Paediatric obesity diagnosis and intervention practices in Australian hospitals - Australia-wide survey.

AIM: Previous studies suggest a lack of a unified approach in identifying and addressing children with obesity while being inpatients in individual Australian hospitals. Our study aimed to describe current clinical practice across Australia and identify discrepancies that can aid in developing a more unified response to children identified with obesity as hospital inpatients. METHODS: A cross-sectional exploratory online survey was distributed to major paediatric in-patient departments in Australia, with a response rate of 68%. Questions focused on education, identification, interventions and attitudes towards a national protocol. RESULTS: Twenty percent of respondents indicated that staff in their department regularly record body mass index, 66% address weight issues and only 8% consistently refer to appropriate outpatient services. Although 88% of respondents believe that a national protocol for addressing paediatric obesity would be beneficial, respondents emphasised concerns regarding their local resources. CONCLUSION: Our study can inform the development of a guideline for a unified response to opportunistically identify children with overweight and obesity as inpatients.

Defective DNA Polymerase α-Primase Leads to X-Linked Intellectual Disability Associated with Severe Growth Retardation, Microcephaly, and Hypogonadism.

Replicating the human genome efficiently and accurately is a daunting challenge involving the duplication of upward of three billion base pairs. At the core of the complex machinery that achieves this task are three members of the B family of DNA polymerases: DNA polymerases α, δ, and ε. Collectively these multimeric polymerases ensure DNA replication proceeds at optimal rates approaching 2 × 103 nucleotides/min with an error rate of less than one per million nucleotides polymerized. The majority of DNA replication of undamaged DNA is conducted by DNA polymerases δ and ε. The DNA polymerase α-primase complex performs limited synthesis to initiate the replication process, along with Okazaki-fragment synthesis on the discontinuous lagging strand. An increasing number of human disorders caused by defects in different components of the DNA-replication apparatus have been described to date. These are clinically diverse and involve a wide range of features, including variable combinations of growth delay, immunodeficiency, endocrine insufficiencies, lipodystrophy, and cancer predisposition. Here, by using various complementary approaches, including classical linkage analysis, targeted next-generation sequencing, and whole-exome sequencing, we describe distinct missense and splice-impacting mutations in POLA1 in five unrelated families presenting with an X-linked syndrome involving intellectual disability, proportionate short stature, microcephaly, and hypogonadism. POLA1 encodes the p180 catalytic subunit of DNA polymerase α-primase. A range of replicative impairments could be demonstrated in lymphoblastoid cell lines derived from affected individuals. Our findings describe the presentation of pathogenic mutations in a catalytic component of a B family DNA polymerase member, DNA polymerase α.

An actin filament population defined by the tropomyosin Tpm3.1 regulates glucose uptake.

Actin has an ill-defined role in the trafficking of GLUT4 glucose transporter vesicles to the plasma membrane (PM). We have identified novel actin filaments defined by the tropomyosin Tpm3.1 at glucose uptake sites in white adipose tissue (WAT) and skeletal muscle. In Tpm 3.1-overexpressing mice, insulin-stimulated glucose uptake was increased; while Tpm3.1-null mice they were more sensitive to the impact of high-fat diet on glucose uptake. Inhibition of Tpm3.1 function in 3T3-L1 adipocytes abrogates insulin-stimulated GLUT4 translocation and glucose uptake. In WAT, the amount of filamentous actin is determined by Tpm3.1 levels and is paralleled by changes in exocyst component (sec8) and Myo1c levels. In adipocytes, Tpm3.1 localizes with MyoIIA, but not Myo1c, and it inhibits Myo1c binding to actin. We propose that Tpm3.1 determines the amount of cortical actin that can engage MyoIIA and generate contractile force, and in parallel limits the interaction of Myo1c with actin filaments. The balance between these actin filament populations may determine the efficiency of movement and/or fusion of GLUT4 vesicles with the PM.

Assessment of the 5-Minute Oxygen Uptake Efficiency Slope in Children With Obesity.

PURPOSE: Poor cardiorespiratory fitness is associated with increased all cause morbidity and mortality. In children with obesity, maximum oxygen uptake (V̇O2max) may not be achieved due to reduced motivation and peripheral fatigue. We aimed to identify a valid submaximal surrogate for V̇O2max in children with obesity. METHOD: Ninety-two children with obesity (7-16 years) completed a maximal exercise treadmill test and entered a three-month exercise and/or nutrition intervention after which the exercise test was repeated (n = 63). Participants were required to reach V̇O2max to be included in this analysis (n = 32 at baseline and n = 13 at both time-points). The oxygen uptake efficiency slope (OUES) was determined as the slope of the line when V̇O2 (L/min) was plotted against log V̇E. Associations between the maximal OUES, submaximal OUES (at 3, 4, 5 and 6 min of the exercise test) and V̇O2max were calculated. RESULTS: In the cross-sectional analysis, V̇O2max (L/min) was strongly correlated with 5-min OUES independent of Tanner puberty stage and sex (R2 = .80, p < .001). Longitudinal changes in V̇O2max were closely reflected by changes in 5-min OUES independent of change in percent body fat (R2 = .63, p < .05). CONCLUSION: The 5-min OUES is a viable alternative to V̇O2max when assessing children with obesity.

Obstructive sleep apnoea in children with obesity.

AIMS: The aim of this study was to identify factors that predict risk of obstructive sleep apnoea (OSA) in obese children, which could aid in prioritising sleep studies. METHODS: A retrospective chart review was undertaken of obese children seen in the KOALA weight management clinic and Sleep clinic. Data collected included demographics, clinical history, examination findings, biochemical markers, and polysomnogram results. RESULTS: Two hundred seventy-two obese children were seen in the KOALA clinic out of which 54 (20%) were also seen in the Sleep clinic because of snoring. Thirty-two were referred by the KOALA clinic; the remaining 22 were referred by other medical practitioners prior to being seen in the KOALA clinic. Thirty-nine had polysomnograms. The time from referral to Sleep clinic ranged from 10 days to 1.5 years with 50% seen within 6 months; with similar time gap between the blood tests and time of polysomnograms. Thirty-six percent (14/39) were reported to have OSA. Six children were Aboriginal/Torres Strait Islander (ATSI) and all had OSA, which was statistically significant (P = 0.004). There was a statistically significant correlation between high-sensitivity C-reactive protein (hs-CRP) and obstructive event index (OEI) in rapid eye movement (REM) sleep. (r = 0.50, P = 0.04). Correlation between low-density lipoprotein (LDL) and OEI in REM was r = 0.36, P = 0.06, which approached significance. CONCLUSIONS: Ethnicity was a significant factor with more obese ATSI children having OSA. The significant correlation between hs-CRP with OEI is consistent with findings of previous studies. Several factors (glycosylated haemoglobin, LDL) approached significance.

The relationship between children's motor proficiency and health-related fitness.

AIMS: The overall purpose of this study was to examine the relationship between motor proficiency and health-related fitness in children. In addition, the study aimed to determine if particular combinations of motor skills have a stronger relationship with individual health-related fitness measures. METHODS: Seventy-seven children (F:28, M:49) (mean age: 11.19 ± 2.74 years) participated in this prospective cohort study. Physical measures included the following: motor proficiency (Bruininks-Oseretsky Test of Motor Proficiency, Second Edition), body mass index (BMI), waist circumference, blood pressure, heart rate and VO(2) peak (mL/kg/min). RESULTS: After factoring in age, motor proficiency as a combined total score had a strong negative relationship with the health-related fitness measures of BMI (r (2) = 0.62, P < 0.001) and waist circumference (r (2) = 0.72, P < 0.001) and a strong positive relationship with VO2 peak (r (2) = 0.78, P = 0.002). Children with lower motor proficiency (≤25th percentile) had a significantly larger mean waist circumference (M = 13.85 cm, 95% confidence interval (CI) (2.05, 25.66), P = 0.01), heavier weight (M = 22.17 kg, 95% CI (2.44, 41.91), P = 0.02) and higher BMI (M = 5.10 kg/m(2) , 95% CI (0.33, 9.87), P = 0.03) than children with higher motor proficiency (≤75th percentile). CONCLUSIONS: Motor proficiency, once corrected for age, is significantly related to a number of health-related measures in children and should therefore be considered a focus for investigation for children with poor health-related fitness (e.g. high BMI and waist circumference percentiles or low cardiorespiratory fitness), as motor incompetence could be an underlying contributing factor to a child's poor physical health.

Child obesity service provision: a cross-sectional survey of physiotherapy practice trends and professional needs.

This study explored current physiotherapy practice trends for management of children who are overweight or obese. The professional needs of physiotherapists working with this population were also assessed, including the perceived need for physiotherapy clinical guidelines for prevention and management of children with obesity. A cross-sectional survey design was used, with questionnaires purposefully distributed through 13 key physiotherapy services throughout Australia. Snowball sampling resulted in completed questionnaires from 64 physiotherapists who provided services to children. Half (n=33, 52%) of respondents provided services specifically to overweight or obese children. Of those providing services, one-quarter had prior training specific to working with this population. Most used multi-disciplinary models (n=16, 76%) and provided under 5h of obesity-related services each week (n=29, 88%). Half (n=16, 49%) used body mass index as an outcome measure but more (n=25, 76%) used bodyweight. Only 14 (42%) assessed motor skills. The majority of respondents (n=57, 89%) indicated a need for physiotherapy guidelines to best manage overweight and obese children. Professional development priorities included: 'Educating children and families', 'Assessment methods' and 'Exercise prescription' for overweight and obese children. This data provides workforce intelligence to guide future professional training and inform development of clinical guidelines for physiotherapists in prevention and management of children with obesity and related chronic disease.

Comparison of Centers for Disease Control and Prevention and World Health Organization references/standards for height in contemporary Australian children: analyses of the Raine Study and Australian National Children's Nutrition and Physical Activity cohorts.

AIM: (i) To compare the Centers for Disease Control and Prevention (CDC) reference and World Health Organization (WHO) standard/reference for height, particularly with respect to short stature and eligibility for growth hormone (GH) treatment by applying them to contemporary Australian children; (ii) To examine the implications for identifying short stature and eligibility for GH treatment. METHODS: Children from the longitudinal Raine Study were serially measured for height from 1991 to 2005 (2-15-year-old girls (660) and boys (702) from Western Australia). In the cross-sectional Australian National Children's Nutrition and Physical Activity survey (2-16-year-old boys (2415) and girls (2379) from all states), height was measured in 2007. Heights were converted to standard deviation scores (SDSs) based on CDC and WHO. RESULTS: Means and standard deviations of height-SDS varied between CDC and WHO definitions and with age and gender within each definition. However, both identified similar frequencies of short stature (<1st centile for GH eligibility), although these were very significantly less than the anticipated 1% (0.1-0.7%) of the Australian cohorts. Mean heights in the Australian cohorts were greater than both the WHO and CDC means. CONCLUSIONS: Neither CDC nor WHO height standardisations accurately reflect the contemporary Australian child population. Australian children are taller than the CDC or WHO height means, and significantly less than 1% of Australian children are defined as being short using either CDC or WHO. This study suggests there may be a case for an Australian-specific standard/reference for height.

Caveolin-1 orchestrates the balance between glucose and lipid-dependent energy metabolism: implications for liver regeneration.

UNLABELLED: Caveolin-1 (CAV1) is a structural protein of caveolae involved in lipid homeostasis and endocytosis. Using newly generated pure Balb/C CAV1 null ((Balb/C)CAV1-/-) mice, CAV1-/- mice from Jackson Laboratories ((JAX)CAV1-/-), and CAV1-/- mice developed in the Kurzchalia Laboratory ((K)CAV1-/-), we show that under physiological conditions CAV1 expression in mouse tissues is necessary to guarantee an efficient progression of liver regeneration and mouse survival after partial hepatectomy. Absence of CAV1 in mouse tissues is compensated by the development of a carbohydrate-dependent anabolic adaptation. These results were supported by extracellular flux analysis of cellular glycolytic metabolism in CAV1-knockdown AML12 hepatocytes, suggesting cell autonomous effects of CAV1 loss in hepatic glycolysis. Unlike in (K)CAV1-/- livers, in (JAX)CAV1-/- livers CAV1 deficiency is compensated by activation of anabolic metabolism (pentose phosphate pathway and lipogenesis) allowing liver regeneration. Administration of 2-deoxy-glucose in (JAX)CAV1-/- mice indicated that liver regeneration in (JAX)CAV1-/- mice is strictly dependent on hepatic carbohydrate metabolism. Moreover, with the exception of regenerating (JAX)CAV1-/- livers, expression of CAV1 in mice is required for efficient hepatic lipid storage during fasting, liver regeneration, and diet-induced steatosis in the three CAV1-/- mouse strains. Furthermore, under these conditions CAV1 accumulates in the lipid droplet fraction in wildtype mouse hepatocytes. CONCLUSION: Our data demonstrate that lack of CAV1 alters hepatocyte energy metabolism homeostasis under physiological and pathological conditions.

Ski-interacting protein (SKIP) interacts with androgen receptor in the nucleus and modulates androgen-dependent transcription.

BACKGROUND: The androgen receptor (AR) is a member of the nuclear receptor (NR) superfamily of ligand-inducible DNA transcription factors, and is the major mediator of male sexual development, prostate growth and the pathogenesis of prostate cancer. Cell and gene specific regulation by the AR is determined by availability of and interaction with sets of key accessory cofactors. Ski-interacting protein (SKIP; SNW1, NCOA62) is a cofactor shown to interact with several NRs and a diverse range of other transcription factors. Interestingly, SKIP as part of the spliceosome is thought to link mRNA splicing with transcription. SKIP has not been previously shown to interact with the AR. RESULTS: The aim of this study was to investigate whether SKIP interacts with the AR and modulates AR-dependent transcription. Here, we show by co-immunoprecipitation experiments that SKIP is in a complex with the AR. Moreover, SKIP increased 5α-dihydrotestosterone (DHT) induced N-terminal/C-terminal AR interaction from 12-fold to almost 300-fold in a two-hybrid assay, and enhanced AR ligand-independent AF-1 transactivation. SKIP augmented ligand- and AR-dependent transactivation in PC3 prostate cancer cells. Live-cell imaging revealed a fast (half-time=129 s) translocation of AR from the cytoplasm to the nucleus upon DHT-stimulation. Förster resonance energy transfer (FRET) experiments suggest a direct AR-SKIP interaction in the nucleus upon translocation. CONCLUSIONS: Our results suggest that SKIP interacts with AR in the nucleus and enhances AR-dependent transactivation and N/C-interaction supporting a role for SKIP as an AR co-factor.

Primary care providers' experience in the management of paediatric type 1 diabetes in Western Sydney, New South Wales.

BACKGROUND AND OBJECTIVES: It is unknown to what degree general practitioners (GPs) are able to diagnose and assist in the management of children with type 1 diabetes (T1D). This study examined the experiences of GPs when faced with paediatric T1D. METHOD: A qualitative study using semistructured interviews was conducted with a sample of GPs in Western Sydney. Data were analysed thematically. RESULTS: Thirty GPs reported varied experiences with paediatric T1D. Two themes emerged: 'You don't think of T1D everyday' (GPs do not frequently encounter T1D) and 'We need to be equipped' (despite low patient numbers, GPs want to be able to recognise, refer and assist in the management of children with T1D). DISCUSSION: There is limited Australian research into GPs' ability to diagnose and manage children with T1D. This study highlights the current level of knowledge and referral practices of a sample of GPs.

Assessing the Relationship between the Gut Microbiota and Inflammatory Bowel Disease Therapeutics: A Systematic Review.

Current inflammatory bowel disease (IBD) treatments including non-biological, biological, and nutritional therapies aim to achieve remission and mucosal healing. Treatment efficacy, however, is highly variable, and there is growing evidence that the gut microbiota influences therapeutic efficacy. The aim of this study was to conduct a systematic review and meta-analysis to define changes in the gut microbiota following IBD treatment and to identify microbial predictors of treatment response. A systematic search using MEDLINE/Embase and PubMed was performed in July 2022. The review was conducted based on the Preferred Reporting Items for Systematic reviews and Meta-Analyses guidelines. Studies were included if they reported longitudinal microbiota analysis (>2 weeks) using next-generation sequencing or high-throughput sequencing of faecal/mucosal samples from IBD patients commencing treatment. Meta-analysis on alpha-diversity changes following infliximab treatment was conducted. Thirty-nine studies met the inclusion criteria, and four studies were included in the meta-analysis. An increase in alpha diversity was observed following treatment with 5-aminosalicylates, corticosteroids, and biological therapies in most studies. Characteristic signatures involving the enrichment of short-chain-fatty-acid-producing bacteria including Faecalibacterium prausnitzii and a reduction of pathogenic bacteria including various Proteobacteria were demonstrated following treatment with specific signatures identified based on treatment outcome. The meta-analysis demonstrated a statistically significant increase in bacterial richness following infliximab treatment (standardised mean difference -1.16 (-1.50, -0.83), p < 0.00001). Conclusion: Distinct microbial signatures are seen following treatment and are associated with treatment response. The interrogation of large longitudinal studies is needed to establish the link between the gut microbiota and IBD therapeutic outcomes.

Whole exome sequencing reveals copy number variants in individuals with disorders of sex development.

Complete androgen insensitivity syndrome (CAIS), where 46,XY individuals present as female, is caused by variants in the androgen receptor gene (AR). We analyzed the DNA of a patient with suspected CAIS using a targeted gene sequencing panel and whole exome sequencing (WES) but did not detect any small nucleotide variants in AR. Analysis of WES data using our bioinformatics pipeline designed to detect copy number variations (CNV) uncovered a rare duplication of exon 2 of AR. Using array comparative genomic hybridization, the duplication was found to span 43.6 kb and is predicted to cause a frameshift and loss of AR protein. We confirmed the power of our WES-CNV detection protocol by identifying pathogenic CNVs in FSHR and NR5A1 in previously undiagnosed patients with disorders of sex development. Our findings illustrate the usefulness of CNV analysis in WES data to detect pathogenic genomic changes that may go undetected using only standard analysis protocols.

New directions in childhood obesity research: how a comprehensive biorepository will allow better prediction of outcomes.

BACKGROUND: Childhood obesity is associated with the early development of diseases such as type 2 diabetes and cardiovascular disease. Unfortunately, to date, traditional methods of research have failed to identify effective prevention and treatment strategies, and large numbers of children and adolescents continue to be at high risk of developing weight-related disease. AIM: To establish a unique 'biorepository' of data and biological samples from overweight and obese children, in order to investigate the complex 'gene × environment' interactions that govern disease risk. METHODS: The 'Childhood Overweight BioRepository of Australia' collects baseline environmental, clinical and anthropometric data, alongside storage of blood samples for genetic, metabolic and hormonal profiles. Opportunities for longitudinal data collection have also been incorporated into the study design. National and international harmonization of data and sample collection will achieve required statistical power. RESULTS: Ethical approval in the parent site has been obtained and early data indicate a high response rate among eligible participants (71%) with a high level of compliance for comprehensive data collection (range 56% to 97% for individual study components). Multi-site ethical approval is now underway. CONCLUSIONS: In time, it is anticipated that this comprehensive approach to data collection will allow early identification of individuals most susceptible to disease, as well as facilitating refinement of prevention and treatment programs.

Exploring the Diagnostic Accuracy of the KidFit Screening Tool for Identifying Children with Health and Motor Performance-Related Fitness Impairments: A Feasibility Study.

Child obesity is associated with poor health and reduced motor skills. This study aimed to assess the diagnostic accuracy of the KidFit Screening Tool for identifying children with overweight/obesity, reduced motor skills and reduced cardiorespiratory fitness. Fifty-seven children (mean age: 12.57 ± 1.82 years; male/female: 34/23) were analysed. The Speed and Agility Motor Screen (SAMS) and the Modified Shuttle Test-Paeds (MSTP) made up the KidFit Screening Tool. Motor Proficiency (BOT2) (Total and Gross) was also measured. BMI, peak-oxygen-uptake (VO2peak) were measured with a representative sub-sample (n = 25). Strong relationships existed between the independent variables included in the KidFit Screening Tool and; BMI (R2 = 0.779, p < 0.001); Gross Motor Proficiency (R2 = 0.612, p < 0.001) and VO2peak (mL/kg/min) (R2 = 0.754, p < 0.001). The KidFit Screening Tool has a correct classification rate of 0.84 for overweight/obesity, 0.77 for motor proficiency and 0.88 for cardiorespiratory fitness. The sensitivity and specificity of the KidFit Screening Tool for identifying children with overweight/obesity was 100% (SE = 0.00) and 78.95%, respectively (SE = 0.09), motor skills in the lowest quartile was 90% (SE = 0.095) and 74.47% (SE = 0.064), respectively, and poor cardiorespiratory fitness was 100% (SE = 0.00) and 82.35% (SE = 0.093), respectively. The KidFit Screening Tool has a strong relationship with health- and performance-related fitness, is accurate for identifying children with health- and performance-related fitness impairments and may assist in informing referral decisions for detailed clinical investigations.

Satisfaction and acceptability of paediatric weight management services amongst parents and carers: A mixed-methods study.

To optimize treatment for children and adolescents with obesity and minimize attrition, consideration of parents' engagement and satisfaction with paediatric weight management services is crucial. The aim of this study was to conduct a mixed-methods evaluation of parental acceptability and satisfaction of available paediatric weight management services in New South Wale, Australia's most populous state. Parents/carers referred to one of six weight management services between March 2018 and July 2019 were invited to participate. The study involved: (a) surveys and one-on-one phone interviews to assess overall satisfaction, acceptability of service design and delivery, treatment expectations, and service accessibility, strengths, weaknesses and areas of improvement; (b) a survey to determine costs to families of attending the service; and (c) a survey assessing families' reasons for treatment non-attendance. N = 146 participants completed the survey to assess service satisfaction and acceptability and 37 of these also participated in phone interviews. Ninety-three per cent were satisfied with the overall care they received and patient weight loss/cessation of weight gain and improvement in the family's overall health were rated as the most valued changes. Content analysis of interviews highlighted participants' recognition of positive changes achieved during treatment and appreciation of the resources provided, and the encouraging/empathetic nature of staff. The most common reasons for treatment attrition were difficulty in accessing the weight management service and flexibility of appointment times. Findings from this study can be utilized in future planning and development of paediatric weight management services to facilitate integrated, responsive and effective care of children and adolescents with obesity.

Rev-erb beta regulates the Srebp-1c promoter and mRNA expression in skeletal muscle cells.

The nuclear hormone receptor, Rev-erb beta operates as a transcriptional silencer. We previously demonstrated that exogenous expression of Rev-erb betaDeltaE in skeletal muscle cells increased Srebp-1c mRNA expression. We validated these in vitro observations by injection of an expression vector driving Rev-erb betaDeltaE expression into mouse tibialis muscle that resulted in increased Srebp-1c mRNA expression. Paradoxically, Rev-erb beta siRNA expression in skeletal muscle cells repressed Srebp-1c expression, and indicated that Rev-erb beta expression was necessary for Srebp-1c expression. ChIP analysis demonstrated that Rev-erb beta was recruited to the Srebp-1c promoter. Moreover, Rev-erb beta trans-activated the Srebp-1c promoter, in contrast, Rev-erb beta efficiently repressed the Rev-erb alpha promoter, a previously characterized target gene. Finally, treatment with the Rev-erb agonist (hemin) (i) increased the trans-activation of the Srebp-1c promoter by Rev-erb beta; and (ii) increased Rev-erb beta and Srebp-1c mRNA expression. These data suggest that Rev-erb beta has the potential to activate gene expression, and is a positive regulator of Srebp-1c, a regulator of lipogenesis.

The association between ketoacidosis and 25(OH)-vitamin D levels at presentation in children with type 1 diabetes mellitus.

BACKGROUND: There is considerable evidence supporting the role of vitamin D deficiency in the pathogenesis of type 1 diabetes mellitus (T1DM). Vitamin D deficiency is also associated with impairment of insulin synthesis and secretion. There have been no formal studies looking at the relationship between 25(OH)-vitamin D(3) and the severity of diabetic ketoacidosis (DKA) in children at presentation with T1DM. OBJECTIVE: To determine the relationship between measured 25(OH)-vitamin D(3) levels and the degree of acidosis in children at diagnosis with T1DM. SUBJECTS: Children presenting with new-onset T1DM at a tertiary children's hospital. METHODS: 25(OH)-vitamin D(3) and bicarbonate levels were measured in children at presentation with newly diagnosed T1DM. Those with suboptimal 25(OH)-vitamin D(3) levels (<50 nmol/L) had repeat measurements performed without interim vitamin D supplementation. RESULTS: Fourteen of the 64 children had low 25(OH)-vitamin D(3) levels at presentation, and 12 of these had low bicarbonate levels (<18 mmol/L) (p = 0.001). Bicarbonate explained 20% of the variation in vitamin D level at presentation (partial r(2) = 0.20, p < 0.001) and ethnic background a further 10% (partial r(2) = 0.10, p = 0.002). The levels of 25(OH)-vitamin D(3) increased in 10 of the 11 children with resolution of the acidosis. CONCLUSIONS: Acid-base status should be considered when interpreting 25(OH)-vitamin D(3) levels in patients with recently diagnosed T1DM. Acidosis may alter vitamin D metabolism, or alternatively, low vitamin D may contribute to a child's risk of presenting with DKA.