentage of IV placements, and ED LOS.

Incidence of diabetic ketoacidosis in newly diagnosed type 1 diabetes children in western Saudi Arabia: 11-year experience.

Background A wide range of reports on the incidence of diabetic ketoacidosis (DKA) at the onset of type 1 diabetes mellitus (T1DM) in children have been published worldwide. Reports from Saudi Arabia are limited. The aim of this study was to assess the incidence, clinical pattern and severity of DKA in children with newly diagnosed T1DM and the association of autoimmune conditions with initial DKA occurrence at King Abdulaziz Medical City - Jeddah. Methods This retrospective chart review was conducted during the period 2005-2015. All newly diagnosed T1DM children during the study period were investigated (n = 390). Data were collected on the demographic characteristics, body mass index (BMI), DKA severity, length of hospital stay and follow-up data on the type of diabetes therapy. Results The incidence of DKA among newly diagnosed T1DM pediatric patients was 37.7% (n = 147). Moderate and severe DKA cases were significantly higher among female children (p = 0.04). Patients diagnosed with DKA had lower BMI (20.87 ± 5.21) than their counterparts (p = 0.03). The median length of hospital stay was higher among severe DKA compared to moderate and mild cases (5.0, 4.5 and 4.0 days, respectively). Conclusions The incidence of DKA among newly diagnosed T1DM is still high compared to developed countries; however, it is relatively lower than previous reports in Saudi Arabia. Immediate interventions, such as awareness campaigns, are vital to reduce the burden of this preventable health sequela among children with DM.

Oxidative Stress Markers in Diabetic Ketoacidosis in Children and Adolescents

Oxidative Stress Markers in Diabetic Ketoacidosis in Children and Adolescents

Diabetic ketoacidosis in children newly diagnosed with type 1 diabetes mellitus: Role of demographic, clinical, and biochemical features along with genetic and immunological markers as risk factors. A 20-year experience in a tertiary Belgian center.

Diabetic ketoacidosis (DKA) is the leading cause of morbidity and mortality in children with type 1 diabetes (T1D). Little is known about the association between genetic and immunological markers and the risk for DKA at onset of T1D. The aim of this study was to create a model foreseeing the onset of DKA in newly diagnosed patients. This retrospective study included 532 T1D children (aged <18 years at diagnosis) recruited in our hospital, from 1995 to 2014. DKA and its severity were defined according to the criteria of ISPAD. Genetic risk categories for developing T1D were defined according to the Belgian Diabetes Registry. Multivariate statistical analyses were applied to investigate risk factors related to DKA at diagnosis. Overall 42% of patients presented DKA at diagnosis. This study outlined the major risk of DKA at diagnosis for younger children (<3 years) and for those belonging to ethnic minorities. Children carrying neutral genotypes had a 1.5-fold increased risk of DKA at diagnosis than those with susceptible or protective genotypes, a paradoxical observation not previously reported. Only solitary positive IA-2A increased the risk of DKA at diagnosis. The proposed model could help to predict the probability of DKA in 70% of newly diagnosed cases. This was the first reported implication of IA-2A positivity and neutral genotypes predisposing to DKA at diagnosis regardless of its severity. Earlier diagnosis through genetic and immunological screening of high-risk children could decrease DKA incidence at diabetes onset.

Is Age a Risk Factor for Cerebral Edema in Children With Diabetic Ketoacidosis? A Literature Review.

Cerebral edema (CE) is a rare but potentially fatal complication of diabetic ketoacidosis (DKA) in children with type 1 diabetes. CE is frequently mentioned as being more common in young children. The primary objective of this study was to review the evidence suggesting that younger age is a risk factor for the development of CE during DKA. The secondary objective was to assess if younger children are at a higher risk of DKA and severe DKA. A literature review was performed, and studies which reported the frequency of CE, DKA and severe DKA in children <3 and 3 to 5years of age were included. Among the 6 studies reporting the frequency of CE that were identified, 5 good-quality studies found no significant association between younger age and higher risk of CE. Twenty-seven studies (DKA frequency: 11.3% to 54%) reported DKA frequency as a function of age. Most published studies found a higher frequency of DKA in children <5years of age (20/25 studies), and in particular in those in the first 2 to 3years of life (8/8 studies). There was inconclusive evidence to determine whether the severity of DKA was influenced by age. In conclusion, the commonly held view that CE is more common in younger children is not supported by the existing literature. Published data suggest that DKA (and possibly severe DKA) is more common in very young children. Regardless of age, all children with DKA should be monitored carefully for the development of CE.

Precipitating Factors, Clinical Features and Outcome of Diabetic Ketoacidosis in Children in a Tertiary Care Hospital of Bangladesh

Background: Diabetic ketoacidosis (DKA) is a major complication of type 1 and type 2 diabetes mellitus and is associated with increased risk of morbidity and mortality. Infections, non-compliance and co-morbid states are most important precipitating causes. Proper identification of the precipitating factor is very important in management of DKA. Clinical feature and management of DKA are well known and have been described in many text books and reviews in literature. However, there are a very few published large studies from Bangladesh. For this reason, this study had evaluated fifty children with Diabetic ketoacidosis and to identify their clinical features, precipitating factors and outcome.&#x0D; Methods: This observational study was done among admitted children with DKA in the deptartment of Paediatrics of Bangladesh Institute of Research and Rehabilitation for Diabetes, Endocrine and Metabolic Disorders (BIRDEM) General Hospital during study period between September 2016 to February 2017.&#x0D; Results: Fifty children were admitted with Diabetic ketoacidosis. Seventy percent were new diabetes cases and the remaining (30%) were known diabetic patient. Majority (62%) were female. Mean age was 9.31 years with 4.40 standard deviation. Infection was the commonest (62%) precipitating factor followed by insulin omission (10%). Major clinical features were dehydration (100%), polyuria (98%), Kussmaul’s breathing (60%) and abdominal pain (38%). Eighty four percent patients improved after treatment and 16% patient developed complications like acute kidney injury and septicaemia. There was no mortality.&#x0D; Conclusion: Infection was the commonest precipitating factor of DKA. Kussmaul’s breathing and dehydration were the commonest clinical features. Most of the patients improved after treatment&#x0D; Birdem Med J 2019; 9(2): 121-126

Diabetic ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes in Tigray, Ethiopia: retrospective observational study.

Background: Diabetic ketoacidosis (DKA) is the most severe acute complication of type 1 diabetes mellitus which results in increased risk of morbidity and mortality especially in developing countries.Objective: To assess prevalence and associated factors of diabetic ketoacidosis in children and adolescents with newly diagnosed type 1 diabetes in hospitals of the Tigray region, Ethiopia.Methods: A facility based retrospective observational study design was conducted in newly diagnosed type 1 diabetic children and adolescents up to the age of 18 years who were registered in 13 general and two referral hospitals from January 1, 2013 to December 30, 2017. The diagnosis of diabetic ketoacidosis was made with the criteria below, Children presenting with polysymptoms, weight loss, vomiting, dehydration, and also the indirect signs or effects of acidosis on respiratory and central nervous systems like Kussmaul breathing, lethargy or coma and biochemically random blood sugar level >11 ml/L, glucosuria and urine ketone >+1 and diagnosed with type 1 diabetes for the first time. Descriptive, Mann–Whitney U and logistic regression analysis were carried out to describe and identify the associated factors with diabetic ketoacidosis.Results: More than three-quarters, 258/328 (78.7%) of the newly diagnosed type 1 diabetes patients, presented with diabetic ketoacidosis at initial diagnosis. Median age of diabetic ketoacidosis patients was 11 years. The patients with diabetic ketoacidosis were younger than nondiabetic ketoacidosis patients (11 vs 13 years, P=0.002). The mortality rate of diabetic ketoacidosis was 4.3%. Young age, presence of precipitating factors and symptoms of DKA/diabetes were found to be highly associated with diabetic ketoacidosis at initial diagnosis.Conclusions: The prevalence of diabetic ketoacidosis was alarmingly high. Young age group patients, precipitating factors and the presence of symptoms of diabetes/DKA like excessive drinking, vomiting and fatigue were highly associated with diabetic ketoacidosis.

Acute renal failure requiring renal replacement therapy in an adolescent with new onset type-I diabetes mellitus presenting with severe diabetic ketoacidosis

Background: Acute renal failure in diabetic ketoacidosis (DKA) is a complex pathophysiological state. Very few reports describe this condition and little is known regarding its optimum management. We report a case of acute renal failure in severe DKA in an adolescent boy. Early renal replacement therapy and maintaining serum osmolality in narrow range has shown complete neurological recovery. There is urgent need for developing guidelines for management of renal failure in DKA in children.

Fluid treatment for children with diabetic ketoacidosis: How do the results of the pediatric emergency care applied research network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (FLUID) Trial change our perspective?

The optimal fluid treatment protocol for children with diabetic ketoacidosis (DKA) has long been a subject of controversy. Until recently, there was no high-quality evidence from randomized clinical trials to support an optimal guideline, and recommendations were mainly based on theoretical considerations. As a consequence, fluid treatment protocols for children with DKA vary between institutions (and countries). In June 2018, the results from the Fluid Therapies Under Investigation in DKA Trial conducted in the Pediatric Emergency Care Applied Research Network were published. This large, factorial-designed randomized controlled trial assessed neurological outcomes of 1387 children with DKA who were treated with one of four fluid protocols that varied in infusion rate and sodium content. In this commentary, we review and discuss the results of this new study and the implications for clinical care of DKA in children.