Pyuria in Children with Diabetic Ketoacidosis.

Acute kidney injury occurs frequently during pediatric diabetic ketoacidosis (DKA). We reviewed urinalyses from 561 children with DKA; pyuria was detected in 19% overall and in 40% of children with more comprehensive urine testing (≥3 urinalyses) during DKA.

Clinical and Laboratory Predictors of Dehydration Severity in Children With Diabetic Ketoacidosis.

STUDY OBJECTIVE: Our primary objective was to characterize the degree of dehydration in children with diabetic ketoacidosis (DKA) and identify physical examination and biochemical factors associated with dehydration severity. Secondary objectives included describing relationships between dehydration severity and other clinical outcomes. METHODS: In this cohort study, we analyzed data from 753 children with 811 episodes of DKA in the Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation Study, a randomized clinical trial of fluid resuscitation protocols for children with DKA. We used multivariable regression analyses to identify physical examination and biochemical factors associated with dehydration severity, and we described associations between dehydration severity and DKA outcomes. RESULTS: Mean dehydration was 5.7% (SD 3.6%). Mild (0 to <5%), moderate (5 to <10%), and severe (≥10%) dehydration were observed in 47% (N=379), 42% (N=343), and 11% (N=89) of episodes, respectively. In multivariable analyses, more severe dehydration was associated with new onset of diabetes, higher blood urea nitrogen, lower pH, higher anion gap, and diastolic hypertension. However, there was substantial overlap in these variables between dehydration groups. The mean length of hospital stay was longer for patients with moderate and severe dehydration, both in new onset and established diabetes. CONCLUSION: Most children with DKA have mild-to-moderate dehydration. Although biochemical measures were more closely associated with the severity of dehydration than clinical assessments, neither were sufficiently predictive to inform rehydration practice.

Clinical Characteristics of Children with Cerebral Injury preceding Treatment of Diabetic Ketoacidosis.

Previous studies have identified more severe acidosis and higher blood urea nitrogen (BUN) as risk factors for cerebral injury during treatment of diabetic ketoacidosis (DKA) in children; however, cerebral injury also can occur before DKA treatment. We found that lower pH and higher BUN levels also were associated with cerebral injury at presentation.

Clinical Trial of Fluid Infusion Rates for Pediatric Diabetic Ketoacidosis.

BACKGROUND: Diabetic ketoacidosis in children may cause brain injuries ranging from mild to severe. Whether intravenous fluids contribute to these injuries has been debated for decades. METHODS: We conducted a 13-center, randomized, controlled trial that examined the effects of the rate of administration and the sodium chloride content of intravenous fluids on neurologic outcomes in children with diabetic ketoacidosis. Children were randomly assigned to one of four treatment groups in a 2-by-2 factorial design (0.9% or 0.45% sodium chloride content and rapid or slow rate of administration). The primary outcome was a decline in mental status (two consecutive Glasgow Coma Scale scores of <14, on a scale ranging from 3 to 15, with lower scores indicating worse mental status) during treatment for diabetic ketoacidosis. Secondary outcomes included clinically apparent brain injury during treatment for diabetic ketoacidosis, short-term memory during treatment for diabetic ketoacidosis, and memory and IQ 2 to 6 months after recovery from diabetic ketoacidosis. RESULTS: A total of 1389 episodes of diabetic ketoacidosis were reported in 1255 children. The Glasgow Coma Scale score declined to less than 14 in 48 episodes (3.5%), and clinically apparent brain injury occurred in 12 episodes (0.9%). No significant differences among the treatment groups were observed with respect to the percentage of episodes in which the Glasgow Coma Scale score declined to below 14, the magnitude of decline in the Glasgow Coma Scale score, or the duration of time in which the Glasgow Coma Scale score was less than 14; with respect to the results of the tests of short-term memory; or with respect to the incidence of clinically apparent brain injury during treatment for diabetic ketoacidosis. Memory and IQ scores obtained after the children's recovery from diabetic ketoacidosis also did not differ significantly among the groups. Serious adverse events other than altered mental status were rare and occurred with similar frequency in all treatment groups. CONCLUSIONS: Neither the rate of administration nor the sodium chloride content of intravenous fluids significantly influenced neurologic outcomes in children with diabetic ketoacidosis. (Funded by the Eunice Kennedy Shriver National Institute of Child Health and Human Development and the Health Resources and Services Administration; PECARN DKA FLUID ClinicalTrials.gov number, NCT00629707 .).

Hypertension during Diabetic Ketoacidosis in Children.

OBJECTIVES: 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. STUDY DESIGN: 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. RESULTS: 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. CONCLUSIONS: 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.

Regional Brain Water Content and Distribution During Diabetic Ketoacidosis.

OBJECTIVE: To characterize regional differences in brain water distribution and content during diabetic ketoacidosis (DKA) in children and determine whether these differences correlate with regional vascular supply. STUDY DESIGN: We compared changes in brain water distribution and water content in different brain regions during DKA by analyzing magnetic resonance diffusion weighted imaging data collected during DKA and after recovery in 45 children (<18 years of age). We measured the apparent diffusion coefficient (ADC) of water in the frontal and occipital cortex, basal ganglia, thalamus, hippocampus, and medulla. Brain water content was also measured in a subset of patients. RESULTS: ADC values were elevated (suggesting vasogenic cerebral edema) in the frontal cortex, basal ganglia, thalamus, and hippocampus during DKA. In contrast, ADC values in the medulla and the occipital cortex were not increased during DKA, and ADC changes in the medulla tended to be negatively correlated with other regions. Regions supplied by the anterior/middle cerebral artery circulation had greater elevations in both ADC and brain water content during DKA compared with regions supplied by the posterior cerebral artery circulation. CONCLUSIONS: ADC changes during DKA in the brainstem contrast with those of other brain regions, and changes in both ADC and brain water content during DKA vary according to regional vascular supply. These data suggest that brainstem blood flow might possibly be reduced during DKA concurrent with hyperemia in other brain regions.

Hydration status moderates the effects of drinking water on children's cognitive performance.

Changes in hydration status throughout the day may affect cognitive performance with implications for learning success in the classroom. Our study tested the hypothesis that the benefit of drinking water on working memory and attention depends upon children's hydration status and renal response to water intake. Fifty-two children aged 9-12 years old were tested under two experimental conditions. The treatment session (Water session) consisted of a standard breakfast with 200 ml water, a baseline test, consumption of 750 ml of water over a period of two hours and subsequently retested. No water was provided after breakfast during the control session. Changes in hydration were assessed via urine samples. Cognitive testing consisted of digit span, pair cancellation, and delayed match to sample tasks. Children who exhibited smaller decreases in urine osmolality following water intake performed significantly better on the water day compared to the control day on a digit-span task and pair-cancellation task. Children who exhibited larger decreases in urine osmolality following water intake performed better on the control day compared to the water day on the digit-span task and pair-cancellation task. These results suggest that focusing on adequate hydration over time may be key for cognitive enhancement.

Cerebral hyperemia measured with near infrared spectroscopy during treatment of diabetic ketoacidosis in children.

OBJECTIVE: To use near infrared spectroscopy (NIRS) to evaluate the timing of onset and duration of cerebral hyperemia during diabetic ketoacidosis (DKA) treatment in children, and to investigate the relationship of cerebral hyperemia to intravenous fluid treatment. STUDY DESIGN: We randomized children aged 8-18 years with DKA to either more rapid or slower intravenous fluid treatment (19 total DKA episodes). NIRS was used to measure rSo2 during DKA treatment. NIRS monitoring began as soon as informed consent was obtained and continued until the patient was transferred out of the critical care unit. RESULTS: rSo2 values above the normal range (>80%) were detected in 17 of 19 DKA episodes (mean rSo2 during initial 8 hours of DKA treatment: 86% ± 7%, range 65%-95%). Elevated rSo2 values were detected as early as the second hour of DKA treatment and persisted for as long as 27 hours. Hourly mean rSo2 levels during treatment did not differ significantly by fluid treatment group. CONCLUSIONS: During DKA treatment, children have elevated rSo2 values consistent with cerebral hyperemia. Hyperemia occurs as early as the second hour of DKA treatment and may persist for ≥ 27 hours. Cerebral rSo2 levels during treatment did not differ significantly in patients treated with slower versus more rapid intravenous rehydration.

Pediatric diabetic ketoacidosis, fluid therapy, and cerebral injury: the design of a factorial randomized controlled trial.

Treatment protocols for pediatric diabetic ketoacidosis (DKA) vary considerably among centers in the USA and worldwide. The optimal protocol for intravenous (IV) fluid administration is an area of particular controversy, mainly in regard to possible associations between rates of IV fluid infusion and the development of cerebral edema (CE), the most common and the most feared complication of DKA in children. Theoretical concerns about associations between osmotic fluid shifts and CE have prompted recommendations for conservative fluid infusion during DKA. However, recent data suggest that cerebral hypoperfusion may play a role in cerebral injury associated with DKA. Currently, there are no existing data from prospective clinical trials to determine the optimal fluid treatment protocol for pediatric DKA. The Pediatric Emergency Care Applied Research Network FLUID (FLuid therapies Under Investigation in DKA) study is the first prospective randomized trial to evaluate fluid regimens for pediatric DKA. This 13-center nationwide factorial design study will evaluate the effects of rehydration rate and fluid sodium content on neurological status during DKA treatment, the frequency of clinically overt CE and long-term neurocognitive outcomes following DKA.

Remote glucose monitoring is feasible for patients and providers using a commercially available population health platform.

Objective: Remote patient monitoring (RPM) holds potential to enable more individualized and effective care for patients with type 1 diabetes (T1D), but requires population analytics to focus limited clinical resources on patients most in need. We explored the feasibility of RPM from patient and provider standpoints using a commercially available data analytic platform (glooko Population Health) among a cohort of youth with T1D. Study design: Patients aged 1-20 years with established T1D (≥12 months) and CGM use (≥3 months) were recruited to participate. Participants' CGM devices were connected to the glooko app and linked to the research team's glooko account during a one-month baseline period. This was followed by a six-month intervention period during which participants with >15% of glucose values >250 mg/dl or >5% of values <70 mg/dl each month were contacted with personalized diabetes management recommendations. Participants were surveyed about their experiences, and effects on glycemic control were estimated via change in glucose management indicator (GMI) generated from CGM data at baseline and completion. Changes in time spent within various glucose ranges were also evaluated, and all glycemic metrics were compared to a non-randomized control group via difference-in-difference regression, adjusting for baseline characteristics. Results: Remote data-sharing was successful for 36 of 39 participants (92%). Between 33%-66% of participants merited outreach each month, and clinician outreach required a median of 10 minutes per event. RPM was reported to be helpful by 94% of participants. RPM was associated with a GMI change of -0.25% (P=0.047) for the entire cohort, and stratified analysis revealed greatest treatment effects among participants with baseline GMI of 8.0-9.4% (GMI change of -0.68%, P=0.047; 19.84% reduction in time spent >250 mg/dl, P=0.005). Conclusions: This study demonstrates the feasibility of RPM for patients with T1D using a commercially available population health platform, and suggests that RPM with clinician-initiated outreach may be particularly beneficial for patients with suboptimal glycemic control at entry. However, larger randomized studies are needed to fully explore the glycemic impact of RPM. Clinical trial registration: https://clinicaltrials.gov/ct2/show/NCT04696640, identifier NCT04696640.

Cognitive function following diabetic ketoacidosis in young children with type 1 diabetes.

INTRODUCTION: Young children with type 1 diabetes (T1D) may be at particularly high risk of cognitive decline following diabetic ketoacidosis (DKA). However, studies of cognitive functioning in T1D typically examine school-age children. The goal of this study was to examine whether a single experience of DKA is associated with lower cognitive functioning in young children. We found that recently diagnosed 3- to 5-year-olds who experienced one DKA episode, regardless of its severity, exhibited lower IQ scores than those with no DKA exposure. METHODS: We prospectively enrolled 46 3- to 5-year-old children, who presented with DKA at the onset of T1D, in a randomized multi-site clinical trial evaluating intravenous fluid protocols for DKA treatment. DKA was moderate/severe in 22 children and mild in 24 children. Neurocognitive function was assessed once 2-6 months after the DKA episode. A comparison group of 27 children with T1D, but no DKA exposure, was also assessed. Patient groups were matched for age and T1D duration at the time of neurocognitive testing. RESULTS: Children who experienced DKA, regardless of its severity, exhibited significantly lower IQ scores than children who did not experience DKA, F(2, 70) = 6.26, p = .003, partial η2  = .15. This effect persisted after accounting for socioeconomic status and ethnicity. CONCLUSIONS: A single DKA episode is associated with lower IQ scores soon after exposure to DKA in young children.

Relationships among biochemical measures in children with diabetic ketoacidosis.

OBJECTIVES: Investigating empirical relationships among laboratory measures in children with diabetic ketoacidosis (DKA) can provide insights into physiological alterations occurring during DKA. We determined whether alterations in laboratory measures during DKA conform to theoretical predictions. METHODS: We used Pearson correlation statistics and linear regression to investigate correlations between blood glucose, electrolytes, pH and PCO2 at emergency department presentation in 1,681 pediatric DKA episodes. Among children with repeat DKA episodes, we also assessed correlations between laboratory measures at the first vs. second episode. RESULTS: pH and bicarbonate levels were strongly correlated (r=0.64), however, pH and PCO2 were only loosely correlated (r=0.17). Glucose levels were correlated with indicators of dehydration and kidney function (blood urea nitrogen (BUN), r=0.44; creatinine, r=0.42; glucose-corrected sodium, r=0.32). Among children with repeat DKA episodes, PCO2 levels tended to be similar at the first vs. second episode (r=0.34), although pH levels were only loosely correlated (r=0.19). CONCLUSIONS: Elevated glucose levels at DKA presentation largely reflect alterations in glomerular filtration rate. pH and PCO2 are weakly correlated suggesting that respiratory responses to acidosis vary among individuals and may be influenced by pulmonary and central nervous system effects of DKA.

Rehydration Rates and Outcomes in Overweight Children With Diabetic Ketoacidosis.

BACKGROUND AND OBJECTIVES: The Pediatric Emergency Care Applied Research Network Fluid Therapies Under Investigation in Diabetic Ketoacidosis (DKA) (FLUID) Trial found that rapid fluid infusion does not increase the risk of cerebral injury. Concern persists, however, whether fluid rates should be adjusted for overweight or obese patients. We used the FLUID Trial database to evaluate associations between fluid infusion rate and outcomes in these patients. METHODS: We compared children and youth who were overweight, obese, or normal weight, in regard to protocol adherence, mental status changes, time to DKA resolution, and electrolyte abnormalities. We investigated associations between outcomes and the amount of fluid received in these groups. RESULTS: Obese children and youth were more likely to receive fluids at rates slower than dictated by protocol. Overweight and obese children and youth in the fast fluid arms, who received fluids per the study protocol based on their measured weight, had similar rates of mental status changes or clinically apparent cerebral injury as those with normal weights. Risk of hypophosphatemia was increased in those receiving larger initial bolus volumes and reduced in those receiving higher rehydration rates. No other metabolic outcomes were associated with rehydration. CONCLUSIONS: Protocol adherence data in the FLUID Trial suggest that physicians are uncomfortable using weight-based fluid calculations for overweight or obese children. However, higher rates of fluid infusion were not associated with increased risk of mental status changes or cerebral injury, suggesting that physicians should not limit fluid resuscitation in obese children and youth with DKA.

Parental marital relationship satisfaction predicts glycemic outcomes in children with type 1 diabetes.

OBJECTIVES: Glycemic outcomes in children with type 1 diabetes (T1D) vary widely, despite uniform care. We hypothesized that glycemic outcomes in children with T1D are affected by the marital relationship satisfaction of the child's parents. METHODS: We evaluated a prospective sample of 51 families with a child with newly diagnosed T1D, including 36 married parent families. We assessed indicators of marital relationship satisfaction and used multiple regression models to determine whether marital relationship satisfaction at diagnosis was associated with mean HbA1c 18-24 months after diagnosis. RESULTS: Marital status and parental relationship satisfaction at the time of the child's T1D diagnosis were associated with HbA1c 18-24 months later. These differences persisted after adjusting for demographic factors associated with glycemia. CONCLUSIONS: The quality of the primary diabetes caregiver's relationship with a spouse predicts glycemic outcomes for children with T1D. Interventions to improve spousal relationships and caregiver support could improve glycemic control in children with T1D.

Parental marital relationship satisfaction is associated with glycemic outcomes in children with type 1 diabetes.

Objectives: We hypothesized that glycemic outcomes in children with type 1 diabetes are linked to marital satisfaction of primary caregivers above and beyond parent neuroticism and child effortful control. Methods: We evaluated a cross-sectional sample of 73 married parent families with a child (ages 7-18 years) with type 1 diabetes of at least 2 years duration. We assessed marital relationship satisfaction, parent neuroticism, and child effortful control through the use of validated questionnaires. We used univariate comparisons and multivariable models to determine whether marital relationship satisfaction was associated with hemoglobin A1c [HbA1c] and whether this association persisted after adjusting for demographic factors and parent neuroticism/child effortful control. Results: In univariate analyses, HbA1c was associated with marital relationship satisfaction of the primary caregiver. In multivariable models adjusting for demographic factors, marital satisfaction remained associated with HbA1c, whereas none of the other factors tested (including family income and race/ethnicity) retained significance. In univariate analyses, child effortful control was also associated with HbA1c. When child effortful control was added to the multivariable model, marital satisfaction remained associated with HbA1c with similar coefficient and confidence intervals describing the relationship between marital satisfaction and hemoglobin A1c. Conclusions: Higher levels of marital satisfaction of the primary diabetes caregiver are associated with glycemic outcomes for children with type 1 diabetes. Interventions to improve spousal relationships may have downstream benefits that could include promoting more optimal child HbA1c levels.

High frequency of cardiac and behavioral complaints as presenting symptoms of hyperthyroidism in children.

OBJECTIVE: Descriptive data characterizing the frequency of various chief complaints and presenting symptomatology in children with hyperthyroidism are lacking. Furthermore, difficulties in recognizing atypical presentations may delay diagnosis and increase morbidity. METHODS: We performed a retrospective review of the medical records of 76 children with hyperthyroidism to characterize their chief complaints at initial presentation to care and document other presenting symptomatology. RESULTS: Cardiac symptoms were the most frequent chief complaint, accounting for 23% of presenting complaints. Major mood and behavior disturbances were also frequently present (21%), but were infrequently cited as the chief complaint (6%). CONCLUSIONS: This study is the first to describe chief complaints separately from the other signs and symptoms of hyperthyroidism noted at the time of presentation to medical attention. Cardiac complaints were the most common: however, complaints associated with behavioral and mood disorders also occurred frequently. Clinicians should be aware of these presentations so that hyperthyroidism is diagnosed promptly to avoid morbidity associated with delayed diagnosis.

Patient Perspectives on Use of Video Telemedicine for Type 1 Diabetes Care in the United States during the COVID-19 Pandemic.

The COVID-19 pandemic has resulted in widespread adoption of telemedicine for management of chronic conditions such as type 1 diabetes (T1D), but few data have been collected about the patient experience and perceived quality of care during this time. We surveyed members of the T1D Exchange patient registry and online community regarding their experiences with and opinions about telemedicine care during the pandemic. Among 2235 survey respondents, 65% had utilized telemedicine. The most common reasons for adopting telemedicine were providers not offering in-person care (66%), concerns about the health risks of in-person care (59%), providers offering (52%) or insurance covering (19%) telemedicine for the first time, and local or state orders to stay home (33%). Among telemedicine users, 62% felt video care was as effective as or more effective than in-person care, and 82% hoped to use telemedicine in the future. The most-cited reason for non-use of telemedicine was that providers were not offering it (49%). Our findings highlight the role of telemedicine in maintaining access to T1D care during the COVID-19 pandemic. Respondents' satisfaction with telemedicine and interest in its continued use signifies the need for ongoing access to this care modality and for the development of telemedicine best practices within T1D care.

Enroller Experience and Parental Familiarity of Disease Influence Participation in a Pediatric Trial.

INTRODUCTION: Acquiring parental consent is critical to pediatric clinical research, especially in interventional trials. In this study we investigated demographic, clinical, and environmental factors associated with likelihood of parental permission for enrollment in a study of therapies for diabetic ketoacidosis (DKA) in children. METHODS: We analyzed data from patients and parents who were approached for enrollment in the Pediatric Emergency Care Applied Research Network (PECARN) Fluid Therapies Under Investigation in DKA (FLUID) trial at one major participating center. We determined the influence of various factors on patient enrollment, including gender, age, distance from home to hospital, insurance status, known vs new onset of diabetes, glycemic control (hemoglobin A1c), DKA severity, gender of the enroller, experience of the enroller, and time of enrollment. Patients whose parents consented to participate were compared to those who declined participation using bivariable and multivariable analyses controlling for the enroller. RESULTS: A total of 250 patient/parent dyads were approached; 177 (71%) agreed to participate, and 73 (29%) declined. Parents of patients with previous episodes of DKA agreed to enroll more frequently than those with a first DKA episode (94.3% for patients with 1-2 previous DKA episodes, 92.3% for > 2 previous episodes, vs 64.9% for new onset diabetes and 63.2% previously diagnosed but no previous DKA). Participation was also more likely with more experienced enrollers (odds ratio [95% confidence interval] of participation for an enroller with more than two years' experience vs less than two years: 2.46 [1.53, 3.97]). After adjusting for demographic and clinical factors, significant associations between participation and both DKA history and enroller experience remained. Patient age, gender, distance of home from hospital, glycemic control, insurance status, and measures of DKA severity were not associated with likelihood of participation. CONCLUSION: Familiarity with the disease process (previously diagnosed diabetes and previous experience with DKA) and experience of the enroller favorably influenced the likelihood of parental permission for enrollment in a study of DKA in children.

Serum Sodium Concentration and Mental Status in Children With Diabetic Ketoacidosis.

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.