Insulin Resistance during normal child growth and development is associated with a distinct blood metabolic phenotype (Earlybird 72).

BACKGROUND: While insulin resistance (IR) is associated with specific metabolite signatures in adults, there have been few truly longitudinal studies in healthy children, either to confirm which abnormalities are present, or to determine whether they precede or result from IR. Therefore, we investigated the association of serum metabolites with IR in childhood in the Earlybird cohort. METHODS: The Earlybird cohort is a well-characterized cohort of healthy children with annual measurements from age 5 to 16 years. For the first time, longitudinal association analyses between individual serum metabolites and homeostatic model assessment (HOMA) of insulin resistance (HOMA-IR) have been performed taking into account the effects of age, growth, puberty, adiposity, and physical activity. RESULTS: IR was higher in girls than in boys and was associated with increasing body mass index (BMI). In longitudinal analysis IR was associated with reduced concentrations of branched-chain amino acids (BCAA), 2-ketobutyrate, citrate and 3-hydroxybutyrate, and higher concentrations of lactate and alanine. These findings demonstrate the widespread biochemical consequences of IR for intermediary metabolism, ketogenesis, and pyruvate oxidation during normal child growth and development. CONCLUSIONS: Longitudinal analysis can differentiate metabolite signatures that precede or follow the development of greater levels of IR. In healthy normal weight children, higher levels of IR are associated with reduced levels of BCAA, ketogenesis, and fuel oxidation. In contrast, elevated lactate concentrations preceded the rise in IR. These changes reveal the metabolite signature of insulin action during normal growth, and they contrast with previous findings in obese children and adults that represent the consequences of IR and obesity.

Insulin resistance is higher in prepubertal girls but switches to become higher in boys at age 16: A Cohort Study (EarlyBird 57).

BACKGROUND: The risk of type 2 diabetes is increasing in teenage girls, and is associated with their greater insulin resistance (IR). HYPOTHESIS: We hypothesized that the adverse metabolic profile of girls (compared with boys) would persist from childhood through adolescence. PATIENTS AND METHODS: Community-based longitudinal cohort of 292 children (147 boys) studied annually from 9 to 16 years. MEASURES: IR (homeostasis-model-assessment-2), high-density lipoprotein-cholesterol (HDL-C), triglycerides, % body-fat (dual-energy x-ray absorptiometry), pubertal stage (age at peak height velocity), physical activity (accelerometry). Multi-level modelling established the age-related trends in IR and lipids and the influence of covariates. RESULTS: Each year from 9 to 15 years, girls had 21% to 63% higher IR than boys (girls mean IR 0.73-1.33, boys 0.51-0.89, P < .005). At 16 years the gender difference was not significant (girls IR 0.60, boys 0.56, P = .45). Girls had lower HDL-C from 9 to 12 years, higher triglycerides from 9 to 14 years, greater adiposity throughout, and earlier puberty, but boys were more active than girls (all P < .05). After adjustment for %-fat, puberty and activity, the gender difference in IR between girls and boys aged 9 to 15 years became non-significant (IR girls 0.66-1.01, boys 0.65-1.04, P > .07). However, after adjustment at 16 years, girls' IR was 25% lower than boys' (girls 0.44, boys 0.63, P = .001), and they had 22% higher HDL-C (P < .001) and 20% lower triglycerides (P = .003). CONCLUSIONS: The higher IR of prepubertal and early pubertal girls diminishes during late puberty, and boys begin to exhibit greater metabolic risk. Despite being leaner and more active, boys at 16 years have higher IR than girls, suggesting future higher risk for diabetes, thus we reject our hypothesis.

Not all waits are equal: an exploratory investigation of emergency care patient pathways.

BACKGROUND: Increasing pressure in the United Kingdom (UK) urgent care system has led to Emergency Departments (EDs) failing to meet the national requirement that 95% of patients are admitted, discharged or transferred within 4-h of arrival. Despite the target being the same for all acute hospitals, individual Trusts organise their services in different ways. The impact of this variation on patient journey time and waiting is unknown. Our study aimed to apply the Lean technique of Value Stream Mapping (VSM) to investigate care processes and delays in patient journeys at four contrasting hospitals. METHODS: VSM timing data were collected for patients accessing acute care at four hospitals in South West England. Data were categorised according to waits and activities, which were compared across sites to identify variations in practice from the patient viewpoint. We included Public and Patient Involvement (PPI) to fully interpret our findings; observations and initial findings were considered in a PPI workshop. RESULTS: One hundred eight patients were recruited, comprising 25,432 min of patient time containing 4098 episodes of care or waiting. The median patient journey was 223 min (3 h, 43 min); just within the 4-h target. Although total patient journey times were similar between sites, the stage where the greatest proportion of waiting occurred varied. Reasons for waiting were dominated by waits for beds, investigations or results to be available. From our sample we observed that EDs without a discharge/clinical decision area exhibited a greater proportion of waiting time following an admission or discharge decision. PPI interpretation indicated that patients who experience waits at the beginning of their journey feel more anxious because they are 'not in the system yet'. CONCLUSIONS: The novel application of VSM analysis across different hospitals, coupled with PPI interpretation, provides important insight into the impact of care provision on patient experience. Measures that could reduce patient waiting include automatic notification of test results, and the option of discharge/clinical decision areas for patients awaiting results or departure. To enhance patient experience, good communication with patients and relatives about reasons for waits is essential.

The diagnosis and lived experience of polycystic ovary syndrome: A qualitative study.

AIMS: To explore the impact of the diagnosis of polycystic ovary syndrome on health/ill health identity, how women experience this diagnosis and their health beliefs. BACKGROUND: Polycystic ovary syndrome is a common and heterogeneous condition, giving rise to a wide range of different health concerns. Previous research on polycystic ovary syndrome has been dominated by the medical perspective and less is known about the experiences and needs of women. DESIGN: A qualitative study of 32 premenopausal adult women with polycystic ovary syndrome (diagnosis confirmed by Rotterdam criteria), aged between 18 and 45 years, recruited from a primary and secondary care setting. METHODS: Thematic analysis of transcripts from 11 focus groups conducted between 2013-2015. RESULTS/FINDINGS: Women identified a range of concerns affecting personal and reproductive identity, health knowledge and beliefs: (1) delays and barriers to diagnosis; (2) general lack of empathy by the medical profession; (3) difficulty in accessing specialist referral; (4) lack of information from professionals; (5) inconsistent and sometimes unsatisfactory experiences with medications; (6) insufficient help and advice regarding in/fertility; (7) relative lack of awareness or concern about longer term risks such as diabetes; and (8) significant discrepancies between the beliefs of women with polycystic ovary syndrome and how they experienced the attitudes of healthcare professionals. CONCLUSIONS: There appears to be a divergence between women's experience and attitudes of healthcare professionals. The diagnosis, support and lived experience of women with polycystic ovary syndrome could be enhanced by better professional recognition of these concerns, improved knowledge and communication about polycystic ovary syndrome and better access to support and specialist advice.

The role of ghrelin in metabolic regulation.

PURPOSE OF REVIEW: To discuss recent research on the role of ghrelin in the regulation of carbohydrate and lipid metabolism in the context of its wider role in regulating energy balance. RECENT FINDINGS: Ghrelin possesses a range of centrally and peripherally mediated metabolic actions influencing insulin glucose homeostasis and fatty acid metabolism and appetite. Although acyl ghrelin was previously thought to be the active hormone, recent evidence suggests that des-acyl ghrelin also possesses activity, and the enzyme ghrelin-O-acyl transferase regulates their interconversion. In partnership with insulin and leptin, ghrelin defends against energy deficit by enhancing hunger, conserving carbohydrate and promoting fat oxidation. In the postprandial state, it contributes to satiety, energy storage and favours glucose oxidation. New research suggests a range of new roles including addictive behaviours, cardiovascular protection, neuroprotection and regeneration and perhaps the ageing process. SUMMARY: Ghrelin functions primarily as a short-term metabolic switch at the onset of fasting, gearing the fuel economy away from glucose uptake, conserving glucose for vital functions, favouring fatty acid oxidation and triggering food-seeking behaviour. The ghrelin system is a potential target for a range of pharmacological interventions, but its pleiotropic nature makes selective treatments challenging.

Blending Behavioural Theory and Narrative Analysis to Explore the Lived Experience of Obesity and Assess Potential Engagement in a UK Weight Management Service: Theory and Narrative Approaches in Weight Management.

BACKGROUND: Current treatments for people with obesity emphasise the need for person-centred approaches that consider complex biopsychosocial factors and value the lived experience of people when attempting to lose weight. METHODS: Narrative interviews (n = 20) were conducted with people living with obesity to explore the causes of their weight gain and their expectations and engagement with treatment at a Weight Management Clinic. A mixed inductive and deductive qualitative analysis identified utterances that represented psychological constructs used to understand self-appraisal and health behaviour. A narrative analysis was used to situate these findings in the context of a participant's life story. RESULTS: Locus of control was a dominant construct evidenced through a person's attributional style and self-efficacy. Transcripts represented a heightened sense of self-understanding and shifts in control, and styles of attribution and efficacy resulted in either stasis or self-actualisation. The Stages of Change model could be applied to narratives to ascertain a patient's motivation to access treatment. Importantly, narrative interviews also allowed for the consideration of how a person's systemic context influenced their weight. CONCLUSION: Narrative interaction supports both self- and shared understandings of the causes and consequences of obesity for individuals, in a non-blaming or shaming manner. It provides an opportunity to enhance engagement through tailored, person-centred treatments.

What is known about the use of weight loss medication in women with overweight/obesity on fertility and reproductive health outcomes? A scoping review.

Pregnancy during or soon after treatment with weight loss medication, particularly glucagon-like peptide-1 receptor agonists (GLP-1 RAs), is contraindicated due to potential teratogenicity. The aim of this scoping review is to investigate what is known about the use of weight loss medication in women of childbearing age in relation to reproductive health outcomes, focusing on the three medications licenced in the United Kingdom at the time of the search. A systematic search of studies that assessed reproductive health outcomes in women taking either orlistat, liraglutide or semaglutide was undertaken in July 2023 and updated in January 2024 across MEDLINE, Embase, CINAHL, Scopus, ClinicalTrials.gov, PROSPERO, Epistemonikos and OpenGrey. Studies focused on polycystic ovarian syndrome, diabetes or animals were excluded. Titles and abstracts were screened, and data from included articles were extracted. After removal of duplicates, 341 titles remained, of which 318 were excluded. Of the final 18 articles included, there were five interventional trials, one retrospective case-control study, six narrative reviews, two systematic reviews, three systematic review protocols and one registry protocol yet to start recruitment. All five interventional trials involved orlistat given preconceptionally, showing no improvement in live birth rate, despite improvement in reproductive hormone levels. There were no studies with primary data about GLP-1 RAs. There were no qualitative studies. There is an absence of primary data about the role of GLP-1 RAs on the reproductive health of women of childbearing age without polycystic ovarian syndrome. Future research should explore short- and long-term effects on reproductive health, pregnancy outcomes and experiences.

Which components of behavioral weight management programs are essential for weight loss in people living with obesity? A rapid review of systematic reviews.

The optimal treatment and organization of care for people with obesity is one of the greatest challenges facing today's health services. While surgery and pharmacotherapy offer effective treatment options for some people with obesity, behavioral interventions are important to support long-term behavioral change. However, little is known about the most effective components of behavioral interventions, and this is especially the case for people with complex or severe obesity (i.e. body mass index [BMI] > 35 kg/m2). Accordingly, the current rapid review aimed to identify which behavior change techniques (BCTs) are effective for weight loss in adults with (severe) obesity. A secondary aim was to review the effects of BCTs on dietary behaviors and physical activity, and psychological outcomes, recognizing that behavioral interventions commonly target these. A search of Scopus, Ovid Medline, and Web of Science resulted in 1227 results, with 22 reviews eligible for inclusion. The most commonly reported BCTs were self-monitoring and goal setting, but these had variable effects on weight in adults with obesity. Combining these BCTs with other self-regulatory techniques led to increased weight loss. Further, for adults with severe obesity, so-called 'nudge' techniques and self-regulatory techniques were associated with greater weight loss. Three reviews also found that while self-monitoring increased physical activity, behavioral commitments increased changes to dietary behaviors. BCTs were not associated with psychological well-being. The review confirms that behavioral interventions have an impact in weight management, including for individuals with more complex or severe obesity, but highlights the need for further investigation of their use within clinical settings.

Development of a group-based behaviour change intervention for people with severe obesity informed by the social identity approach to health.

INTRODUCTION: Interventions to support behaviour change in people living with chronic health conditions increasingly use patient groups as the mode of delivery, but these are often designed without consideration of the group processes that can shape intervention outcomes. This article outlines a new approach to designing group-based behaviour change interventions that prioritizes recipients' shared social identity as group members in facilitating the adoption of established behaviour change techniques (BCTs). The approach is illustrated through an example drawn from research focused on people living with severe obesity. METHODS: A prioritization process was undertaken in collaboration with stakeholders, including behaviour change experts, clinicians, and a former patient to develop an evidence-based, group intervention informed by the social identity approach to health. Three phases of development are reported: (1) identification of the health problem; (2) delineation of intervention mechanisms and operationalization of BCTs for group delivery and (3) intervention manualization. The fourth phase, intervention testing and optimization, is reported elsewhere. RESULTS: A group-based behaviour change intervention was developed, consisting of 12 group sessions and 3 one-to-one consultations. The intervention aimed to support the development of shared social identity among recipients, alongside the delivery of evidence-based BCTs, to improve the likelihood of successful intervention and health outcomes among people living with severe obesity. CONCLUSIONS: A manualized intervention, informed by the social identity approach to health, was systematically designed with input from stakeholders. The development approach employed can inform the design of behavioural interventions in other health contexts where group-based delivery is planned.

Raising awareness of polycystic ovary syndrome.

AIM: To identify women's experience of receiving information about polycystic ovary syndrome (PCOS), and develop an information booklet. METHOD: Women from Cornwall with a diagnosis of PCOS participated in focus groups to discuss their experiences of the condition. FINDINGS: Participants described difficulties in sourcing credible and helpful information about PCOS. CONCLUSION: A booklet was produced for women with PCOS to improve their knowledge of the condition.

A Qualitative Exploration of Patient and Staff Experiences of the Receipt and Delivery of Specialist Weight Management Services in the UK.

BACKGROUND: Addressing the increasing prevalence of obesity is a global public health priority. Severe obesity (body mass index > 40) reduces life expectancy, due to its association with people developing complications (e.g. diabetes, cancer, cardiovascular disease), and greatly impairs quality of life. The National Health Service (NHS) in the UK provides specialist weight management services (SWMS) for people with severe obesity, but key uncertainties remain around patient access to and engagement with weight management services, as well as pathways beyond the service. METHODS: In this multiple methods study, using online forum data and semi-structured interviews, stakeholders' experiences of delivering and receiving SWMS were explored. Using the web search engine Google with keywords and web address (URL) identifiers, relevant public online platforms were sourced with snowball sampling and search strings used to identify threads related to people's experiences of accessing SWMS (n = 57). Interviews were conducted with 24 participants (nine patients, 15 staff), and data from all sources were analysed thematically using the framework approach. RESULTS: Six themes related to access to and engagement with SWMS emerged during data analysis: (1) making the first move, (2) uncertainty and confusion, (3) resource issues, (4) respect and understanding, (5) mode of delivery, and (6) desire for ongoing support. CONCLUSION: There is a mixed and varied picture of SWMS provision across the UK. The service offered is based on local clinical decision making and available resources, resulting in a range of patient experiences and perspectives. Whilst service capacity issues and patient anxiety were seen as barriers to accessing care, peer support and positive clinical and group interactions (connectedness between individuals) were considered to increase engagement.

Dietary Intakes of Folate, Vitamin D and Iodine during the First Trimester of Pregnancy and the Association between Supplement Use and Demographic Characteristics amongst White Caucasian Women Living with Obesity in the UK.

Folate, vitamin D and iodine are key micronutrients in pregnancy, with deficiency associated with poor maternal and infant outcomes. For folate and vitamin D especially, deficiency is more common amongst women with obesity and recommended intakes and guidance on supplementation varies worldwide. The present study aims to investigate dietary and supplementary intakes of these micronutrients amongst a population of pregnant women with obesity in the United Kingdom, alongside key maternal demographic characteristics. Expectant women (n = 75) with a body mass index ≥ 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Participants were asked about their supplement use preconception and during trimester one in a baseline questionnaire which also asked about demographic characteristics. Women also completed a four day diet diary from which dietary and supplemental intakes of micronutrients intakes were estimated. Folic acid was taken by 96% of women at any point in trimester 1, whilst only 26% of women took the higher 5 mg dose recommended for women with obesity in the UK. For vitamin D and iodine, 56% and 44% of women met the UK RNI, respectively. Maternal age was positively associated with taking supplements of any kind and the 5 mg folic acid supplement, whilst parity was inversely associated with both outcomes. This study strengthens the rationale for further work to be done raising awareness of the need for women with obesity to supplement both with a higher dose of folic acid and vitamin D and to be aware of the role of iodine during pregnancy.

A group-based behavioural intervention for weight management (PROGROUP) versus usual care in adults with severe obesity: a feasibility randomised controlled trial protocol.

BACKGROUND: Approximately 15 million people in the UK live with obesity, around 5 million of whom have severe obesity (body mass index (BMI) ≥35kg/m2). Having severe obesity markedly compromises health, well-being and quality of life, and substantially reduces life expectancy. These adverse outcomes are prevented or ameliorated by weight loss, for which sustained behavioural change is the cornerstone of treatment. Although NHS specialist 'Tier 3' Weight Management Services (T3WMS) support people with severe obesity, using individual and group-based treatment, the current evidence on optimal intervention design and outcomes is limited. Due to heterogeneity of severe obesity, there is a need to tailor treatment to address individual needs. Despite this heterogeneity, there are good reasons to suspect that a structured group-based behavioural intervention may be more effective and cost-effective for the treatment of severe obesity compared to usual care. The aims of this study are to test the feasibility of establishing and delivering a multi-centre randomised controlled clinical trial to compare a group-based behavioural intervention versus usual care in people with severe obesity. METHODS: This feasibility randomised controlled study is a partially clustered multi-centre trial of PROGROUP (a novel group-based behavioural intervention) versus usual care. Adults ≥18 years of age who have been newly referred to and accepted by NHS T3WMS will be eligible if they have a BMI ≥40, or ≥35 kg/m2 with comorbidity, are suitable for group-based care and are willing to be randomised. Exclusion criteria are participation in another weight management study, planned bariatric surgery during the trial, and unwillingness or inability to attend group sessions. Outcome assessors will be blinded to treatment allocation and success of blinding will be evaluated. Clinical measures will be collected at baseline, 6 and 12 months post-randomisation. Secondary outcome measures will be self-reported and collected remotely. Process and economic evaluations will be conducted. DISCUSSION: This randomised feasibility study has been designed to test all the required research procedures and additionally explore three key issues; the feasibility of implementing a complex trial at participating NHS T3WMS, training the multidisciplinary healthcare teams in a standard intervention, and the acceptability of a group intervention for these particularly complex patients. TRIAL REGISTRATION: ISRCTN number 22088800.

Human RBP4 adipose tissue expression is gender specific and influenced by leptin.

OBJECTIVE: The role of retinol-binding protein-4 (RBP4) in human insulin resistance remains controversial, which may in part be explained by a gender-specific secretion of RBP4 in adipose tissue (AT). The aim of the study was to determine gender-specific depot expression of RBP4 and to identify metabolic parameters and cytokines/adipokines associated with RBP4. RESEARCH DESIGN AND METHODS: The study is an ex-vivo prospective analysis of paired AT-samples from 22 men and 26 women of similar age [men: 43·4 ± 13 (mean ± SD)years, women: 44·1 ± 12 years], BMI (men: 41·9 ± 18kg/m(2) , women: 38·4 ± 11kg/m(2) ) and homeostasis model assessment of insulin resistance taken during elective surgery and ex-vivo culture using visceral-AT (VAT)-explants (n = 10). Plasma RBP4 and cytokines were measured by ELISA and mRNA expression in AT by real-time PCR. VAT-explants were cultured with recombinant leptin and insulin and RBP4 determined by western blot analyses. RESULTS: Overall subcutaneous AT (SCAT)-RBP4 mRNA expression was higher than VAT-expression [3·1 ± 0·26 signal units (SU; mean ± SE) vs 1·79 ± 0·18SU, n = 48, P < 0·0001], but neither correlated with circulating RBP4. SCAT-RBP4 expression was higher in women and correlated with BMI (r =-0·5, P = 0·009) and fat mass (r= -0·5, P = 0·002). VAT-RBP4 correlated positively with GLUT-4 expression and adiponectin in men only (r= 0·54, P = 0·03 and r = 0·64, P < 0·002, respectively) when correcting for age and fat mass. Multiple regression determined leptin AT-expression as a positive predictor of AT-RBP4 in women (SCAT: ß = 0·50, P = 0·002; VAT: ß = 0·58, P = 0·003) and adiponectin for VAT-RBP4 in men (ß = 0·69; P=0·001). AT-RBP4 mRNA expression showed no relation with insulin resistance. Leptin stimulated RBP-4 secretion ex-vivo, whilst insulin did not affect RBP4. CONCLUSION: AT-derived RBP4-mRNA expression is gender specific and regulated by leptin. Circulating RBP4 levels appear to be independent of AT-RBP4 secretion.

The relationship between gestational weight gain, maternal upper-body subcutaneous fat changes and infant birth size: A pilot observational study amongst women with obesity.

BACKGROUND: It is widely acknowledged that maternal obesity and excessive gestational weight gain (GWG) are associated with increased risk of fetal macrosomia and recent studies have suggested a role for the timing and composition of GWG. AIMS: To examine the effect of the rate of change in GWG and maternal upper-body subcutaneous fat on neonatal anthropometric outcomes in a pilot observational study amongst women with obesity. STUDY DESIGN: Expectant women with a body mass index (BMI) > 30 kg/m2 at first antenatal appointment were recruited at 12 weeks gestation. Maternal height, weight and skinfold thickness (SFT) measurements were collected at baseline and repeated at 28 and 36 weeks gestation. Following delivery, World Health Organisation (WHO)-UK infant birthweight z-scores were calculated, and infant anthropometric measurements were obtained. RESULTS: The sum of upper body SFT measurements increased in mid-pregnancy (0.08 ± 0.71 mm/week) and decreased in late pregnancy (-0.04 ± 1.17 mm/week). After adjustment for maternal age, BMI and parity, mid- but not late- pregnancy GWG was positively associated with infant birthweight z-score (p<0.05), while mid- but not late-pregnancy changes in the sum of SFT were inversely associated with infant birthweight z-score (p<0.01). CONCLUSIONS: The present study suggests that mid- rather than late-pregnancy changes in weight and upper-body subcutaneous fat are associated with infant birthweight. Further research is required in larger, more diverse populations to explore whether pregnancy interventions aiming to improve maternal and offspring health can be personalised beyond BMI and GWG.

The Effectiveness and Usability of Online, Group-Based Interventions for People With Severe Obesity: Protocol for a Systematic Review.

BACKGROUND: Globally, obesity is a growing crisis. Despite obesity being preventable, over a quarter of the UK adult population is currently considered clinically obese (typically body mass index ≥35 kg/m2). Access to treatment for people with severe obesity is limited by long wait times and local availability. Online and group-based interventions provide means of increasing the accessibility of obesity prevention and treatment services. However, there has been no prior review of the effectiveness of group-based interventions delivered online for people with severe obesity. OBJECTIVE: The purpose of this systematic review protocol is to provide an evaluation of the effectiveness and usability of different types of online, group-based interventions for people with severe obesity. METHODS: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocols (PRISMA-P) and the Population, Intervention, Comparator, Outcome, and Study (PICOS) frameworks were used to structure this review. The review will systematically search 7 databases: MEDLINE, Embase, the Cumulative Index of Nursing and Allied Health Literature, APA PsycNet, Web of Science, CENTRAL, and the ProQuest Dissertations and Theses databases. Two authors (MM-I and LB) will independently screen the titles and abstracts of identified articles, select studies for inclusion based on the eligibility criteria, and extract data into a standardized form. Any disagreements will be discussed and resolved by a third reviewer (EM) if necessary. Risk of bias will be assessed using the Cochrane Collaboration Risk of Bias 2 tool and a descriptive analysis will be used to evaluate effectiveness and usability. RESULTS: The systematic review has not yet been started. It is expected to be completed and submitted for publication by December 2021. CONCLUSIONS: This systematic review will summarize the effectiveness and usability of online, group-based interventions for people with obesity. It will identify the types of online delivery that have the strongest support to help inform the development of more useful and engaging interventions for people with severe obesity. TRIAL REGISTRATION: National Institute for Health Research, PROSPERO CRD42021227101; https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021227101. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): PRR1-10.2196/26619.

Contrasting impact of androgens on male and female adiposity, fat distribution and insulin resistance in childhood and adolescence (EarlyBird 75).

OBJECTIVES: To investigate associations between androgens (testosterone, dehydroepiandrosterone sulphate [DHEAS] and androstenedione), adiposity, fat distribution and insulin resistance (IR) during childhood and adolescence. METHODS: Three hundred and seven children (170 [55.4%] boys; 137 [44.6%] girls) recruited at age 5 and studied annually until age 16: androgens (liquid chromatography tandem-mass spectrometry), anthropometry, body composition (dual-energy x-ray absorptiometry) and IR (homeostasis model assessment). RESULTS: Early adiposity was associated with earlier detection of androstenedione in both sexes, and DHEAS in boys. At puberty, higher androgen levels were associated with favourable metabolic changes in boys, but adverse metabolic effects in girls. In boys, higher free testosterone (FT) was associated with lower body fat and android/gynoid fat ratio (AGR) (both P < .001), but in girls higher total testosterone was associated with higher AGR. In girls only, higher androstenedione (P = .02) and FT (P = .01) was associated with higher IR during puberty. CONCLUSIONS: In pre-pubertal children, adiposity is associated with higher secretion of androgen precursors. After pubertal onset, higher testosterone is associated with lower adiposity and AGR in boys, but higher AGR and IR in girls. Therefore, androgens have modest sex-specific associations with children's total body fat, fat distribution and IR.

Contributions of Fat and Carbohydrate Metabolism to Glucose Homeostasis in Childhood Change With Age and Puberty: A 12-Years Cohort Study (EARLYBIRD 77).

Puberty-a period when susceptibility to the onset of Type 2 diabetes (T2D) increases-is marked with profound physiological and metabolic changes. In the EarlyBird cohort, children who developed impaired fasting glycemia in adolescence already exhibited higher fasting blood glucose at 5 years of age, independent of their body mass index (BMI), suggesting that pubertal factors may modify existing predisposition. Understanding how the physiological changes during childhood influence glucose homeostasis and how the central energy metabolism may help deciphering the mechanisms that underlie the risk of developing T2D in children and adults. We investigated these associations by analyzing glycemic variations with molecular markers of central energy metabolism, substrate oxidation status and pubertal stages in the EarlyBird cohort. The EarlyBird study is a non-interventional, prospective cohort study, that recruited 307 healthy UK children at age 5, and followed them annually throughout childhood for 12 years. Longitudinal data on blood biochemistry, respiratory exchange ratio, and anthropometry, available from 150 children were integrated with fasting glycemia. The gradual rise in blood glucose during childhood associates with age-dependent changes in molecular processes and substrate oxidation status, namely (i) greater pre-pubertal fat utilization, ketogenesis, and fatty acid oxidation, and (ii) greater pubertal carbohydrate oxidation and glycolytic metabolism (Cori and Cahill Cycles) associated with different amino acid exchanges between muscle and other tissues (proline, glutamine, alanine). Since children's metabolic and nutritional requirements evolve during childhood, this study has potential clinical implications for the development of nutritional strategies for disease prevention in children.

Admission Decision-Making in Hospital Emergency Departments: The Role of the Accompanying Person.

In resource-stretched emergency departments, people accompanying patients play key roles in patients' care. This article presents analysis of the ways health professionals and accompanying persons talked about admission decisions and caring roles. The authors used an ethnographic case study design involving participant observation and semi-structured interviews with 13 patients, 17 accompanying persons and 26 health care professionals in four National Health Service hospitals in south-west England. Focused analysis of interactional data revealed that professionals' standardization of the patient-carer relationship contrasted with accompanying persons' varied connections with patients. Accompanying persons could directly or obliquely express willingness, ambivalence and resistance to supporting patients' care. The drive to avoid admissions can lead health professionals to deploy conversational skills to enlist accompanying persons for discharge care without exploring the meanings of their particular relationship with the patients. Taking a relationship-centered approach could improve the attention to accompanying persons as co-producers of health care and participants in decision-making.

Genetic Susceptibility Determines ß-Cell Function and Fasting Glycemia Trajectories Throughout Childhood: A 12-Year Cohort Study (EarlyBird 76).

OBJECTIVE: Previous studies suggested that childhood prediabetes may develop prior to obesity and be associated with relative insulin deficiency. We proposed that the insulin-deficient phenotype is genetically determined and tested this hypothesis by longitudinal modeling of insulin and glucose traits with diabetes risk genotypes in the EarlyBird cohort. RESEARCH DESIGN AND METHODS: EarlyBird is a nonintervention prospective cohort study that recruited 307 healthy U.K. children at 5 years of age and followed them throughout childhood. We genotyped 121 single nucleotide polymorphisms (SNPs) previously associated with diabetes risk, identified in the adult population. Association of SNPs with fasting insulin and glucose and HOMA indices of insulin resistance and ß-cell function, available from 5 to 16 years of age, were tested. Association analysis with hormones was performed on selected SNPs. RESULTS: Several candidate loci influenced the course of glycemic and insulin traits, including rs780094 (GCKR), rs4457053 (ZBED3), rs11257655 (CDC123), rs12779790 (CDC123 and CAMK1D), rs1111875 (HHEX), rs7178572 (HMG20A), rs9787485 (NRG3), and rs1535500 (KCNK16). Some of these SNPs interacted with age, the growth hormone-IGF-1 axis, and adrenal and sex steroid activity. CONCLUSIONS: The findings that genetic markers influence both elevated and average courses of glycemic traits and ß-cell function in children during puberty independently of BMI are a significant step toward early identification of children at risk for diabetes. These findings build on our previous observations that pancreatic ß-cell defects predate insulin resistance in the onset of prediabetes. Understanding the mechanisms of interactions among genetic factors, puberty, and weight gain would allow the development of new and earlier disease-management strategies in children.