Transient albuminuria in the setting of short-term severe hyperglycemia in type 1 diabetes.

In a cohort of 1817 children with type 1 diabetes (T1D), short-term hyperglycemia was associated with transient albuminuria (11 % during new-onset T1D without diabetic ketoacidosis (DKA), 12 % during/after DKA, 6 % during routine screening). Our findings have implications regarding future risk of diabetic kidney disease and further investigation is needed.

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.

Spatiospectral image processing workflow considerations for advanced MR spectroscopy of the brain.

Magnetic resonance spectroscopy (MRS) is one of the few non-invasive imaging modalities capable of making neurochemical and metabolic measurements in vivo. Traditionally, the clinical utility of MRS has been narrow. The most common use has been the "single-voxel spectroscopy" variant to discern the presence of a lactate peak in the spectra in one location in the brain, typically to evaluate for ischemia in neonates. Thus, the reduction of rich spectral data to a binary variable has not classically necessitated much signal processing. However, scanners have become more powerful and MRS sequences more advanced, increasing data complexity and adding 2 to 3 spatial dimensions in addition to the spectral one. The result is a spatially- and spectrally-variant MRS image ripe for image processing innovation. Despite this potential, the logistics for robustly accessing and manipulating MRS data across different scanners, data formats, and software standards remain unclear. Thus, as research into MRS advances, there is a clear need to better characterize its image processing considerations to facilitate innovation from scientists and engineers. Building on established neuroimaging standards, we describe a framework for manipulating these images that generalizes to the voxel, spectral, and metabolite level across space and multiple imaging sites while integrating with LCModel, a widely used quantitative MRS peak-fitting platform. In doing so, we provide examples to demonstrate the advantages of such a workflow in relation to recent publications and with new data. Overall, we hope our characterizations will lower the barrier of entry to MRS processing for neuroimaging researchers.

Disparities in Insulin Pump Use Among Spanish-Speaking Children With Type 1 Diabetes Compared to Their Non-Hispanic White Peers: Mixed Methods Study.

BACKGROUND: Disparities in Insulin Pump Use Among Spanish-Speaking Children With Type 1 Diabetes Compared to Their Non-Hispanic White Peers: Mixed Methods Study. OBJECTIVE: We aimed to investigate the use of insulin pumps and continuous glucose monitoring (CGM) devices among Spanish-language-preferring children in our clinic population and to identify specific barriers to technology use. METHODS: First, we assessed rates and patterns of diabetes technology use (eg, insulin pumps and CGM devices) in a sample of 76 children (38 Spanish-language preferring and 38 non-Hispanic White). We compared rates of technology use, average length of time between diabetes diagnosis and initiation of insulin pump or CGM device, and rates of discontinuation of these devices between the Spanish-language-preferring and non-Hispanic White children. Second, to understand specific barriers to technology use, we compared responses to a questionnaire assessing decision-making about insulin pumps. RESULTS: Spanish-language-preferring patients had lower rates of insulin pump use, even after controlling for age, gender, age at diagnosis, and type of health insurance. Spanish-language-preferring participants were more likely to report concerns over learning to use an insulin pump and were more likely to discontinue using an insulin pump after starting one. CONCLUSIONS: These data confirm demographic disparities in insulin pump use among children with T1D and provide new insights about insulin pump discontinuation among Spanish-language-preferring children. Our findings suggest a need for improved patient education about insulin pump technology in general and improved support for Spanish-language-preferring families with T1D after initiation of pump therapy.

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.

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.

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.

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.

Multimodal neuroimaging in pediatric type 1 diabetes: a pilot multisite feasibility study of acquisition quality, motion, and variability.

Type 1 diabetes (T1D) affects over 200,000 children and is associated with an increased risk of cognitive dysfunction. Prior imaging studies suggest the neurological changes underlying this risk are multifactorial, including macrostructural, microstructural, and inflammatory changes. However, these studies have yet to be integrated, limiting investigation into how these phenomena interact. To better understand these complex mechanisms of brain injury, a well-powered, prospective, multisite, and multimodal neuroimaging study is needed. We take the first step in accomplishing this with a preliminary characterization of multisite, multimodal MRI quality, motion, and variability in pediatric T1D. We acquire structural T1 weighted (T1w) MRI, diffusion tensor MRI (DTI), functional MRI (fMRI), and magnetic resonance spectroscopy (MRS) of 5-7 participants from each of two sites. First, we assess the contrast-to-noise ratio of the T1w MRI and find no differences between sites. Second, we characterize intervolume motion in DTI and fMRI and find it to be on the subvoxel level. Third, we investigate variability in regional gray matter volumes and local gyrification indices, bundle-wise DTI microstructural measures, and N-acetylaspartate to creatine ratios. We find the T1-based measures to be comparable between sites before harmonization and the DTI and MRS-based measures to be comparable after. We find a 5-15% coefficient of variation for most measures, suggesting ~150-200 participants per group on average are needed to detect a 5% difference across these modalities at 0.9 power. We conclude that multisite, multimodal neuroimaging of pediatric T1D is feasible with low motion artifact after harmonization of DTI and MRS.

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.

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.

Effects of TRAM-34 and minocycline on neuroinflammation caused by diabetic ketoacidosis in a rat model.

INTRODUCTION: Diabetic ketoacidosis (DKA) causes acute and chronic neuroinflammation that may contribute to cognitive decline in patients with type 1 diabetes. We evaluated the effects of agents that reduce neuroinflammation (triarylmethane-34 (TRAM-34) and minocycline) during and after DKA in a rat model. RESEARCH DESIGN AND METHODS: Juvenile rats with DKA were treated with insulin and saline, either alone or in combination with TRAM-34 (40 mg/kg intraperitoneally twice daily for 3 days, then daily for 4 days) or minocycline (45 mg/kg intraperitoneally daily for 7 days). We compared cytokine and chemokine concentrations in brain tissue lysates during DKA among the three treatment groups and in normal controls and diabetic controls (n=9-15/group). We also compared brain inflammatory mediator levels in these same groups in adult diabetic rats that were treated for DKA as juveniles. RESULTS: Brain tissue concentrations of chemokine (C-C) motif ligand (CCL)3, CCL5 and interferon (IFNγ) were increased during acute DKA, as were brain cytokine composite scores. Both treatments reduced brain inflammatory mediator levels during acute DKA. TRAM-34 predominantly reduced chemokine concentrations (chemokine (C-X-C) motif ligand (CXCL-1), CCL5) whereas minocycline had broader effects, (reducing CXCL-1, tumor necrosis factor (TNFα), IFNγ, interleukin (IL) 2, IL-10 and IL-17A). Brain inflammatory mediator levels were elevated in adult rats that had DKA as juveniles, compared with adult diabetic rats without previous DKA, however, neither TRAM-34 nor minocycline treatment reduced these levels. CONCLUSIONS: These data demonstrate that both TRAM-34 and minocycline reduce acute neuroinflammation during DKA, however, treatment with these agents for 1 week after DKA does not reduce long-term neuroinflammation.

Feasibility and Impact of Remote Glucose Monitoring Among Patients With Newly Diagnosed Type 1 Diabetes: Single-Center Pilot Study.

BACKGROUND: Caregivers of children with newly diagnosed type 1 diabetes (T1D) maintain close contact with providers for several weeks to facilitate rapid adjustments in insulin dosing regimens. Traditionally, patient glucose values are relayed by telephone for provider feedback, but digital health technology can now enable the remote sharing of glucose data via mobile apps. OBJECTIVE: The aim of this study was to test the feasibility of remote glucose monitoring in a population of children and adolescents with newly diagnosed T1D and to explore whether remote monitoring alters habits for self-review of glucose data or perceived ease of provider contact in this population as compared to a nonrandomized control group. METHODS: Data were collected from families who chose to participate in remote monitoring (intervention group) as well as from patients receiving usual care (control group). The intervention group received Bluetooth-capable glucose meters and Apple iPod Touch devices. Patient-generated glucose data were passively relayed from the meter to the iPod Touch and then to both the electronic health record (EHR) and a third-party diabetes data platform, Tidepool. The principal investigator reviewed glucose data daily in the EHR and Tidepool and contacted the participants as needed for insulin dose adjustments during the time between hospital discharge and first clinic appointment. Families in the control group received usual care, which involved keeping written records of glucose values and contacting the diabetes team daily by telephone to relay data and receive treatment recommendations. A total of 40 families (20 for the intervention group and 20 for the control group) participated in the study. All families were surveyed at 1 month and 6 months regarding self-review of glucose data and ease of contacting the diabetes team. RESULTS: Patient-generated glucose data were remotely accessible for 100% of the participants via Tidepool and for 85% via the EHR. Survey data indicated that families in the intervention group were more likely than those in the control group to review their glucose data using mobile health apps after 1 month (P<.001), but by 6 months, this difference had disappeared. Perceived ease of contacting the clinical team for assistance was lower for the intervention group after 6 months (when receiving usual care) in comparison to during the intervention period (P=.48) and compared with a control group who did not have exposure to remote monitoring (P=.03). CONCLUSIONS: Remote glucose monitoring is feasible among pediatric patients with newly diagnosed T1D and may be associated with the earlier adoption of mobile health apps for self-management. The use of broadscale remote monitoring for T1D in the future will depend on improved access to Bluetooth-enabled mobile devices for all patients, improved interoperability of mobile health apps to enable data transfer on Android as well as Apple devices, and new provider workflows to handle large-scale panel management based on patient-generated health data. TRIAL REGISTRATION: ClinicalTrials.gov NCT04106440; https://clinicaltrials.gov/ct2/show/NCT04106440.

Association of Acute Kidney Injury During Diabetic Ketoacidosis With Risk of Microalbuminuria in Children With Type 1 Diabetes.

Importance: Diabetic kidney disease is among the most important causes of end-stage kidney disease worldwide. Risk factors for diabetic kidney disease remain incompletely defined. Recent studies document a high frequency of acute kidney injury (AKI) during diabetic ketoacidosis (DKA) in children, raising the question of whether these AKI episodes might contribute to future risk of diabetic kidney disease. Objective: To determine whether episodes of AKI occurring during DKA in children are associated with increased risk of development of microalbuminuria. Design, Setting, and Participants: This retrospective review of medical records included children with type 1 diabetes with 1 or more urine albumin levels measured during routine diabetes care from 2 university-affiliated urban tertiary children's hospitals in the United States from January 2006 to December 2019. Age at diagnosis of diabetes, hemoglobin A1c levels, episodes of DKA, pH and creatinine levels during DKA, and urine albumin and creatinine measurements were analyzed. Cox proportional hazards regression models were used to identify variables affecting the hazard rate for microalbuminuria development. Analyses began January 2021 and ended May 2021. Exposures: Episodes of DKA and episodes of AKI occurring during DKA. Main Outcomes and Measures: AKI occurrence and AKI stage were determined from serum creatinine measurements during DKA using Kidney Disease: Improving Global Outcomes criteria. Microalbuminuria was defined as urine albumin-to-creatinine ratio of 30 mg/g or more or excretion of 30 mg or more of albumin in 24 hours. Results: Of 2345 children, the mean (SD) age at diagnosis was 9.4 (4.4) years. One or more episodes of DKA occurred in 963 children (41%), and AKI occurred during DKA in 560 episodes (47%). In multivariable models adjusting for the associations of age at diagnosis and mean hemoglobin A1c level since diagnosis, each episode of AKI during DKA was associated with a hazard ratio of 1.56 (95% CI, 1.3-1.87) for development of microalbuminuria. Four or more episodes increased the hazard rate by more than 5-fold. DKA episodes without AKI did not significantly increase the hazard rate for microalbuminuria development after adjusting for other covariates. Conclusions and Relevance: These data demonstrate that episodes of AKI occurring during DKA in children with type 1 diabetes are significantly associated with risk of developing microalbuminuria. Greater efforts are necessary to reduce the frequency of DKA.

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.