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Obesity is a growing challenge for our society. Current management strategies are limited by low adherence and adverse effects, making novel treatments critical to the success of reducing obesity and its co-morbidities. Liver-expressed antimicrobial peptide 2 (LEAP2) is an endogenous ghrelin antagonist with anorexiant effects. However, effect of LEAP2 on key cardiometabolic risk factors in people with overweight and obesity is unclear.In this cross-sectional study, we sought to identify associations between LEAP2 levels and cardiometabolic risk factors, including body composition (dual X-ray absorptiometry), insulin and glucose metabolism (oral and intravenous glucose tolerance tests and hyperinsulinemic euglycemic clamps), plasma lipids and inflammation markers (ELISA and multiplex assays).In 65 participants with overweight or obesity (63.1% male, mean age 31.3 ± 8.5), LEAP2 levels were associated with total body fat, but not with BMI or waist-hip ratio in both univariable and age- and sex-adjusted models (p 0.05). Higher LEAP2 was also positively associated with higher insulin secretion in univariable (p = 0.047) and multivariable models adjusted for age, sex and body fat (p = 0.03), but not with fasting glucose levels (p= 0.05). Higher LEAP2 levels were associated insulin resistance (p = 0.07) after adjustment for age and sex, but the association disappeared after an additional adjustment for body fat (p = 0.2). There was an inverse association between LEAP2 levels and nuclear factor kappa-B (NFκB) activity in the peripheral blood mononuclear cells in age-, sex- and body fat-adjusted models (p = 0.04). There were no associations with cardiovascular risk factors (lipids, blood pressure) or other inflammation markers.These results provide important insights into the association between LEAP2 and cardiometabolic health in a high-risk population of individuals with overweight and obesity. This is a first report of an association between LEAP2 and insulin secretion, insulin sensitivity and NFκB activity. LEAP2 may represent an important potential therapeutic target to promote insulin secretion in people with type 2 diabetes and obesity.Clinicaltrials.gov - NCT02112721.

Background Preeclampsia is a substantial pregnancy burden that may lead to poor feto-maternal outcomes, particularly in developing countries. It complicates 8% of pregnancies worldwide, resulting in high feto-maternal morbidity and mortality if not appropriately addressed. Despite significant development in obstetric care management in the Kingdom of Saudi Arabia (KSA), prompt recognition of the problem and the necessary care and expertise are vital to tackle this complication. Hence, we studied feto-maternal outcomes in our setting. This study aims to assess the maternal and fetal outcomes of preeclampsia with and without severe features in King Abdulaziz University Hospital (KAUH), Jeddah, KSA. This study aims to identify the maternal and fetal outcomes of preeclampsia among pregnant patients in KAUH, evaluate the role of antepartum follow-up on maternal and fetal outcomes of preeclampsia, and correlate the maternal and fetal complications of preeclampsia. Methodology A retrospective, cross-sectional, hospital-based study was conducted in KAUH, Jeddah, KSA. A total of 83 patients (mean age: 32 ± 6.28) who were admitted with the diagnosis of preeclampsia from 2019 to 2021 were included in the study. Feto-maternal-related outcomes were analyzed in terms of complications. A descriptive statistical method was utilized for the analysis. Results The mean gestational ages where preeclampsia developed with and without severe features were 33.32 weeks and 36 weeks, respectively. There were no significant relationships between preeclampsia and neonatal outcomes. However, there was a significant relationship between preeclampsia with severe features and overall maternal complications without an inclination to a specific complication. Overall, 62% of patients who did not undergo an antenatal follow-up developed preeclampsia with severe features, and 72.2% of these cases were admitted through the emergency department. Conclusions Preeclampsia can have life-threatening effects on both the mother and the fetus; thus, follow-ups and early recognition are recommended to drastically improve morbidity and mortality and provide effective management in line with international and national guidelines to reduce the likelihood of unfavorable outcomes.

Background: There are two variants of spontaneous bacterial peritonitis (SBP) include, culture negative neutrocytic ascites (CNNA) and culture positive SBP. Some suggested that, the clinical presentation of two variants is nearly similar, however, other reported that, patients with culture positive have a more severe course and higher mortality than CNNA. The aim of this study is to determine the clinical characteristics and predictors of CNNA in comparison to culture positive SBP. Materials and methods: This study included 300 consecutive patients with HCV related cirrhotic ascites. All patients underwent abdominal paracentesis and the ascitic fluid was processed for cell count and culture. Clinical and laboratory parameters of these patients were recorded at index admission.. Results: Out of 300 patients included in the study, 150 patients had SBP. Among the 150 patients with SBP, 100 patients were culture positive SBP (culture positive SBP with ascitic fluid PMNL ≥250 cells/m3) and 50 patients were CNNA (culture negative SBP with ascitic fluid PMNL ≥250 cells/m3). Compared to patients with culture positive SBP, patients with CNNA showed, a significant decrease as regards, fever, prevalence of DM, hepatic encephalopathy, platelets, blood PMNL and ascetic PMNL. Logistic regression analysis demonstrated that, decreased platelets count, blood PMNL and ascetic PMNL were independent predictor factors for CNNA. Conclusion: Patients with CNNA have a lower incidence of fever, prevalence of diabetes mellitus, hepatic encephalopathy, blood PMNL and ascetic PMNL versus culture positive SBP. Independent predictors of culture negative SBP are decreased platelets, blood PMNL and ascetic PMNL.

Diabetes mellitus (DM) is one of the three most common chronic diseases worldwide. This study aimed to determine the prevalence of diabetic polyneuropathy (DPN) among patients with diabetes.This cross-sectional study was carried out on DM patients who visited King Abdulaziz University Hospital (KAUH) between August 2021 and February 2022. We used the Michigan Neuropathy Screening Instrument (MNSI) questionnaire to determine if the patients had DN. In addition, we used the Global Physical Activity Questionnaire (GPAQ) to assess the level of physical activity (PA) in these DM patients.A total of 336 patients consented to participate in the study. We found a DN prevalence of 23.8% amongst DM patients treated at the KAUH. In addition, the prevalence of DN amongst T1DM and T2DM patients was found to be 16% and 24.4%, respectively. Furthermore, we found that 65% of DM patients developed complications, with a significant correlation observed between the duration of DM and the development of complications. However, patient age and sex were non-statistically significantly correlated with the development of complications. Analysis of the GPAQ showed that among the 249 patients who completed the questionnaire, none had a high physical activity level, while 4% and 96% had moderate and low physical activity levels, respectively. No association was found between physical activity and patients' age, sex, type of DM, duration of DM, and development of complications.DN prevalence amongst DM patients treated at KAUH was 23.8%. The duration of diabetes was found to be a risk factor for DN. However, patient age and sex were non-statistically significantly associated with DN.

Polycystic ovary syndrome (PCOS) is an endocrinologic condition affecting one in five women of reproductive age. PCOS is often characterized by disruptions to the menstrual cycle, development of male-pattern hair growth (hirsutism), and polycystic ovary morphology. Recently, PCOS has been linked to metabolic dysfunction, with 40 to 80% of women characterized as overweight or obese. Despite these well-known negative health effects of PCOS, 75% of sufferers remain undiagnosed. This is most likely due to the variability in symptom presentation and the lack of a definitive test for the condition. Metabolomics, which is a platform used to analyze and characterize a large number of metabolites, has recently been proposed as a potential tool for investigating the metabolic pathways that could be involved in the pathophysiology of PCOS. In doing so, novel biomarkers could be identified to improve diagnosis and treatment of PCOS. This review aims to summarize the findings of recent metabolomic studies that highlight metabolic-specific molecules which are deranged in PCOS, to identify potential biomarkers for the condition. Current limitations for metabolomic studies are discussed, as well as future directions to progress the field toward further validation and integration into clinical practice.

Young people in residential out-of-home care often exhibit health and psychosocial challenges, which can emerge from childhood trauma. A body of research has examined the wellbeing of these young p...

IntroductionMaternal metabolic disease states (such as gestational and pregestational diabetes and maternal obesity) are reaching epidemic proportions worldwide and are associated with adverse maternal and fetal outcomes. Despite this, their aetiology remains incompletely understood. Lactogenic hormones, namely, human placental lactogen (hPL) and prolactin (PRL), play often overlooked roles in maternal metabolism and glucose homeostasis during pregnancy and (in the case of PRL) postpartum, and have clinical potential from a diagnostic and therapeutic perspective. This paper presents a protocol for a systematic review which will synthesise the available scientific evidence linking these two hormones to maternal and fetal metabolic conditions/outcomes.Methods and analysisMEDLINE (via OVID), CINAHL and Embase will be systematically searched for all original observational and interventional research articles, published prior to 8 July 2021, linking hPL and/or PRL levels (in pregnancy and/or up to 12 months postpartum) to key maternal metabolic conditions/outcomes (including pre-existing and gestational diabetes, markers of glucose/insulin metabolism, postpartum glucose status, weight change, obesity and polycystic ovary syndrome). Relevant fetal outcomes (birth weight and placental mass, macrosomia and growth restriction) will also be included. Two reviewers will assess articles for eligibility according to prespecified selection criteria, followed by full-text review, quality appraisal and data extraction. Where possible, meta-analysis will be performed; otherwise, a narrative synthesis of findings will be presented.Ethics and disseminationFormal ethical approval is not required as no primary data will be collected. The results will be published in a peer-reviewed journal and presented at conference meetings, and will be used to inform future research directions.PROSPERO registration numberCRD42021262771.

IntroductionType 2 diabetes (T2D) has a complex etiology which is not fully elucidated. Identification of gene perturbations and hub genes of T2D may assist in personalizing care.ObjectivesWe aimed to identify highly perturbed genes and hub genes associated with T2D in different tissues of adult humans via an extensive workflow.MethodsWorkflow comprised five sequential steps: systematic review of NCBI GEO database; identification and classification of differentially expressed genes (DEG); identification of highly perturbed genes via meta-analysis; identification of hub genes via network analysis; downstream analyses. Three meta-analytic strategies: random effects model (REM); vote counting approach (VC); p-value combining approach (CA), were applied. Nodes having above average betweenness, closeness, and degree in the network were defined as hub genes. Downstream analyses included gene ontologies, Kyoto Encyclopedia of Genes and Genomes pathways, metabolomics, COVID-19 related genes, and Genotype-Tissue Expression profiles.ResultsAnalysis of 27 eligible microarrays identified 6284 DEG (4592 down-regulated and 1692 up-regulated) within four tissue types. Tissue-specific gene expression was significantly greater than tissue non-specific (shared) gene expression. Meta-analysis of DEG identified 49, 27, and 8 highly perturbed genes via REM, VC, and CA, respectively, producing a compiled set of 79 highly perturbed (41 down-regulated and 38 up-regulated) genes. The 28 hub genes comprised 13 up-regulated, 9 down-regulated, and 6 predicted genes. Downstream analyses identified enrichments of: shared genes with other diabetes phenotypes; insulin synthesis and action related pathways and metabolomics; mechanistic associations with apoptosis and immunity-related pathways, COVID-19 related gene sets; and cell types demonstrating over- and under-expression of marker genes of T2D.ConclusionsWe identified highly perturbed genes and hub genes of T2D and revealed their associations with other diabetes phenotypes and COVID-19 as well as pathophysiological manifestations such as those related to insulin, immunity, and apoptosis. Broader utility of the proposed pipeline is envisaged.

IntroductionObesity is observed in a majority of women with polycystic ovarian syndrome (PCOS). Using body mass index (BMI) as a proxy, previous Mendelian randomization studies revealed general obesity potentially causes PCOS. Central obesity frequently demonstrates a stronger association with PCOS, although evidence on its causality is sparse.ObjectivesTo investigate causal effects of both central- and general- obesity on the development of PCOS via two-sample Mendelian randomization (2SMR).MethodsSummary GWAS data of female-only, large-sample cohorts of European ancestry were retrieved for anthropometric markers of central obesity (waist circumference (WC), hip circumference (HC), waist-to-hip ratio (WHR)) and general obesity (BMI and its constituent variables – weight and height), from the IEU Open GWAS Project. As the outcome data, we acquired summary data from a large-sample GWAS (96391 samples; 219 cases and 96172 controls) from the FinnGen cohort. Four 2SMR methods were applied: inverse variance weighted (IVW); MR Egger (MRE); weighted median (WME); weighted mode (WMO). Single SNP-, leave-one-out-, heterogeneity-, horizontal pleiotropy- and outlier- analyses were conducted. Genetic architectures underlying causal associations were explored.ResultsAll SNPs selected as instrumental variables demonstrated no weak instrument bias (F > 10). Three anthropometric exposures, namely, BMI (OR: 5.55 – 7.24, WC (OR: 6.79 – 24.56), and HC (OR: 6.78 – 24.56), significantly causally associated with PCOS as per IVW, WME, and WMO models. Single SNP- and leave-one-out- sensitivity analysis results were indicative of robust causal estimates. No significant heterogeneity, horizontal pleiotropy, and outliers were observed. We observed a considerable degree of overlap (7 SNPs; 17 genes) across significant causal findings as well as a number of SNPs and genes that were not shared between causal associations.ConclusionsThis study revealed that both and general- and central obesity potentially cause PCOS. Findings underscore the importance of addressing obesity and adiposity for the prevention and management of PCOS.

Background and objectiveType 1 diabetes (TID) is a complex, polygenic disorder, the etiology of which is not fully elucidated. Machine learning (ML) genomics could provide novel insights on disease dynamics while high-dimensionality remains a challenge. This study aimed to identify marker genes of incident T1D in peripheral blood mononuclear cells (PBMC) of children via a ML strategy attuned to high-dimensionality.MethodsUsing samples from 105 children (81 with incident T1D and 24 healthy controls), we analyzed microarray transcriptomics via a workflow consisting of three sequential steps: application of dimension reduction strategies on the processed transcriptome; ML on the reduced gene expression matrix; and downstream network analyses to demarcate seed nodes (statistically significant genes) and hub genes. Sixteen dimension-reduction algorithms belonging to three groups (3 tailored; 3 regularizations; 10 classic) were applied. Four ML algorithms (multivariate adaptive regression splines, adaptive boosting, random forests, XGB-DART) were trained on the reduced feature set and internally-validated using repeated, 10-fold cross-validation. Marker genes were determined via variable importance metrics. Seed nodes were identified by the ‘OmicsNet’ platform while nodes having above average betweenness, closeness, and degree in the network were demarcated as hub genes.ResultsThe processed gene expression matrix comprised 13515 genes which was reduced to contain 1003 genes collectively selected by dimension reduction algorithms. All four ML algorithms on this reduced feature set attained perfect and uniform predictive performance on internal validation. On removal of redundancies, variable importance metrics identified 30 marker genes of incident T1D in this cohort, while Early Growth Response 2 (EGR2) was uniformly selected by all four ML algorithms as the most important marker gene. Network analyses classified all 30 marker genes as seed nodes. Additionally, we identified 14 hub genes, 7 of which were found to be marker genes of incident T1D elucidated by ML.ConclusionsWe identified marker genes of incident T1D in PBMC of children via a ML analytic strategy attuned to the high dimensional structure of microarrays, with downstream analyses providing high biological plausibility. The demonstrated ML strategy would be useful in analyzing other high-dimensional biomedical data for biomarker discovery.

ContextCardiovascular disease is a major public health problem and represents a significant burden of disease globally. Lifestyle interventions have their limitations and an intervention that will effectively address cardiovascular risk factors to help reduce this growing burden of disease is required.ObjectiveCarnosine and other histidine-containing dipeptides (HCDs) have exerted positive effects on cardiovascular risk factors and diseases in animal and human studies. The authors conducted a systematic review and meta-analysis examining the effects of HCDs on cardiovascular outcomes in line with the PRISMA guidelines.Data SourcesThe Medline, Medline in process, Embase, Cumulative Index of Nursing and Allied Health, and All EBM databases were searched from inception until January 25, 2019, for randomized controlled trials (RCTs) examining the effects of HCDs on cardiovascular outcomes, compared with placebo or controls.Data ExtractionBasic characteristics of the study and populations, interventions, and study results were extracted. The grading of recommendations assessment, development, and evaluation approach was used to assess the quality of evidence for each outcome.Data AnalysisA total of 21 studies were included. Of these, 18 were pooled for meta-analysis (n = 913). In low risk of bias studies, HCD-supplemented groups had lower total cholesterol (n = 6 RCTs; n = 401; weighted mean difference [WMD], −0.32 mmol/L [95%CI, −0.57 to −0.07], P = 0.01) and triglyceride levels (n = 6 RCTs; n = 401; WMD, −0.14 mmol/L [95%CI, −0.20 to −0.08], P ConclusionsCarnosine and other HCDs may have a role in improving lipid profiles. Larger studies with sufficient follow-up are necessary to confirm these findings and explore the use of HCDs in the prevention of cardiovascular diseases.Systemic Review RegistrationPROSPERO registration no.: CRD42017075354

Mental health and developmental challenges that emerge in early childhood can be associated with difficulty in social interactions and behavioural regulation. With educational policies increasingly...

A growing body of research evidence suggests universal (Tier 1) Social and Emotional Learning (SEL) interventions in early childhood education and care settings can improve children’s social and em...

The aim of this study was to explore and better understand the enablers and barriers of implementation and how these impact on the organisational successes and challenges of adopting The Sanctuary Model, as perceived by residential care staff. Following ethics approval, three semi-structured interviews and six focus groups were conducted with residential care staff between February and July, 2020. Participants identified a number of enablers, presented in the subthemes: (a) social support systems and resources; (b) shared trauma-informed knowledge and understanding; and (c) leadership and champions. These enablers influenced organisational successes in adopting: (a) the Sanctuary Commitments; (b) the S.E.L.F Framework; (c) Reflective Practice and Supervision; and (d) Trauma Theory. A number of barriers hindering implementation were identified. These were reflected in the subthemes: (a) informal practice; (b) lack of practice-based training; (c) poor introduction to young people; and (d) resources. These barriers impacted on organisational challenges faced in residential out-of-home care including: (a) The Sanctuary Model Toolkit and (b) young people’s behaviour and engagement. Comparisons from this study and previous findings identified by executive and upper management staff (decision makers) are discussed. Key findings indicate that when implementing, sustaining and embedding The Sanctuary Model, organisations need to become trauma-informed rather than ‘do’ trauma-informed care and organisations need to “live and breathe” The Sanctuary Model Commitments, be connected and inclusive of one another, use trauma-informed language and feel safe.

Polycystic Ovary Syndrome (PCOS) is a common endocrine disorder affecting up to 13 % of women. Lifestyle interventions are first-line treatments, however attrition in women with PCOS is high. This review summarises current evidence on barriers to lifestyle management in PCOS and suggested strategies for overcoming these challenges, mapped to the Capability, Opportunity, Motivation and Behaviour model.Physical capability for lifestyle changes may be impacted by altered gut hormone regulation and energy expenditure in PCOS. This may contribute to difficulties with weight management. The higher prevalence of eating disorders, disordered eating, fatigue and sleep disturbances are further barriers. Psychological capability may be reduced due psychological symptoms and lack of critical health literacy. Women with PCOS face similar challenges in terms of Opportunity to make lifestyle changes as other women of reproductive age. However, these are complicated by features more common in PCOS including body dissatisfaction. Motivation to adopt healthy lifestyles may be impacted by suboptimal risk perception and intrinsic motivation.To address these barriers, screening for and management of eating disorders, disordered eating, depression, and Obstructive Sleep Apnoea should be undertaken as per international evidence-based guidelines. A weight-neutral approach may be appropriate with disordered eating. Building capability among health professionals to better partner with women with PCOS on their management is essential in addressing health literacy gaps. Behavioural strategies that target risk perception and build intrinsic motivation should be utilised. More research is required to understand optimal self-management strategies, risk perception, energy homeostasis and overcoming attrition in women with PCOS.

Previous studies have suggested that soy products may be beneficial for cardiometabolic health, but current evidence regarding their effects in type 2 diabetes mellitus (T2DM) remain unclear. The aim of this systematic review and meta-analysis was to determine the impact of soy product consumption on cardiovascular risk factors in patients with T2DM. PubMed, Scopus, Embase, and the Cochrane library were systematically searched from inception to March 2021 using relevant keywords. All randomized controlled trials (RCTs) investigating the effects of soy product consumption on cardiovascular risk factors in patients with T2DM were included. Meta-analysis was performed using random-effects models and subgroup analysis was performed to explore variations by dose and baseline risk profile. A total of 22 trials with 867 participants were included in this meta-analysis. Soy product consumption led to a significant reduction in serum concentrations of triglycerides (TG) (WMD: -24.73 mg/dL; 95% CI: -37.49, -11.97), total cholesterol (TC) (WMD: -9.84 mg/dL; 95% CI: -15.07, -4.61), low density lipoprotein (LDL) cholesterol (WMD: -6.94 mg/dL; 95% CI: -11.71, -2.17) and C-reactive protein (CRP) (WMD: -1.27 mg/L; 95% CI: -2.39, -0.16). In contrast, soy products had no effect on high density lipoprotein (HDL) cholesterol, fasting blood sugar (FBS), fasting insulin, hemoglobin A1c (HbA1c), homeostatic model assessment of insulin resistance (HOMA-IR), systolic and diastolic blood pressure (SBP/DBP) or body mass index (BMI) (all P ≥ 0.05). In subgroup analyses, there was a significant reduction in FBS after soy consumption in patients with elevated baseline FBS (>126 mg/dL) and in those who received higher doses of soy intake (>30 g/d). Moreover, soy products decreased SBP in patients with baseline hypertension (>135 mmHg). Our meta-analysis suggests that soy product consumption may improve cardiovascular parameters in patients with T2DM, particularly in individuals with poor baseline risk profiles. However, larger studies with longer durations and improved methodological quality are needed before firm conclusions can be reached.

Polycystic ovary syndrome (PCOS) affects 1 in 5 women of reproductive age, and is characterized by menstrual irregularities, clinical or biochemical hyperandrogenism, and the presence of polycystic ovary morphology. One of the recommended treatment strategies in the international evidence-based guidelines is lifestyle modification, which includes diet and exercise, with the aim of improving a range of health outcomes. The incurable nature of PCOS reinforces the importance of developing novel and innovative symptomatic relief strategies, which are currently the only available approaches for improving quality of life for these women. Women with PCOS tend to be nutrient deficient in many common vitamins and minerals, thought to be associated with the psychological (depression, anxiety, etc.) and physiological (insulin resistance, diabetes, infertility, etc.) sequelae of the condition. Nutrient supplementation and the integration of complementary medicine as adjuncts to traditional lifestyle-based therapies in PCOS could therefore provide additional benefits to these women. In this review, we synthesize the evidence regarding nutrient supplementation and complementary therapies in PCOS, predominantly from randomized controlled trials, systematic reviews, and meta-analyses, to provide an overview of the state of knowledge in this field. The evidence to date suggests that specific vitamins (B-12, inositols, folate, vitamins D, E, and K), vitamin-like nutrients (bioflavonoids and α-lipoic acid), minerals (calcium, zinc, selenium, and chromium picolinate), and other formulations (melatonin, ω-3 fatty acids, probiotics, and cinnamon), as well as some complementary approaches such as acupuncture and yoga may be beneficial in PCOS. However, there remain areas of uncertainty and key limitations in the literature that must be overcome before these therapies can be integrated into routine clinical practice.

Breastfeeding is internationally recognized as the recommended standard for infant nutrition, informed by evidence of its multiple benefits for both mother and baby. In the context of common metabolic conditions such as polycystic ovary syndrome, diabetes (type 1, type 2, and gestational), and obesity, breastfeeding may be particularly beneficial for both mother and infant. However, there is evidence of delayed lactogenesis and reduced breastfeeding rates and duration in women with these conditions, and the effects of altered maternal metabolic environments on breastmilk composition (and potentially infant outcomes) are incompletely understood. In this review, we explore the relationships between maternal metabolic conditions, lactogenesis, breastfeeding, and breastmilk composition. We examine relevant potential mechanisms, including the central role of insulin both in lactogenesis and as a milk-borne hormone. We also describe the bioactive and hormonal components of breastmilk and how these may link maternal and infant health.

Undernutrition adversely affects fertility. A low body weight is associated with delayed conception. When conception does occur, undernutrition could also adversely affect pregnancy outcomes. Low prepregnancy BMI (2) is associated with increased risk of early miscarriage, preterm labour, anaemia, insufficient weight gain, and impaired intrauterine fetal growth. On the other hand, overweight and obesity are associated with increased risk of gestational diabetes, pre-eclampsia, and other complications during pregnancy and delivery. Weight loss through energy restriction, with or without exercise, improves reproductive function in overweight or obese women. Aside from body weight and energy status, maternal macronutrient, and micronutrient intakes before and during pregnancy would also influence pregnancy outcomes. Studies in mostly nutritionally at-risk women reported that balanced energy/protein supplementation (> 25% energy from protein) may increase the risk of small-for-gestational-age (SGA) infants. Reducing glycaemic index or glycaemic load of maternal diet may reduce the risk of large-for-gestational-age (LGA) births or gestational diabetes. In terms of micronutrients, current evidence supports folic acid supplementation (at least 400 µg/day) to reduce the risk of fetal abnormalities, iodine supplementation for women at risk of iodine deficiency to prevent complications in fetal physical and mental development, and iron supplementation to reduce the risk of maternal anaemia where required.

Introduction Carnosine is a naturally occurring dipeptide abundant in the skeletal and cardiac muscle and brain, which has been shown to improve glucose metabolism and cardiovascular risk. This study showed that carnosine supplementation had positive changes on plasma lipidome. Here, this study aimed to establish the relationship of muscle carnosine and serum carnosinase-1 with cardiometabolic risk factors and the lipidome. Methods and Results This study profiles >450 lipid species in 65 overweight/obese nondiabetic individuals. Intensive metabolic testing is conducted using direct gold-standard measures of adiposity, insulin sensitivity and secretion, as well as measurement of serum inflammatory cytokines and adipokines. Muscle carnosine is negatively associated with 2-h glucose concentrations, whereas serum carnosinase-1 levels are negatively associated with insulin sensitivity and positively with IL-18. O-PLS and machine learning analyses reveal a strong association of muscle carnosine with ether lipids, particularly arachidonic acid-containing plasmalogens. Carnosinase-1 levels are positively associated with total phosphatidylethanolamines, but negatively with lysoalkylphosphatidylcholines, trihexosylceramides, and gangliosides. In particular, alkylphosphatidylethanolamine species containing arachidonic acid are positively associated with carnosinase-1. Conclusion These associations reinforce the role of muscle carnosine and serum carnosinase-1 in the interplay among low-grade chronic inflammation, glucose homeostasis, and insulin sensitivity This studyhas been funded by Instituto de Salud Carlos III through the project“PI18/01022” (Co-funded by European Regional Development Fund “Away to make Europe”). This work was supported by the National Healthand Medical Research Council (NHMRC) of Australia (APP1047897). JordiMayneris-Perxachs is funded by the Miguel Servet Program from the Insti-tuto de Salud Carlos III (ISCIII CP18/00009), co-funded by the EuropeanSocial Fund “Investing in your future.” A.M. is supported by a Peter Do-herty Biomedical Research Fellowship provided by the NHMRC. N.N. isa Monash Partners Health Services Research Fellow. B.dC. is supportedby a Royal Australasian College of Physicians Fellows Career DevelopmentFellowship. and is the recipient of the NHMRC grant, which funded thisstudy Open Access funding provided thanks to the CRUE-CSIC agreement with Wiley

Gestational diabetes mellitus (GDM) is the fastest growing type of diabetes, affecting between 2 to 38% of pregnancies worldwide, varying considerably depending on diagnostic criteria used and sample population studied. Adverse obstetric outcomes include an increased risk of macrosomia, and higher rates of stillbirth, instrumental delivery, and birth trauma. Metabolomics, which is a platform used to analyse and characterise a large number of metabolites, is increasingly used to explore the pathophysiology of cardiometabolic conditions such as GDM. This review aims to summarise metabolomics studies in GDM (from inception to January 2021) in order to highlight prospective biomarkers for diagnosis, and to better understand the dysfunctional metabolic pathways underlying the condition. We found that the most commonly deranged pathways in GDM include amino acids (glutathione, alanine, valine, and serine), carbohydrates (2-hydroxybutyrate and 1,5-anhydroglucitol), and lipids (phosphatidylcholines and lysophosphatidylcholines). We also highlight the possibility of using certain metabolites as predictive markers for developing GDM, with the use of highly stratified modelling techniques. Limitations for metabolomic research are evaluated, and future directions for the field are suggested to aid in the integration of these findings into clinical practice.

Vitamin D regulates adipokine production in vitro; however, clinical trials have been inconclusive. We conducted secondary analyses of a randomized controlled trial to examine whether vitamin D supplementation improves adipokine concentrations in overweight/obese and vitamin D-deficient adults. Sixty-five individuals with a BMI ≥ 25 kg/m2 and 25-hydroxyvitamin D (25(OH)D) ≤ 50 nmol/L were randomized to oral cholecalciferol (100,000 IU single bolus followed by 4,000 IU daily) or matching placebo for 16 weeks. We measured BMI, waist-to-hip ratio, % body fat (dual X-ray absorptiometry), serum 25(OH)D (chemiluminescent immunoassay) and total adiponectin, leptin, resistin, and adipsin concentrations (multiplex assay; flow cytometry). Sun exposure, physical activity, and diet were assessed using questionnaires. Fifty-four participants completed the study (35M/19F; mean age = 31.9 ± 8.5 years; BMI = 30.9 ± 4.4 kg/m2). After 16 weeks, vitamin D supplementation increased 25(OH)D concentrations compared with placebo (57.0 ± 21.3 versus 1.9 ± 15.1 nmol/L, p 0.05). After adjustment for baseline values, season, sun exposure, and dietary vitamin D intake, there was a greater increase in adiponectin (β[95%CI] = 13.7[2.0, 25.5], p = 0.02) and leptin (β[95%CI] = 22.3[3.8, 40.9], p = 0.02) in the vitamin D group compared with placebo. Results remained significant after additional adjustment for age, sex, and % body fat (p

Back pain is currently the greatest cause of disability worldwide, and there are very limited therapeutic options available. Vitamin D deficiency and obesity are both risk factors for back pain. The few randomised controlled trials examining the effects of vitamin D supplementation on back pain have methodological limitations and largely include non-vitamin D deficient participants. Thus, the aim of this study was to determine whether vitamin D supplementation improves back pain symptoms in vitamin D deficient and overweight or obese, otherwise healthy adults. Sixty-five overweight or obese adults (BMI ≥ 25 kg/m2) with vitamin D deficiency (25-hydroxyvitamin D [25(OH)D] concentrations ≤50 nmol/L) were randomised to a bolus oral dose of 100,000 IU followed by 4000 IU cholecalciferol/day or matching placebo for 16 weeks. We measured 25(OH)D concentrations (chemiluminescent immunoassays) and self-reported back pain (Chronic Pain Grade Questionnaire) before and after the intervention. Lifestyle habits including sun exposure, physical activity, and diet were collected using questionnaires. Fifty-four participants completed the study, of which 49 had complete data for back pain and were included in the present analyses (31 M/18 F; mean ± SD age: 31.8 ± 8.9 years; BMI: 31.1 ± 4.5 kg/m2). After the 16-week intervention, 25(OH)D levels increased significantly with vitamin D supplementation compared with placebo (55.7 ± 20.9 versus 3.9 ± 14.4 nmol/L, respectively, p 0.05). However, in those with 25(OH)D concentrations

Vitamin D deficiency has been implicated in the pathophysiology of cardiometabolic disorders including obesity, type 2 diabetes mellitus, cardiovascular diseases and polycystic ovary syndrome. Despite a large number of experimental and observational studies supporting a role for vitamin D in these pathologies, randomized controlled trials have reported little to no effect of vitamin D supplementation in the prevention or treatment of these disorders, although some results remain ambiguous. Polymorphisms in genes related to vitamin D metabolism, particularly in the vitamin D receptor and binding protein and the metabolizing enzyme 1-α-hydroxylase, have emerged as potential contributors to these divergent results. It is now becoming increasingly recognized that the effects and potential benefits of vitamin D supplementation may vary by several factors including vitamin D deficiency status, ethnicity and/or the presence of genetic variants, which affect individual responses to supplementation. However, these factors have seldom been explored in the available literature. Future trials should consider inter-individual differences and, in particular, should aim to clarify whether certain subgroups of individuals may benefit from vitamin D supplementation in the context of cardiometabolic health.

Jordan is one of the few countries in the Middle East that has very limited resources of fossil fuel such as natural gas and crude oil. The country is fast growing with a population growth rate of 1.8%. The Gross Domestic Product (GDP) of Jordan reached USD 40.4 billion in 2015 with a population exceeding 9.96 million. Food and energy demands are increasing every year. Energy security and maintaining energy flow to meet the yearly demands are the biggest economic challenges facing Jordan. Renewable energies are the most vital solutions that provide energy security and accelerate economic growth. There are numerous studies and projects that focused on solar and wind power systems as an energy mix strategy. However, biomass to energy is not deeply explored in Jordan. Biofuel production from renewable biomass has a big potential for biogas and bioethanol production. The biofuels in Jordan can play significant roles in reducing dependency on imported oil and gas, and significantly reduce Jordan’s energy bill. The bioethanol utilization as a source of fuel can reduce the oil import bill by mixing it with classical gasoline. From a mechanical point of view, a normal car engine can handle up to 10% bioethanol blend without engine modifications. The bioethanol blend can save up to 200 kt of imported oil which will have a direct impact on the Jordanian economy. Jordan has a big biogas production potential despite the very humble projects for biogas production from renewable resources. The available resources for direct biogas production can replace about 5% of the total gas consumption for power generation. In this paper, we will discuss the right policy and mechanism to implement biofuel mix and blend which aims at reducing the energy bill.

Early childhood educators play an important role in supporting children’s social and emotional development. While a growing body of research has examined the impact of curriculum-based social and emotional learning (SEL) programs on child outcomes, the approaches educators use to strengthen children’s social and emotional functioning through their everyday practices are less defined. This study explored Australian early childhood educators’ perspectives on children’s social and emotional development, the approaches educators use to encourage children’s social and emotional skills, the enablers and barriers to SEL within the preschool environment, and the additional support needed. Thirty Early Childhood Education and Care professionals participated in semi-structured interviews and focus group discussions. Findings suggest children’s social–emotional development is at the forefront of educator planning, practice, and reflection. Participants described utilising various approaches to support children’s social and emotional skills, embedded within interactions and relationships with children and families. Specifically, strategies could be grouped into four broad categories: a nurturing and responsive educator–child relationship, supporting SEL through everyday interactions and practice, utilising the physical environment to encourage SEL, and working in partnership with caregivers. There was, however, inconsistency in the variety and type of approaches identified. Time constraints, group size, educator confidence and capability, high staff turnover, and limited guidance regarding high-quality social and emotional pedagogy were identified as key barriers. Participants sought practical strategies that could be embedded into daily practice to build upon current knowledge.

The rising incidence of obesity and type 2 diabetes is contributing to the escalating burden of disease globally. These metabolic disorders are closely linked with diet and in particular with carbohydrate consumption; hence, it is important to understand the underlying mechanisms that influence carbohydrate metabolism. Amylase, the enzyme responsible for the digestion of starch, is coded by the genes AMY1A, AMY1B, and AMY1C (salivary amylase) and AMY2A and AMY2B (pancreatic amylase). Previous studies demonstrate wide variations in AMY1A copy numbers, which can be attributed to several genetic, nutritional, and geographical diversities seen in populations globally. Current literature suggests that AMY1A copy number variations are important in obesity and other cardiometabolic disorders through their effects on glucose and lipid homeostasis, inflammatory markers, and the gut microbiome. This review synthesizes the available evidence to improve understanding of the role of AMY1A in obesity and related cardiometabolic risk factors and disorders including insulin resistance and type 2 diabetes, cardiovascular risk and inflammation, and the gut microbiome.

The gut microbiota encompasses a diverse community of bacteria that carry out various functions influencing the overall health of the host. These comprise nutrient metabolism, immune system regulation and natural defence against infection. The presence of certain bacteria is associated with inflammatory molecules that may bring about inflammation in various body tissues. Inflammation underlies many chronic multisystem conditions including obesity, atherosclerosis, type 2 diabetes mellitus and inflammatory bowel disease. Inflammation may be triggered by structural components of the bacteria which can result in a cascade of inflammatory pathways involving interleukins and other cytokines. Similarly, by-products of metabolic processes in bacteria, including some short-chain fatty acids, can play a role in inhibiting inflammatory processes. In this review, we aimed to provide an overview of the relationship between the gut microbiota and inflammatory molecules and to highlight relevant knowledge gaps in this field. Based on the current literature, it appears that as the gut microbiota composition differs between individuals and is contingent on a variety of factors like diet and genetics, some individuals may possess bacteria associated with pro-inflammatory effects whilst others may harbour those with anti-inflammatory effects. Recent technological advancements have allowed for better methods of characterising the gut microbiota. Further research to continually improve our understanding of the inflammatory pathways that interact with bacteria may elucidate reasons behind varying presentations of the same disease and varied responses to the same treatment in different individuals. Furthermore, it can inform clinical practice as anti-inflammatory microbes can be employed in probiotic therapies or used to identify suitable prebiotic therapies.

Background Primary congenital glaucoma (PCG) is a congenital anomaly arising from an unusual development of the filtration angle, causing a remarkable rise in intraocular pressure (IOP) that is irrelevant to other ocular or systemic deformities. Purpose The aim of the current study was to evaluate the surgical outcome in PCG patients between 2011 and February 2019. Methods This was a retrospective study of PCG patients who underwent trabeculotomy, trabeculectomy, deep sclerectomy, Ahmed valve, and/or cyclophotocoagulation (CPC) at a tertiary hospital. The IOP must be equal or less than 21 mmHg with or without medication to be designated a successful surgery. Results A total of 80 eyes (41 patients) were included in the study, with a slight male predominance of 65.9%. At presentation, the most reported age group was under 30 days (46.3%). Moreover, deep sclerotomy was the most common procedure, followed by CPC, which were performed in 48 (58.5%) and 18 (21.9%) eyes, respectively. In the overall group, the mean initial IOP was 23.65±8.52 mmHg, while the mean IOP was 16.73±8.56 mmHg at final follow-ups (p < 0.001), with a 46% reduction. The mean axial length showed a slight progression from 21.11±2.58 at the initial visit to 22.92±3.57 mm at the last follow-up (p

Maternal vitamin D deficiency has been associated with adverse neonatal outcomes, however, existing results are inconsistent. Current data focus on total 25-hydroxyvitamin D (25(OH)D) as the common measure of vitamin D status, while additional measures including vitamin D-binding protein (VDBP) and free and bioavailable metabolites have not been explored in relation to neonatal outcomes. We examined whether VDBP and total, free, and bioavailable vitamin D metabolites in early pregnancy are associated with subsequent neonatal outcomes. In this retrospective analysis of 304 women in early pregnancy (&lt, 20 weeks gestation), demographic and anthropometric data were collected and total 25(OH)D (chemiluminescent assay), VDBP (polyclonal enzyme-linked immunosorbent assay (ELISA)) and albumin (automated colorimetry) were measured in bio-banked samples. Free and bioavailable 25(OH)D were calculated using validated formulae. Neonatal outcomes were derived from a medical record database. Higher maternal total and free 25(OH)D concentrations were associated with higher neonatal birthweight (&beta, = 5.05, p = 0.002 and &beta, = 18.06, p = 0.02, respectively), including after adjustment for maternal covariates including age, body mass index (BMI) and ethnicity (all p &le, 0.04). Higher total 25(OH)D and VDBP concentrations were associated with a lower likelihood of neonatal jaundice (odds ratio [OR] [95%CI] = 0.997 [0.994, 1.000], p = 0.04 and 0.98 [0.96, 0.99], p = 0.03, respectively), but these were attenuated after adjustment for the above maternal covariates (both p = 0.09). Our findings suggest a novel association between free 25(OH)D and neonatal birthweight. Total 25(OH)D concentrations were also associated with birthweight, and both total 25(OH)D and VDBP were associated with jaundice, but the latter were not significant after adjustment. These results suggest a potential link between these metabolites and neonatal outcomes, however, further large-scale prospective studies are warranted.

Background: Vitamin D-binding protein (VDBP) has been implicated in several adverse pregnancy outcomes either directly or indirectly via influencing the concentrations of biologically active vitamin D metabolites. However, human studies exploring these metabolites in pregnancy remain sparse. Here, we examine whether VDBP and total, free, and bioavailable 25-hydroxyvitamin D (25(OH)D) metabolites in early pregnancy are associated with subsequent adverse pregnancy outcomes. Methods: We conducted a retrospective analysis of 304 pregnant women in early pregnancy (&lt, 20 weeks gestation). The demographic characteristics, anthropometric data, and total 25(OH)D were measured and plasma or serum samples were collected and bio-banked. Using these samples, we measured VDBP (polyclonal ELISA) and albumin (automated colorimetry), and calculated free and bioavailable 25(OH)D using validated formulae. Pregnancy outcomes were derived from scanned medical records. Regression models were used to analyse the relationships between vitamin D metabolites in early pregnancy and subsequent pregnancy outcomes (gestational diabetes mellitus (GDM), pre-eclampsia, preterm birth), with adjustment for predetermined clinically relevant maternal factors including age, body mass index (BMI), and ethnicity. Results: Lower VDBP concentrations were associated with higher glucose levels and a greater likelihood of developing GDM at 26&ndash, 28 weeks gestation (odds ratio [OR] (95% CI) = 0.98 (0.97,0.99), p = 0.015). This finding remained significant after adjustment for maternal covariates including age, BMI, and ethnicity (&beta, = &minus, 0.003, p = 0.03). Lower total, free and bioavailable 25(OH)D, but not VDBP, were associated with a shorter length of gestation, but only the relationship with total 25(OH)D remained significant after adjustment for the above maternal covariates (&beta, = 0.02, p = 0.006). Conclusions: This is the first study to examine VDBP, and total, free and bioavailable 25(OH)D in relation to pregnancy outcomes in a well characterised multi-ethnic cohort of pregnant women. Our findings show that VDBP and total 25(OH)D are associated with GDM and length of gestation, respectively, however, further investigations using large-scale prospective studies are needed to confirm our findings.

IntroductionGestational diabetes mellitus (GDM) is a common disorder of pregnancy and contributes to adverse pregnancy outcomes. Metformin is often used for the prevention and management of GDM; however, its use in pregnancy continues to be debated. The Metformin in Pregnancy Study aims to use individual patient data (IPD) meta-analysis to clarify the efficacy and safety of metformin use in pregnancy and to identify relevant knowledge gaps.Methods and analysisMEDLINE, EMBASE and all Evidence-Based Medicine will be systematically searched for randomised controlled trials (RCT) testing the efficacy of metformin compared with placebo, usual care or other interventions in pregnant women. Two independent reviewers will assess eligibility using prespecified criteria and will conduct data extraction and quality appraisal of eligible studies. Authors of included trials will be contacted and asked to contribute IPD. Primary outcomes include maternal glycaemic parameters and GDM, as well as neonatal hypoglycaemia, anthropometry and gestational age at delivery. Other adverse maternal, birth and neonatal outcomes will be assessed as secondary outcomes. IPD from these RCTs will be harmonised and a two-step meta-analytic approach will be used to determine the efficacy and safety of metformin in pregnancy, with a priori adjustment for covariates and subgroups to examine effect moderators of treatment outcomes. Sensitivity analyses will assess heterogeneity, risk of bias and the impact of trials which have not provided IPD.Ethics and disseminationAll IPD will be deidentified and studies contributing IPD will have ethical approval from their respective local ethics committees. This study will provide robust evidence regarding the efficacy and safety of metformin use in pregnancy, and may identify subgroups of patients who may benefit most from this treatment modality. Findings will be published in peer-reviewed journals and disseminated at scientific meetings, providing much needed evidence to inform clinical and public health actions in this area.

Background: Polycystic Ovary Syndrome (PCOS), a common endocrine disorder in women of reproductive age, increases the risk for cardiometabolic morbidity. While regular exercise is effective in reducing cardiometabolic risk, women with PCOS may experience condition-specific barriers to exercise thereby limiting its efficacy. Aim: To determine the effect of exercise on cardiometabolic risk factors in women with PCOS. Methods: Five databases (Cochrane, EMBASE, Medline, Scopus and SPORTDiscus) were searched up to December of 2021. Eligible studies included: a randomised controlled design; participants with a diagnosis of PCOS; aerobic and/or resistance exercise intervention lasting ≥4 weeks; cardiometabolic outcomes. Meta-analyses were performed to determine the effect of exercise versus non-exercising control on cardiometabolic outcomes. Results: Of the 4517 studies screened, 18 studies were analysed involving 593 participants. When compared with control, exercise significantly improved cardiorespiratory fitness (weighted mean difference {WMD} = 4.00 mL/kg/min, 95% CI: 2.61 to 5.40, p < 0.001) and waist circumference (WMD = −1.48 cm, 95% CI: −2.35 to −0.62, p = 0.001). Systolic blood pressure, fasting blood glucose, insulin resistance, and lipid profiles remained unchanged. Conclusions: Regular exercise may improve cardiorespiratory fitness and waist circumference in women with PCOS. Further large-scale studies are required to determine whether exercise interventions improve various biochemical and anthropometric parameters in women with PCOS and more severe cardiometabolic abnormalities.

Supplementation with histidine-containing dipeptides has been shown to improve obesity and glycaemic outcomes in animal and human studies. We conducted a systematic review and meta-analysis of randomized controlled trials to examine these effects. Electronic databases were searched investigating the effects of histidine-containing dipeptides supplementation on anthropometric and glycaemic outcomes. Meta-analyses were performed using random-effects models to calculate the weighted mean difference and 95% confidence interval. There were 30 studies for the systematic review and 23 studies pooled for meta-analysis. Histidine-containing dipeptide groups had a lower waist circumference (WMD [95% CI] = -3.53 cm [-5.65, -1.41], p = 0.001) and HbA1c level (WMD [95% CI] = -0.76% (8.5 mmol/mol) [-1.29% (14.3 mmol/mol), -0.24% (2.8 mmol/mol)], p = 0.004) at follow-up compared with controls. In sensitivity analyses of studies with low risk of bias, waist circumference, HbA1c, and fasting glucose levels (WMD [95% CI] = -0.63 mmol/L [-1.09, -0.18], p = 0.006) were significantly lower in intervention groups versus controls. There was also a trend toward lower fat mass (p = 0.09), insulin resistance (p = 0.07), and higher insulin secretion (p = 0.06) in intervention versus control groups. Supplementation with histidine-containing dipeptides may reduce central obesity and improve glycaemic outcomes. Further studies exploring histidine-containing dipeptide use in obesity and diabetes prevention and treatment are warranted.

Scope Reduced amylase 1 (AMY1) copy numbers are associated with obesity, insulin resistance, and inflammation. Although mechanisms linking AMY1 copy number with metabolic disorders are poorly understood, recent findings suggest that lipids play a key role. Methods and results Plasma lipidomic signatures associated with AMY1 copy number are explored in 57 non-diabetic overweight/obese subjects aged 18-60. Serum amylase and inflammatory cytokines levels are also measured. AMY1 copy number is strongly associated with the serum amylase concentration. Participants are divided into low-(≤4) and high-(>4) AMY1 carriers based on the median. Low-AMY1 carriers have higher BMI and fat mass. They also have higher levels of dihexosylceramides (R = -0.27, p = 0.044), cholesterol esters (CE) (R = -0.32, p = 0.020), alkylphosphatidylcholines [PC(O)] (R = -0.33, p = 0.014), and sphingomyelins (SM) (R = -0.38, p = 0.005). From 459 lipid species, 28 differ between low- and high-AMY1 carriers. These include CE species with long-chain PUFA; PC(O) and PC plasmalogens containing arachidonic acid; and PC, mono-, di-, and tri-hexosylceramides, and SM containing saturated fatty acids (mainly C16:0 and C20:0). This lipidomic signature is strongly associated with inflammatory cytokines, which are also negatively associated with the AMY1 copy number. Conclusion A lipidomics signature associated with low AMY1 copy numbers is revealed, which is linked to obesity and chronic low-grade inflammation.

Vitamin D is reported to have anti-inflammatory properties; however the effects of vitamin D supplementation on inflammation in patients with heart failure (HF) have not been established. We performed a systematic review and meta-analysis examining effects of vitamin D supplementation on inflammatory markers in patients with HF. MEDLINE, CINAHL, EMBASE, All EBM, and Clinical Trials registries were systematically searched for RCTs from inception to 25 January 2017. Two independent reviewers screened all full text articles (no date or language limits) for RCTs reporting effects of vitamin D supplementation (any form, route, duration, and co-supplementation) compared with placebo or usual care on inflammatory markers in patients with heart failure. Two reviewers assessed risk of bias and quality using the grading of recommendations, assessment, development, and evaluation approach. Seven studies met inclusion criteria and six had data available for pooling (n = 1012). In meta-analyses, vitamin D-supplemented groups had lower concentrations of tumor necrosis factor-alpha (TNF-α) at follow-up compared with controls (n = 380; p = 0.04). There were no differences in C-reactive protein (n = 231), interleukin (IL)-10 (n = 247) or IL-6 (n = 154) between vitamin D and control groups (all p > 0.05). Our findings suggest that vitamin D supplementation may have specific, but modest effects on inflammatory markers in HF.

The diagnosis of polycystic ovary syndrome (PCOS) remains challenging due to limited data regarding normative cut-offs for the diagnostic features in different subpopulations. We aim to conduct a systematic review, build a comprehensive repository of de-identified individual participant data (IPD), and define normative ranges and diagnostic cut-offs for all PCOS diagnostic features. We will conduct a systematic search of MEDLINE and EMBASE databases for studies that assessed PCOS diagnostic features in unselected women. Two reviewers will assess eligibility and perform quality appraisal. Authors of included studies will be invited to contribute IPD. Primary variables include directly assessed modified Ferriman Gallwey (mFG) scores; menstrual cycle lengths; follicle number per ovary (FNPO), ovarian volume (OV), anti-Müllerian hormone (AMH); circulating androgens, including total testosterone (TT), free testosterone, bioavailable testosterone, free androgen index (FAI), androstenedione (A4), and dehydroepiandrosterone sulphate (DHEAS). Normative ranges and cut-offs will be defined using cluster analysis. Monash University Human Research Ethics Committee granted ethical approval (26938/0 1/12/2020), all IPD will be de-identified and primary studies have ethical approval from their institutional ethics committees. Findings will clarify distinction between PCOS and non-PCOS populations, and inform the update of the international evidence-based guidelines for the assessment and management of PCOS.

The novel coronavirus severe acute respiratory syndrome (SARS-CoV-2) has progressed rapidly from an outbreak to a global pandemic, with new variants rapidly emerging. Coronavirus disease 2019 (COVID-19), the disease resulting from SARS-CoV-2 infection, can lead to multiorgan damage. Due to the extremely contagious and fatal nature of the virus, it has been a priority of medical research to find effective means of treatment. Amid this search, the role of vitamin D in modulating various aspects of the innate and adaptive immune system has been discussed. This review aims to consolidate the research surrounding the role of vitamin D in the treatment and prevention of COVID-19. While there are some conflicting results reported, the consensus is that vitamin D has a host of immunomodulatory effects which may be beneficial in the context of COVID-19 and that low levels of vitamin D can result in dysfunction of crucial antimicrobial effects, potentially contributing to poor prognosis. Studies also show that the effects of low vitamin D can be mitigated via supplementation, although the benefits of vitamin D supplementation in the treatment of COVID-19 remain controversial.

SCOPE: Iron plays an important role in the pathogenesis of insulin resistance (IR) and type 2 diabetes. Recent studies suggest a role of specific lipids in the induction of IR, but the potential relationships between iron and lipid metabolites in relation to IR have not been explored. Therefore, the aim of the study is to evaluate the association among iron, IR, and the lipidome. METHODS AND RESULTS: The plasma lipidome, IR, parameters of iron metabolism, and several cytokines and adipokines in 65 overweight/obese participants are measured. Measurements of IR correlate positively with ferritin, a measure of iron storage (r = 0.35, p = 0.005), and negatively with adiponectin (r = −0.30, p = 0.02). The serum ferritin/adiponectin ratio has a stronger association with IR (r = 0.41, p

Evidence from observational studies indicates a role for vitamin D in kidney function and progression to chronic kidney disease. Findings from animal studies have proposed underlying mechanisms including increased activation of the renin-angiotensin system, increased blood pressure, insulin resistance and chronic low-grade inflammation. However, human studies are limited by confounders arising from heterogeneous samples of participants. We examined the relationship between 25(OH)D and estimated glomerular filtration rate (eGFR) in a predominantly obese otherwise healthy and drug-naive population with no history of chronic kidney disease (CKD). One hundred and twenty one non-diabetic (75 g oral glucose tolerance test; OGTT) volunteers (70 males and 51 females), aged 18–57 years participated in the study. Median 25(OH)D level was 37 nmol/L with no difference by sex. Twenty six participants (21.5%) had 25(OH)D

Vitamin D deficiency has reached epidemic proportions worldwide and has recently been linked to cardiometabolic risk factors including obesity, insulin resistance, hypertension, dyslipidemia, as well as type 2 diabetes and cardiovascular disease. The objective of this study was to examine the associations between circulating 25-hydrovitamin D (25(OH)D) levels and cardiometabolic risk factors using direct measures of adiposity, glucose intolerance, and insulin resistance, as well as lipids, blood pressure, and plasma markers of inflammation. We measured circulating 25(OH)D, physical activity (International Physical Activity Questionnaire- IPAQ), anthropometry (body mass index (BMI), waist-to-hip ratio (WHR), % body fat (dual energy X-ray absorptiometry)), metabolic parameters (fasting and 2-h plasma glucose levels during oral glucose tolerance test; insulin sensitivity (M, hyperinsulinaemic-euglycaemic clamp), and cardiovascular and inflammatory profiles (blood pressure (BP), pulse pressure (PP), mean arterial pressure (MAP), plasma lipid levels, white blood cell count (WBC), and plasma high-sensitivity C-reactive protein levels (hsCRP)) in 111 healthy, non-diabetic adults (66 males/45 females; age 31.1 ± 9.2 years; % body fat 36.0 ± 10.2%). Mean 25(OH)D was 39.8 ± 19.8 nmol/L with no difference between genders (p = 0.4). On univariate analysis, 25(OH)D was associated with% body fat (r = −0.27; p = 0.005), 2-h glucose (r = −0.21; p = 0.03), PP (r = 0.26; p = 0.006), and insulin sensitivity (r = 0.20, p = 0.04), but not with age, BMI, WHR, fasting glucose, BP, MAP, lipids, or inflammatory markers (all p > 0.05). After adjusting for age and sex, 25(OH)D remained associated with% body fat (β = −0.12%; p = 0.003), 2-h glucose (β = −0.13 mmol/L; p = 0.02), PP (β = 0.12 mmHg; p = 0.009), and insulin sensitivity (β = 0.22 mg/kg/min; p = 0.03), and became associated with fasting glucose (β = −0.04 mmol/L; p = 0.04) and hsCRP (β = −0.51 mg/L; p = 0.04). After adjusting for age, sex, and % body fat, 25(OH)D was no longer associated with insulin sensitivity, 2-h glucose, or hsCRP, but remained associated with fasting glucose (β = −0.05 mmol/L; p = 0.03) and PP (β = 0.10 mmHg; p = 0.03). 25(OH)D remained associated with fasting glucose (β = −0.06 mmol/L; p = 0.02) after hsCRP and physical activity were added to the model with % body fat, age, and sex. ​These cross-sectional data suggest that associations between vitamin D and cardiometabolic risk among healthy, non-diabetic adults are largely mediated by adiposity. Large-scale intervention and mechanistic studies are needed to further investigate whether vitamin D has an independent role in the prevention and/or management of cardiometabolic risk and disease.

Background: Vitamin D supplementation has been proposed as a potential strategy to prevent type 2 diabetes. Existing clinical trials have been limited by short duration, low doses of vitamin D, variability in participants' vitamin D-deficiency status, and the use of surrogate measures of body composition, insulin sensitivity, and insulin secretion.Objective: To address existing knowledge gaps, we conducted a double-blind, randomized, placebo-controlled trial to investigate whether vitamin D supplementation that is provided in a sufficient dose and duration to vitamin D-deficient individuals would improve insulin sensitivity or secretion as measured with the use of gold-standard methods. We hypothesized that vitamin D supplementation would improve insulin sensitivity and secretion compared with placebo.Design: Sixty-five overweight or obese, vitamin D-deficient (25-hydroxyvitamin D [25(OH)D] concentration ≤50 nmol/L) adults were randomly assigned to receive either a bolus oral dose of 100,000 IU cholecalciferol followed by 4000 IU cholecalciferol/d or a matching placebo for 16 wk. Before and after the intervention, participants received gold-standard assessments of body composition (via dual X-ray absorptiometry), insulin sensitivity (via hyperinsulinemic-euglycemic clamps), and insulin secretion [via intravenous-glucose-tolerance tests (IVGTTs)].Results: Fifty-four participants completed the study [35 men and 19 women; mean ± SD age: 31.9 ± 8.5 y; body mass index (in kg/m2): 30.9 ± 4.4]. 25(OH)D increased with vitamin D supplementation compared with placebo (57.0 ± 21.3 compared with 1.9 ± 15.1 nmol/L, respectively; P = 0.02). Vitamin D and placebo groups did not differ in change in insulin sensitivity (0.02 ± 2.0 compared with -0.03 ± 2.8 mg · kg-1 · min-1, respectively; P = 0.9) or first-phase insulin secretion (-21 ± 212 compared with 24 ± 184 mU/L, respectively; P = 0.9). Results remained nonsignificant after adjustment for age, sex, percentage of body fat, sun exposure, physical activity, and dietary vitamin D intake (P > 0.1).Conclusions: Vitamin D supplementation does not improve insulin sensitivity or secretion in vitamin D-deficient, overweight or obese adults, despite using high-dose vitamin D supplementation and robust endpoint measures. Therefore, it is unlikely that vitamin D supplementation would be an effective strategy for reducing diabetes risk even in vitamin D-deficient populations. This trial was registered at clinicaltrials.gov as NCT02112721.

Background: Low serum amylase has been implicated in the pathogenesis of obesity and insulin resistance. Copy number variations (CNVs) in the salivary amylase gene (AMY1) correlate with serum amylase, and CNVs Objective: To examine whether AMY1 CNVs are associated with cardiometabolic risk factors. Methods: In overweight or obese (BMI >25kg/m2), otherwise healthy adults, we measured AMY1 copy numbers (qPCR); serum amylase (commercial assay); anthropometry (BMI; body composition by dual-energy X-ray absorptiometry); cardiovascular parameters (blood pressure, plasma lipids by ELISA); fasting and 2-h glucose levels post-75g oral glucose tolerance test (glucose oxidase method), insulin sensitivity (hyperinsulinemic-euglycemic clamp), insulin secretion (intravenous glucose tolerance test), and serum inflammation markers (LEGENDplex™, Biolegend). Results: Fifty-nine adults (58% males) aged 31.27 ± 8.61 were included in the study. Based on previous studies and median values, participants were divided into low CNV and high CNV carrier groups for individuals with ≤4 and >4 AMY1 CNVs, respectively. Low AMY1 CNV carriers (n=29) had a higher BMI (32.65 ± 5.37 vs. 30.28 ± 3.51 kg/m2, p = 0.04), % fat mass (40.76 ± 12.22 vs. 33.13 ± 8.60%, p = 0.008), and LDL-c (3.25 ± 0.80 vs. 2.87 ± 0.63 mmol/L, p = 0.04) compared with the high AMY1 CNV group (n=30), as well as higher levels of interleukins [IL]-6, -1β, -10, and tumor necrosis factor-alpha (all p0.1). Conclusions: Our results suggest that low AMY1 CNVs are associated with increased obesity, cardiovascular risk, and inflammation. Disclosure C. Marquina: None. A. Mousa: None. N. Naderpoor: None. B. de Courten: None.

Background: The burden of obesity and type 2 diabetes is rapidly increasing. Carnosine (β alanyl L-histidine), a dipeptide with anti-inflammatory, anti-glycating, and anti-oxidative properties, may be a potential strategy to mitigate cardiometabolic risk factors. However, studies examining the effects of carnosine and related histidine-containing dipeptides (HCDs; e.g., beta-alanine) on cardiometabolic risk have been inconsistent. Objective: We conducted a systematic review and meta-analysis examining the effects of all HCDs on cardiometabolic risk factors in all population groups. Methods: MEDLINE, CINAHL, EMBASE, and EBM were searched for randomized controlled trials investigating the effects of carnosine and/or HCDs on cardiometabolic risk factors, compared with placebo, usual care, or other interventions. Meta-analyses using random-effects models were used to calculate the mean difference (MD) and 95% confidence interval (CI) for each outcome. Results: Forty- nine RCTs totaling 1709 participants were included. Carnosine and/or HCD supplementation lowered waist circumference (n= 162, MD [95% CI]= -3.53 cm [-5.65,1.41], p=0.001); post-prandial glucose (PPG) (n=230, MD [95% CI]= -0.79 mmol/L [-1.23,-0.35], p=0.0004), HbA1c (n=283, MD [95% CI]= -0.37% [-0.64,-0.10], p=0.006) and C-reactive protein (CRP) (n=272, MD [95% CI]= -0.43 mg/L [-0.64,-0.22], p< 0.0001) compared with control. In sensitivity analyses of RCTs using carnosine only, PPG, HbA1c, and CRP remained significantly lower with carnosine supplementation (all p Conclusion: Our findings provide level 1 evidence that carnosine and HCDs have potential benefits for prevention and treatment of diabetes. Disclosure K. Aravind Menon: None. A. Mousa: None. C. Marquina: None. B. de Courten: None.

Emerging evidence suggests a role for the gut microbiota in glucose metabolism and diabetes. Few studies have examined the associations between the faecal microbiome and insulin sensitivity and secretion using gold-standard methods in high-risk populations prior to diabetes onset. We investigated the relationships between faecal microbiota composition (16S rRNA sequencing) and gold-standard measures of insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) and insulin secretion (intravenous glucose tolerance test) in 38 overweight or obese otherwise healthy individuals. Genus Clostridium was positively associated with insulin sensitivity, and genera Dialister and Phascolarctobacterium were related to both insulin sensitivity and secretion. Insulin sensitivity was associated with a higher abundance of Phascolarctobacterium and lower abundance of Dialister. Those with higher insulin secretion had a higher abundance of Dialister and lower abundance of Bifidobacterium, compared to those with lower insulin secretion. Body mass index (BMI) was positively correlated with Streptococcus abundance whereas Coprococcus abundance was negatively correlated to BMI and percent body fat. These results suggest that faecal microbiota is related to insulin sensitivity and secretion in overweight or obese adults. These correlations are distinct although partially overlapping, suggesting different pathophysiological pathways. Our findings can inform future trials aiming to manipulate gut microbiome to improve insulin sensitivity and secretion and prevent type 2 diabetes.