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Type 2 diabetes (T2D) rates in children and adolescents are rising globally. T2D is a complex and aggressive disease in children with several comorbidities, high treatment failure rates, and insulin needs within a few years from diagnosis. While myriads of pharmacotherapies are licensed to treat adults with T2D, treatments accessible to children and adolescents have been limited until recently. Metformin is an old drug with multiple beneficial metabolic health effects beyond glycemic control. This review discusses Metformin's origins, its mechanisms of action, and evidence for its use in the pediatric population to treat and prevent T2D. We also explore the evidence for its use as an obesity therapy, which is the primary driver of T2D, and T2D-driven comorbidities. While emerging therapies create new horizons for managing pediatric T2D, Metformin remains an inexpensive and safe part of the treatment plans of many T2D children globally for its beneficial metabolic effects. [ABSTRACT FROM AUTHOR]

Historique L'obésité est un problème sanitaire mondial. Étant donné la perturbation généralisée causée par la pandémie de COVID-19, il est important d'en évaluer l'effet chez les enfants ayant des troubles de santé chroniques. La présente étude évalue la santé des patients pédiatriques obèses inscrits à un programme de gestion du poids d'un hôpital de soins tertiaires avant la pandémie de COVID-19, puis un an après le début de la pandémie. Méthodologie Les chercheurs ont mené une analyse rétrospective des dossiers de patients de deux à 17 ans inscrits à une clinique pédiatrique de gestion du poids. Ils ont comparé les effets en matière de santé mentale (nouvelles orientations en psychologie, en travail social, dans un programme de troubles alimentaires, incidence de dysrégulation de l'alimentation, idéation suicidaire ou automutilation) et de santé physique (mesures anthropométriques) avant la pandémie, puis un an après le début de la pandémie. Résultats Chez les 334 enfants vus pendant l'une ou l'autre période, le nombre d'orientations en psychologie (12,4 % par rapport à 26, 5 %; p=0,002) et le résultat composite sur la santé mentale (17,2 % par rapport à 30,2 %; p=0,005) se sont creusés pendant la pandémie comparativement à auparavant. Dans un sous-groupe d'enfants (n=30) dont ils connaissaient les mesures anthropométriques au cours des deux périodes, le taux de diminution du score z de l'indice de masse corporelle était plus faible (−1,5 [2,00] par rapport à −0,3 [0,73]/année; p=0,002) et l'adiposité, plus élevée (−0,8 [4,64] par rapport à 2,7 [5,54] %/année; p=0,043) pendant la pandémie. Exposé La pandémie a influé sur la santé mentale et physique des enfants obèses inscrits à une clinique de gestion du poids. L'étude démontre un effet négatif sur la santé mentale et une amélioration moins marquée des mesures anthropométriques, mais les futures recherches, lorsque les patients auront repris les soins en clinique, permettront d'examiner nos résultats à la lumière de nouvelles mesures objectives. [ABSTRACT FROM AUTHOR]

Background Obesity is a global public health concern. Given the widespread disruption caused by the SARS-CoV-2 pandemic, it is important to evaluate its impact on children with chronic health conditions. This study examines the health of paediatric patients with obesity enrolled in a tertiary hospital weight management program, before and 1 year into the COVID-19 pandemic. Methods This is a retrospective chart review of patients aged 2 to 17 years enrolled in a paediatric weight management clinic. Mental health outcomes (i.e. new referrals to psychologist, social work, eating disorder program, incidence of dysregulated eating, suicidal ideation, and/or self-harm) and physical health (anthropometric measures) were compared before and 1 year into the pandemic. Results Among the 334 children seen in either period, there was an increase in referrals to psychologist (12.4% versus 26.5%; P=0.002) and the composite mental health outcome (17.2% versus 30.2%; P=0.005) during the pandemic compared with pre-pandemic. In a subset of children (n=30) with anthropometric measures in both periods, there was a lower rate of decline in BMIz score (–1.5 [2.00] versus –0.3 [0.73]/year; P=0.002) and an increase in adiposity (–0.8 [4.64] versus 2.7 [5.54]%/year; P=0.043) during the pandemic. Discussion The pandemic has impacted the mental and physical health of children with obesity engaged in a weight management clinic. While our study provides evidence of a negative impact on mental health outcomes and less improvement in anthropometric measures, future research when patients return to in-person care will enable further examination of our findings with additional objective measures. [ABSTRACT FROM AUTHOR]

Abstract Obesity is a worldwide pandemic representing one of the major challenges that societies face around the globe. Identifying the mechanisms involved in its development and propagation will help the development of preventative and therapeutic strategies that may help control its rising rates. Obesity is associated with chronic low-grade inflammation, and this is believed to be one of the major contributors to the development of insulin resistance, which is an early event in obesity and leads to type 2 diabetes when the pancreas fails to keep up with increased demand for insulin. In this review, we discuss the role of macrophages in mediation of inflammation in obesity in metabolic organs including adipose tissue, skeletal muscle and liver. The presence of immune cells at the interface with metabolic organs modulates both metabolic function and inflammatory responses in these organs, and may provide a potential therapeutic target to modulate metabolic function in obesity.

Objective: Prescription opioid misuse has led to a new cohort of opioid use disorder (OUD) patients who were introduced to opioids through a legitimate prescription. This change has caused a shift in the demographic profile of OUD patients from predominantly young men to middle age and older people. The management of OUD includes medication-assisted treatment (MAT), which produces varying rates of treatment response. In this study, we will examine whether the source of first opioid use has an effect on treatment outcomes in OUD. Using a systematic review of the literature, we will investigate the association between source of first opioid introduction and treatment outcomes defined as continuing illicit opioid use and poly-substance use while in MAT. Methods: Medline, EMBASE, CINHAL, and PsycInfo were searched from inception to December 31st, 2019 inclusive using a comprehensive search strategy. Five pairs of reviewers conducted screening and data extraction independently in duplicate. The review is conducted and reported according to the PRISMA guidelines. A random-effects model was used for meta analyses assuming heterogeneity among the included studies. Results: The initial search results in 27,345 articles that were screened, and five observational studies were included in the qualitative and quantitative analyses. Our results found that those who were introduced to opioids through a legitimate prescription were significantly less likely to have illicit opioid use (0.70, 95% CI 0.50, 0.99) while on MAT. They were also less likely to use cannabis (0.54, 95% CI 0.32, 0.89), alcohol (0.75, 95% CI 0.59, 0.95), cocaine (0.50, 95% CI 0.29, 0.85), and injection drug use (0.25, 95% CI 0.14, 0.43) than those introduced to opioids through recreational means. Conclusion: This study shows that the first exposure to opioids, whether through a prescription or recreationally, influences prognosis and treatment outcomes of opioid use disorder. Although the increased pattern of prescribing opioids may have led to increased OUD in a new cohort of patients, these patients are less likely to continue to use illicit drugs and have a different prognostic and clinical profile that requires a tailored approach to treatment. Systematic Review Registration: PROSPERO CRD42017058143. [ABSTRACT FROM AUTHOR]

Growth hormone deficiency (GHD) in children has significant impacts on growth and metabolism. Two-agent GH stimulation tests are commonly used to diagnose GHD, and these tests are generally considered safe. We report the case of a 5-year 5-month-old boy with a history of anaplastic ependymoma who underwent GH stimulation testing for growth deceleration using clonidine and arginine. He developed bilateral calf myalgia and gross hematuria within 24 hours of the tests. Myalgia and hematuria resolved spontaneously. Importantly, the literature review and database searches for hematuria identified 6 cases with clonidine and 20 cases with arginine. This case highlights an unusual combination of adverse reactions to clonidine and arginine in children undergoing GH stimulation testing to assess for GHD. Pediatric endocrinologists need to be aware of the potential for these side effects to allow appropriate management, and further studies are needed to clarify the mechanisms and frequency of these side effects. We recommend that patients and families need to be counselled about hematuria as an association of GH testing with these medications. [ABSTRACT FROM AUTHOR]

Most children are surviving acute lymphoblastic leukemia (ALL) today. Yet, the emergence of cardiometabolic comorbidities in this population may impact long-term outcomes including the quality of life and lifespan. Obesity is a major driver of cardiometabolic disorders in the general population, and in ALL patients it is associated with increased risk of hypertension, dysglycemia, and febrile neutropenia when compared with lean ALL patients undergoing therapy. This systematic review aims to assess the current evidence for bariatric interventions to manage obesity in children with ALL. The primary outcome for this systematic review was the change in BMI z-score with implementation of the interventions studied. Literature searches were conducted in several databases. Ten publications addressing the study question were included in this review, and five studies were used in the meta-analysis to assess the impact of the bariatric interventions on obesity. The BMI z-score did not change significantly with the interventions. However, the quality of evidence was low, which precluded the recommendation of their use. In conclusion, prospective, rigorous, adequately powered, and high-quality longitudinal studies are urgently needed to deliver effective lifestyle interventions to children with ALL to treat and prevent obesity. These interventions, if successful, may improves cardiometabolic health outcomes and enhance the quality of life and life expectancy in children with ALL. [ABSTRACT FROM AUTHOR]

Summary: Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes (T2D). The role of the immune system in skeletal muscle (SM) inflammation and insulin sensitivity is not yet well characterized. As SM IR is an important determinant of glycaemia, it is critical that the muscle‐immune phenotype is mapped to help design interventions to target T2D. This systematic review synthesized the evidence for SM macrophage content and phenotype in humans and murine models of obesity, and the association of muscle macrophage content and phenotype with IR. Results were synthesized narratively, as we were unable to conduct a meta‐analysis. We included 28 studies (n=10 human, n=18 murine), and all studies detected macrophage markers in SM. Macrophage content was positively associated with IR. In humans and mice, there was variability in muscle macrophage content and phenotype in obesity. Overall certainty in the evidence was low due to heterogeneity in detection methods and incompleteness of data reporting. Macrophages are detected in human and murine SM in obesity and a positive association between macrophage content and IR is noted; however, the standardization of markers, detection methods, and reporting of study details is warranted to accurately characterize macrophages and improve the potential for creating specific and targeted immune‐based therapies in obesity. [ABSTRACT FROM AUTHOR]

Introduction Acute lymphoblastic leukaemia is the most common paediatric cancer. Survivors of childhood acute lymphoblastic leukaemia (SALL) are at risk of obesity and related cardiometabolic diseases including type 2 diabetes, hypertension, stroke and cardiovascular events. Therefore, it is important to address obesity in this population as this may help mitigate future cardiometabolic comorbidities. In this systematic review, we aim to assess current treatment strategies including lifestyle interventions, pharmacotherapy and bariatric surgery to manage overweight and obesity in SALL. Methods and analysis We will search the following databases for primary studies: CINAHL, SPORTDiscus, EMBASE, MEDLINE, PsycINFO, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews. In addition, unpublished primary studies will be searched in ClinicalTrials.gov as well as conference proceedings, presentations, abstracts, editorials and ProQuest Dissertations and Theses A&I. Reviewers will perform title, abstract, and full-text screening as well as data abstraction and risk of bias assessment independently with a third reviewer to be consulted to resolve disagreements. Searches will be run and updated through May 1st, 2018. The overall quality of the evidence will be determined using the Grading of Recommendations, Assessment, Development, and Evaluation criteria for each outcome. A meta-analysis will be performed if two studies deploying similar interventions, populations, and design and outcomes are identified. Ethics and dissemination As individual patient data will not be included, we do not require ethics approval. This review will be published in a peer-reviewed journal. PROSPERO registration number CRD42016051031. [ABSTRACT FROM AUTHOR]

Background: Adolescent idiopathic scoliosis (AIS) is the most common form of scoliosis in children, and its cause remains unknown. The Immune-metabolic CONnections to Scoliosis (ICONS) Study was designed to elucidate the potential mechanisms by which immune system-paraspinal muscle crosstalk contributes to the development of AIS. In this report, we document the evaluation of ICONS Study feasibility. Methods: This study was conducted at a tertiary pediatric academic center in Hamilton, Ontario, Canada. We included boys and girls, aged 10-17 years with a diagnosis of AIS requiring corrective spinal surgery. Exclusion criteria included patients on high-dose steroids, immunosuppressive therapy, anti-thrombotic medications, those with an active infection for 15 days before participation, autoimmune disease, pregnancy, and patients who were unwilling to consent. Pre-determined feasibility criteria included permission to approach participants and recruitment rates of 80%, consenting of at least 80% of participants to provide biological samples, 90% or higher case report form and questionnaire completion, resources to be sufficient in at least 80% of recruitments, and the ability to successfully collect and process 80% or more of the biological samples needed for this study. Results: Between August 2013 and October 2014, we identified 32 potential participants with AIS, but had the resources to approach only 16, of which 12 (75%) agreed to be approached by the research team, and all consented to participate. Of the 12 participants recruited, 11 questionnaire packages and muscle biopsies (91.7% for each objective) were collected, while other biological samples (serum, plasma, whole blood for DNA and RNA processing, urine) were collected from all participants. Conclusions: The ICONS study protocols and procedures are feasible. However, recruitment rates were less than predicted. For the full study, we plan on prolonging the recruitment phase and the inclusion of additional centers to achieve recruitment targets. [ABSTRACT FROM AUTHOR]

Objectives: The current global rates of obesity and type 2 diabetes are staggering. In order to implement effective management strategies, it is imperative to understand the mechanisms of obesity-induced insulin resistance and diabetes. Macrophage infiltration and inflammation of the adipose tissue in obesity is a well-established paradigm, yet the role of macrophages in muscle inflammation, insulin resistance and diabetes is not adequately studied. In this systematic review, we will examine the evidence for the presence of macrophages in skeletal muscle of obese humans and mice, and will assess the association between muscle macrophages and insulin resistance. We will identify published studies that address muscle macrophage content and phenotype, and its association with insulin resistance. We will search MEDLINE/PubMed, EMBASE, and Web of Science for eligible studies. Grey literature will be searched in ProQuest. Quality assessment will be conducted using the Systematic Review Centre for Laboratory Animal Experimentation risk of bias Tool for animal studies. Results: The findings of this systematic review will shed light on immune-metabolic crosstalk in obesity, and allow the consideration of targeted therapies to modulate muscle macrophages in the treatment and prevention of diabetes. The review will be published in a peer-reviewed journal and presented at conferences. [ABSTRACT FROM AUTHOR]

Background: Overweight and obesity are well-known risk factors for cardiometabolic diseases including hypertension, myocardial infarction, stroke, and type 2 diabetes in the general population. Survivors of childhood brain tumors (SCBT) are at risk of premature mortality, and recent evidence suggests that these cardiometabolic diseases are potential emerging determinants of survival and quality of life. Therefore, the rates of overweight and obesity in this population need to be examined to assess their impact on outcomes. The objective of this systematic review is to examine the prevalence of overweight and obesity in SCBT. The secondary aim of this review is to evaluate whether SCBT have higher adiposity compared to the general population. Methods: Searches will be conducted in MEDLINE, CINAHL, EMBASE, Cochrane Database of Systematic Reviews, Cochrane Central Register of Controlled Trials, PubMed, and Database of Abstracts of Reviews of Effect. For gray literature, we will search ProQuest Dissertations and Theses A&I and Web of Science. Two reviewers will independently screen all articles against predetermined eligibility criteria and complete data abstraction, risk of bias, and quality assessments. The primary outcome includes the prevalence of overweight or obesity. The secondary outcomes involve waist-to-hip ratio, waist-to-height ratio, body fat percentage, and skinfold thickness. Meta-analysis will be performed when two or more studies with similar design, populations, and outcomes are available. Discussion: This review will summarize current data on the prevalence of overweight and obesity in SCBT. This will help the development of an understanding of the scale of overweight and obesity in this population and guide the design of interventions that will improve outcomes. [ABSTRACT FROM AUTHOR]

A 19-month-old boy was referred for progressive weight gain. His past medical history included congenital hypothyroidism and developmental delay. Physical examination revealed characteristics of Albright Hereditary Osteodystrophy, macrocephaly, and calcinosis cutis. He had hypocalcemia, hyperphosphatemia, and elevated Parathyroid Hormone levels. Genetic testing revealed a known mutation of GNAS gene, confirming the diagnosis of Pseudohypoparathyroidism Type Ia (PHP-Ia) (c.34C>T (p.G1n12X)). He had a normal brain MRI at three months, but developmental delay prompted a repeat MRI that revealed Chiari Malformation Type I (CM-I) with hydrocephalus requiring neurosurgical intervention. This was followed by improvement in attaining developmental milestones. Recently, he was diagnosed with growth hormone deficiency. This case suggests the potential association of CM-I with PHP-Ia. Larger studies are needed to assess whether CM-I with hydrocephalus are common associations with PHP-Ia and to define potential genetic links between these conditions. We propose a low threshold in performing brain MRI on PHP-1a patients, especially those with persistent developmental delay to rule out CM-I. Early intervention may improve neurodevelopmental outcomes and prevent neurosurgical emergencies. [ABSTRACT FROM AUTHOR]

Background: The prevalence of type 2 diabetes mellitus (T2DM) in children and adolescents is increasing. This has spurred the development and publication of clinical practice guidelines (CPGs) for the management of paediatric T2DM. Given the long-term complications of T2DM, optimal management is important to prevent or delay these complications. However, the quality of published CPGs has not yet been empirically evaluated. Our objective is to systematically appraise all published CPGs for the management of T2DM in children and adolescents. Methods: We will identify all published CPGs that address T2DM in children and adolescents through MEDLINE, Embase, CINAHL, Trip, and the National Guideline Clearinghouse and will screen diabetes and paediatric societies and associations' websites. Search records will be screened in duplicate for inclusion. Grey literature will be covered by systematically searching publications of all relevant diabetes societies and associations and other health organizations for CPGs that meet our inclusion criteria. CPGs deemed eligible for inclusion will be retrieved. Quality assessment will be conducted using the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool by a team of four appraisers. Scaled scores of the AGREE II will be used to gauge the overall quality of CPGs. Discussion: The results of this review will be disseminated through presentations at local, national, and international conferences and publication in a peer-reviewed journal. The results of this review can help improve the reporting of future guidelines, inform decisions of policy-makers to endorse CPGs, and affect the choice of guideline use in clinical practice. [ABSTRACT FROM AUTHOR]

Introduction: Adolescent idiopathic scoliosis (AIS) affects up to 3% of children around the world. There is limited knowledge of AIS aetiopathogenesis, and this evidence is needed to develop new management strategies. Paraspinal muscle in AIS demonstrates evidence of differential fibrosis based on curve sidedness. Fibrosis is the hallmark of macrophage-driven inflammation and tissue remodelling, yet the mechanisms of fibrosis in paraspinal muscle in AIS are poorly understood. Objectives: The primary objective of this study is to determine the influence of curve sidedness on paraspinal muscle inflammation. Secondary objectives include defining the mechanisms of macrophage homing to muscle, and determining muscle-macrophage crosstalk in muscle fibrosis in AIS. Methods and analysis: This is a cross-sectional study conducted in a tertiary paediatric centre in Hamilton, Ontario, Canada. We will recruit boys and girls, 10-17 years of age, who are having surgery to correct AIS. We will exclude children who have an active infection or are on immunosuppressive therapies within 2 weeks of surgery, smokers and pregnant girls. Paraspinal muscle biopsies will be obtained at the start of surgery. Also, blood and urine samples will be collected from participants, who will fill questionnaires about their lifestyle. Anthropometric measures will also be collected including height, weight, waist and hip circumferences. Ethics and dissemination: This study has received ethics authorisation by the institutional review board. This work will be published in peer-reviewed journals and will be presented in oral and poster formats at scientific meetings. Discussion: This study will explore the mechanisms of paraspinal muscle inflammation, remodelling and fibrosis in AIS. This will help identify pathways and molecules as potential therapeutic targets to treat and prevent AIS. It may also yield markers that predict scoliosis progression and response to treatment in these children. [ABSTRACT FROM AUTHOR]

Background: Pediatric brain tumors are the most common solid tumors in children. Advances in understanding the hallmarks of cancer biology and novel therapies have led to an increasing number of survivors of childhood brain tumors (SCBT). However, these survivors are at an increased risk of obesity and cardiometabolic disorders that affect their quality of life and lifespan. It is important to define effective strategies to treat and prevent obesity in this population. This systematic review aims to investigate the effectiveness of lifestyle interventions, pharmacotherapy, and bariatric surgery on treating obesity in SCBT. Methods: Searches will be conducted in PubMed, MEDLINE, EMBASE, PsycINFO, SPORTDiscus, CINAHL, Cochrane Database of Systematic Review, Cochrane Central Register of Controlled Trials (CENTRAL), and Database of Abstracts of Reviews of Effect (DARE). In addition, ClinicalTrials.gov and ProQuest Dissertations and Theses A&I will be searched to identify relevant gray literature. The reference lists of eligible articles will be searched for additional studies. All screening, quality assessment, and data abstraction will be done independently by two reviewers. We will perform meta-analysis if there are sufficient studies. Discussion: This review will summarize evidence for the effectiveness of interventions used to reduce obesity risk in SCBT. This has significant implications for SCBT, as it can identify gaps in knowledge and provide insights into the development of new interventions to manage obesity in survivors, which may improve their outcomes. [ABSTRACT FROM AUTHOR]

Background: Chronic pain is the most commonly reported comorbidity among patients with opioid addiction receiving methadone maintenance treatment (MMT), with an estimated prevalence ranging between 30% and 55%. Evidence suggests that patients with comorbid pain are at high risk for poor treatment response, including continued illicit substance use. Due to the important relationship between the presence of pain and illicit substance abuse within the MMT setting, it is imperative that we target our efforts toward understanding the characteristics of this patient population. Methods: The primary objective of this study was to explore the clinical and inflammatory profile of MMT patients reporting comorbid pain. This multicenter study enrolled patients (n=235) on MMT for the treatment of opioid dependence. Clinical history and blood and urine data were collected. Blood samples were obtained for estimating the serum levels of inflammatory markers (tumor necrosis factor [TNF]-α, interleukin-1 receptor antagonist [IL-1ra], IL-6, IL-8, IL-10, interferon [IFN]-γ and chemokine (C–C motif) ligand 2 [CCL2]). The study objectives were addressed using a descriptive statistical summary and a multivariable logistic regression model constructed in STATA version 12. Results: Among the participants eligible for inclusion (n=235), serum IFN-γ level and substance abuse behavior proved to be important delineating characteristics for the detection of comorbid pain. Analysis of inflammatory profile showed IFN-γ to be significantly elevated among patients reporting comorbid pain (odds ratio [OR]: 2.02; 95% confidence interval [CI]: 1.17, 3.50; P=0.01). Patients reporting comorbid pain were also found to have an increase in positive opioid urine screens (OR: 1.02; 95% CI: 1.00, 1.03; P=0.01), indicating an increase in illicit opioid consumption. Conclusion: MMT patients with comorbid pain were shown to have elevated IFN-γ and higher rates of continued opioid abuse. The ability to objectively distinguish between patients with comorbid pain may help to both improve the prediction of poor responders to MMT as well as identify treatment approaches such as anti-inflammatory medications as safe alternatives for MMT patients with comorbid pain. [ABSTRACT FROM AUTHOR]

Global rates of type 2 diabetes in children and adolescents have increased significantly over the past three decades. Type 2 diabetes is a relatively new disease in this age group, and there is a dearth of information about how to structure treatment programs to manage its comorbidities and complications. In this paper, we describe the design and implementation of a personalized multidisciplinary, family-centered, pediatric and adolescent type 2 diabetes program at a tertiary pediatric center in Hamilton, Ontario, Canada. We report the process of designing and implementing such a program, and show that this multidisciplinary program led to improvement in glycated hemoglobin (n=17, 8% at baseline versus 6.4% at 1 year, 95% confidence interval (0.1-0.28), P-value <0.0001) and stabilized body mass index, with lowered C-peptide and no change in fitness or metabolic biomarkers of lipid metabolism and liver function. As type 2 diabetes becomes more prevalent in youth, the need for programs that successfully address the complex nature of this disease is central to its management and to mitigate its long-term adverse outcomes. [ABSTRACT FROM AUTHOR]

Objectives: The aim of this study was to test the feasibility of recruitment and performance of study procedures of the Canadian Study of Determinants of Endometabolic Health in ChIlDrEn (CanDECIDE) study, which was designed to assess the determinants of endocrine and metabolic health in survivors of childhood brain tumours. Setting: A single paediatric tertiary care centre in Hamilton, Ontario, Canada. Participants: We included boys and girls, aged 5 years and older, who were lean (body mass index (BMI) below 85th centile for age and gender) or overweight/obese (BMI 85th centile or above for age and gender). We excluded children on steroids or immunosuppressant therapy, smokers and those who had an active infection for the 2 weeks prior to participation. Outcomes: Feasibility targets included recruitment rate of at least 50%, the consenting of 80% of participants to provide biological samples, 90% questionnaire completion rate and the ability to process biological samples from at least 80% of participants. Results: We approached 210 potential participants, and of the 112 (53%) who agreed to participate, 30 (26.8%) completed the study visit over 7 months. All participants agreed to fast, provide biological samples and complete the questionnaires. Sample collection was successful in 97% (29/30) of participants and laboratory procedures were feasible in 100% of collected samples. We also tested resources required for the conduct of the full study including personnel, space, laboratory equipment and procedures and determined that they are all feasible. Conclusions: Recruitment and consenting of patients for the CanDECIDE study may be feasible. However, we are considering prolonging recruitment duration and collaboration with other centres to meet recruitment targets due to lower than expected recruitment rate. Completion of questionnaires and implementation of sample processing protocols are feasible. [ABSTRACT FROM AUTHOR]

Obesity is associated with chronic low-grade inflammation that involves infiltration of macrophages into metabolic organs such as skeletal muscle. Exercise enhances skeletal muscle insulin sensitivity independently of weight loss; but its role in regulating muscle inflammation is not fully understood. We hypothesized that exercise training would inhibit skeletal muscle inflammation and alter macrophage infiltration into muscle independently of weight loss. Wild type C57BL/6 male mice were fed a chow diet or a high-fat diet (HFD, 45% calories fat) for 6 weeks. Then, mice maintained on the HFD either remained sedentary (HFD Sed) or exercised (HFD Ex) on a treadmill for another 6 weeks. The exercise training protocol involved conducting intervals of 2 min in duration followed by 2 min of rest for 60 min thrice weekly. Chow-fed control mice remained sedentary for the entire 12 weeks. Muscle cytokine and macrophage gene expression analysis were conducted using qRT- PCR, and muscle macrophage content was also measured using immunohistochemistry. Muscle cytokine protein content was quantified using a cytokine array. The HFD increased adiposity and weight gain compared to chow-fed controls. HFD Sed and HFD Ex mice had similar body mass as well as total and visceral adiposity. However, despite similar adiposity, exercise reduced inflammation and muscle macrophage infiltration. We conclude that Endurance exercise training modulates the immune-metabolic crosstalk in obesity independently of weight loss, and may have potential benefits in reducing obesity-related muscle inflammation. [ABSTRACT FROM AUTHOR]

Background: Childhood obesity has reached epidemic proportions and is impacting children's health globally. In adults, obesity is associated with chronic low-grade inflammation that leads to insulin resistance, which is one of the important mechanisms through which dysregulation of metabolism occurs. There is limited information available about the contribution of inflammation to metabolic health in obese children, and how individual and lifestyle factors impact this risk. One of the paediatric groups at risk of higher rates of obesity includes the survivors of childhood brain tumours. The aim of this study was to evaluate the mechanisms that contribute to inflammation in obese survivors of childhood brain tumours. Methods and analysis: This is a prospective cohort study. We will recruit lean and obese survivors of childhood brain tumours, and a control group composed of lean and obese children with no history of tumours. We will measure circulating and urinary cytokine levels and cytokine gene expression in monocytes. In addition, the methylation patterns of cytokine genes and that of toll-like receptor genes will be evaluated. These will be correlated with individual and lifestyle factors including age, sex, ethnicity, puberty, body mass index, fasting lipid levels, insulin sensitivity, diet, exercise, sleep, stress and built environment. The sample size calculation showed that we need 25 participants per arm Ethics and dissemination: This study has received ethics approval from the institutional review board. Once completed, we will publish this work in peer-reviewed journals and share the findings in presentations and posters in meetings. Discussion: This study will permit the interrogation of inflammation as a contributor to obesity and its complications in obese survivors of childhood brain tumours and compare them with lean survivors and lean and obese controls with no history of tumours, which may help identify therapeutic and preventative interventions to combat the rising tide of obesity. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D) was an adult disease until recently, but the rising rates of obesity around the world have resulted in a younger age at presentation. Children who have T2D have several comorbidities and complications reminiscent of adult diabetes, but these are appearing in teens instead of midlife. In this review, we discuss the clinical presentation andmanagement options for youth with T2D. We discuss the elements of lifestyle intervention programs and allude to pharmacotherapeutic options used in the treatment of T2D youth.We also discuss comorbidities and complications seen in T2D in children and adolescents. [ABSTRACT FROM AUTHOR]

Obesity is associated with insulin resistance and increased risk for developing type 2 diabetes. Enlarged adipocytes develop resistance to the anti-lipolytic action of insulin. Elevated levels of fatty acids in the plasma and interstitial fluids lead to whole-body insulin resistance by disrupting normal insulin-regulated glucose uptake and glycogen storage in skeletal muscle. A new understanding has been cultivated in the past 5 to 10 years that adipocytes and macrophages (resident or bone marrow-derived) in adipose tissue of obese animals and humans are activated in a pro-inflammatory capacity and secrete insulin resistance-inducing factors. However, only recently have fatty acids themselves been identified as agents that engage toll-like receptors of the innate immunity systems of macrophages, adipocytes and muscle cells to trigger pro-inflammatory responses. This review summarizes our observations that fatty acids evoke the release of pro-inflammatory factors from macrophages that consequently induce insulin resistance in muscle cells. [ABSTRACT FROM AUTHOR]

A 10-year-old boy known to have type 1 diabetes presented to the emergency department with history of sudden onset of rightsided hemiplegia after exercise. He did not respond to oral glucose administration, but had an almost immediate resolution of symptoms with intravenous bolus of dextrose. Hemiplegic hypoglycemia is a rare complication in diabetic children, mostly affects the right side of the body, and is rarely recurrent. Children have normal brain imaging and angiography testing, and electroencephalogram may show slow-wave activity. The recovery takes place within 24 hours, and the prognosis is excellent with no focal neurological deficits noted. Our patient responded within minutes to intravenous dextrose, which is unusual and has not been reported previously. The mechanisms leading to development of hypoglycemic hemiplegia are unclear, but may involve effects of hypoglycemia on intracellular signaling pathways or molecules on motor neurons, as recent studies have shown normal brain cell glucose uptake and metabolism in hypoglycemia. While hypoglycemic hemiplegia is rare, it is a frightening experience to caregivers, and efforts should concentrate on its prevention by preventing hypoglycemia. [ABSTRACT FROM AUTHOR]

Children with brain tumors (CBT) are at high risk of cardiovascular diseases and type 2 diabetes compared to the general population. Recently, adiposity has been reported to be more informative for cardiometabolic risk stratification than body mass index (BMI) in the general population. The goal of this study is to describe the adiposity phenotype in CBT, and to establish adiposity determinants. We recruited CBT (n = 56) and non-cancer controls (n = 106). Percent body fat (%FM), waist-to-hip ratio (WHR) and waist-to-height ratio (WHtR) were measured to determine total and central adiposity, respectively. Regression analyses were used to evaluate adiposity determinants. CBT had higher total and central adiposity compared to non-cancer controls despite having similar BMI measurements. Those with tumors at the supratentorial region had increased total and central adiposity, while those who received radiotherapy had increased total adiposity. In conclusion, CBT have increased total and central adiposity in the presence of similar BMI levels when compared to non-cancer controls. Adiposity, especially central adiposity, is a potential cardiometabolic risk factor present relatively early in life in CBT. Defining interventions to target adiposity may improve long-term outcomes by preventing cardiometabolic disorders in CBT. [ABSTRACT FROM AUTHOR]