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Abstract It is unclear whether polycystic ovary syndrome (PCOS) is an independent risk factor for adverse birth outcomes in the offspring of affected women. Here, we investigate the association of PCOS with birth outcomes in the offspring of women with PCOS overall and by potential confounders. This systematic review and meta-analysis included 73 studies and 92,881 offspring of women with and without PCOS from inception until 13th July 2022. We report that mothers with PCOS are younger and have higher body mass index (BMI) around conception and have greater gestational weight gain. The odds of preterm birth, fetal growth restriction and low birth weight are higher and mean birthweight is lower in PCOS of which a lower mean birthweight and a higher small for gestational age are probably independent of BMI. This work informed the recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome, emphasizing that PCOS status should be captured at pregnancy to identify risk and improve birth outcomes in the offspring.

Abstract Screening for polycystic ovary syndrome (PCOS) in antenatal care is inadequate, largely owing to the lack of clarity around whether PCOS is an independent risk factor for pregnancy complications. This systematic review and meta-analysis include 104 studies and 106,690 pregnancies in women with and without PCOS from inception until 13th July 2022. We report that women with PCOS are younger and have higher body mass index (BMI) around conception and have greater gestational weight gain. The odds of miscarriage, gestational diabetes mellitus, gestational hypertension, pre-eclampsia and cesarean section are higher in women with PCOS. The increased odds of adverse outcomes in PCOS remain significant when age and BMI are matched and when analyses are restricted to high-quality studies. This work informed the recommendations from the 2023 international evidence-based guideline for the assessment and management of polycystic ovary syndrome, emphasizing that PCOS status should be captured in all women who are planning to, or have recently become pregnant to facilitate prevention of adverse outcomes and improve pregnancy outcomes.

Background Polycystic ovary syndrome (PCOS) is the most prevalent female endocrinopathy. Although increased cardiovascular risk factors are well established for the syndrome, PCOS remains overlooked within the realm of cardiology. We conducted a systematic review and meta‐analysis on the risk of clinical cardiovascular disease (CVD) events in women with PCOS to inform the 2023 International Evidence‐Based PCOS Guideline. Methods and Results A systematic review and meta‐analysis was conducted comparing the risk of clinical CVD events in women with and without PCOS. Medline (Ovid), PsycInfo (Ovid), EMBASE, All EBM (Ovid), and CINAHL were searched from January 1, 2017, until March 1, 2023, to update the 2018 PCOS Guideline. Pooled odds ratios (ORs), incidence rate ratios (IRRs), and hazard ratios (HRs) were calculated. Twenty studies involving 1.06 million women (369 317 with PCOS and 692 963 without PCOS) were included. PCOS was associated with higher risk of composite CVD (OR, 1.68 [95% CI, 1.26–2.23]; I2 = 71.0%), composite ischemic heart disease (OR, 1.48 [95% CI, 1.07–2.05]; I2 = 81.0%), myocardial infarction (OR, 2.50 [95% CI, 1.43–4.38]; I2 = 83.3%), and stroke (OR, 1.71 [95% CI, 1.20–2.44]; I2 = 81.4%). The relationship with cardiovascular mortality was less clear (OR, 1.19 [95% CI, 0.53–2.69]; I2 = 0%). Meta‐analyses of IRRs support these findings. Results from pooled HRs were limited by the small number of studies and significant heterogeneity. Conclusions This review provides evidence and highlights the importance of recognizing PCOS as a significant risk factor for CVD morbidity. The 2023 International Evidence‐Based PCOS Guideline now recommends awareness of increased CVD risk and comprehensive risk assessment in PCOS to help mitigate the burden of CVD in this common and high‐risk condition.

abstract: This research aims to detect different types of Arabic offensive language in twitter. It uses a multiclass classification system in which each tweet is categorized into one or more of the offensive language types based on the used word(s). In this study, five types are classified, which are: bullying, insult, racism, obscene, and non-offensive. To classify the abusive language, a cascaded model consisting of Bidirectional Encoder Representation of Transformers (BERT) models (AraBERT, ArabicBERT, XLMRoBERTa, GigaBERT, MBERT, and QARiB), deep learning models (1D-CNN, BiLSTM), and Radial Basis Function (RBF) is presented in this work. In addition, various types of machine learning models are utilized. The dataset is collected from twitter in which each class has the same number of tweets (balanced dataset). Each tweet is assigned to one or more of the selected offensive language types to build multiclass and multilabel systems. In addition, a binary dataset is constructed by assigning the tweets to offensive or non-offensive classes. The highest results are obtained from implementing the cascaded model started by ArabicBERT followed by BiLSTM and RBF with an accuracy, precision, recall, and F1-score of 98.4%, 98.2%,92.8%, and 98.4%, respectively. RBF records the highest results among the utilized traditional classifiers with an accuracy, precision, recall, and F1-score of 60% for each measurement individually, while KNN records the lowest results obtaining 45%, 46%, 45%, and 43% in terms of accuracy, precision, recall, and F1-score, respectively.

Summary: Background: Anti-androgens and combined oral contraceptive pills (COCPs) may mitigate hyperandrogenism-related symptoms of polycystic ovary syndrome (PCOS). However, their efficacy and safety in PCOS remain unclear as previous reviews have focused on non-PCOS populations. To inform the 2023 International Evidence-based Guideline in PCOS, we conducted the first systematic review and meta-analysis investigating the efficacy and safety of anti-androgens in the management of hormonal and clinical features of PCOS. Methods: We systematically searched MEDLINE, Embase, PsycInfo, All EBM reviews, and CINAHL up to 28th June 2023 for randomised controlled trials (RCTs) examining oral anti-androgen use, alone or in combination with metformin, COCPs, lifestyle, or other interventions, in women of any age, with PCOS diagnosed by Rotterdam, National Institutes of Health or Androgen Excess & PCOS Society criteria, and using a form of contraception. Non-English studies and studies of less than 6 months duration or which used the same anti-androgen regimen in both/all groups were excluded in order to establish efficacy for the clinical outcomes of interest. Three authors screened articles against selection criteria and assessed risk of bias and quality using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework. Critical outcomes (prioritised during guideline development for GRADE purposes) included weight, body mass index (BMI), irregular cycles, hirsutism, liver function, and quality of life. Random effects meta-analyses were conducted where appropriate. This study is registered with PROSPERO, CRD42022345640. Findings: From 1660 studies identified in the search, 27 articles comprising 20 unique studies were included. Of these, 13 studies (n = 961) were pooled in meta-analysis. Seven studies had a high risk of bias, nine moderate and four low. Anti-androgens included finasteride, flutamide, spironolactone, or bicalutamide. In meta-analysis, anti-androgens + lifestyle were superior to metformin + lifestyle for hirsutism (weighted mean difference [WMD] [95% CI]: −1.59 [−3.06, −0.12], p = 0.03; I2 = 74%), SHBG (7.70 nmol/l [0.75, 14.66], p = 0.03; I2 = 0%), fasting insulin and fasting insulin: glucose ratio (−2.11 μU/ml [−3.97, −0.26], p = 0.03; I2 = 0% and −1.12 [−1.44, −0.79], p

Abstract Polycystic ovary syndrome (PCOS) is a common condition affecting reproductive-aged women with reproductive, metabolic and psychological consequences. Weight and lifestyle (diet, physical activity and behavioural) management are first-line therapy in international evidence-based guidelines for PCOS. While these recommend following population-level diet and physical activity guidelines, there is ongoing interest and research in the potential benefit of including psychological and sleep interventions, as well as a range of traditional, complimentary and integrative medicine (TCIM) approaches, for optimal management of PCOS. There is limited evidence to recommend a specific diet composition for PCOS with approaches including modifying protein, carbohydrate or fat quality or quantity generally having similar effects on the presentations of PCOS. With regards to physical activity, promising evidence supports the provision of vigorous aerobic exercise, which has been shown to improve body composition, cardiorespiratory fitness and insulin resistance. Psychological and sleep interventions are also important considerations, with women displaying poor emotional wellbeing and higher rates of clinical and subclinical sleep disturbance, potentially limiting their ability to make positive lifestyle change. While optimising sleep and emotional wellbeing may aid symptom management in PCOS, research exploring the efficacy of clinical interventions is lacking. Uptake of TCIM approaches, in particular supplement and herbal medicine use, by women with PCOS is growing. However, there is currently insufficient evidence to support integration into routine clinical practice. Research investigating inositol supplementation have produced the most promising findings, showing improved metabolic profiles and reduced hyperandrogenism. Findings for other supplements, herbal medicines, acupuncture and yoga is so far inconsistent, and to reduce heterogeneity more research in specific PCOS populations, (e.g. defined age and BMI ranges) and consistent approaches to intervention delivery, duration and comparators are needed. While there are a range of lifestyle components in addition to population-recommendations for diet and physical activity of potential benefit in PCOS, robust clinical trials are warranted to expand the relatively limited evidence-base regarding holistic lifestyle management. With consumer interest in holistic healthcare rising, healthcare providers will be required to broaden their knowledge pertaining to how these therapies can be safely and appropriately utilised as adjuncts to conventional medical management.

IntroductionThe aim of the study was to identify available polycystic ovary syndrome (PCOS) models of care (MoCs) and describe their characteristics and alignment with the international PCOS guideline.MethodsOvid MEDLINE, All EBM, PsycINFO, Embase, and CINAHL were searched from inception until 11 July 2022. Any study with a description of a PCOS MoC was included. Non-evidence-based guidelines, abstracts, study protocols, and clinical trial registrations were excluded. We also excluded MoCs delivered in research settings to minimize care bias. Meta-analysis was not performed due to heterogeneity across MoCs. We describe and evaluate each MoC based on the recommendations made by the international evidence-based guideline for assessing and managing PCOS.ResultsOf 3,671 articles, six articles describing five MoCs were included in our systematic review. All MoCs described a multidisciplinary approach, including an endocrinologist, dietitian, gynecologist, psychologist, dermatologist, etc. Three MoCs described all aspects of PCOS care aligned with the international guideline recommendations. These include providing education on long-term risks, lifestyle interventions, screening and management of emotional well-being, cardiometabolic diseases, and the dermatological and reproductive elements of PCOS. Three MoCs evaluated patients’ and healthcare professionals’ satisfaction, with generally positive findings. Only one MoC explored the impact of their service on patients’ health outcomes and showed improvement in BMI.ConclusionThere is limited literature describing PCOS MoCs in routine practice. Future research should explore developing cost-effective co-created multidisciplinary PCOS MoCs globally. This may be facilitated by the exchange of best practices between institutions with an established MoC and those who are interested in setting one up.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=346539, identifier CRD42022346539.

Lifestyle strategies are considered first-line treatment for the management of polycystic ovary syndrome (PCOS). However, complementary therapies, including nutrient supplementation, have been identified as a potential adjunct therapy. Therefore, we systematically mapped the available literature to identify the type and frequency of the use of nutraceutical and micronutrient supplementation for the management of PCOS features. A systematic search of the literature was conducted using CINAHL, Cochrane reviews, Medline, PsycINFO, Scopus and LILACS. All types of study designs were included if they reported on the use of nutraceuticals and/or micronutrient supplementation on features of PCOS in women aged ≥18 years. A total of 344 articles were included. Forty-one supplements were identified, with the most frequently investigated being inositols (n = 86), vitamin D (n = 53), N-acetylcysteine (n = 27) and omega-3 fatty acids (n = 25). Reproductive outcomes were the most commonly reported (n = 285; 83%), followed by metabolic (n = 229; 67%), anthropometric (n = 197; 57%) and psychological (n = 8; 2%). Our results identified that nutraceutical and micronutrient supplementation require further investigation of psychological outcomes in women with PCOS. Moreover, adequately powered primary studies are warranted to investigate therapeutic doses needed for clinical benefits.

Summary: Background: Polycystic ovary syndrome (PCOS) is a common endocrine condition in women of reproductive age that often presents with reproductive, metabolic, and psychological symptoms. While exercise is part of the management of PCOS, it is unclear which form of exercise may be most effective and for which outcomes. Aim: In order to inform the updated 2023 International evidence-based guideline for the assessment and management of polycystic ovary syndrome, this systematic review aimed to determine the exercise modality that provides the greatest improvement in anthropometric, metabolic, hormonal/reproductive, and psychological outcomes in adult women with PCOS. Methods: Five databases were searched from inception to July 2022. Studies eligible for inclusion consisted of those in a PCOS population, that compared two exercise modalities, and reported at least one anthropometric, metabolic, hormonal/reproductive, and/or psychological outcome. Screening, data extraction, and methodological quality assessments were conducted by two independent reviewers. Methodological quality assessment was performed using the Cochrane Risk of Bias tool and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines were used to determine the certainty of evidence. Meta-analysis was performed utilising Comprehensive Meta-Analysis software, Version 3. Results: Of the 4739 records identified, five unique studies were eligible for inclusion in the systematic review and meta-analysis, comprising a total of 216 individuals. Meta-analyses comparing high-intensity interval training (HIIT) to moderate-intensity continuous training (MICT) on anthropometric, metabolic, and hormonal/reproductive parameters found no statistically significant differences in outcomes between groups, and the certainty of evidence was graded as low or very low. Results from single studies showed that HIIT was more effective than MICT for menstrual regularity (odds ratio [95% confidence interval] ​= ​7.875 [1.105, 56.125], p ​= ​0.039, very low certainty). HIIT vs resistance training, and diet ​+ ​MICT vs diet ​+ ​MICT ​+ ​resistance training were examined by a single study each, and no statistically significant differences were found for any outcome, with the certainty of evidence ranked as very low. Conclusion: To date, there are insufficient RCTs comparing exercise modalities in individuals with PCOS to establish with certainty whether one form of exercise is superior to another for the management of PCOS.

During pregnancy, the fetoplacental unit is key in the pronounced physiological endocrine changes which support pregnancy, fetal development and survival, birth and lactation. In healthy women, pregnancy is characterized by changes in insulin sensitivity and increased maternal androgen levels. These are accompanied by a suite of mechanisms that support fetal growth, maintain glucose homeostasis and protect both mother and fetus from adverse effects of pregnancy induced insulin and androgen excess. In pregnancies affected by endocrine, metabolic disorders such as polycystic ovary syndrome (PCOS), diabetes and obesity, there is an imbalance of beneficial and adverse impacts of pregnancy induced endocrine changes. These inter-related conditions are characterized by an interplay of hyperinsulinemia and hyperandrogenism which influence fetoplacental function and are associated with adverse pregnancy outcomes including hypertensive disorders of pregnancy, macrosomia, preterm delivery and caesarean section. However, the exact underlying mechanisms and relationships of the endocrine and metabolic milieu in these disorders and the impact they have on the prenatal endocrine environment and developing fetus remain poorly understood. Here we aim to review the complex endocrine and metabolic interactions in healthy women during normal pregnancies and those in pregnancies complicated by hyperinsulinemic disorders (PCOS, diabetes and obesity). We also explore the relationships between these endocrine and metabolic differences and the fetoplacental unit, pregnancy outcomes and the developing fetus.

Abstract 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.

ContextPre-clinical evidence suggests that prolactin has important metabolic functions in pregnancy and postpartum, in addition to lactogenic actions.ObjectiveTo explore the relationship between prolactin and maternal metabolic outcomes in human pregnancy and postpartum, particularly in relation to gestational diabetes mellitus (GDM).Data sourcesMEDLINE via OVID, CINAHL plus, Embase.Study selectionEligible studies included women who were pregnant or up to 12 months postpartum, reporting at least one maternal serum prolactin level in relation to key metabolic outcomes including GDM, glycaemic parameters, obesity, and gestational weight gain.Data extractionTwo independent reviewers extracted data.Data synthesisTwenty-six articles were included. Meta-analysis showed no relationship between maternal prolactin levels and GDM status, with a weighted mean difference of -2.14 ng/mL (95% CI -12.54 to 8.27 ng/mL, p=0.7) between GDM and controls in early pregnancy (n=3 studies) and -3.89 ng/mL (95% CI, -15.20 to 7.41 ng/mL, p=0.5) in late pregnancy (n=11 studies). In narrative synthesis of other outcomes (due to study heterogeneity and/or lack of data), prolactin levels were not associated with maternal glycaemic or weight-related parameters during pregnancy, but in the postpartum period (particularly with lactation) a high-prolactin environment was associated with low circulating insulin and beta-cell function, and increased insulin sensitivity.ConclusionsCurrent evidence from human studies does not clearly support a relationship between prolactin and metabolic parameters during pregnancy, including with GDM status. Elevated prolactin was associated with lower insulin and beta-cell function and higher insulin sensitivity in the post-partum period, but the direction of causality remains unclear.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier [CRD42021262771].

There are conflicting results on the effect of diet on fertility. This study aimed to assess the effect of different dietary patterns on fertility outcomes in populations who conceive spontaneously and those requiring assisted reproductive technology (ART). A systematic search and meta-analysis were performed for studies investigating dietary patterns or whole diets in reproductive aged women requiring ART or conceived naturally. Outcomes were live births, pregnancy rates and infertility rates. In amount of 15,396 studies were screened with 11 eligible studies. Ten different diet patterns were grouped broadly into categories: Mediterranean, Healthy or Unhealthy. For the Mediterranean diet, on excluding high risk-of-bias studies (n = 3), higher adherence was associated with improved live birth/pregnancy rates in ART [OR 1.91 (95% CI 1.14–3.19, I2 43%)] (n = 2). Adherence to various Healthy diets was associated with improved ART outcomes (ProFertility diet and Dutch Dietary Guidelines) and natural conception outcomes (Fertility diet). However, due to the variability in Healthy diets’ components, results were not pooled. Studies demonstrated preliminary evidence for the role of dietary patterns or whole diets in improving pregnancy and live birth rates. However, due to heterogeneity across the literature it is currently unclear which diet patterns are associated with improvements in fertility and ART outcomes.

Women affected by maternal pregestational diabetes mellitus (type 1 or type 2) or by polycystic ovary syndrome experience an increased risk of pregnancy complications, as well as suboptimal lactation outcomes. The hormone prolactin plays important roles in pregnancy and postpartum, both as a metabolic and lactogenic hormone. We aimed to explore, through a systematic review, the relationship between pregestational maternal metabolic conditions and prolactin levels in pregnancy and postpartum. MEDLINE via OVID, CINAHL Plus, and Embase were searched from inception to 9 May 2022. Eligible studies included women who were pregnant or up to 12 months postpartum and had a pre-existing diagnosis of type 1 or type 2 diabetes mellitus or polycystic ovary syndrome; with reporting of at least one endogenous maternal serum prolactin level during this time. Two independent reviewers extracted the data. Eleven studies met the eligibility criteria. The studies were too diverse and heterogeneous to enable meta-analysis. Overall, prolactin levels appeared to be lower in pregnancies affected by type 1 diabetes mellitus. There was little data in polycystic ovary syndrome or type 2 diabetes pregnancy, but prolactin increment across pregnancy in polycystic ovary syndrome emerged as an area for future study. During postpartum, lactation difficulties in women with metabolic disease present before pregnancy are well-described, but the relationship to prolactin remains unclear. Overall, preliminary evidence suggests that pre-existing maternal metabolic disease may alter prolactin dynamics in pregnancy and postpartum. Further well-designed studies in modern cohorts, with standardised collection and serial sampling across pregnancy and postpartum, are required to clarify these associations.

Background: MicroRNAs (miRNAs) are sought-after biomarkers of complex, polygenic diseases such as type 2 diabetes (T2D). Data-driven biocomputing provides robust and novel avenues for synthesizing evidence from individual miRNA seq studies. Objective: To identify miRNA markers associated with T2D, via a data-driven, biocomputing approach on high throughput transcriptomics. Materials and methods: The pipeline consisted of five sequential steps using miRNA seq data retrieved from the National Center for Biotechnology Information Gene Expression Omnibus platform: systematic review; identification of differentially expressed miRNAs (DE-miRNAs); meta-analysis of DE-miRNAs; network analysis; and downstream analyses. Three normalization algorithms (trimmed mean of M-values; upper quartile; relative log expression) and two meta-analytic algorithms (robust rank aggregation; Fisher's method of p-value combining) were integrated into the pipeline. Network analysis was conducted on miRNet 2.0 while enrichment and over-representation analyses were conducted on miEAA 2.0. Results: A total of 1256 DE-miRNAs (821 downregulated; 435 upregulated) were identified from 5 eligible miRNA seq datasets (3 circulatory; 1 adipose; 1 pancreatic). The meta-signature comprised 9 miRNAs (hsa-miR-15b-5p; hsa-miR-33b-5p; hsa-miR-106b-3p; hsa-miR-106b-5p; hsa-miR-146a-5p; hsa-miR-483-5p; hsa-miR-539-3p; hsa-miR-1260a; hsa-miR-4454), identified via the two meta-analysis approaches. Two hub nodes (hsa-miR-106b-5p; hsa-miR-15b-5p) with above-average degree and betweenness centralities in the miRNA-gene interactions network were identified. Downstream analyses revealed 5 highly conserved- (hsa-miR-33b-5p; hsa-miR-15b-5p; hsa-miR-106b-3p; hsa-miR-106b-5p; hsa-miR-146a-5p) and 7 highly confident- (hsa-miR-33b-5p; hsa-miR-15b-5p; hsa-miR-106b-3p; hsa-miR-106b-5p; hsa-miR-146a-5p; hsa-miR-483-5p; hsa-miR-539-3p) miRNAs. A total of 288 miRNA-disease associations were identified, in which 3 miRNAs (hsa-miR-15b-5p; hsa-miR-106b-3p; hsa-miR-146a-5p) were highly enriched. Conclusions: A meta-signature of DE-miRNAs associated with T2D was discovered via in-silico analyses and its pathobiological relevance was validated against corroboratory evidence from contemporary studies and downstream analyses. The miRNA meta-signature could be useful for guiding future studies on T2D. There may also be avenues for using the pipeline more broadly for evidence synthesis on other conditions using high throughput transcriptomics.

IntroductionUsing body mass index (BMI) as a proxy, previous Mendelian randomization (MR) studies found total causal effects of general obesity on polycystic ovarian syndrome (PCOS). Hitherto, total and direct causal effects of general- and central obesity on PCOS have not been comprehensively analyzed.ObjectivesTo investigate the causality of central- and general obesity on PCOS using surrogate anthropometric markers.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, we acquired summary data from a large-sample GWAS (118870 samples; 642 cases and 118228 controls) within the FinnGen cohort. Total causal effects were assessed via univariable two-sample Mendelian randomization (2SMR). Genetic architectures underlying causal associations were explored. Direct causal effects were analyzed by multivariable MR modelling.ResultsInstrumental variables demonstrated no weak instrument bias (F > 10). Four anthropometric exposures, namely, weight (2.69-77.05), BMI (OR: 2.90-4.06), WC (OR: 6.22-20.27), and HC (OR: 6.22-20.27) demonstrated total causal effects as per univariable 2SMR models. We uncovered shared and non-shared genetic architectures underlying causal associations. Direct causal effects of WC and HC on PCOS were revealed by two multivariable MR models containing exclusively the anthropometric markers of central obesity. Other multivariable MR models containing anthropometric markers of both central- and general obesity showed no direct causal effects on PCOS.ConclusionsBoth and general- and central obesity yield total causal effects on PCOS. Findings also indicated potential direct causal effects of normal weight-central obesity and more complex causal mechanisms when both central- and general obesity are present. Results underscore the importance of addressing both central- and general obesity for optimizing PCOS care.

Overheating of photovoltaic (PV) panels decreases their efficiency and lifetime, and subsequently increases the levelized cost of energy (LCOE). Passive PV cooling would enhance the PV operational stability and durability. The cooling tower (CT) technology offers an attractive approach for zero-cost capability. In this work, we developed and customized a CT specific for passive PV cooling. Since the dense downdrafted cooled air gained high velocity, a turbine was installed at the bottom of the CT for power production. At the height’s ambient temperature, the CT cooled the air from 50 °C down to 30 °C. The cooled air at 30 °C has enough capacity to cool the PV panels. This cooling capacity improved the average annual efficiency of the PV panels by 6.83%. The design specifications of the CT have the highest performance, with the maximum radius of PV area of panels that can be cooled at 50 m. Furthermore, the current design could operate during the night for power production with minimum operational cost.

Human placental lactogen (hPL) is a placental hormone which appears to have key metabolic functions in pregnancy. Preclinical studies have putatively linked hPL to maternal and fetal outcomes, yet—despite human observational data spanning several decades—evidence on the role and importance of this hormone remains disparate and conflicting. We aimed to explore (via systematic review and meta-analysis) the relationship between hPL levels, maternal pre-existing and gestational metabolic conditions, and fetal growth. MEDLINE via OVID, CINAHL plus, and Embase were searched from inception through 9 May 2022. Eligible studies included women who were pregnant or up to 12 months post-partum, and reported at least one endogenous maternal serum hPL level during pregnancy in relation to pre-specified metabolic outcomes. Two independent reviewers extracted data. Meta-analysis was conducted where possible; for other outcomes narrative synthesis was performed. 35 studies met eligibility criteria. No relationship was noted between hPL and gestational diabetes status. In type 1 diabetes mellitus, hPL levels appeared lower in early pregnancy (possibly reflecting delayed placental development) and higher in late pregnancy (possibly reflecting increased placental mass). Limited data were found in other pre-existing metabolic conditions. Levels of hPL appear to be positively related to placental mass and infant birthweight in pregnancies affected by maternal diabetes. The relationship between hPL, a purported pregnancy metabolic hormone, and maternal metabolism in human pregnancy is complex and remains unclear. This antenatal biomarker may offer value, but future studies in well-defined contemporary populations are required.

Insulin resistance (IR) and chronic low-grade inflammation are risk factors for chronic diseases including type 2 diabetes (T2D) and cardiovascular disease. This study aimed to investigate two dietary indices: Mediterranean Diet Score (MDS) and Dietary Inflammatory Index (DII®), and their associations with direct measures of glucose metabolism and adiposity, and biochemical measures including lipids, cytokines and adipokines in overweight/obese adults. This cross-sectional study included 65 participants (males = 63%; age 31.3 ± 8.5 years). Dietary intake via 3-day food diaries was used to measure adherence to MDS (0–45 points); higher scores indicating adherence. Energy-adjusted DII (E-DII) scores were calculated with higher scores indicating a pro-inflammatory diet. IR was assessed using hyperinsulinemic euglycemic clamps, insulin secretion by intravenous glucose tolerance test, adiposity by dual-energy X-ray absorptiometry, and circulating cytokine and adipokine concentrations by multiplex assays. Higher MDS was associated with greater insulin sensitivity (β = 0.179; 95%CI: 0.39, 0.318) after adjusting for age, sex and % body fat, and lower NF-κB, higher adiponectin and adipsin in unadjusted and adjusted models. Higher E-DII score was associated with increased total cholesterol (β = 0.364; 95%CI: 0.066, 0.390) and LDL-cholesterol (β = 0.305; 95%CI: 0.019, 0.287) but not with adiposity, glucose metabolism, cytokines or adipokines. Greater MDS appears to be associated with decreased IR and inflammatory markers in overweight/obese adults.

Infertility is a global health concern affecting 48 million couples and 186 million individuals worldwide. Infertility creates a significant economic and social burden for couples who wish to conceive and has been associated with suboptimal lifestyle factors, including poor diet and physical inactivity. Modifying preconception nutrition to better adhere with Food-Based Dietary Guidelines (FBDGs) is a non-invasive and potentially effective means for improving fertility outcomes. While several dietary patterns have been associated with fertility outcomes, the mechanistic links between diet and infertility remain unclear. A key mechanism outlined in the literature relates to the adverse effects of inflammation on fertility, potentially contributing to irregular menstrual cyclicity, implantation failure, and other negative reproductive sequelae. Therefore, dietary interventions which act to reduce inflammation may improve fertility outcomes. This review consistently shows that adherence to anti-inflammatory diets such as the Mediterranean diet (specifically, increased intake of monounsaturated and n-3 polyunsaturated fatty acids, flavonoids, and reduced intake of red and processed meat) improves fertility, assisted reproductive technology (ART) success, and sperm quality in men. Therefore, integration of anti-inflammatory dietary patterns as low-risk adjunctive fertility treatments may improve fertility partially or fully and reduce the need for prolonged or intensive pharmacological or surgical interventions.

Background: Nutrient supplements are widely used for type 2 diabetes (T2D), yet evidence-based guidance for clinicians is lacking. Methods: We searched the four electronic databases from November 2015–December 2021. The most recent, most comprehensive, high-ranked systematic reviews, meta-analyses, and/or umbrella reviews of randomised controlled trials in adults with T2D were included. Data were extracted on study characteristics, aggregate outcome measures per group (glycaemic control, measures of insulin sensitivity and secretion), adverse events, and Grading of Recommendations Assessment, Development, and Evaluation (GRADE) assessments. Quality was assessed using A Measurement Tool to Assess Systematic Reviews Version 2.0 (AMSTAR 2). Results: Twelve meta-analyses and one umbrella review were included. There was very low certainty evidence that chromium, Vitamin C, and omega-3 polyunsaturated fatty acids (Ω-3 PUFAs) were superior to placebo for the primary outcome of glycated hemoglobin (HbA1c) (Mean Difference/MD −0.54, −0.54 and ES −0.27, respectively). Probiotics were superior to placebo for HbA1c (Weighted Mean Difference/WMD −0.43%). There was very low certainty evidence that Vitamin D was superior to placebo for lowering HbA1c in trials of

ObjectivesUsing a nationally-representative, cross-sectional cohort, we examined nutritional markers of undiagnosed type 2 diabetes in adults via machine learning.MethodsA total of 16429 men and non-pregnant women ≥ 20 years of age were analysed from five consecutive cycles of the National Health and Nutrition Examination Survey. Cohorts from years 2013-2016 (n = 6673) was used for external validation. Undiagnosed type 2 diabetes was determined by a negative response to the question "Have you ever been told by a doctor that you have diabetes?" and a positive glycaemic response to one or more of the three diagnostic tests (HbA1c > 6.4% or FPG >125 mg/dl or 2-hr post-OGTT glucose > 200mg/dl). Following comprehensive literature search, 114 potential nutritional markers were modelled with 13 behavioural and 12 socio-economic variables. We tested three machine learning algorithms on original and resampled training datasets built using three resampling methods. From this, the derived 12 predictive models were validated on internal- and external validation cohorts. Magnitudes of associations were gauged through odds ratios in logistic models and variable importance in others. Models were benchmarked against the ADA diabetes risk test.ResultsThe prevalence of undiagnosed type 2 diabetes was 5.26%. Four best-performing models (AUROC range: 74.9%-75.7%) classified 39 markers of undiagnosed type 2 diabetes; 28 via one or more of the three best-performing non-linear/ensemble models and 11 uniquely by the logistic model. They comprised 14 nutrient-based, 12 anthropometry-based, 9 socio-behavioural, and 4 diet-associated markers. AUROC of all models were on a par with ADA diabetes risk test on both internal and external validation cohorts (p>0.05).ConclusionsModels performed comparably to the chosen benchmark. Novel behavioural markers such as the number of meals not prepared from home were revealed. This approach may be useful in nutritional epidemiology to unravel new associations with type 2 diabetes.

Background: Back pain is the leading cause of disability worldwide and is associated with obesity and chronic low-grade inflammation. Alterations in intestinal microbiota may contribute to the pathogenesis of back pain through metabolites affecting immune and inflammatory responses.Aims and Methods: We compared the gut microbiota composition in a cohort of 36 overweight or obese individuals with or without self-reported back pain in the preceding month. Participants were characterized for anthropometry; bone health; metabolic health; inflammation; dietary intake; and physical activity.Results: Demographic, clinical, biochemical characteristics, diet and physical activity were similar between participants with (n = 14) or without (n = 22) back pain. Individuals with back pain had a higher abundance of the genera Adlercreutzia (p = 0.0008; FDR = 0.027), Roseburia (p = 0.0098; FDR = 0.17), and Uncl. Christensenellaceae (p = 0.02; FDR = 0.27) than those without back pain. Adlercreutzia abundance remained higher in individuals with back pain in the past 2 weeks, 6 months, and 1 year. Adlercreutzia was positively correlated with BMI (rho = 0.35, p = 0.03), serum adipsin (rho = 0.33, p = 0.047), and serum leptin (rho = 0.38, p = 0.02).Conclusions: Our findings suggest that back pain is associated with altered gut microbiota composition, possibly through increased inflammation. Further studies delineating the underlying mechanisms may identify strategies for lowering Adlercreutzia abundance to treat back pain.

Over the last decade, mobile technology has emerged as a potentially useful platform to facilitate weight management and tackle the current obesity epidemic. Clinicians are being more frequently asked to give advice about the usefulness of mobile apps and many individuals have already integrated apps into their attempts to manage weight. Hence, it is imperative for clinicians involved in weight management to be aware of the latest developments and knowledge about available mobile apps and their usefulness in this field. A number of newly published studies have demonstrated promising results of mobile-based interventions for weight management across different populations, but the extent of their effectiveness remains widely debated. This narrative literature review synthesizes the latest evidence, primarily from randomized controlled trials (RCTs), regarding the clinical use of mobile applications for weight management, as well as highlight key limitations associated with their use and directions for future research and practice. Overall, evidence suggests that mobile applications may be useful as low-intensity approaches or adjuncts to conventional weight management strategies. However, there is insufficient evidence to support their use as stand-alone intensive approaches to weight management. Further research is needed to clarify the extent of utility of these applications, as well as the measures required to maximize their potential both as stand-alone approaches and adjuncts to more intensive programs.

Introduction Gestational 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 analysis MEDLINE, 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 dissemination All 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.

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.

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.

A number of studies have examined the role of vitamin D in reproductive processes and disorders of pregnancy such as gestational diabetes mellitus (GDM). Although observational studies have linked maternal vitamin D deficiency with a plethora of adverse pregnancy outcomes including GDM, intervention trials generally do not support the use of vitamin D supplementation for GDM prevention or management. This narrative review provides an up-to-date overview and critical appraisal of randomised controlled trials (RCTs) to describe the current state of knowledge regarding the efficacy of vitamin D supplementation for preventing and/or managing GDM. Overall, although RCT data indicates a potential benefit of vitamin D in maternal glycaemic control, results are highly disparate and the data published to date have not conclusively established the efficacy of vitamin D in GDM prevention. There are, however, several limitations within the existing literature, including some considerable challenges that are unique to vitamin D trials, which should be carefully considered in the interpretation of the evidence and design of future studies. For now, many unanswered questions remain, and there is still a need for adequately powered and well-designed trials before routine supplementation can be recommended in the context of GDM.

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 (p = 0.002 and β = 18.06, p = 0.02, respectively), including after adjustment for maternal covariates including age, body mass index (BMI) and ethnicity (all p ≤ 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.

Vitamin D-binding protein (VDBP), the main carrier of vitamin D, has recently been implicated in reproductive health and pregnancy outcomes including endometriosis, polycystic ovary syndrome (PCOS), pre-eclampsia, and gestational diabetes mellitus (GDM). Improved methods for measuring VDBP and an increased understanding of its role in biological processes have led to a number of newly published studies exploring VDBP in the context of pregnancy. Here, we synthesize the available evidence regarding the role of VDBP in reproductive health and pregnancy, and we highlight areas requiring further study. Overall, low levels of maternal serum VDBP concentrations have been associated with infertility, endometriosis, PCOS and spontaneous miscarriage, as well as adverse pregnancy outcomes including GDM, pre-eclampsia, preterm birth and fetal growth restriction. However, increased VDBP concentration in cervicovaginal fluid has been linked to unexplained recurrent pregnancy loss and premature rupture of membranes. Some genetic variants of VDBP have also been associated with these adverse outcomes. Further studies using more accurate VDBP assays and accounting for ethnic variation and potential confounders are needed to clarify whether VDBP is associated with reproductive health and pregnancy outcomes, and the mechanisms underlying these relationships.

Objective: To compare cardiometabolic risk factors including cytokine and adipokine concentrations between individuals with and without back pain.Methods: In 62 overweight/obese adults (BMI ≥ 25 kg/m2; 23F/39M), we collected data on: self-reported back pain; anthropometry [BMI, waist circumference, body composition (dual energy X-ray absorptiometry—DEXA)]; metabolic parameters [fasting glucose; insulin sensitivity (hyperinsulinaemic-euglycaemic clamps)]; cardiovascular parameters (blood pressure, lipids); serum inflammation markers [high-sensitivity C-reactive protein (hsCRP; immunoturbidimetric-assay), tumor necrosis factor-alpha (TNF-α), interleukin (IL)-6, and IL-10 (multiplex-assay)]; and adipokines [leptin, adipsin, resistin, and adiponectin (multiplex-assay)].Results: Participants who reported having back pain in the past month (n = 24; 39%) had higher BMI (mean ± SD = 33.8 ± 6.3 vs. 30.2 ± 4.1 kg/m2, p = 0.008), fat-mass (39.9 ± 12.3 vs. 33.9 ± 9.8%, p = 0.04), and waist circumference (109.6 ± 16.8 vs. 101.0 ± 9.3 cm, p = 0.01) compared to those without back pain (n = 38; 61%). No differences were observed in cardiometabolic parameters, inflammatory markers, or adiponectin or resistin concentrations. Those reporting back pain had higher adipsin concentrations compared to those without back pain [median (IQR) = 744 (472–2,804) vs. 721 (515–867) ng/ml, p = 0.03], with a trend for higher leptin [5.5 (1.5–24.3) vs. 2.3 (1.5–6.7) ng/ml, p = 0.05], both of which persisted after adjustment for age and sex. Adipsin remained associated with back pain independently of adiposity (BMI, waist, fat-mass, or total %body fat; all p ≤ 0.03).Conclusions: Greater obesity, and higher adipsin and leptin concentrations were observed in those who reported back pain in the past month compared to those without back pain, and adipsin was associated with back pain independently of adiposity. Larger studies are needed to determine if adipsin could be a novel therapeutic target for prevention and/or treatment of back pain.

Type 2 diabetes mellitus (T2DM) is a complex chronic disease affecting over 400 million people worldwide. Managing T2DM and its associated complications in individual patient consultations poses substantial challenges to physicians due to limited time and resources and lack of access to multidisciplinary teams. Shared medical appointments (SMAs) are consecutive medical consultations provided by a physician in a group setting, where integrated medical care and patient education are delivered in a single session. SMAs allow physicians to deliver the same level of care to multiple patients at the same time, thereby maximizing available resources. However, the effectiveness and practicality of SMAs in the management of T2DM remains unknown. This narrative review summarizes current and emerging evidence regarding the effectiveness of SMAs in improving clinical outcomes in patients with T2DM, as well as whether SMAs are associated with reduced costs and improved diabetes-related behavioral and lifestyle changes. An extensive literature search was conducted on major electronic databases including PubMed and Google Scholar using keywords, including SMAs, group visits, and T2DM to identify all studies of SMAs in patients with T2DM. Studies in type 1 diabetes or mixed or unspecified populations were excluded, as well as studies where SMAs did not involve a physician since these do not meet the classical definition of a SMA. Nineteen studies were identified and are included in this review. Overall, current evidence suggests that SMAs delivered regularly over time may be effective in improving glycemic outcomes, diabetes knowledge, and some diabetes-related behaviors. However, the main limitation of existing studies was the paucity of comparisons with standard care which limits the ability to draw conclusions regarding whether SMAs are superior to standard care in T2DM management. Moreover, the small number of studies and substantial heterogeneity in study designs, populations, and interventions creates difficulties in establishing the practicality and efficiency of SMAs in the clinical care setting. We conclude that there remains a need for larger studies to identify populations who may or may not benefit from the SMA model of care and to clarify the potential benefits and barriers to implementing SMAs into routine diabetes care.

Neurological, neurodegenerative, and psychiatric disorders represent a serious burden because of their increasing prevalence, risk of disability, and the lack of effective causal/disease-modifying treatments. There is a growing body of evidence indicating potentially favourable effects of carnosine, which is an over-the-counter food supplement, in peripheral tissues. Although most studies to date have focused on the role of carnosine in metabolic and cardiovascular disorders, the physiological presence of this di-peptide and its analogues in the brain together with their ability to cross the blood-brain barrier as well as evidence from in vitro, animal, and human studies suggest carnosine as a promising therapeutic target in brain disorders. In this review, we aim to provide a comprehensive overview of the role of carnosine in neurological, neurodevelopmental, neurodegenerative, and psychiatric disorders, summarizing current evidence from cell, animal, and human cross-sectional, longitudinal studies, and randomized controlled trials.

Nutritional status during pregnancy can have a significant impact on maternal and neonatal health outcomes. Requirements for macronutrients such as energy and protein increase during pregnancy to maintain maternal homeostasis while supporting foetal growth. Energy restriction can limit gestational weight gain in women with obesity; however, there is insufficient evidence to support energy restriction during pregnancy. In undernourished women, balanced energy/protein supplementation may increase birthweight whereas high protein supplementation could have adverse effects on foetal growth. Modulating carbohydrate intake via a reduced glycaemic index or glycaemic load diet may prevent gestational diabetes and large-for-gestational-age infants. Certain micronutrients are also vital for improving pregnancy outcomes, including folic acid to prevent neural tube defects and iodine to prevent cretinism. Newly published studies support the use of calcium supplementation to prevent hypertensive disorders of pregnancy, particularly in women at high risk or with low dietary calcium intake. Although gaps in knowledge remain, research linking nutrition during pregnancy to maternofoetal outcomes has made dramatic advances over the last few years. In this review, we provide an overview of the most recent evidence pertaining to macronutrient and micronutrient requirements during pregnancy, the risks and consequences of deficiencies and the effects of supplementation on pregnancy outcomes.

Introduction The extraskeletal role of vitamin D is being increasingly recognised. This has important clinical implications, as vitamin D deficiency has reached epidemic proportions worldwide. Vitamin D has proposed anti-inflammatory properties, yet the role of vitamin D supplementation in reducing inflammation remains largely unknown. The purpose of this review is to investigate the impact of vitamin D supplementation on inflammation, and to identify relevant knowledge gaps in the field.Methods and analysis Medline, CINAHL, EMBASE and All EBM will be systematically searched for randomised controlled trials (RCTs) and systematic reviews of RCTs, comparing vitamin D supplementation with placebo, usual care or other pharmacological or non-pharmacological interventions. One reviewer will assess articles for eligibility according to prespecified selection criteria, after which 2 independent reviewers will perform data extraction and quality appraisal. Meta-analyses will be conducted where appropriate.Ethics and dissemination Formal ethical approval is not required as no primary data is collected. This systematic review will identify potential clinical implications of vitamin D deficiency and supplementation, and will be disseminated through a peer-reviewed publication and at conference meetings, to inform future research on the efficacy of vitamin D supplementation for inflammation and inflammatory diseases.PROSPERO registration number CRD42016037104.

Adipokines play an important role in the regulation of glucose metabolism. We have previously shown that carnosine supplementation in overweight or obese non-diabetic individuals improves glucose metabolism but does not change adiponectin concentrations. However, its effect on other adipokines has not been investigated. Herein we further determined the effect of carnosine supplementation on serum adipsin, resistin and leptin. Twenty-two overweight or obese otherwise healthy adults were randomly assigned to receive either 2 g of carnosine (n = 13) or identically looking placebo (n = 9) for 12 weeks. Serum adipsin, leptin and resistin were analyzed using a bead-based multiplex assay. Carnosine supplementation decreased serum resistin concentrations compared to placebo (mean change from baseline: −35 ± 83 carnosine vs. 35 ± 55 ng/mL placebo, p = 0.04). There was a trend for a reduction in serum leptin concentrations after carnosine supplementation (−76 ± 165 ng/mL carnosine vs. 20 ± 28 ng/mL placebo, p = 0.06). The changes in leptin and resistin concentrations were inversely related to the change in concentration for urinary carnosine (r = −0.72, p = 0.0002; r = −0.67, p = 0.0009, respectively), carnosine-propanal (r = −0.56, p = 0.005; r = −0.63, p = 0.001, respectively) and carnosine-propanol (r = −0.61, p = 0.002; r = −0.60, p = 0.002, respectively). There were no differences between groups in change in adipsin concentrations. Our findings show carnosine supplementation may normalize some, but not all, of the serum adipokine concentrations involved in glucose metabolism, in overweight and obese individuals. Further clinical trials with larger samples are needed to confirm these results.

Vitamin D has been suggested to play a role in glucose metabolism. However, previous findings are contradictory and mechanistic pathways remain unclear. We examined the relationship between plasma 25-hydroxyvitamin D (25(OH)D), insulin sensitivity, and insulin signaling in skeletal muscle and adipose tissue. Seventeen healthy adults (Body mass index: 26 ± 4; Age: 30 ± 12 years) underwent a hyperinsulinemic-euglycemic clamp, and resting skeletal muscle and adipose tissue biopsies. In this cohort, the plasma 25(OH)D concentration was not associated with insulin sensitivity (r = 0.19, p = 0.56). However, higher plasma 25(OH)D concentrations correlated with lower phosphorylation of glycogen synthase kinase-3 (GSK-3) αSer21 and βSer9 in skeletal muscle (r = −0.66, p = 0.015 and r = −0.53, p = 0.06, respectively) and higher GSK-3 αSer21 and βSer9 phosphorylation in adipose tissue (r = 0.82, p < 0.01 and r = 0.62, p = 0.042, respectively). Furthermore, higher plasma 25(OH)D concentrations were associated with greater phosphorylation of both protein kinase-B (AktSer473) (r = 0.78, p < 0.001) and insulin receptor substrate-1 (IRS-1Ser312) (r = 0.71, p = 0.01) in adipose tissue. No associations were found between plasma 25(OH)D concentration and IRS-1Tyr612 phosphorylation in skeletal muscle and adipose tissue. The divergent findings between muscle and adipose tissue with regard to the association between 25(OH)D and insulin signaling proteins may suggest a tissue-specific interaction with varying effects on glucose homeostasis. Further research is required to elucidate the physiological relevance of 25(OH)D in each tissue.