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Aim: Metabolic comorbidities such as obesity type 2 diabetes, insulin resistance, glucose intolerance, dyslipidemia are the major contributors for lower life expectancy and reduced patient compliance during antipsychotic therapy in patients with severe mental illnesses such as schizophrenia, bipolar disorder, and depression. TRPM8 activation by menthol is also reported to alleviate high fat diet-induced obesity in mice. Additionally, this TRPM8 activation leads to increase in gene expression of thermogenic genes in white adipocytes and dietary menthol was found to increase browning of WAT along with improved glucose utilization. Therefore, we aimed to evaluate the plausible role of TRPM8 channels in olanzapine-induced metabolic alterations in female balb/c mice., Methods: 6 weeks olanzapine (6 mg kg -1 , per oral) model was used in female balb/c mice. Pharmacological manipulation of TRPM8 channel was done using menthol and N-(3-aminopropyl)-2-[(3-methylphenyl)methoxy]-N-(2-thienylmethyl)-benzamide (AMTB), the agonist and antagonist respectively., Key Results: Menthol co-treatment for six weeks prevented olanzapine-induced metabolic alterations such as weight gain, increased food intake, decreased energy expenditure, adiposity, liver lipid accumulation, systemic inflammation and insulin resistance. Although no significant change in TRPM8 mRNA expression was found in the hypothalamus, however, some of the protective effects of menthol were absent in presence of AMTB indicating possible involvement of TRPM8 channels., Conclusion: Our results suggest possible therapeutic implications of menthol in the management of antipsychotic-induced weight gain and other metabolic alterations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Introduction: Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) has been introduced as a superior term to describe steatosis on a background of metabolic dysregulation and is slated to become the leading cause of HCC worldwide, as the incidence of metabolic comorbidities is increasing. As such, MASLD has evolved into an important public health issue, potentially leading to higher rates of liver mortality and end-stage liver disease. To this end, understanding the association between MASLD and HCC may allow for the identification of better interventions and novel therapeutic strategies., Areas Covered: The authors provide a review of current knowledge on HCC development among patients with MASLD, with insights into molecular pathways and current and future therapeutic strategies., Expert Opinion: MASLD has a strong association with the risk of HCC development, as metabolic comorbidities induce dysregulation in molecular pathways, leading to insulin-resistance, oxidative stress, and chronic inflammation, thus causing progression to cirrhosis and eventually to HCC. Therapeutic strategies focused on reducing diabetes-associated complications, as well as the prevalence of obesity and smoking can improve patient outcomes and reduce HCC incidence. Future studies on the molecular background of metabolic alterations may help devise new therapeutic approaches aiming to improve the current management of MASLD-HCC.

This document updates the "Clinical practice guidelines for the prevention, diagnosis and treatment of obesity" issued by the Nutrition Committee of the Argentine Pediatric Society, published in Archivos Argentinos de Pediatría in 2011. Obesity has a multifactorial etiology. It is recommended to diagnose it taking into account anthropometry, personal and family history, and clinical data that indicate complications (sleep apnea, elevated alanine transaminase and/or glycemia, and other components of the metabolic syndrome). It is proposed to know the risks and management of the hospitalized patient with obesity. This document reinforces the role of a healthy lifestyle as the main therapeutic strategy, recognizing the possibility of other treatments with very precise indications (pharmacological and surgical). Considering that obesity is a chronic disease, access to treatment must be guaranteed and patient follow-up must be promoted through the intervention of an interdisciplinary team., (Sociedad Argentina de Pediatría.)

The microbiota in humans consists of trillions of microorganisms that are involved in the regulation of the gastrointestinal tract and immune and metabolic homeostasis. The gut microbiota (GM) has a prominent impact on the pathogenesis of metabolic syndrome (MetS). This process is reciprocal, constituting a crosstalk process between the GM and MetS. In this review, GM directly or indirectly inducing MetS via the host-microbial metabolic axis has been systematically reviewed. Additionally, the specifically altered GM in MetS are detailed in this review. Moreover, short-chain fatty acids (SCFAs), as unique gut microbial metabolites, have a remarkable effect on MetS, and the role of SCFAs in MetS-related diseases is highlighted to supplement the gaps in this area. Finally, the existing therapeutics are outlined, and the superiority and shortcomings of different therapeutic approaches are discussed, in hopes that this review can contribute to the development of potential treatment strategies., (© The Author(s) 2024. Published by Oxford University Press on behalf of the International Life Sciences Institute. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Metabolic syndrome is a significant risk factor for poor graft outcomes in kidney transplant (KT) patients. However, the effects of variability in metabolic parameters on graft outcomes in KT patients have not been completely elucidated. A total of 852 KT patients were included from the Korean Organ Transplantation Registry. The study exposure was variability in body mass index (BMI) or other metabolic parameters measured at 6 months, 1 year, and 2 years after KT. Patients were classified into tertiles according to the degree of variability. The primary outcome was a composite of adverse kidney outcomes, such as death-censored graft loss or ≥ 30% decline in estimated glomerular filtration rate. The adverse kidney outcomes occurred in 73 (8.6%) participants. The high-BMI variability group had a higher risk for adverse kidney outcomes compared to the low-variability group. High variabilities in triglyceride, fasting blood glucose, and systolic blood pressure were also associated with adverse kidney outcomes. Furthermore, high variability in metabolic syndrome-related composite indices, such as the triglyceride and glucose index and metabolic variability scores, showed a higher risk for adverse kidney outcomes. In conclusion, high variability in metabolic parameters could be associated with an increased risk of adverse kidney outcome in KT patients., (© 2024. The Author(s).)

Phenolic acids, essential compounds in whole grains, are renowned for their health-enhancing antioxidant and anti-inflammatory properties. Variations in concentration, particularly of hydroxybenzoic and hydroxycinnamic acids, are observed among grain types. Their antiobesity and antidiabetes effects are linked to their modulation of key signaling pathways like AMPK and PI3K, crucial for metabolic regulation and the body's response to inflammation and oxidative stress. Processing methods significantly influence phenolic acid content and bioavailability in whole grains. Thermal techniques like boiling, baking, or roasting can degrade these compounds, with loss influenced by processing conditions. Nonthermal methods such as germination, fermentation, or their combination, can protect or enhance phenolic acid content under ideal conditions. Novel nonthermal approaches like ultrahigh pressure (UHP), irradiation, and pulsed electric fields (PEF) show promise in preserving these compounds. Further research is needed to fully comprehend the impact mechanisms of these innovative methods on the nutritional and sensory attributes of cereals.

The aim of this study was to assess the sleep status of middle-aged and elderly adults in Bengbu City, Anhui Province, China, to identify the major dietary patterns, and to analyze the association of different sleep duration and dietary patterns with metabolic syndrome (MetS) and its related influencing factors, as well as to explore the predictive value of sleep duration and dietary patterns. A cross-sectional analysis was performed utilizing data collected from the Community-based Cardiovascular and Health Promotion Study 2019 (COCHPS 2019) conducted in Bengbu. The definition of MetS adhered to the criteria of Guidelines for the Prevention and Treatment of Dyslipidemia in Chinese Adults (2016 Revision). Dietary information was obtained using the Food Frequency Questionnaire (FFQ) to assess dietary intake over the past year. Principal component analysis (PCA) was performed to identify dominant dietary patterns. A logistic regression model was developed to analyze the associations among sleep duration, dietary patterns, and MetS, and a decision tree (DT) model was developed to compare factors affecting MetS and screen people at high risk for MetS. The prevalence of MetS was 13.4% among the 9132 middle-aged and elderly residents over 45 years of age included in COCHPS 2019. Participants were divided into short (< 6 h/d), normal (6-8 h/d), and long (> 8 h/d) groups based on their daily sleep duration. Three dietary patterns were identified by PCA, the fruit-milk pattern, the tubers-meat pattern, and the vegetable-cereal pattern. After adjusting for covariables, logistic regression analysis showed that long sleep duration was significantly negatively associated with MetS. The fruit-milk and vegetable-cereal patterns were negatively associated with MetS, whereas the tubers-meat pattern was positively correlated with MetS. The results of the DT model analysis showed that the vegetable-cereal pattern is the most important factor impacting MetS, followed by marital status, the tubers-meat pattern, the fruit-milk pattern, exercise, sleep duration, and gender. The DT model also screened out five types of MetS high-risk groups. The results of our study indicate that normal sleep duration and consumption of either a fruit-milk or vegetable-cereal diet may lower the likelihood of developing MetS in middle-aged and elderly adults., (© 2024. The Author(s).)

Background: This study utilized large-scale population data from the National Health and Nutrition Examination Survey (NHANES) to elucidate the relationship between the Klotho protein and metabolic syndrome along with its components. We further investigated the possible mediating effect of inflammation on these relationships. Our objective was to identify biomarkers for risk stratification and potential therapeutic targets for metabolic syndrome., Methods: This study enrolled 13,119 participants aged 40-79 years, spanning five NHANES cycles from 2007 to 2016, with complete information on metabolic syndrome and the Klotho protein. The definition of metabolic syndrome followed the criteria of the National Cholesterol Education Program-Adult Treatment Panel III. Survey-weighted logistic regression and subgroup analysis were used to explore the associations between serum Klotho protein levels and metabolic syndrome, along with its components. Mediation analysis was performed to investigate the mediating effects of inflammation-related markers, including white blood cells, neutrophils, lymphocytes, monocytes, the neutrophil-to-lymphocyte ratio (NLR), the platelet-to-lymphocyte ratio (PLR), the systemic immune-inflammation index (SII) and the monocyte-to-HDL ratio (MHR), with the aim of elucidating how the Klotho protein influences the onset and progression of metabolic syndrome., Results: The study participants had an average age of 56.06 years (95% CI: 55.76-56.37), with a Klotho protein concentration of 798.10 pg/ml (95% CI: 656.50-980.50) and a 43.77% prevalence of metabolic syndrome (n = 5742). In the crude model, Klotho was negatively correlated with metabolic syndrome and its components, including central obesity, hypertension, and hypertriglyceridemia. After adjusting for all confounding factors, Klotho was demonstrated to be negatively associated only with metabolic syndrome (OR: 0.82, 95% CI: 0.70-0.97), hypertension (OR: 0.83, 95% CI: 0.70-0.98), and hypertriglyceridemia (OR: 0.78, 95% CI: 0.67-0.91). Subgroup and interaction analyses revealed significant interactions between age, sex, race/ethnicity, body mass index, and Klotho. Additionally, mediation analysis demonstrated that leukocytes, neutrophils and monocytes accounted for 34.78%, 31.91% and 7.13%, respectively, of the associations between Klotho and metabolic syndrome., Conclusion: The serum concentration of Klotho protein was negatively associated with metabolic syndrome, with the relationship being partly mediated by systemic immune inflammation. The findings of this research revealed that the Klotho protein may be a valuable biomarker for risk stratification and a potential therapeutic target for metabolic syndrome., (© 2024. The Author(s).)

Background: We evaluated the influence of subclinical hypothyroidism (SCH) on insulin resistance (IR), cardiometabolic risk, and obesity in childbearing-age women without diabetes., Methods: This cross-sectional investigation included 282 women, aged 18 to 35 years, from rural and suburban Sri Lanka. Anthropometric and biochemical parameters, including IR and lipid/thyroid profiles, were recorded. Data were compared between SCH and euthyroidism (EU) for controls (normal weight) and cases (overweight/obese)., Results: The overall rates of SCH, EU, IR, and metabolic syndrome (MetS) were 40.42%, 59.57%, 73.40%, and 24.46%, respectively. Both controls and cases included individuals with SCH; overall, 168 participants (59.57%) had EU, while 114 (40.42%) exhibited SCH. IR was significantly associated with SCH in both weight groups (P<0.05). Among those with SCH, the odds ratios (ORs) for IR were >2 (95% confidence interval [CI], 0.45 to 3.87) in controls and >6 (95% CI, 3.52 to 8.41) in cases. Similarly, the ORs for MetS were >1 (95% CI, 0.38 to 4.16) in controls and >11 (95% CI, 8.73 to 15.01) in cases. Dyslipidemia and hypertriglyceridemia were significantly more prevalent in the SCH group (P<0.05). Women with SCH exhibited higher mean values for all obesity indices compared to their EU counterparts, surpassing normal thresholds (P<0.05). Among obesity measures, visceral adiposity index (VAI) demonstrated the highest area under the curve and sensitivity for assessing SCH and cardiovascular disease (CVD) risk., Conclusion: SCH must be identified and managed in young women to help prevent diabetes and cardiometabolic disorders. VAI may aid in precisely detecting SCH and CVD.

Objective: To explore the association between the Oxidative Balance Score (OBS), which represents the balance of multiple oxidative stress-related dietary and lifestyle exposures, and the risk of metabolic syndrome (MetS)., Methods: A population-based cross-sectional study design was adopted and 16,850 participants in NHANES database were included in the statistics analysis stage. The OBS was constructed by combining information from 20 a priori selected pro- and antioxidant factors. Weighted logistic regression and restricted cubic splines (RCS) were used to estimate the association between OBS and MetS., Results: Participants in the highest OBS quartile, indicating low oxidative stress (OS) levels, exhibited a significantly lower risk of MetS (odds Ratio [OR] = 0.55, 95% confidence Interval [CI]: 0.47-0.64) compared to the lowest quartile. Specifically, higher OBS was inversely associated with abdominal obesity (OR = 0.61, 95% CI: 0.54-0.69), hypertension (OR = 0.69, 95% CI: 0.58-0.83), elevated triglycerides (OR = 0.68, 95% CI: 0.57-0.82), low high-density lipoprotein cholesterol (HDL-C) levels (OR = 0.60, 95% CI: 0.50-0.70) and fasting blood glucose (FBG) levels (OR = 0.74, 95% CI: 0.62-0.88). The observed inverse association between OBS and hypertension or FBG levels appeared to primarily influenced by BMI. The association between dietary OBS intervals and elevated FBG levels was not statistically significant in men, whereas the risk was lower by 25% in women., Conclusions: A higher OBS, representing a balance of multiple oxidative stress-related dietary and lifestyle exposures, is associated with a lower risk of MetS. Therefore, adhering to an antioxidant diet and lifestyle may help prevent the occurrence of metabolic disorders., (© 2024. The Author(s).)

Heart failure is a multifactorial disease, the percentage of patients with heart failure caused by metabolic syndrome is increasing year by year. The effect of gut flora dysbiosis on metabolic syndrome and heart failure has received widespread attention in recent years. Drugs to treat the condition urgently need to be discovered. C20DM, as a precursor compound of ginsenoside, is a small molecule compound obtained by biosynthetic means and is not available in natural products. In this project, we found that C20DM could improve the diversity of gut flora and elevate the expression of intestinal tight junction proteins-Occludin, Claudin, ZO-1, which inhibited the activity of the TLR4-MyD88-NF-kB pathway, and as a result, reduced myocardial inflammation and slowed down heart failure in metabolic syndrome mice. In conclusion, our study suggests that C20DM can treat heart failure by regulating gut flora, and it may be a candidate drug for treating metabolic syndrome-induced heart failure., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Insulin resistance is a hallmark feature of metabolic syndrome (MetSyn). The triglyceride-glucose (TyG) index is considered a reliable surrogate measure of insulin resistance. However, the efficacy of the TyG-index combined with adiposity measures for identifying MetSyn in U.S. adults is unknown., Methods: In the present cross-sectional study, 2746 men and women from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) with physical and laboratory characteristics were included. Predictive powers (estimated by the area under the curve of receiver operating characteristic [ROC-AUC]) of TyG-index combined with adiposity for MetSyn were compared with other traditional surrogate markers of insulin resistance including the TyG index, homeostatic assessment of insulin resistance (HOMA-IR), 1/fasting insulin, and quantitative insulin sensitivity check index (QUICKI)., Results: Predictive power of TyG-WHtR (ROC-AUC: 0.875) for MetSyn was highest, followed by TyG-WC (0.866), TyG-BMI (0.845), TyG index (0.832), HOMA-IR (0.820), QUICKI (0.820) and 1/fasting insulin (0.786). TyG-WHtR and TyG-WC showed significantly higher ROC-AUCs compared with TyG-index, HOMA-IR, 1/fasting insulin, and QUICKI (p ≤ 0.001)., Conclusions: TyG index combined with adiposity metrics is more effective in predicting MetSyn when compared to insulin resistance surrogates (TyG index, HOMA-IR, 1/fasting insulin, and QUICKI) which has been widely used in large cohort observational studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Asia Oceania Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.)

Carboxylesterase 2 (CES2) is expressed mainly in liver and intestine, but most abundantly in intestine. It hydrolyzes carboxylester, thioester, and amide bonds in many exogenous and endogenous compounds, including lipids. CES2 therefore not only plays an important role in the metabolism of many (pro-)drugs, toxins and pesticides, directly influencing pharmacology and toxicology in humans, but it is also involved in energy homeostasis, affecting lipid and glucose metabolism. In this study we investigated the pharmacological and physiological functions of CES2. We constructed Ces2 cluster knockout mice lacking all eight Ces2 genes (Ces2 -/- strain) as well as humanized hepatic or intestinal CES2 transgenic strains in this Ces2 -/- background. We showed that oral availability and tissue disposition of capecitabine were drastically increased in Ces2 -/- mice, and tissue-specifically decreased by intestinal and hepatic human CES2 (hCES2) activity. The metabolism of the chemotherapeutic agent vinorelbine was strongly reduced in Ces2 -/- mice, but only marginally rescued by hCES2 expression. On the other hand, Ces2 -/- mice exhibited fatty liver, adipositis, hypercholesterolemia and diminished glucose tolerance and insulin sensitivity, but without body mass changes. Paradoxically, hepatic hCES2 expression rescued these metabolic phenotypes but increased liver size, adipose tissue mass and overall body weight, suggesting a "healthy" obesity phenotype. In contrast, intestinal hCES2 expression efficiently rescued all phenotypes, and even improved some parameters, including body weight, relative to the wild-type baseline values. Our results suggest that the induction of intestinal hCES2 may combat most, if not all, of the adverse effects of metabolic syndrome. These CES2 mouse models will provide powerful preclinical tools to enhance drug development, increase physiological insights, and explore potential solutions for metabolic syndrome-associated disorders., (© 2024. The Author(s).)

The objective of our study is to measure perirenal fat thickness using MRI in individuals with steatotic liver disease and investigate the relationship between perirenal fat thickness and metabolic syndrome. This retrospective study included consecutive patients with steatotic liver disease who underwent magnetic resonance imaging-proton density fat fraction from October 2018 to February 2020. Among them, patients with crossed fused kidneys or who underwent nephrectomy were excluded. The metabolic abnormalities were reviewed; presence of hypertension, type 2 diabetes, abdominal circumference, triglyceride, and high-density lipoprotein. Perirenal fat was measured in four directions in both kidneys and the total sum of them was calculated. A total of 250 patients (140 males and 110 females) were included. Perirenal fat thickness showed a moderate correlation with waist circumference, creatinine, and hepatic fat fraction (all p < 0.001). Perirenal fat thickness was significantly higher in patients with metabolic syndrome than in patients without (76.8 mm vs. 65.1 mm, p = 0.004). In multivariable regression analysis, the group with high perirenal fat thickness had as significantly higher odd ratio of 2.71 compared to the low group. The perirenal fat thickness is independently associated with metabolic syndrome in patients with steatotic liver disease., (© 2024. The Author(s).)

Previous studies have pointed to a potential link between Obstructive Sleep Apnea (OSA) and gastrointestinal diseases, suggesting that this relationship might be influenced by the presence of Metabolic Syndrome. However, the exact role of these factors in determining gastrointestinal diseases has not been thoroughly explored. In our study, we utilized data from the Genome-wide Association Studies (GWAS) database, focusing on OSA, metabolic syndrome characteristics such as Body Mass Index (BMI), waist circumference, triglycerides, cholesterol, hypertension, type 2 diabetes, and common gastrointestinal diseases including chronic gastritis, gastric ulcers, irritable bowel syndrome, colorectal cancer, inflammatory bowel disease, cholecystitis, nonalcoholic fatty liver, and dyspepsia. By applying Single-variable and Multi-variable Mendelian randomization methods, we aimed to assess the correlation between OSA and gastrointestinal diseases and investigate whether this correlation is influenced by metabolic syndrome. Our findings revealed a strong association between OSA and an increased risk of chronic gastritis, gastric ulcers, inflammatory bowel disease, and nonalcoholic fatty liver disease. No significant connections were found with irritable bowel syndrome, colorectal cancer, cholecystitis, or dyspepsia. Additionally, OSA was linked to metabolic syndrome traits like BMI, waist circumference, triglycerides, hypertension, and type 2 diabetes. Further analysis showed that BMI, triglycerides, and hypertension were causally related to inflammatory bowel disease; BMI, waist circumference, hypertension, and type 2 diabetes to nonalcoholic fatty liver disease; and triglycerides, hypertension, and type 2 diabetes to chronic gastritis. The multivariable analysis indicated that hypertension mediates the relationship between OSA and chronic gastritis; BMI, triglycerides, and hypertension mediate the link between OSA and inflammatory bowel disease; and waist circumference mediates the connection between OSA and nonalcoholic fatty liver disease. To wrap up, this finding helps us understand how these issues might be related and stresses the role of metabolic syndrome in preventing them, which could lessen their effect on health., (© 2024. The Author(s).)

Heart failure with preserved ejection fraction (HFpEF) constitutes more than half of all HF cases, yet evidence-based therapies remain lacking due to limited understanding of its underlying pathological mechanisms. Our study aimed to uncover early pathological mechanisms in HFpEF by exposing mice to dietary conditions resembling a Western diet-rich in fats, salt, and low in fiber-alongside excess mineralocorticoids to replicate significant aspects of human HFpEF. Echocardiography was performed at both 3-week and 6-week intervals post-challenge, revealing cardiac alterations as early as 3-weeks. While ejection fraction remained preserved, mice exhibited signs of diastolic dysfunction, reduced stroke volume, and left atrial enlargement. Additionally, changes in pulmonary flow velocities were noted by the 3-week mark, suggesting elevated pulmonary pressure. Extracardiac comorbidities included organ congestion, increased adiposity, impaired glucose tolerance, and hypercholesterolemia. Molecular analyses unveiled evidence of low-grade inflammation, oxidative stress, and impaired NO-cGMP-PKG signaling, contributing to the observed decrease in titin phosphorylation, thereby impacting myocardial stiffness. Additionally, impaired NO signaling might have influenced the alterations observed in coronary flow reserve. Moreover, dysregulation of calcium signaling in cardiomyocytes and reduced SR load were observed. Interestingly, elevated phosphorylation of cMyBP-C was linked to preserved ejection fraction despite reduced SR load. We also observed intestinal atrophy, possibly due to low dietary fiber intake and diminished gut perfusion, potentially contributing to systemic low-grade inflammation. These findings reveal how excess mineralocorticoids-salt-induced hypertension, and dietary factors, like high-fat and low-fiber intake, contribute to cardiac dysfunction and metabolic disturbances, offering insights into early HFpEF pathology in this model.

Aims: Endometriosis (EM) and metabolic disorders are frequent health problems among reproductive-aged women worldwide. Cardio-metabolic risk profile of women with EM is not well understood. We aimed to investigate the cardio-metabolic risk profile of Iranian reproductive-aged women with EM., Methods: This study included 976 female participants aged 20-45 years of Tehran Lipid and Glucose Study. Endometriosis was diagnosed based on the participants' self-reported previous diagnosis of EM, which was confirmed by reviewing the relevant medical documentation. All biochemical measures (low-density lipoprotein cholesterol [LDL], high-density lipoprotein cholesterol [HDL], triglycerides [TG], and fasting blood glucose concentrations [FBG]) and measurement of systolic blood pressure (SBP) and diastolic blood pressure (DBP) and anthropometric parameters were performed according to the standard protocol of TLGS. Logistic regression analysis was performed to estimate the odds ratio of cardio-metabolic disease., Results: Of the 976 study participants, 161 individuals (16.5%) had a confirmed diagnosis of endometriosis. There were no significant differences in the median of metabolic parameters among women with and without endometriosis (p > 0.05). The prevalence of metabolic syndrome was significantly higher in women with EM group compared to the non-EM group (21.9% vs. 14.9%). The presence of endometriosis was associated with an increased odds of metabolic syndrome (adjusted odds ratio 1.99 [95% CI 1.20-3.30]; p = 0.007). And endometriosis significantly increased odds of low HDL by 2.07 (1.02-4.20); after adjustment, it still remained significant (p = 0.03). Endometriosis also increased odds of high waist circumstance significantly (1.58 [1.06-2.37]; p = 0.02)., Conclusions: Women with endometriosis may be at an increased risk of developing metabolic syndrome, high waist circumstance and low HDL compared to their counterparts without the condition. Given the potential cardio-metabolic implications, healthcare providers should consider assessing the metabolic profile of women diagnosed with endometriosis., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Individuals diagnosed with Chronic Obstructive Pulmonary Disease (COPD) are exposed to an increased risk of metabolic syndrome (MetS), which negatively affects their health outcomes and quality of life. Lifestyle interventions have shown promise in managing MetS. This study outlines the protocol for a web-based multimodal self-care program, Digital Metabolic Rehabilitation, for managing MetS in patients with COPD. The Digital Metabolic Rehabilitation is a single-arm pilot trial that integrates the Canadian Health Advanced by Nutrition and Graded Exercise (CHANGE) Program and a web-based wellness platform. The web-based wellness platform employed in this study is My Viva Plan (MVP)®, which integrates a holistic, multicomponent approach to promote wellness. The intervention will primarily focus on lifestyle changes for patients with COPD. Over 6 months, participants will use the web-based wellness platform and engage in weekly online support group sessions. Fifty patients diagnosed with stage I-II COPD and MetS will participate. Blood tests, anthropometrics, body composition, physical function, muscle strength, physical activity, energy metabolism, quality of life and mental health will be assessed at baseline, 3, and 6 months. The Digital Metabolic Rehabilitation program aims to explore whether a multimodal integrative intervention delivered through a web-based wellness platform can be implemented by patients with COPD with MetS. By combining the expertise of the CHANGE Program with the digital delivery format, the intervention seeks to enhance self-monitoring and foster better self-management practices. The protocol outlines a novel and potentially impactful intervention for managing MetS in patients with COPD., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: CMP has previously received honoraria and/or paid consultancy from Almased. NM has since become an employee of My Viva Plan. BRS receives a Mitacs Accelerate program fellowship partially funded by My Viva Inc. AR, LC, MFP, DK – no conflicts of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Alcohol-related liver disease and metabolic-dysfunction-associated steatotic liver disease are the most common causes of chronic liver disease. Globally, alcohol intake, and metabolic syndrome driven by excessive caloric intake and sedentary lifestyle have steadily increased over the past decades. Given the high prevalence rates of both excessive alcohol consumption and components of metabolic syndrome, both can frequently coexist in the same individuals and impact their lives. In this article, we review the impact of alcohol and metabolic syndrome on liver-related outcomes., Competing Interests: Disclosure Dr Z. M. Younossi is a consultant to BMS, GSK, Cymabay, Ipsen, Abbott, Novo Nordisk, Madrigal, Merck, Siemens, and Intercept. Other authors have no conflict of interest to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Little is known about the cardiorespiratory fitness (CRF)-cardiometabolic risk relationship in Latin American pediatric populations across different age/sex groups, especially when considering the potential effects of adiposity on the association. We evaluated cross-sectional associations between VO 2max and cardiometabolic risk variables (CMRV), and verified whether the associations were independent of adiposity markers in school-aged children and adolescents from Cali, Colombia., Methods: The sample consisted of 1206 children aged 5-17 years. CMRV were fasting glucose, HDL and LDL cholesterol, triglycerides, systolic, and diastolic pressure. Logistic regressions were conducted for associations of age/sex-specific tertiles of VO 2max with age/sex-specific highest tertiles of CMRV (except HDL-C, lowest tertile) and a CMR cluster (> 2 CMRV in extreme tertiles), adjusting for socioeconomic stratum, and adiposity markers (BMI, body fat percentage, and waist circumference)., Results: Overweight/obesity ranged from 15% to 18% with no difference by sex. In children aged 5-11 years, high VO 2max (highest tertile vs. lowest) was inversely associated with the CMR cluster [Odds ratio (95% confidence interval): 0.18 (0.06-0.47), p < 0.05] independently of adjustment for any adiposity marker in boys but not in girls. In the age group of 12-17 years, there were initially significant VO 2max - CMR cluster and VO 2max - CMRV associations but attenuated by adiposity adjustment. In girls, high VO 2max was inversely associated with high systolic blood pressure regardless of adjustment for adiposity markers., Conclusion: VO 2max is inversely associated with cardiometabolic risk, but adiposity influences the association. The adiposity-independent association among younger boys requires further research. Interventions to tackle cardiometabolic risk in childhood may primarily focus on reducing excess adiposity, and secondarily on improvement of CRF., (© 2024 Wiley Periodicals LLC.)

Insulin resistance, defined as an impaired biological response to insulin stimulation in target tissues, arises most frequently in the presence of central obesity. Although obesity is generally associated with increased bone mass, recent data challenge this view and, if complicated by T2DM, obese patients are at high risk for fragility fractures. IR may play a key role in this increased fracture risk through effects on bone quality rather than bone quantity. Further understanding of the mechanisms and approaches to prevent osteoporotic fractures in IR-related diseases is needed., Clinical Relevance: The dramatic increase in obesity and metabolic syndrome (MetS) over the last half-century has led to a worldwide epidemic of type 2 diabetes mellitus (T2DM) as well as in the incidence of insulin resistance (IR). IR is defined as an impaired biological response to insulin stimulation in target tissues and is primarily related to the liver, muscle, and adipose tissue. The most frequent underlying cause is central obesity, and it is known that excess abdominal adipose tissue secretes increased amounts of free fatty acids, which directly affects insulin signalling, reduces glucose uptake in muscle, and triggers excessive triglyceride synthesis and gluconeogenesis in the liver. When pancreatic β cells are unable to secrete the higher levels of insulin needed, T2DM, the main complication of IR, occurs., Observations: Although obesity is generally associated with increased bone mass, recent data challenge this view and highlight the multifaceted nature of the obesity-bone relationship. Patients with T2DM are at significant risk for well-known complications of diabetes, including retinopathy, nephropathy, macrovascular disease, and neuropathy, but it is clear that they are also at high risk for fragility fractures. Moreover, recent data provide strong evidence that IR may key role in the increased fracture risk observed in both obesity and T2DM., Conclusions: In this concise review article, the role of IR in increased risk of osteoporotic fractures in MetS, obesity, and T2DM is discussed and summarised, including consideration of the need for fracture risk assessment as a 'preventive measure', especially in patients with T2DM and chronic MetS with abdominal obesity. Personalised and targeted diagnostic and therapeutic approaches to prevent osteoporotic fractures in IR-related diseases are needed and could make significant contributions to health outcomes., (© 2024. International Osteoporosis Foundation and Bone Health and Osteoporosis Foundation.)

Purpose: To investigate the association between metabolic syndrome and perirenal fat stranding (PRFS), which is defined as linear or curvilinear soft tissue densities in the perirenal fat on computed tomography (CT)., Material and Methods: Adults who had abdominal CT for health screening at a single institution between October 2022 and March 2023 were included retrospectively. Two radiologists assessed the extent of PRFS for each CT and graded it as absent, mild/moderate, and severe. Logistic regression analyses were used to investigate the associations between PRFS and metabolic syndrome-related factors, as well as age and gender., Results: Among 701 participants (mean age, 56.8 years ± 9.7; 336 women and 365 men), 87 (12.4%) had mild (n = 80) or moderate (n = 7) PRFS. None had severe PRFS. The presence of PRFS was independently associated with higher body mass index (odds ratio [OR], 2.561 and 9.842 for overweight and obese, respectively; p ≤ 0.001), elevated blood pressure with or without anti-hypertensive medication (OR, 2.232; p = 0.015), anti-diabetic medication (OR, 3.129; p < 0.001), and lipid-lowering medication (OR, 1.919; p = 0.019), older age (OR, 4.545 and 9.109 for 50-59 years and ≥ 60 years, respectively; p ≤ 0.002), and male gender (OR, 10.065; p < 0.001). Sixty three of 87 (72.4%) participants with PRFS had metabolic syndrome, while 265 of 614 (43.2%) participants without PRFS did (p < 0.001)., Conclusion: Incidental mild or moderate PRFS may be associated with the presence of metabolic syndrome or related disorders in otherwise healthy adults., Competing Interests: Declarations Conflict of interests The authors have no relevant financial or non-financial interests to disclose. Ethical approval Institutional Review Board approval was obtained and the requirement for written informed consent was waived., (© 2024. Italian Society of Medical Radiology.)

Metabolic syndrome (MetS) increases the risk of coronary artery disease, but effects of this condition on the working myocardium remain to be fully elucidated. In the present study we evaluated the consequences of diet-induced metabolic disorders on cardiac function and myocyte performance using female mice fed with Western diet. Animals maintained on regular chow were used as control (Ctrl). Mice on the Western diet (WesD) had increased body weight, impaired glucose metabolism, preserved diastolic and systolic function, but increased left ventricular (LV) mass, with respect to Ctrl animals. Moreover, WesD mice had reduced heart rate variability (HRV), indicative of altered cardiac sympathovagal balance. Myocytes from WesD mice had increased volume, enhanced cell mechanics, and faster kinetics of contraction and relaxation. Moreover, levels of cAMP and protein kinase A (PKA) activity were enhanced in WesD myocytes, and interventions aimed at stabilizing cAMP/PKA abrogated functional differences between Ctrl and WesD cells. Interestingly, in vivo β-adrenergic receptor (β-AR) blockade normalized the mechanical properties of WesD myocytes and revealed defective cardiac function in WesD mice, with respect to Ctrl. Collectively, these results indicate that metabolic disorders induced by Western diet enhance the cAMP/PKA signaling pathway, a possible adaptation required to maintain cardiac function., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Introduction: The cumulative impact of metabolic syndrome (MetS) components on micro- and macrovascular disease in metabolic dysfunction-associated steatotic liver disease (MASLD) is unclear. We aimed to determine whether the number of the MetS components increases the risk of micro- and macrovascular disease in patients with MASLD., Methods: We performed a retrospective cohort study of electronic medical records using the TriNetX network, a global federated database. The exposure arm was patients with hepatic steatosis (defined via International Classification of Diseases, 10th Revision coding, or modified hepatic steatosis index), and ≥1 MetS components (obesity/central adiposity, insulin resistance, hypertension, or dyslipidaemia), compared with a reference arm of adults without any MetS components or hepatic steatosis. Our propensity score matched (1:1) for confounders with 5 years of follow-up. Primary outcomes included microvascular (peripheral neuropathy, retinopathy, and nephropathy) and macrovascular (cardiovascular events, cerebrovascular accidents, and peripheral vascular disease) disease. Secondary analyses assessed the impact of additional MetS components on these outcomes, as well as the impact of sex., Results: MASLD, defined by hepatic steatosis and insulin resistance (n = 15 937), carried the highest risk of microvascular disease (HR 13.93 (95% CI 8.55-22.68)), whilst MASLD, defined by hepatic steatosis and hypertension (n = 53 028), carried the highest risk of macrovascular disease (7.23 (6.45-8.13)). MASLD with all MetS components carried greatest risk of both micro- (31.20 (28.88-33.70) (n = 462 789)) and macrovascular (8.04 (7.33-8.82) (n = 336 010)) disease., Conclusion: We demonstrate a differential effect of MetS components on micro- and macrovascular disease risk in patients with MASLD, with a cumulative impact of multiple MetS on overall risk. The impact of MetS components was most pronounced in women. Aggressive metabolic risk factor management is critical for prevention of micro- and macrovascular complications., (© 2024 The Author(s). Liver International published by John Wiley & Sons Ltd.)

Aim: Poor cardiorespiratory fitness has been suggested to increase the risk of chronic diseases in obesity. We investigated the ability of key variables from cardiopulmonary exercise testing (CPET) to predict all-cause mortality in an obese cohort., Methods: The sample included 469 participants of both sexes (mean age 40 ± 13 years) who underwent a CPET for clinical reasons between 1 March 2009 and 1 December 2023. All-cause mortality was the prognostic endpoint. A receiver operating characteristic analysis was performed to establish optimal cut-points for CPET variables. Kaplan-Meier and Cox regression analyses were used to determine the association between CPET variables and all-cause mortality., Results: There were 46 deaths during a mean follow-up period of 69 ± 48 months, resulting in an annual mortality rate of 2%. Despite the sample being made up of mostly women (70%), there were more deaths in men (18 vs. 6%, p < 0.001).The optimal thresholds for discrimination of survival were as follows: (a) peak oxygen uptake (pVO 2 ) ≤16 mL/kg/min; (b) minute ventilation/carbon dioxide production (V E /VCO 2 ) slope ≥31; (c) ventilatory power ≤5.8 mmHg; and (d) circulatory power ≤2980 mmHg/mL O 2 /min. Kaplan-Meier survival plots revealed a significant positive association between lower pVO 2 , circulatory power and ventilatory power values and survival (log-rank, p < 0.001) and higher mortality for men than women. Adjusted Cox regression models showed that a pVO 2 ≤16 mL/kg/min had a 20-fold higher risk of mortality when compared with >16 mL/kg/min., Conclusion: Given the strong association of VO 2 , ventilatory efficiency, circulatory and ventilatory power with all-cause mortality, our findings support the notion that poorer cardiorespiratory fitness is associated with a poor prognosis in patients with obesity., (© 2024 John Wiley & Sons Ltd.)

Objectives: To assess the association between overactive bladder syndrome (OAB) and the metabolic syndrome (MetS)., Patients and Methods: A population-based study was conducted to compare OAB patients with age-, sex- and ethnicity-matched control subjects regarding the prevalence of the parameters of the MetS, with respect to obesity, hyperlipidemia, hypertension and diabetes mellitus. The characteristics of the OAB population were assessed. Adjusted odds ratios (OR) were calculated by logistic regression., Results: 110 024 OAB patients and 220 455 controls. were identified. OAB was associated with a higher prevalence of MetS (35.4% vs. 27.5%, p < 0.001). The fully adjusted OR for MetS in patients with OAB compared to controls was 1.44; 95% confidence interval (CI) 1.42-1.46; p < 0.001. Among metabolic parameters, obesity was found to be the strongest factor associated with OAB (OR 1.55, 95% CI 1.53-1.58, p < 0.001), and higher high-density lipoprotein cholesterole levels (>50) had a protective effect on the risk of OAB (OR 0.75, 95% CI 0.73-0.76, p < 0.001)., Conclusions: Data from this cohort suggest that OAB is positively associated with MetS. Clinicians approaching patients with OAB should be aware of this association. A multimodal treatment focusing on the MetS may be considered in these patients., (© 2024 Wiley Periodicals LLC.)

Garlic exhibits hypolipidemic, hypoglycemic, and cardiovascular benefits. The inconsistent results of garlic preparations on adipogenesis have caused more confusion in the public and academia. The compounds responsible for the anti-adipogenesis effect of garlic remain unknown. The present study aimed to verify the real anti-adipogenesis and anti-obesity component in garlic and explored its possible effects in metabolic syndrome. We verified the real anti-adipogenesis and anti-obesity components of garlic in 3T3-L1 preadipocytes and a 10-week-high fat diet (HFD)-induced obese mice. In vitro, two water-soluble and four typical lipid-soluble compounds of garlic were tested for their anti-adipogenesis. Then, the water-soluble compound, alliin, and two processing methods produced garlic oils, were evaluated in vivo study. Mice received oral administration of alliin (25 mg/kg) and garlic oils (15 mg/kg) daily for 8 weeks. Serum lipids, parameters of obesity, and indicators involved in regulating glycolipid metabolism were examined. Our findings confirmed that both water-soluble and lipid-soluble organosulfur compounds of garlic contributed to garlic's anti-adipogenesis effect, in which water-soluble sulfides, especially alliin, exhibited greater potency. Alliin possessed potent effects of anti-obesity and improvement in glucose and lipid metabolism in HFD-induced obese mice. Alliin mediated these effects partly attributed to its modulation of enzymatic activities within glycolipid metabolism and activating PPARγ signaling pathway. In contrast to odorous lipid-soluble sulfides, alliin is odorless, stable, and safe, and is an ideal nutraceutical or even medicinal candidates for the treatment of metabolic diseases. Alliin could be used to standardize the quality of garlic products., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Bipolar disorder (BD) is a complex and severe mental illness that causes significant suffering to patients. In addition to the burden of depressive and manic symptoms, patients with BD are at an increased risk for metabolic syndrome (MetS). MetS includes factors associated with an increased risk of atherosclerotic cardiovascular disease (CVD) and type 2 diabetes mellitus (T2DM), which may increase the mortality rate of patients with BD. Several studies have suggested a link between BD and MetS, which may be explained at an epigenetic level. We have focused on epigenetic mechanisms to review the causes of metabolic risk in BD., (© 2024 World Obesity Federation.)

Background: Metabolic syndrome and diabetes in obese individuals are strong risk factors for development of inflammatory bowel disease (IBD) and colorectal cancer. The pathogenic mechanisms of low-grade metabolic inflammation, including chronic hyperglycemic stress, in disrupting gut homeostasis are poorly understood. In this study, we sought to understand the impact of a hyperglycemic environment on intestinal barrier integrity and the protective effects of small molecular weight (35 kDa) hyaluronan on epithelial barrier function., Methods: Intestinal organoids derived from mouse colon were grown in normal glucose media (5 mM) or high glucose media (25 mM) to study the impact of hyperglycemic stress on the intestinal barrier. Additionally, organoids were pretreated with 35 kDa hyaluronan (HA35) to investigate the effect of hyaluronan on epithelial barrier under high glucose stress. Immunoblotting as well as confocal imaging was used to understand changes in barrier proteins, quantitative as well as spatial distribution, respectively. Alterations in barrier function were measured using trans-epithelial electrical resistance and fluorescein isothiocyanate flux assays. Untargeted proteomics analysis was performed to elucidate mechanisms by which HA35 exerts a protective effect on the barrier. Intestinal organoids derived from receptor knockout mice specific to various HA receptors were utilized to understand the role of HA receptors in barrier protection under high glucose conditions., Results: We found that high glucose stress decreased the protein expression as well as spatial distribution of two key barrier proteins, zona occludens-1 (ZO-1) and occludin. HA35 prevented the degradation or loss of ZO-1 and maintained the spatial distribution of both ZO-1 and occludin under hyperglycemic stress. Functionally, we also observed a protective effect of HA35 on the epithelial barrier under high glucose conditions. We found that HA receptor, layilin, was involved in preventing barrier protein loss (ZO-1) as well as maintaining spatial distribution of ZO-1 and occludin. Additionally, proteomics analysis showed that cell death and survival was the primary pathway upregulated in organoids treated with HA35 under high glucose stress. We found that XIAP associated factor 1 (Xaf1) was modulated by HA35 thereby regulating apoptotic cell death in the intestinal organoid system. Finally, we observed that spatial organization of both focal adhesion kinase (FAK) as well as F-actin was mediated by HA35 via layilin., Conclusion: Our results highlight the impact of hyperglycemic stress on the intestinal barrier function. This is of clinical relevance, as impaired barrier function has been observed in individuals with metabolic syndrome. Additionally, we demonstrate barrier protective effects of HA35 through its receptor layilin and modulation of cellular apoptosis under high glucose stress., Competing Interests: Conflict of interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Objective: The complement system has been associated with the etiopathogenesis of rheumatoid arthritis (RA). Insulin resistance (IR) and metabolic syndrome (MetS) are prevalent among patients with RA. The aim of this study was to explore the relationship between a comprehensive evaluation of the complement system and IR, as well as MetS, in patients with RA., Methods: A total of 339 nondiabetic patients with RA were recruited. Functional assays of the 3 complement pathways were assessed. Additionally, serum levels of the following individual components of the complement system were measured: C1q (classical); lectin (lectin); C2, C4, and C4b (classical lectin); factor D and properdin (alternative); C3 and C3a (common); C5, C5a, and C9 (terminal); as well as the factor I and C1 inhibitor regulators. IR and β cell function indices were calculated using the homeostatic model assessment. Criteria for MetS were applied. Multivariable linear regression analysis was performed to investigate the association between the complement system and IR in patients with RA., Results: Many elements of the upstream and common complement pathways, but not the functional tests of the 3 routes, correlated positively with higher levels of IR and β cell function. However, after multivariable adjustment for factors associated with IR, these relationships were lost. Conversely, the presence of MetS in patients with RA maintained a relationship with higher levels of C1q, C4, C3, properdin, and factor I after adjusting for confounders., Conclusion: There is a positive correlation between the complement system and MetS among nondiabetic patients with RA. This association is independent of traditional IR factors., (Copyright © 2024 by the Journal of Rheumatology.)

Introduction: Loss-of-control (LOC) eating, or the subjective experience of being unable to stop eating, is a hallmark feature of binge-eating episodes, which are also characterized by consuming an unusually large amount of food. However, regardless of the size of eating episode, LOC-eating may be a risk factor for adverse health outcomes. This systematic review and meta-analysis comprehensively examine the relationship of LOC-eating with cardiometabolic health components and inflammatory markers., Methods: Search procedures were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guidelines in six electronic databases. Studies of adult or youth samples published in English from the year 2000 onward were included. Given heterogeneity in age groups and adjustment for body mass index across studies, these factors were included as meta-regression moderators., Results: Fifty-eight studies were identified through the literature search. Among individuals with (versus without) LOC-eating, relative risk ratios provided evidence of a greater relative risk for metabolic syndrome, hypertension, and dyslipidemia; standardized mean differences also provided evidence of higher waist circumference and impaired levels of fasting plasma glucose, high-density lipoprotein (HDL)-cholesterol, and triglycerides, but not blood pressure. Age group did not impact cardiometabolic health components. Body mass index differences moderated the effect on waist circumference. A narrative review of inflammatory markers revealed mixed findings linking inflammatory markers to LOC-eating., Discussion: Overall, evidence for the relationship between LOC-eating and impaired cardiometabolic health underscores LOC-eating as an important early intervention target for prevention of serious adverse health outcomes., (© 2024 The Author(s). Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

Introduction: Sodium-glucose cotransporter-2 inhibitors are antidiabetic medications that have been shown to decrease cardiovascular events and heart failure-related mortality in clinical studies. We attempt to examine the complex interplay between metabolic syndrome and the sodium-glucose cotransporter-2 inhibitor canagliflozin (CAN) in a clinically relevant model of chronic myocardial ischemia., Methods: Twenty-one Yorkshire swine were fed a high-fat diet starting at 6 weeks of age to induce metabolic syndrome. At 11 weeks, all underwent placement of an ameroid constrictor around the left circumflex coronary artery to induce chronic myocardial ischemia. After 2 weeks, swine received either control (CON) (n = 11) or CAN 300 mg by mouth daily (n = 10) for 5 weeks, whereupon all underwent terminal harvest., Results: There was a significant increase in cardiac output and heart rate with a decrease in pulse pressure in the CAN group compared with CON (all P values < .05). The CAN group had a significant increase in capillary density (P = .02). There was no change in myocardial perfusion or arteriolar density. CAN induced a significant increase in markers of angiogenesis, including Phospho-endothelial nitric oxide synthase, Endothelial nitric oxide synthase, vascular endothelial growth factor receptor-1, heat shock protein 70, and extracellular signal-regulated kinases (all P values < .05), plausibly resulting in capillary angiogenesis., Conclusions: CAN treatment leads to a significant increase in capillary density and augmented cardiac function in a swine model of chronic myocardial ischemia in the setting of metabolic syndrome. This work further elucidates the mechanism of sodium-glucose cotransporter-2 inhibitors in patients with cardiac disease; however, more studies are needed to determine if this increase in capillary density plays a role in the improvements seen in clinical studies., Competing Interests: Conflict of Interest Statement The authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handing or reviewing manuscripts for which they may have a conflict of interest. The editor and reviewers of this article have no conflicts of interest., (Copyright © 2024 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.)

Background and Aims: The purpose of this study was to investigate the combined impact of variations in physical activity (PA) and sitting time (ST) on the risk of developing metabolic syndrome (MetS). Methods: This study was conducted on a cohort of adults from the general population, aged 40-69 years, who participated in the KOGES community-based cohort study over a span of 10 years. Changes in PA and ST were assessed using the results from PA questionnaires completed during baseline and follow-up surveys. The diagnosis of MetS was determined according to the criteria established by the International Diabetes Federation. To evaluate the combined effect of PA and ST changes on the incidence of MetS, we calculated hazard ratios and 95% confidence intervals using a Cox proportional hazards regression model. Result: The incidence of MetS was reduced by 39% (HR = 0.61, 95% CI = 0.46-0.82) for increased ST/increased PA and 26% (HR = 0.74, 95% CI = 0.58-0.94) for decreased ST/increased PA, compared with increased ST/decreased PA, respectively. In addition, this study confirmed that the combined impact of changes in PA and ST, based on the domain of PA, on the incidence of MetS varied. Conclusion: Changes in ST and PA are associated with the risk of developing MetS. These findings lay the groundwork for further research on the relationship between changes in PA, ST, and the occurrence of diseases.

Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals with obesity, liver lesions in steatosis and steatohepatitis, and the intestinal lamina propria. LAMs can also emerge in the metabolically demanding microenvironment of certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, and self-renewal, and, ultimately, their acute and chronic functional impact on the development of metabolic diseases. Further studies need to clarify whether and under which circumstances LAMs drive disease progression or resolution and how their phenotype can be modulated to ameliorate metabolic disorders., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background and Aims: DXA-measured visceral adipose tissue (VAT DXA ) is associated with adverse cardiometabolic risk profiles in cross-sectional studies, but longitudinal associations have not been investigated. We examined the longitudinal associations of baseline and change in VAT DXA with future cardiometabolic risk in Australian participants of the Busselton Healthy Ageing study., Methods and Results: We studied 3569 participants (54.7% female, aged 46-70 years) with data on VAT DXA (GE Lunar Prodigy) and cardiometabolic risk factors at baseline and 6 years follow-up. The associations were examined using logistic and linear regression models, adjusting for baseline age and lifestyle factors. Mean baseline VAT DXA mass was 1653 ± 880 g and 855 ± 580 g, and mean change in VAT DXA +99 ± 500 g and +58 ± 312 g in males and females, respectively. Among all participants, 182 males (11.3%) and 197 females (10.1%) developed incident metabolic syndrome (MetS). Baseline VAT DXA was associated with incident MetS with an adjusted odds ratio of 2.53 (95% CI: 2.03, 3.15) in males and 2.78 (2.30, 3.36) in females per SD increment. There was a graded positive association between longitudinal change in VAT DXA and MetS severity z score in both sexes adjusted for baseline VAT (P < 0.001). All the above associations remained significant after further adjustment for baseline or change in BMI, waist circumference or waist-to-hip ratio in respective models (all P < 0.001)., Conclusions: Higher baseline and greater longitudinal increase in VAT DXA are independently associated with raised cardiometabolic risk over time, and may serve as useful markers for identifying middle-aged individuals at increased cardiometabolic risk., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Protease-activated receptor-1 (PAR1) has emerged as an important link between coagulation and the complications of obesity including metabolic dysfunction-associated steatotic liver disease (MASLD). PAR1 is expressed by various cells and cleaved by different proteases to generate unique tethered agonists that activate distinct signaling pathways. Mice expressing PAR1 with an R41Q mutation have disabled canonical thrombin-mediated signaling, whereas R46Q mice express PAR1 resistant to noncanonical signaling by activated protein C., Methods: Mice with whole body and hepatocyte-selective PAR1 deficiency as well as PAR1 R41Q and R46Q mice were fed a high-fat diet (HFD) to induce MASLD., Results: HFD-fed R41Q mice displayed reduced hepatic steatosis and liver/body weight ratio. In contrast, HFD-fed R46Q mice displayed increased relative liver weight and hepatic steatosis alongside increased serum alanine aminotransferase activity. Surprisingly, despite the distinct impact of PAR1 mutations on steatosis, selective deletion of PAR1 in hepatocytes had no impact. To evaluate a viable PAR1-targeted approach, mice with HFD-induced obesity were treated with the allosteric PAR1 modulator NRD-21, which inhibits canonical PAR1 inflammatory signaling but promotes PAR1 protective, noncanonical anti-inflammatory signaling. NRD-21 treatment reduced plasma tumor necrosis factor-alpha, serum alanine aminotransferase activity, hepatic steatosis, and insulin resistance (Homeostatic Model Assessment for Insulin Resistance) but increased plasma active glucagon-like peptide-1., Conclusion: The results suggest that nonhepatocellular canonical PAR1 cleavage drives MASLD in obese mice and provide translational proof-of-concept that selective pharmacologic modulation of PAR1 yields multiple metabolic benefits in experimental obesity., Competing Interests: Declaration of competing interests C.D. is Chief Strategy Officer and Chief Executive Officer at Function Therapeutics, which provided NRD-21 for these studies. Function Therapeutics did not provide financial support. Beyond research support noted in acknowledgments, no other authors have relevant conflicts of interests to disclose., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

The role of copper in the etiology of metabolic syndrome (MetS) is uncertain. We evaluated associations of plasma copper concentrations with MetS and its components in a cross-sectional study of 198 children ages 7-12 years and 378 adult parents from eight Mesoamerican countries. In children, the outcome was a metabolic risk score based on waist circumference, insulin resistance, mean arterial pressure (MAP), and blood lipids. In adults, we defined MetS per Adult Treatment Panel III criteria. Plasma copper was not significantly related to MetS in children or adults; however, children with copper above the median had a MAP score 0.04 (95% CI, 0.002, 0.08; P = 0.04) adjusted units higher and a HDL-cholesterol score 0.07 (95% CI, - 0.13, - 0.003; P = 0.04) adjusted units lower than those with lower copper concentrations. In adults, copper was positively related to abdominal obesity. Longitudinal studies to confirm the deleterious role of copper on MetS components are warranted., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Nutrition is largely affected in bipolar disorder (BD), however, there is a lack of understanding on the relationship between dietary categories, BD, and the prevalence of metabolic syndrome. The objective of this study is to examine dietary trends in BD and it is hypothesized that diets with increased consumption of seafood and high-fiber carbohydrates will be correlated to improved patient outcomes, and a lower frequency of metabolic syndrome., Methods: This retrospective cohort study includes two French cohorts. The primary cohort, FACE-BD, includes 268 stable BD patients. The second cohort, I-GIVE, includes healthy controls, both stable and acute BD and schizophrenia patients. Four dietary categories were assessed: meat, seafood, low-fiber and high-fiber carbohydrates. Dietary data from two food frequency questionnaires were normalized using min-max scaling and assessed using various statistical analyses., Results: In our primary cohort, the increased high-fiber carbohydrate consumption was correlated to lower prevalence of metabolic syndrome and improved mood. Low-fiber carbohydrate consumption is associated with higher BMI, while higher seafood consumption was correlated to improved mood and delayed age of onset. Results were not replicated in our secondary cohort., Limitations: Our populations were small and two different dietary questionnaires were used; thus, results were used to examine similarities in trends., Conclusions: Overall, various dietary trends were associated with metabolic syndrome, BMI, lactate, mood and age of onset. Improving our understanding of nutrition in BD can provide mechanistic insight, clinically relevant nutritional guidelines for precision medicine and ultimately improve the quality of lives for those with BD., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Aim: We aimed to investigate the impact of metabolic syndrome (MetS) on the outcomes of stroke patients with large-artery atherosclerosis who underwent reperfusion therapy., Methods: A retrospective analysis was carried out on patients receiving reperfusion therapy for atherothrombotic stroke between January 2019 and May 2021. MetS was diagnosed according to the AHA/NHLBI criteria. The primary outcome was the composite outcome of disability (modified Rankin Scale [mRS] score 3-5), death or stroke recurrence within 3 months of stroke onset. Secondary outcomes included disability and death within 3 months as well as hemorrhagic transformation (HT) and symptomatic intracranial hemorrhage (sICH) within 24 hours after reperfusion treatment. The independent association of MetS with the above outcomes and the highly correlated components of MetS was examined using binary logistic regression analysis., Results: A total of 174 patients were enrolled. MetS patients had a higher proportion of the composite outcome (p = 0.012), disability (p = 0.029) and HT (p = 0.049) than those without MetS, except for death (p = 0.375) and sICH (p = 0.306). Following adjustments, MetS remained independently associated with the composite outcome (adjusted OR, 3.011 [95 %CI 1.372-6.604]; p = 0.006) and disability (adjusted OR, 2.727 [95 %CI 1.220-6.098]; p = 0.015), but not HT (adjusted OR, 1.872 [95 %CI 0.854-4.104]; p = 0.117). Hypertriglyceridemia was remarkedly associated with the composite outcome (adjusted OR, 9.746 [95 % CI 2.402-39.536]; p = 0.001) and disability (adjusted OR, 6.966 [95 % CI 1.889-25.692]; p = 0.004)., Conclusion: MetS is independently associated with an increased risk of composite outcome and disability in patients with large-artery atherosclerosis stroke receiving reperfusion therapy, and hypertriglyceridemia is the main component that drives the effect of MetS on outcomes., Competing Interests: Declaration of competing interest The authors declare no conflict of interest in this work., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: As metabolic dysfunction-associated steatotic liver disease (MASLD) management extends into primary care, little is known about patterns of specialty referral for affected patients. We determined the proportion of primary care patients with MASLD that received a gastroenterology (GI) consultation and compared advanced fibrosis risk between patients with and without a referral., Methods: This retrospective study of electronic health record data from a primary care clinic included patients with MASLD, no competing chronic liver disease diagnoses, and no history of cirrhosis. Referral to GI for evaluation and management (E/M) any time after MASLD ascertainment was the outcome. Fibrosis-4 Index (FIB-4) scores were calculated, categorized by advanced fibrosis risk, and compared by receipt of a GI E/M referral. Logistic regression models were developed to determine the association of FIB-4 risk with receipt of a GI referral., Results: The cohort included 652 patients of which 12% had FIB-4 scores (≥2.67) at high-risk for advanced fibrosis. Overall, 31% of cohort patients received a GI referral for E/M. There was no difference in the proportion of patients with high (12% vs. 12%, p=0.952) risk FIB-4 scores by receipt of a GI E/M referral. In adjusted logistic regression models, high-risk FIB-4 scores (OR 1.01; 95% CI 0.59 - 1.71) were not associated with receipt of a referral., Conclusions: Only 30% of patients in this primary care MASLD cohort received a GI E/M referral during the study period, and those patients with a referral did not differ by FIB-4 advanced fibrosis risk., Competing Interests: Declaration of competing interest All authors report no conflicts of interest with this work., (Copyright © 2024 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Metabolic syndrome (MetS) is a prevalent public health problem. Uric acid (UA) is increased by MetS. We investigated whether administration of UA and 10% fructose (F) would accelerate MetS formation and we also determined the effects of irisin and exercise. We used seven groups of rats. Group 1 (control); group 2 (sham); group 3 (10% F); group 4 (1% UA); group 5 (2% UA); group 6 (10% F + 1% UA); and Group 7, (10% F + 2% UA). After induction of MetS (groups 3 -7), Group 3 was divided into three subgroups: 3A, no further treatment; 3B, irisin treatment; 3C, irisin treatment + exercise. Group 4, 1% UA, which was divided into three subgroups: 4A, no further treatment; 4B, irisin treatment; 4C, Irisin treatment + exercise. Group 5, 2% UA, which was divided into three subgroups: 5A, no further treatment; 5B, irisin treatment; 5C, irisin treatment + exercise. Group 6, 10% F + 1% UA, which was divided into three subgroups: 6A, no further treatment; 6B, irisin treatment; 6C, irisin treatment + exercise. Group 7, 10% F + 2% UA, which was divided into three subgroups: 7A, no further treatment; 7B, irisin treatment; 7C, irisin treatment + exercise., İrisin was administered 10 ng/kg irisin intraperitoneally on Monday, Wednesday, Friday, Sunday each week for 1 month. The exercise animals (in addition to irisin treatment) also were run on a treadmill for 45 min on Monday, Wednesday, Friday, Sunday each week for 1 month. The rats were sacrificed and samples of liver, heart, kidney, pancreas, skeletal muscles and blood were obtained. The amounts of adropin (ADR) and betatrophin in the tissue supernatant and blood were measured using an ELISA method. Immunohistochemistry was used to detect ADR and betatrophin expression in situ in tissue samples. The duration of these experiments varied from 3 and 10 weeks. The order of development of MetS was: group 7, 3 weeks; group 6, 4 weeks; group 5, 6 weeks; group 4, 7 weeks; group 3, 10 weeks. Kidney, liver, heart, pancreas and skeletal muscle tissues are sources of adropin and betatrophin. In these tissues and in the circulation, adropin was decreased significantly, while betatrophin was increased significantly due to MetS; irisin + exercise reversed this situation. We found that the best method for creating a MetS model was F + UA2 supplementation. Our method is rapid and simple. Irisin + exercise was best for preventing MetS.

Background: There is a growing body of evidence suggesting the association between psoriasis (PsO) and psoriatic arthritis (PsA) separately with metabolic syndrome (MS) in different populations. The literature is relatively scarce in terms of comparing the prevalence of MS in PsO and PsA with controls without systemic inflammatory diseases., Objective: We aimed to assess the prevalence of MS among patients with PsO, PsA, and a control group without systemic inflammatory disease, in addition to investigating the risks of MS occurrence and its different components in each group., Methods: This is a cross-sectional case-control study with three groups of patients: PsO, PsA, and control. The diagnosis of MS was defined according to the modified 2009 NCTEP ATP III criteria. Patients underwent thorough physical examination and fasting blood samples., Results: A total of 195 patients were included in this analysis (PsO = 50; PsA = 64, and controls = 81). The prevalence of MS in the control, PsO, and PsA groups was 37%, 56%, and 57.8%, respectively (p < 0.001). Waist circumference (p = 0.013) and arterial hypertension (p < 0.001) were the most significant components of MS in patients with PsO and PsA. Multivariate analysis confirmed an independent risk of MS in women, elderly patients, obese patients, patients with hyperglycemia, and patients with psoriasis, especially PsA (OR = 6.2 [CI 95% 2.4-16.2], p < 0.001)., Conclusion: MS is more prevalent in patients with PsA, which can be determined by the increase in inflammatory pathways., Competing Interests: The authors report no conflicts of interest involved in the production of this manuscript., (© 2024 Acioly et al.)

Benign prostatic hyperplasia (BPH), a common cause of lower urinary tract symptoms (LUTS), has been recently regarded as a metabolic disease. Metabolic syndrome (MetS) is a constellation of metabolic disarrangements, including insulin resistance, obesity, hypertension, and dyslipidemia, and it has been established that these components of MetS are important contributing factors exacerbating the degree of prostatic enlargement and bladder outlet obstruction among patients with BPH. Clinical and experimental studies demonstrated that many molecules, such as insulin, insulin-like growth factor 1 (IGF-1), androgen and estrogen, and adipokines, are involved in the overlapping pathogenesis of BPH and MetS, indicating that clinicians might be able to simultaneously alleviate or cure two diseases by choosing appropriate medications. This article aims to systematically review the pathophysiological aspect and traditional etiology and pathogenesis of BPH and discuss the intricate association between MetS and BPH from the molecular point of view, in an attempt to provide stronger evidence for better treatment of two diseases., Competing Interests: Declaration of competing interest No potential conflict of interest was reported by the authors., (Copyright © 2024. Published by Elsevier Inc.)

Background: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Serum uric acid (SUA), a product of purine metabolism, has been implicated in HF progression. However, the association between hyperuricaemia and the short-term readmission and mortality in patients with HF remains controversial., Methods: In this retrospective cohort study, we analysed data from a HF database specific to the Chinese population. The primary endpoint was short-term readmission or all-cause mortality within 90 days. Participants with HF were categorised into normouricaemia group (NUA) and hyperuricaemia group (HUA) based on a SUA threshold of 420 µmol/L. The association between SUA and primary endpoint was evaluated using Kaplan-Meier survival curves and Cox regression analysis., Results: Baseline characteristics revealed significant differences between NUA and HUA groups, with the latter exhibiting a higher prevalence of males, chronic kidney disease (CKD) and elevated levels of various biomarkers. During a 90-day follow-up, 493 (26.6%) participants reached the primary endpoint, with a higher incidence observed in the HUA group at 31.2%, compared with 20.1% in the NUA group. When a threshold effect was identified at 420 µmol/L, a non-linear association was observed between SUA and the primary endpoint. After adjusting for gender, age, New York Heart Association class, CKD, systolic blood pressure (SBP) and potassium, the HUA group exhibited a higher risk for the primary endpoint compared with the NUA group (HR: 1.40, 95% CI: 1.14 to 1.72, p=0.001). Additionally, the risk increased across quartiles of SUA (P for trend=0.002). Furthermore, stratified analyses indicated a stronger association in patients without CKD (P interaction=0.033)., Conclusion: Hyperuricaemia is independently associated with an increased risk of short-term readmission and mortality in patients with HF. Our findings suggest that monitoring and managing SUA could be crucial in improving patient with HF outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background & Aims: Given the technological advances in 3D smartphone (SP) anthropometry, this technique presents a unique opportunity to improve metabolic syndrome (MetS) screening through optimal waist circumference (WC) landmarking procedures. Thus, the purpose of this study was to evaluate the associations between individual MetS risk factors and nine independent WC sites collected using tape measurement or SP anthropometrics and to determine the differences in MetS severity and prevalence when using these different WC measurement locations., Methods: A total of 130 participants (F:74, M:56; age: 27.8 ± 11.1) completed this cross-sectional evaluation. Using traditional tape measurement, WC was measured at the lowest rib (WC Rib ), superior iliac crest (WC Iliac ), and between the WC Rib and WC Iliac (WC Mid ). Additionally, WC measurements were automated using a SP application at six sites along the torso. MetS risk factors were used to calculate MetS severity (MetS index ) and prevalence. Associations were evaluated using multiple linear regression, the effect of each WC site on MetS index was analyzed using mixed-models ANCOVA, and differences in MetS prevalence using WC Iliac as the current standard were determined using sensitivity, specificity, chi-squared tests, and odds ratios., Results: The reference SP-WC (SP Ref ) and WC Rib demonstrated the largest associations (all p < 0.001) with HDL cholesterol (SP Ref : -0.48; WC Rib : -0.49), systolic (SP Ref : 0.32; WC Rib : 0.30) and diastolic blood pressure (SP Ref : 0.34; WC Rib : 0.32), and fasting blood glucose (SP Ref : 0.38; WC Rib : 0.37). SP Ref and WC Rib were the only WC without significantly different MetS index ; yet demonstrated lower MetS index and sensitivity (SP Ref : 77.8 %; WC Rib : 74.1 %) relative to WC Iliac , the conventional (or standard) WC measure., Conclusions: Compared to the current standard, SP Ref and WC Rib protocols are more highly associated with individual MetS risk factors and produce different MetS index and diagnoses; highlighting the need for new MetS WC protocols. Given the surge in remote/mobile healthcare, SP Ref may be an alternative to traditional methods in this context but requires further investigation before implementation., Competing Interests: Declaration of competing interest The authors declare no conflicts of interest., (Copyright © 2024 European Society for Clinical Nutrition and Metabolism. Published by Elsevier Ltd. All rights reserved.)

While visceral fat measured by dual-energy X-ray absorptiometry (DXA) is accurate in identifying middle-aged people at increased cardiometabolic risk, consistent data for the elderly are still lacking. We aimed to investigate the association between DXA-derived visceral adipose tissue (VAT) and metabolic syndrome (MetS) and to establish optimal cutoffs for VAT to predict MetS in a low-income elderly Brazilian cohort. A total of 449 women and 258 men (≥65 years) from the community were enrolled in this study. Participants underwent clinical and laboratory evaluations, along with body composition analysis by Hologic Discovery A densitometer. VAT was measured in the android region of the DXA scan. MetS was diagnosed using NCEP-ATPIII criteria. Multivariate logistic regression analyzed the relationship between VAT and MetS. Receiver-operating characteristic (ROC) curve analysis evaluated VAT's predictive accuracy for MetS, with optimal cutoffs determined by Youden's test to balance sensitivity and specificity. Mean ages were 76.6 ± 4.7 years for men and 77.1 ± 4.9 years for women. Mean BMIs were 26.5 ± 3.8 kg/m 2 for men and 29.0 ± 5.2 kg/m 2 for women. One hundred and seventy-five (41.5 %) men and 274 (61 %) women had MetS. After adjustments for confounders, multivariate analysis showed that VAT was independently associated with MetS in both men (OR 1.41, 95%CI 1.15-1.72) and women (OR 1.33, 95%CI 1.16-1.54, per each 100 g increase). Optimal VAT cutoffs to predict MetS were 642.5 g for men (AUC = 0.740) and 600.5 g for women (AUC = 0.729). Subanalysis for non-overweight/non-obese subjects yielded lower VAT cutoffs. Thus, VAT measured by DXA was significantly associated with MetS in older adults, regardless of BMI, emphasizing the critical role of VAT in predicting MetS. Therefore, VAT by DXA holds promise for evaluating MetS risk in the elderly. Further longitudinal studies are needed to investigate VAT's impact on major cardiovascular event incidence in this demographic., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Recent studies have shown that both metabolic syndrome and circadian rhythm syndrome are firmly associated with the occurrence of cardiovascular disease (CVD), with insulin resistance playing a significant role. The estimated glucose disposal rate (eGDR) is considered to be a reliable surrogate marker for insulin resistance. However, the relationship between eGDR and CVD under different metabolic and circadian rhythm states has not been thoroughly studied, and large-scale prospective cohort studies are needed to clarify this relationship., Methods: This study is based on the China Health and Retirement Longitudinal Study (CHARLS), recruiting individuals aged 45 and above with complete eGDR data. The eGDR was calculated by the formula: eGDR(mg/kg/min) = 21.158 - (0.09 × WC) - (3.407 × hypertension) - (0.551 × HbA1c) [WC (cm), hypertension (yes = 1/no = 0), and HbA1c (%)] (Zabala et al. in Cardiovasc Diabetol 20(1):202; 2021).Participants were divided into four subgroups based on the quartiles (Q) of eGDR.The cumulative incidence rates and hazard ratios (HR) with 95% confidence intervals (CI) were calculated, with the lowest eGDR quartile (representing the highest degree of insulin resistance) as the reference. Participants were further divided into subgroups based on the diagnosis of Metabolic syndrome (MetS) or circadian syndrome (CircS) to explore the relationship between eGDR and CVD under different metabolic and circadian rhythm conditions. The dose-response relationship between eGDR and CVD incidence was investigated using a restricted cubic spline (RCS) based on a Cox regression model. Receiver operating characteristic (ROC) curves were generated to assess the predictive value of eGDR for CVD incidence. A clinical decision curve analysis (DCA) was also conducted to assess the clinical utility of the basic model., Results: 6507 participants were included, with a median age of 58 years [52 years, 64 years], and 55% were female. Over a median follow-up duration of 87 months, 679 first-episode CVD events were recorded, including heart disease and stroke. The RCS curves demonstrated a significant dose-response relationship between eGDR and the incidence of first-presentation CVD in different metabolic and circadian rhythm subgroups (all P-values < 0.001, non-linearity P > 0.05). eGDR exhibited a significant linear relationship with all outcomes (non-linearity P < 0.05). The Kaplan-Meier cumulative incidence curves showed that as eGDR levels increased, the cumulative incidence rates of first CVD, heart disease, and stroke gradually decreased from Q1 to Q4 groups. Significant differences were observed across all metabolic and circadian rhythm subgroups (log-rank test P < 0.001). Through the Cox proportional hazards model, we confirmed a significant association between baseline eGDR levels and first-onset CVD, heart disease, and stroke. Subgroup analyses indicated that the predictive ability of eGDR for CVD risk varied across different Body mass index (BMI) (P for interaction = 0.025) and age (P for interaction = 0.045) subgroups. Mediation analysis revealed that CircS partially mediated this association. Furthermore, time-dependent ROC curves demonstrated the potential of eGDR as a predictor of CVD risk, revealing possible differences in the model's application across different cardiovascular conditions., Conclusion: eGDR is an independent predictor of CVD risk, with lower eGDR levels being closely associated with a higher risk of CVD (including heart disease and stroke). In populations with MetS or CircS, the association between lower eGDR levels and increased risk is more pronounced., (© 2024. The Author(s).)

Rising global pediatric obesity rates, increase non-alcoholic fatty liver disease (NAFLD) and metabolic syndrome (MetS) prevalence, with MetS being a NAFLD risk factor. NAFLD can be asymptomatic, with liver function tests insensitive to mild disease, and liver biopsy, risking complications. Thus, we investigated multiparametric MRI (mpMRI) metrics of liver fat (proton density fat fraction, PDFF) and disease activity (fibro-inflammation; iron-corrected T1, cT1), in a Hispanic pre-pubertal pediatric cohort, with increased risk of NAFLD. Pre-pubertal boys (n = 81) of varying Body-Mass Index (BMI) were recruited in Mexico City. Most children (81%) had normal liver transaminase levels, 38% had high BMI, and 14% had ≥ 3 MetS risk factors. Applying mpMRI thresholds, 12%, 7% and 4% of the cohort had NAFLD, NASH and high-risk NASH respectively. Participants with ≥ 3 MetS risk factors had higher cT1 (834 ms vs. 737 ms, p = 0.004) and PDFF (8.7% vs. 2.2%, p < 0.001) compared to those without risk factors. Those with elevated cT1 tended to have high BMI and high insulin (p = 0.005), HOMA-IR (p = 0.005) and leptin (p < 0.001). The significant association of increased risk of MetS with abnormal mpMRI, particularly cT1, proposes the potential of using mpMRI for routine pediatric NAFLD screening of high-risk (high BMI, high MetS risk score) populations., (© 2024. The Author(s).)

Introduction: Metabolic syndrome (MetS) manifests resembling pathophysiological mechanisms with Parkinson's disease (PD). Current research on the overall population has emphasized MetS as a freestanding risk factor for cognition. This research aims to explore the impact of MetS on cognition in Parkinson's patients., Method: We involved subjects identified as having early-stage PD patients. The MetS was diagnosed dependent on parameters overviewed in the National Cholesterol Education Program's Adult Treatment Panel III. The clinical severity and stages in patients with PD were dependent on the disease rating scales. The cognition was evaluated by the Turkısh version of the Montreal Cognitive Assessment Scale (MoCA-TR). The cases were categorized according to cognitive failure: mild cognitive impairment in PD (PD-MCI), and PD dementia (PDD)., Results: Metabolic syndrome was present in 39.6% of the participants. 22.0% of patients were in the normal cognition, 29.1% in the PD-MCI group, and 48.9% in the PD-D group. The cognitive scores in patients with MetS is considerably lower than MetS negative group. A statistically notable inverse association was detected between fasting blood glucose levels and the visual-spatial/executive functions, naming, language, and orientation scores. The multivariate logistic regression analysis showed individuals with MetS were found to have an 11.308 times higher risk of PD-D (odds ratio [OR]: 11,3, 95% confidence interval [CI]: 1.61-79.2 )., Conclusion: We discerned the occurrence of MetS in PD raises the possibility of advancing dementia. This suggests that considering MetS in this patient group could contribute to the effective management of dementia., (© 2024. Fondazione Società Italiana di Neurologia.)

Background/objectives: The Planetary Health Diet Index (PHDI) was recently introduced to assess adherence to the EAT-Lance recommendations. In this study, we aimed to evaluate the relationship between PHDI and metabolic syndrome (MS)., Subjects/methods: We used the data of 6465 participants from the PERSIAN cohort study at Mashhad University of Medical Sciences, Mashhad, Iran. Diet was assessed using a 130-item Food Frequency Questionnaire (FFQ). The PHDI comprises sixteen components and is scored between 0 and 150 points. We first assessed the validity and reliability of the PHDI for this population. We used regression logistic models to assess the relationships between PHDI and MS and its related indicators., Results: The average PHDI score was 52.3 ± 9. The Cronbach's alpha value was 0.53. After controlling for age and sex, the PHDI was positively related to the Diet Quality Index-International (DQI-I) and was negatively related to carbon and water footprints (p < 0.001). PHDI quartile was negatively associated with MS, hypo-HDL cholesterolemia, and abdominal obesity after controlling for confounders (P < 0.05)., Conclusion: The validity and reliability of the PHDI were found to be satisfactory for the Iranian population we studied. Our results showed that a higher PHDI was potentially related to a reduced likelihood of MS, hypo-HDL cholesterolemia, and abdominal obesity., (© 2024. The Author(s).)