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Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

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At least 19 records
All sourcesNASA NTRSDOE OSTI
DOE OSTI2023

Bullying among children with heart conditions, National Survey of Children’s Health, 2018–2020

Abstract Children with chronic illnesses report being bullied by peers, yet little is known about bullying among children with heart conditions. Using 2018–2020 National Survey of Children’s Health data, the prevalence and frequency of being bullied in the past year (never; annually or monthly; weekly or daily) were compared between children aged 6–17 years with and without heart conditions. Among children with heart conditions, associations between demographic and health characteristics and being bullied, and prevalence of diagnosed anxiety or depression by bullying status were examined. Differences were assessed with chi-square tests and multivariable logistic regression using predicted marginals to produce adjusted prevalence ratios and 95% confidence intervals. Weights yielded national estimates. Of 69,428 children, 2.2% had heart conditions. Children with heart conditions, compared to those without, were more likely to be bullied (56.3% and 43.3% respectively; adjusted prevalence ratio [95% confidence interval] = 1.3 [1.2, 1.4]) and bullied more frequently (weekly or daily = 11.2% and 5.3%; p < 0.001). Among children with heart conditions, characteristics associated with greater odds of weekly or daily bullying included ages 9–11 years compared to 15–17 years (3.4 [2.0, 5.7]), other genetic or inherited condition (1.7 [1.0, 3.0]), ever overweight (1.7 [1.0, 2.8]), and a functional limitation (4.8 [2.7, 8.5]). Children with heart conditions who were bullied, compared to never, more commonly had anxiety (40.1%, 25.9%, and 12.8%, respectively) and depression (18.0%, 9.3%, and 4.7%; p < 0.01 for both). Findings highlight the social and psychological needs of children with heart conditions.

Cardiovascular System & Cardiology↗
DOE OSTI2023

Incidence and predictors of tuberculosis among children receiving antiretroviral therapy in the Wolaita Zone: A retrospective cohort study

Tuberculosis is the leading cause of morbidity and mortality among children living with the human immunodeficiency virus (HIV), mainly in sub-Saharan Africa, including Ethiopia. Tuberculosis remains a significant health concern for HIV-positive children in Ethiopia. There is a paucity of data on the incidence and predictors of tuberculosis among children living with HIV on antiretroviral therapy in the Wolaita zone. Hence, this study aimed to assess the incidence and predictors of tuberculosis among children living with HIV on antiretroviral therapy in the Wolaita zone between January 2010 to December 2020. A retrospective cohort study was conducted among 389 children receiving antiretroviral therapy in Wolaita zone health facilities between January 2010 to December 2020. The checklist was adapted from the standardized antiretroviral treatment (ART) follow-up form currently used by the institutions’ ART clinics. The Kaplan-Meier survival function and Log-rank were used to estimate the survival for each categorical variable to compare the survival between different exposure groups. Both bivariable and multivariable parametric survival Gompertz models were fitted to identify predictors of tuberculosis among HIV-positive children. The association was summarized using an adjusted hazard ratio (AHR), and statistical significance was declared at 95% CI and p-value < 0.05. The goodness of the model fit was assessed using a Cox-Snell residual plot. The incidence rate of tuberculosis among children living with HIV was 3.5 (95% CI 2.7–4.5) per 100 child years. World Health Organization clinical stage III or IV (AHR = 2.31, 95% CI [1.26, 4.22]), hemoglobin level <10 g/dL (AHR = 2.87, 95% CI [1.51, 5.45]), fair or poor ART adherence (AHR = 4.4, 95% CI[2.18, 9.05]), underweight (AHR = 2.55, 95% CI [1.45, 4.51]), age >10 years (AHR = 3.62; 95% CI [1.29, 10.0]), and cotrimoxazole preventive therapy (AHR = 0.23; 95% CI [0.08, 0.60]) were among the independent predictors of TB occurrence. The incidence of tuberculosis among children on ART was high. HIV-positive children presenting with advanced disease staging (III and IV), anemia, “fair” and “poor” ART adherence, underweight, age above ten years, and not receiving cotrimoxazole preventive therapy were at higher risk of TB. Therefore, counseling on ART adherence, early diagnosis, and prompt treatment of anemia and malnutrition are recommended to avert tuberculosis.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Estimating the Effects of Soil Remediation on Children’s Blood Lead near a Former Lead Smelter in Omaha, Nebraska, USA

Lead exposures from legacy sources threaten children’s health. Soil in Omaha, Nebraska, was contaminated by emissions from a lead smelter and refinery. The U.S. Environmental Protection Agency excavated and replaced contaminated soil at the Omaha Lead Superfund Site between 1999 and 2016. The goal of this study was to assess the association of soil lead level (SLL) and soil remediation status with blood lead levels (BLLs) in children living near or on the site. We linked information on SLL at residential properties with children’s BLLs and assigned remediation status to children’s BLL measurements based on whether their measurements occurred during residence at remediated or unremediated properties. We examined the association of SLL and remediation status with elevated BLL (EBLL). We distinguished the roles of temporal trend and the intervention with time-by-intervention-status interaction contrasts. All analyses estimated odds ratios (ORs) with a generalized estimating equations approach to ensure robustness under the complex correlations among BLL measurements. All analyses controlled for relevant covariates including children’s characteristics. EBLL (> 5 μg/dL ) was associated with both residential SLL [e.g., OR=2.00; 95% confidence interval (CI): 1.83, 2.19; > 400–800 vs. ≤ 200 ppm] and neighborhood SLL [e.g., OR=1.85 (95% CI: 1.62, 2.11; > 400–800 vs. ≤ 200 ppm)] before remediation but only with neighborhood SLL after remediation. The odds of EBLL were higher before remediation [OR 1.52 (95% CI: 1.34, 1.72)]. Similarly, EBLL was positively associated with preremediation status in our interaction analysis [interaction OR=1.18 (95%CI: 1.02, 1.37)]. Residential and neighborhood SLLs were important predictors of EBLLs in children residing near or on this Superfund site. Neighborhood SLL remained a strong predictor following remediation. Our data analyses showed the benefit of soil remediation. Results from the interaction analyses should be interpreted cautiously due to imperfect correspondence of remediation times between remediation and comparison groups. https://doi.org/10.1289/EHP8657

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2023

Neurobehavioral symptoms in children born extremely preterm: A Swedish National Study

Abstract Aim To determine the prevalence of neurobehavioral symptoms at 6.5 years in children born extremely preterm (EPT, <27 weeks' gestation). Methods Population‐based cohort study of infants born EPT in Sweden from 2004 to 2007. Of 486 survivors 375 were assessed and compared with 369 matched term‐born controls. EPT children free from neurosensory and intellectual disabilities (neurodevelopmental disabilities [NDD]‐free, n = 236) were compared separately. Standardised questionnaires were used to assess parental ratings of hyperactivity and attention, emotional, peer‐relation, conduct and social problems; and deficits in perception, language and memory. Results EPT children had more reported problems in all assessed neurobehavioral domains than controls, with more than three times greater odds for most outcomes. Except for conduct problems, increased problems were identified also in NDD–free children. The odds of having neurobehavioral problems in ≥3 co‐occurring domains were five (whole EPT group) and three (NDD‐free group) times higher than in controls. Conclusion EPT children with or without NDD have more neurobehavioral problems in multiple domains than term peers. Ongoing assessments of behaviour until school age or beyond should recognise early symptoms of attention, everyday social problems, perceptual, emotional or language difficulties.

Serenius, Fredrik↗
DOE OSTI2020

Children, Income, and the Impact of Home Delivery on Household Shopping Trips

Expanding e-commerce and delivery benefit consumers through increased flexibility and convenience. However, there is a potential impact on vehicle miles traveled (VMT) by delivery and personal vehicles, and the resulting energy consumption, air quality, and congestion. Delivery trips could replace personal vehicle trips, but, if not a replacement, could add to (or supplement) shopping-related VMT for a given household. Here, we examined the benefits of e-commerce to consumers and the impact on personal shopping trips, and how these differed across item types, household child status, and income. We found that high-income households and households with children cared relatively more about time saving from deliveries. We found that, on average, deliveries substituted for 12% of vehicle shopping trips, but supplemented personal shopping trips for 9% of purchase deliveries. Underlying these averages were two main types of households: those for whom all deliveries substitute for trips (between 55% and 70% of households) and those for whom all deliveries supplement trips (between 20% and 35% of households). There was significant heterogeneity across households with and without children and with high or low incomes with respect to the use of delivery. Although time savings were more likely to motivate higher-income households and households with children to use delivery, this did not translate through to these households substituting for more of their trips; deliveries of prepared meals for both these categories of household were relatively more likely (15% for households with children, and 12% for higher-income households) to supplement, and not substitute for, personal trips.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2024

Investigation of inter-subject variation in ultrafine particle deposition across human nasal airways: A study involving children, adults, and the elderly

Occupational and environmental exposure to toxic nanoparticles, driven by the rapid expansion of nanotechnology, raises significant respiratory health concern. Numerous studies have explored airflow and particle dynamics in adult nasal airways, but understanding the impact of age-related anatomical changes in children and the elderly remains limited. This study systematically investigates age-related anatomical variations and associated influence on nasal airflow dynamics and ultrafine particle deposition characteristics. Using Computational Fluid-Particle Dynamics (CFPD) method, simulation was conducted under diverse inhalation conditions spanning a wide age range, including: two children (5 years old), two young adults (in their twenties), and two elderly (over 77 years old). Our results reveal distinctive variations across age groups in anatomical dimensions, which affect distribution of wall shear stress where the elderly and children display unique patterns distinct from the young adults. While total deposition efficiency differs significantly between children and adults, filtration efficiency in the subregion with most deposition, main respiratory, remains consistent. However, inter-subject differences are observed in the vestibular and olfactory regions,emphasizing nuanced impact of age-related anatomical variations. Overall and subregional empirical equations for deposition efficiency were developed by incorporating the combined diffusion parameter, Sc a Δ b , corroborating the use of geometrical characteristic parameters for each specific subject in predicting nasal deposition efficiency across age groups. Our findings contribute to predictive nanoparticle exposure analysis in nasal airways across different age groups, thereby enhancing respiratory healthcare for individuals across the life span.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2024

Physiologically based modeling reveals different risk of respiratory depression after fentanyl overdose between adults and children

Despite a rapid increase in pediatric mortality rate from prescription and illicit opioids, there is limited research on the dose-dependent impact of opioids on respiratory depression in children, the leading cause of opioid-associated death. In this article, we extend a previously developed translational model to cover pediatric populations by incorporating age-dependent pharmacokinetic, pharmacodynamic, and physiological changes compared to adults. Our model reproduced previous perioperative clinical findings that adults and children have similar risk of respiratory depression at the same plasma fentanyl concentration when specific endpoints (minute ventilation, CO 2 tension in the blood) were used. However, our model points to a potential caveat that, in a perioperative setting, routine use of mechanical ventilation and supplemental oxygen maintained the blood and tissue oxygen partial pressures in patients and prevented the use of oxygen-related endpoints to evaluate the consequences of respiratory depression. In a community setting when such oxygenation procedures are not immediately available, our model suggests that the higher oxygen demand and reduced cerebrovascular reactivity could make children more susceptible to severe hypoxemia and brain hypoxia, even with the same plasma fentanyl concentration as adults. Our work indicates that when developing intervention strategies to protect children from opioid overdose in a community setting, these pediatric-specific factors may need to be considered.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Characterization of Oral Candida spp. Biofilms in Children and Adults Carriers from Eastern Europe and South America

Background: Candida albicans and non-Candida albicans Candida species (NCACs) are known to colonize and invade various tissues, including the oral mucosa. In this work, we aimed to characterize mature biofilms of several Candida spp. clinical isolates (n = 33) obtained from the oral mucosa of children, adults, and elders of Eastern Europe and South America. Methods: Each strain was evaluated for its capacity to form biofilms in terms of total biomass using the crystal violet assay and for matrix components production (proteins and carbohydrates) using the BCA and phenol-sulfuric tests, respectively. The effect of different antifungals on biofilm formation was studied. Results: in the children’s group, a predominance of C. krusei (81%) was observed, while, among adults, the main species was C. albicans (59%). Most strains showed a reduced response to antimicrobial drugs when in biofilm form (p < 0.01). Moreover, it was observed that strains isolated from children produced more matrix, with higher levels of protein and polysaccharides. Conclusions: children were more likely to be infected by NCACs than adults. More importantly, these NCACs were able to form biofilms richer in matrix components. This finding is of clinical importance, particularly in pediatric care, since stronger biofilms are highly associated with antimicrobial resistance, recurrent infections, and higher therapeutic failure.

Alves, Anelise Maria Costa Vasconcelos (ORCID:0000↗
DOE OSTI2020

Estimation of Body Fat Percentage for Clinical Pharmacokinetic Studies in Children

Obesity is a prevalent childhood condition and the degree of adiposity appears likely to be an important covariate in the pharmacokinetics (PKs) of many drugs. We undertook these studies to facilitate the evaluation and, where appropriate, quantification of the covariate effect of body fat percentage (BF%) on PK parameters in children. We examined two large databases to determine the values and variabilities of BF% in children with healthy body weights and in those with obesity, comparing the accuracy and precision of BF% estimation by both clinical methods and demographically derived techniques. Additionally, we conducted simulation studies to evaluate the utility of the several methods for application in clinical trials. BF% was correlated with body mass index (BMI), but was highly variable among both children with healthy body weights and those with obesity. Bio‐impedance and several demographically derived techniques produced mean estimates of BF% that differed from dual x‐ray absorptiometry by < 1% (accuracy) and a SD of 5% or less (precision). Simulation studies confirmed that when the differences in precision among the several methods were small compared with unexplained between‐subject variability of a PK parameter, the techniques were of similar value in assessing the contribution of BF%, if any, as a covariate for that PK parameter. The combination of sex and obesity stage explained 68% of the variance of BF% with BMI. The estimation of BF% from sex and obesity stage can routinely be applied to PK clinical trials to evaluate the contribution of BF% as a potential covariate.

Green, Thomas P.↗
DOE OSTI2022

The Impact of Radiation Therapy in Children and Adolescents With Metastatic Rhabdomyosarcoma

There is limited evidence to define the role of radiation therapy in children with metastatic rhabdomyosarcoma (mRMS). In the international BERNIE study, children with mRMS or non-RMS soft tissue sarcoma were randomized to receive standard chemotherapy with or without bevacizumab, with radiation therapy to all disease sites recommended after chemotherapy cycle 6. We retrospectively evaluated the impact of radiation therapy on survival in the mRMS cohort.

62 RADIOLOGY AND NUCLEAR MEDICINE↗
DOE OSTI2025

Gut microbiome changes with micronutrient supplementation in children with attention–deficit/hyperactivity disorder: the MADDY study

Micronutrients have demonstrated promise in managing inattention and emotional dysregulation in children with attention-deficit/hyperactivity disorder (ADHD). The biological mechanism by which micronutrients improve these symptoms remains unclear. One plausible pathway is through the gut-brain axis, the bi-directional communication network that links the gastrointestinal tract with the brain. This study examines changes in gut microbiome composition and diversity after micronutrients supplementation in children with ADHD (N=44) and sheds light on potential mechanisms responsible for the response to micronutrients as measured by clinician-rated global impression. Participants from this investigation represent a sub-group of the Micronutrients for ADHD in Youth (MADDY) study, a double blind randomized controlled study in which participants received either micronutrients or a placebo for 8 weeks, followed by an 8-week open label extension with micronutrients for all participants. Stool samples collected at baseline, week 8, and week 16 were analyzed using 16S rRNA amplicon sequencing targeting the V4 hypervariable region. Pairwise compositional analyses served as the primary means for investigating changes in gut microbiome composition between micronutrients versus placebo groups and responders versus non-responders. A significant change in microbial evenness, as measured by alpha diversity, was observed following micronutrients, and the phylum Actinobacteriota decreased in the micronutrients group compared to placebo. Additionally, two bacterial families: Rikenellaceae and Oscillospiraceae, exhibited a significant increase in change of gut microbiome composition following micronutrients between responders and non-responders. These findings suggest that micronutrients modulated the composition of the gut microbiome and point towards specific bacterial changes associated with response to micronutrients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2022

Analyzing Relationships Between Economic and Neighborhood-Related Social Determinants of Health and Intensive Care Unit Length of Stay for Critically Ill Children With Medical Complexity Presenting With Severe Sepsis

Objectives: Of the Social Determinants of Health (SDoH), we evaluated socioeconomic and neighborhood-related factors which may affect children with medical complexity (CMC) admitted to a Pediatric Intensive Care Unit (PICU) in Shelby County, Tennessee with severe sepsis and their association with PICU length of stay (LOS). We hypothesized that census tract-level socioeconomic and neighborhood factors were associated with prolonged PICU LOS in CMC admitted with severe sepsis in the underserved community. Methods: This single-center retrospective observational study included CMC living in Shelby County, Tennessee admitted to the ICU with severe sepsis over an 18-month period. Severe sepsis CMC patients were identified using an existing algorithm incorporated into the electronic medical record at a freestanding children's hospital. SDoH information was collected and analyzed using patient records and publicly available census-tract level data, with ICU length of stay as the primary outcome. Results: 83 encounters representing 73 patients were included in the analysis. The median PICU LOS was 9.04 days (IQR 3.99–20.35). The population was 53% male with a median age of 4.1 years (IQR 1.96–12.02). There were 57 Black/African American patients (68.7%) and 85.5% had public insurance. Based on census tract-level data, about half (49.4%) of the CMC severe sepsis population lived in census tracts classified as suffering from high social vulnerability. There were no statistically significant relationships between any socioeconomic and neighborhood level factors and PICU LOS. Conclusion: Pediatric CMC severe sepsis patients admitted to the PICU do not have prolonged lengths of ICU stay related to socioeconomic and neighborhood-level SDoH at our center. A larger sample with the use of individual-level screening would need to be evaluated for associations between social determinants of health and PICU outcomes of these patients.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2023

Risk of hematological malignancies from CT radiation exposure in children, adolescents and young adults

Over one million European children undergo computed tomography (CT) scans annually. Although moderate- to high-dose ionizing radiation exposure is an established risk factor for hematological malignancies, risks at CT examination dose levels remain uncertain. Here we followed up a multinational cohort (EPI-CT) of 948,174 individuals who underwent CT examinations before age 22 years in nine European countries. Radiation doses to the active bone marrow were estimated on the basis of body part scanned, patient characteristics, time period and inferred CT technical parameters. We found an association between cumulative dose and risk of all hematological malignancies, with an excess relative risk of 1.96 (95% confidence interval 1.10 to 3.12) per 100 mGy (790 cases). Similar estimates were obtained for lymphoid and myeloid malignancies. Results suggest that for every 10,000 children examined today (mean dose 8 mGy), 1–2 persons are expected to develop a hematological malignancy attributable to radiation exposure in the subsequent 12 years. Our results strengthen the body of evidence of increased cancer risk at low radiation doses and highlight the need for continued justification of pediatric CT examinations and optimization of doses.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Climate impacts associated with reduced diet diversity in children across nineteen countries

It is widely anticipated that climate change will negatively affect both food security and diet diversity. Diet diversity is especially critical for children as it correlates with macro and micronutrient intake important for child development. Despite these anticipated links, little empirical evidence has demonstrated a relationship between diet diversity and climate change, especially across large datasets spanning multiple global regions and with more recent climate data. Here we use survey data from 19 countries and more than 107 000 children, coupled with 30 years of precipitation and temperature data, to explore the relationship of climate to child diet diversity while controlling for other agroecological, geographic, and socioeconomic factors. We find that higher long-term temperatures are associated with decreases in overall child diet diversity, while higher rainfall in the previous year, compared to the long-term average rainfall, is associated with greater diet diversity. Examining six regions (Asia, Central America, North Africa, South America, Southeast Africa, and West Africa) individually, we find that five have significant reductions in diet diversity associated with higher temperatures while three have significant increases in diet diversity associated with higher precipitation. In West Africa, increasing rainfall appears to counterbalance the effect of rising temperature impacts on diet diversity. In some regions, the statistical effect of climate on diet diversity is comparable to, or greater than, other common development efforts including those focused on education, improved water and toilets, and poverty reduction. These results suggest that warming temperatures and increasing rainfall variability could have profound short- and long-term impacts on child diet diversity, potentially undermining widespread development interventions aimed at improving food security.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2021

Congenital Malformations and Perinatal Deaths Among the Children of Atomic Bomb Survivors: A Reappraisal

From 1948 to 1954, the Atomic Bomb Casualty Commission conducted a study of pregnancy outcomes among births to atomic bomb survivors (Hiroshima and Nagasaki, Japan) who had received radiation doses ranging from 0 Gy to near-lethal levels. Past reports (1956, 1981, and 1990) on the cohort did not identify significant associations of radiation exposure with untoward pregnancy outcomes, such as major congenital malformations, stillbirths, or neonatal deaths, individually or in aggregate. We reexamined the risk of major congenital malformations and perinatal deaths in the children of atomic bomb survivors (n = 71,603) using fully reconstructed data to minimize the potential for bias, using refined estimates of the gonadal dose from Dosimetry System 2002 and refined analytical methods for characterizing dose-response relationships. The analyses showed that parental exposure to radiation was associated with increased risk of major congenital malformations and perinatal death, but the estimates were imprecise for direct radiation effects, and most were not statistically significant. Nonetheless, the uniformly positive estimates for untoward pregnancy outcomes among children of both maternal and paternal survivors are useful for risk assessment purposes, although extending them to populations other than the atomic bomb survivors comes with uncertainty as to generalizability.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

Children explain in‐ and out‐group behavior differently

Abstract Adults manifest a number of attributional biases in explaining the behavior of in‐ versus out‐group members. The present study investigated the developmental origins of such biased explanation. Children from majority and minority populations in Israel, and from majority populations in Germany ( N = 165), were asked to explain the behavior of in‐ and out‐group members. Across ages and groups, children more often referred to group membership when explaining an out‐group as compared to an in‐group member’s behavior; and more often to individual factors when explaining an in‐group as compared to an out‐group member’s behavior. These findings are consistent with the early emergence of fundamental differences in the conceptualizations of in‐ and out‐group members.

Essa, Francine↗
DOE OSTI2022

Nonsynonymous amino acid changes in the α-chain of complement component 5 influence longitudinal susceptibility to Plasmodium falciparum infections and severe malarial anemia in kenyan children

Background: Severe malarial anemia (SMA; Hb < 5.0 g/dl) is a leading cause of childhood morbidity and mortality in holoendemic Plasmodium falciparum transmission regions such as western Kenya. Methods: We investigated the relationship between two novel complement component 5 (C5) missense mutations [rs17216529:C>T, p(Val145Ile) and rs17610:C>T, p(Ser1310Asn)] and longitudinal outcomes of malaria in a cohort of Kenyan children (under 60 mos, n = 1,546). Molecular modeling was used to investigate the impact of the amino acid transitions on the C5 protein structure. Results: Prediction of the wild-type and mutant C5 protein structures did not reveal major changes to the overall structure. However, based on the position of the variants, subtle differences could impact on the stability of C5b. The influence of the C5 genotypes/haplotypes on the number of malaria and SMA episodes over 36 months was determined by Poisson regression modeling. Genotypic analyses revealed that inheritance of the homozygous mutant (TT) for rs17216529:C>T enhanced the risk for both malaria (incidence rate ratio, IRR = 1.144, 95%CI: 1.059–1.236, p = 0.001) and SMA (IRR = 1.627, 95%CI: 1.201–2.204, p = 0.002). In the haplotypic model, carriers of TC had increased risk of malaria (IRR = 1.068, 95%CI: 1.017–1.122, p = 0.009), while carriers of both wild-type alleles (CC) were protected against SMA (IRR = 0.679, 95%CI: 0.542–0.850, p = 0.001). Conclusion: Collectively, these findings show that the selected C5 missense mutations influence the longitudinal risk of malaria and SMA in immune-naïve children exposed to holoendemic P. falciparum transmission through a mechanism that remains to be defined.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2025

Persistent urinary metabolic signatures in children with type 1 diabetes

There are an estimated 3.7 million people with undiagnosed type 1 diabetes (T1D), living primarily in poor areas of the globe. Therefore, there is a need for non-invasive, affordable tests to provide accurate diagnosis despite the time post-disease onset and fasting state. Here, we studied persistent urinary T1D biomarkers that can be used to develop such tests. Here, we analyzed the urine metabolomes of three independent cohorts of samples collected within 48 h (from Indiana University), and 1 year (from University of Colorado) and 1–10 years (6 years in average) (from Children’s National Medical Center) post-diagnosis. Samples were submitted to gas chromatography-mass spectrometry and machine learning an0alyses to determine diagnostic metabolite panels. The data were also mapped into a metabolic pathway to understand persistently regulated processes in T1D. Seven metabolites showed consistent increases in all three cohorts: d-glucose, d-mannose, myo-inositol, 3-hydroxyisobutyric acid, gluconolactone, d-gluconic acid, and d-glucuronic acid. A combination of machine learning analysis and metabolite ratios as biomarker candidates diagnosed T1D with high sensitivity and specificity across different cohorts and times. Mapping the regulated metabolites into a pathway showed impairment in glycolysis and overflow of glucose towards other pathways in subjects with T1D that was persistent over time. We identified and cross-validated highly specific and sensitive urinary biomarkers. This opens opportunities to develop affordable, robust, and non-invasive tests. The results also show that most of the biomarkers were signatures of dysregulated glucose metabolism.

Type 1 diabetes↗