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Purpose of Review: Due to technical requirements and high cost, equilibrium dialysis-free testosterone (T) measurements are not commonly available in clinical practice. Clinicians rely on calculated free T (cFT) as a proxy. This review discusses using free T as a second-line assessment, highlighting its relevance in preventing misdiagnosis and overtreatment of male hypogonadism., Recent Findings: While there is consensus on measuring total T - comprising sex hormone-binding globulin (SHBG)-bound, albumin-bound, and free T - as a first step in diagnosing male hypogonadism, evidence confirms that aging and conditions like obesity influence both total T and SHBG levels. Furthermore, low free T has been associated with symptoms of androgen deficiency, even in men with normal total T. Clinicians should, however, be aware of limitations of free T calculations, particularly the lack of standardization. Recent developments include establishing age-stratified free T reference ranges measured by equilibrium dialysis., Summary: Free T remains a subject of longstanding controversy. Factors such as age and obesity can alter total T and SHBG levels. Free T serves as a second-line indicator of androgen exposure, taking SHBG fluctuations into account. Given that commonly used free T calculators only provide approximations of free T, there is a need to further standardize free T calculators., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aim: Elevated C-reactive protein (CRP), a marker of inflammation, is common in many chronic conditions. We aimed to examine to what extent elevated CRP in chronic conditions could be explained by concurrent adiposity., Materials and Methods: This cross-sectional study analysed UK Biobank data on 10 chronic conditions reported at baseline. Linear regression models explored the extent to which CRP concentrations were elevated in each condition, unadjusted; adjusted for sociodemographic confounders and lifestyle and body mass index (BMI) in a series of models; or adjusted for BMI and waist circumference together or for adiposity alone., Results: After exclusion of participants with a potential acute infection at baseline, we tested the association in 292 772 UK Biobank participants. Linear regression showed that elevated CRP concentration was associated with all included conditions. After adjustment for sociodemographic confounders, lifestyle and BMI, chronic kidney disease, heart failure, liver disease, psoriasis, rheumatoid arthritis and chronic obstructive pulmonary disease were still associated with elevated CRP. In contrast, the association between prevalent diabetes, prior myocardial infarction (MI), hypertension and sleep apnoea and CRP could be mostly explained by adiposity alone. For example, the 42% higher CRP concentrations in diabetes compared to those without diabetes in the unadjusted model (lnCRP β: 0.35; 95% confidence interval [CI]: 0.32-0.37, p < 0.001) were completely attenuated after adjustment for BMI (lnCRP β: -0.07; 95% CI: -0.09-0.05, p < 0.001)., Conclusions/interpretation: In diabetes, MI, hypertension and sleep apnoea and elevated CRP appears to be accounted for by the greater adiposity typically evident in these conditions. However, for the other conditions, systemic inflammation cannot be explained by excess adiposity alone., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This comprehensive systematic review and meta-analysis sought to investigate the impact of chia seed supplementation on obesity indicators and metabolic factors. Through a thorough search of relevant studies up to April 2024, 14 clinical trials involving 835 participants were included in the analysis. The findings revealed a notable decrease in triglyceride levels across both higher and lower doses of chia seeds, with weighted mean differences (WMD) of -8.69 mg/dL and -13.11 mg/dL, respectively. Additionally, a statistically significant reduction in LDL-C levels was observed solely in the higher dosage group, showing a WMD of -4.77 mg/dL. Moreover, although the decrease in systolic blood pressure (-2.78 mmHg) compared to the control group was statistically significant, it was only observed with the higher dosage. These results suggest that chia supplementation may offer beneficial effects on dyslipidemia, hypertension, and body weight, potentially mitigating the risk of cardiovascular disease., Competing Interests: Conflicts of Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: The relationship between serum calcium and occurrence of MHO (metabolically healthy obesity) and MUNO (metabolically unhealthy non-obesity) remains unclear, and distinguishing these two phenotypes is difficult within primary healthcare units. This study explores that relationship., Methods: This survey included 28590 adults from the National Health and Nutrition Examination Survey (NHANES) 2001-2018. Obesity phenotypes were categorized based on BMI and presence or absence of metabolic syndrome components. Weighted multivariate logistic regression analyses were used to assess the association between serum calcium levels and the obesity phenotype. Restricted cubic spline analysis characterized dose-response relationships, and stratified analyses explored these relationships across sociodemographic and lifestyle factors., Results: The overall prevalence of MHO and MUNO were 2.6% and 46.6%, respectively. After adjusting for covariates, serum calcium exhibited a negative association with MHO [OR (95%): 0.49 (0.36,0.67), p  < 0.001], while exhibiting a positive association with MUNO [OR (95%): 1.48 (1.26,1.84), p  < 0.001]. Additionally, we found a non-linear association between serum calcium levels and the incidences of MHO and MUNO. Stratified analyses demonstrated a strong negative correlation between serum calcium levels and MHO occurrence across various subgroups. There was no significant interaction between calcium and stratified variables except sex; the association between calcium and the occurrence of MHO was remarkable in female patients. Meanwhile, the predictive ability of serum calcium level for the occurrence of MUNO among all patients was consistent across various subgroups. There was a significant interaction between calcium level and stratified variables based on age, sex, race, and smoking status; the association was remarkable in older (≥ 40 years old), white, none or less smoking, and female patients., Conclusions: A significant correlation was identified between serum calcium levels and MHO or MUNO. The findings suggest that serum calcium levels may serve as an indicator for more accurate assessment and diagnosis of MUNO and MHO, especially among individuals with abdominal obesity.

Background: Traditional forms of exercise affect immune, metabolic, and myokine responses and contribute to a multitude of health benefits. Whole body vibration (WBV) has recently emerged as an exercise mimetic that may be more tolerable for those individuals that cannot perform traditional exercise. However, the myokines response to acute WBV in humans has yet to be fully elucidated., Objective: To characterize the decorin and myostatin response to acute whole body vibration (WBV) and determine the impact of adiposity, sex, and race., Subjects: One hundred twenty-nine adults (32.8 ± 0.4 years, 66.7% female, 53.5% non-Hispanic Black) were recruited as part of an ongoing, longitudinal twin cohort parent study. Participants were classified into three groups: those with obesity (OB: ≥30 kg/m 2 ), those who are overweight (OW: ≥25 and <30 kg/m 2 ), or those with normal weight (NW: <25 kg/m 2 ) based on BMI., Methods: Blood was collected at baseline (PRE), immediately post (POST), and 1 h (1H), 3 h (3H), and 24 h (24H) post WBV. The acute WBV protocol consisted of 10 cycles of 1 min of vibration exercise followed by 30 s of standing rest., Results: The response was similar between NW and OW, so these groups were combined for analysis (NW/OW: BMI < 30 kg/m 2 ). Overall, circulating concentrations of decorin were higher (p < 0.001) POST (8.80 ± 0.19 pg/mL) and significantly lower (p's ≤ 0.005) at 1H (8.66 ± 0.19 pg/mL) and 3H (8.68 ± 0.19 pg/mL), compared to PRE (8.71 ± 0.19 pg/mL). Decorin POST was greater (p = 0.016) in the OB group (8.82 ± 0.18 pg/mL) compared to the NW/OW group (8.77 ± 0.20 pg/mL). Overall, myostatin was higher (p = 0.002) POST (54.93 ± 1.04 pg/mL) and lower (p < 0.001) at 24H (49.13 ± 1.04 pg/mL) compared to PRE (53.49 ± 1.04 pg/mL). The myostatin response was lower (p's ≤ 0.001) in female and non-Hispanic White individuals compared to male and non-Hispanic Black individuals, respectively., Conclusions: A single bout of WBV can facilitate the release of decorin and myostatin into circulation, a similar response to traditional exercise. Additionally, adiposity, sex and race should be considered when evaluating the myokines response to WBV., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: All study protocols were performed in accordance with the human subjects regulations and approved by the Institutional Review Board at Augusta University (IRB#1323570). Informed consent was obtained from all participants., (© 2024. The Author(s).)

Aims: To explore the potential of N-terminal pro-B natriuretic peptide (NTproBNP) in identifying adverse outcomes, particularly cardiovascular adverse outcomes, in a population with obesity, and to establish a risk prediction model., Methods: The data for this study were obtained from the National Health and Nutrition Examination Survey (NHANES) for 6772 participants without heart failure, for the years 1999 to 2004. Multivariable Cox regression models, cubic spline restricted models and Kaplan-Meier curves were used to evaluate the relationship between NTproBNP and both all-cause mortality and cardiovascular mortality. Predictive models were established using seven machine learning methods, and evaluation was conducted using precision, recall, F1 score, accuracy, and area under the curve (AUC) values., Results: During the population follow-up, out of 6772 participants, 1554 died, with 365 deaths attributed to cardiovascular disease. After adjusting for relevant covariates, NTproBNP levels ≥300 pg/mL were positively associated with both all-cause mortality (hazard ratio [HR] 3.00, 95% confidence interval [CI] 2.48, 3.67) and cardiovascular mortality (HR 6.05, 95% CI 3.67, 9.97), and remained significant across different body mass index (BMI) strata. However, in participants without abdominal obesity, the correlation between NTproBNP and cardiovascular mortality was significantly reduced. Among the seven machine learning methods, logistic regression demonstrated better predictive performance for both all-cause mortality (AUC 0.86925) and cardiovascular mortality (AUC 0.85115). However, establishing accurate cardiovascular mortality prediction models for non-abdominal obese individuals proved challenging., Conclusion: The study showed that NTproBNP can serve as a predictive factor for all-cause mortality and cardiovascular mortality in individuals with different BMIs, including obese individuals. However, significant cardiovascular mortality correlation was observed only for NTproBNP levels ≥300 pg/mL, and only among participants with abdominal obesity., (© 2024 John Wiley & Sons Ltd.)

Objective: To investigate the association between female sexual function and metabolic features among women with polycystic ovary syndrome (PCOS) during reproductive age., Method: This was a cross-sectional study in which 288 women with PCOS and 180 women without PCOS between the ages of 20 and 40 years were evaluated. All women had serum total testosterone, androstenedione, DHEA-S, fasting glucose, total cholesterol, HDL-C, LDL-C, and triglyceride levels analyzed. The McCoy Female Sexual Questionnaire (MFSQ) was applied to all studied women. Exploratory factor analysis and reliability analysis were done after data collection. The factor loadings of MFSQ domains were compared between women with PCOS and controls., Results: Average factor loadings of the MFSQ sexuality domain and MFSQ sexual partner domain were significantly lower in the PCOS group when compared to controls. There was no correlation between the two sexual function domains of the MFSQ and the PCOS features either in the PCOS group or the controls., Conclusion: PCOS is a heterogeneous disease with different metabolic components, such as insulin resistance, obesity, and hyperandrogenism. Although sexual function among women with PCOS was lower than controls, no differences were found in metabolic features of the PCOS and non-PCOS groups with relation to sexual function determined by the MFSQ.

Objective: To investigate the effect of body mass index (BMI) on progesterone (P) level on trigger day in gonadotropin-releasing hormone antagonist (GnRH-ant) cycles., Methods: This study was a retrospective cohort study. From October 2017 to April 2022, 412 in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) patients who were treated with GnRH-ant protocol for controlled ovarian hyperstimulation (COH) in the reproductive center of our hospital were selected as the research objects. Patients were divided into three groups according to BMI level: normal weight group ( n  = 230):18.5 kg/m 2 ≤BMI < 24 kg/m 2 ; overweight group ( n  = 122): 24 kg/m 2 ≤BMI < 28 kg/m 2 ; Obesity group ( n  = 60): BMI ≥ 28 kg/m 2 . Variables with p  < .10 in univariate analysis (BMI, basal FSH, basal P, FSH days, Gn starting dose and E 2 level on trigger day) and variables that may affect P level on trigger day (infertility factors, basal LH, total FSH, HMG days and total HMG) were included in the multivariate logistic regression model to analyze the effect of BMI on P level on trigger day of GnRH-ant protocol., Results: After adjustment for confounding factors, compared with that in normal weight patients, the risk of serum P elevation on trigger day was significantly lower in overweight and obese patients (OR = 0.434 and 0.199, respectively, p  < .05)., Conclusion: The risk of P elevation on trigger day in GnRH-ant cycles decreased with the increase of BMI, and BMI could be used as one of the predictors of P level on trigger day in GnRH-ant cycles.

Purpose: Dyslipidemia plays a pivotal role in increasing cardiovascular risk. In clinical practice the misleading association between altered lipid profile and obesity is common, therefore genetically inherited dyslipidemias may not completely be addressed among patients with overweight. Thus, we aim to investigate the influence of overweight and obesity on the lipid phenotype in a cohort of patients with different forms of dyslipidemia., Methods: A retrospective analysis was conducted on patients with dyslipidemia from 2015 to 2022. Patients were stratified in familial hypercholesterolemia (FH), familial combined hyperlipidemia (FCHL), non-familial hyperlipidemia or polygenic hypercholesterolemia (PH). Clinical characteristics and lipid profile were evaluated., Results: Of the total of 798 patients, 361 were affected by non-familial hyperlipidemia (45.2%), while FCHL, FH and PH was described in 19.9%, 14.0% and 20.9% of patients, respectively. Overweight prevalence was higher in FCHL and non-familial hyperlipidemia patients than FH and PH patients. Subjects with overweight and obesity were independently associated with lower levels of high-density lipoprotein cholesterol (HDL-C) compared to patients with normal weight (52.4 and 46.0 vs 58.1, respectively; p < 0.0001); levels of triglycerides (TG) and non-HDL-C were higher in patients with overweight and obesity than patients with normal weight (257.3 and 290.9 vs 194.8, and 221.5 and 219.6 vs 210.1, p < 0.0001 and p = 0.01, respectively), while no differences were observed between patients with overweight and obesity., Conclusion: While dyslipidemias can be influenced by various factors, an important determinant may lie in genetics, frequently acting as an underlying cause of altered lipid profiles, even in cases of overweight conditions., (© 2024. The Author(s).)

The aim of this study was to evaluate the relationship between biomarkers of chronic inflammation, insulin resistance, and zinc transporter ZnT1 expression in human visceral adipose tissue. Visceral adipose tissue obtained from 47 adults undergoing laparoscopic surgery for cholecystectomy was used to analyze ZnT1 mRNA expression by RT-qPCR. ZnT1 mRNA levels were compared between subjects with normal weight, overweight, and obesity. A significantly lower ZnT1 expression was observed in overweight and obesity compared with normal-weight subjects (p = 0.0016). Moreover, subjects with normal weight had significantly higher serum zinc concentration (97.7 ± 13.1 mg/L) than subjects with overweight (87.0 ± 12.8 mg/L) and obesity (83.1 ± 6.6 mg/L) (p = 0.002). Pearson test showed a positive correlation between serum zinc concentrations and ZnT1 mRNA expression in visceral adipose tissue (r = 0.323; p = 0.031) and a negative correlation with body mass index (r =  - 0.358; p = 0.013). A linear regression model was used to analyze the associations between ZnT1 mRNA expression and serum zinc levels, insulin resistance (HOMA2-IR), serum adipokines (leptin and adiponectin), and serum inflammation biomarkers (tumor necrosis factor alpha, interleukin-6, and C-reactive protein). Interestingly, leptin concentrations were negatively associated with ZnT1 mRNA expression (p = 0.012); however, no significant associations were found for the rest of the analyzed variables. Future research is needed to analyze the causality of negative association between ZntT1 expression in visceral adipose tissue and leptin., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Neuregulin 4 (Nrg4) is a brown adipose tissue-derived adipokine that greatly affects systemic metabolism and improves metabolic derangements. Although abnormal circulating levels of Nrg4 are common in obesity, it remains elusive whether low or elevated levels of this batokine are associated with the onset of metabolic diseases., Aim: To assess Nrg4 levels and its role as a feasible biomarker to predict the severity of obesity, gestational diabetes mellitus (GDM), type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD), and cardiovascular diseases (CVD)., Methods: A search for relevant studies was performed systematically using prominent search engines, including PubMed, Google Scholar, and Embase, by following PRISMA guidelines., Results: Ample clinical evidence reported low serum/plasma levels of Nrg4 in obesity and these were inversely proportional to the indices of metabolic syndrome, including body mass index, waist circumference, triglycerides, fasting plasma glucose, and homoeostatic model assessment for insulin resistance as well as high-sensitivity C-reactive protein. Low circulating Nrg4 levels may aid in the prediction of morbid obesity, and subsequent GDM, T2DM, NAFLD, and CVD., Conclusion: Current clinical evidence emphasizes that the circulating levels of Nrg4 are decreased in morbid obesity, and it also highlights that Nrg4 May serve as a potential prognostic biomarker for obesity-related metabolic diseases.

Purpose: One of the key functions of brown adipose tissue is its positive impact on metabolism. This study aimed to examine the potential involvement of brown fat-related hormones in the development of metabolically healthy obesity. Specifically, we sought to compare the levels of NRG4, FGF21, and irisin between metabolically healthy and unhealthy individuals with obesity., Methods: Patients with BMI ≥ 30 kg/m 2 and aged between 20 and 50 years were included in the study. Among these patients, those who did not have any metabolic syndrome criteria except for increased waist circumference were defined as metabolically healthy obese. Age, gender, BMI, body fat, and muscle mass, matched metabolically healthy and unhealthy obese groups were compared in terms of FGF21, irisin, and NRG4 levels., Results: Metabolically healthy and unhealthy obese groups were similar in terms of age and gender. There was no difference between the two groups in terms of BMI, weight, total body fat, muscle, fat-free mass, distribution of body fat and muscle mass. No statistically significant difference was found between irisin, NRG4, and FGF21 levels between metabolically healthy and unhealthy individuals with obesity. It was found that irisin had a significant inverse correlation with BMI and body fat percentage., Conclusion: The present study showed no difference between metabolically healthy and unhealthy obese individuals in terms of irisin, FGF21, and NRG4 levels. The weak association between irisin and BMI and body fat percentage may suggest a potential link between irisin with metabolic health., Competing Interests: Compliance with ethical standards Conflict of interest The authors declare no competing interests. Ethical approval The study was approved by the Ethical Committee of the Clinical Research of Göztepe Training and Research Hospital with number 2020/0577 on 30.09.2020. (Clinical Trial Gov Number NCT05232695). Research involving human and animal participants All procedures performed in this study, which involves human participants, were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Informed consent Informed consent was obtained from all individual participants included in the study., (© 2024. The Author(s).)

The obesity epidemic among children has become a major public health issue, and the presence of childhood insulin resistance (IR) has been demonstrated prior to the onset of type 2 diabetes mellitus. However, it is unclear whether the metabolomic signature is associated with weight loss interventions in obese children with IR. Thirty-six obese children with IR were selected from the weight loss camp (Shenzhen Sunshine Xing Yada health Technology Co., LTD). Clinical parameters were collected before and after weight loss intervention. Targeted metabolomics of plasma samples was performed by ultra-performance liquid chromatography coupled to the tandem mass spectrometry, and principal component analysis, variable importance in projection, and orthogonal partial least squares discriminant analysis were used to obtain the differentially expressed metabolites. Pathway analysis was conducted with the Homo sapiens (HSA) sets in the Kyoto Encyclopedia of Genes and Genomes. We used machine learning algorithms to obtain the potential biomarkers and Spearman correlation analysis to clarify the association between potential biomarkers and clinical parameters. We found that clinical parameters and metabolite clusters were significantly changed in obese children with IR before and after weight loss intervention. Mechanistically, weight loss intervention significantly changed 61 metabolites in obese children with IR. Furthermore, 12 pathways were significantly changed. Moreover, the machine learning algorithm found 6 important potential biomarkers. In addition, these potential biomarkers were strongly associated with major clinical parameters. These data indicate different metabolomic profiles in obese children with IR after weight loss intervention, providing insights into the clinical parameters and metabolite mechanisms involved in weight loss programs., (© 2024. The Author(s).)

Background: Obesity represents a significant risk factor for the development of metabolic abnormalities. However, it is not inevitable that all individuals with obesity will develop these disorders. Selenium has been demonstrated to play a role in maintaining metabolic homeostasis in vivo , with the ability to regulate relevant signaling pathways involved in glucose and lipid metabolism processes. Previous studies have indicated that selenium concentrations in obese individuals are higher than those reported in the general population. These findings the question of whether altered selenium concentrations may act as important triggers for accelerating metabolic imbalances in the obese population. The aim of this study was to examine the potential correlation between serum selenium concentrations and the risk of developing metabolic abnormalities in individuals with obesity., Methods: The present study included 6,125 participants from the 2011-2018 National Health and Nutrition Examination Survey (NHANES) who were aged between 20 and 80 years, with a body mass index (BMI) of 30 kg/m 2 or greater, and met the inclusion and exclusion criteria. Weighted generalized linear regression analyses were conducted to evaluate the associations between serum selenium concentrations and the conversion of metabolically healthy obesity (MHO) to metabolically unhealthy obesity (MUO). A generalized additive model (GAM) and a two-piecewise linear regression model were employed to investigate the saturation threshold effect between selenium and MUO. The correlation between different selenium concentration intervals and metabolic diseases was evaluated by categorizing selenium concentrations according to the saturation threshold. Furthermore, this study investigated the correlation between serum selenium and lipid concentrations in obese females and between serum selenium and blood pressure in obese males., Results: The weighted prevalence of MUO in the study population was 48.35%. After rigorous adjustment for sociodemographic, physical, and laboratory test covariates, the weighted odds ratio (OR) of MUO increased by 44% for every 1 µM increase (approximately 78.74 µg) in the serum selenium concentration (weighted OR=1.44; 95% CI=1.09 - 1.91; P =0.018). Second, GAM analysis and saturation threshold analyses revealed an inverted U-shaped relationship between serum selenium and metabolic abnormalities in males, with a corresponding inflection point (K) of 2.82 µM. When the serum selenium concentration was below the K-value, the effects of serum selenium were mainly on blood pressure, especially diastolic blood pressure (DBP) (weighted β: 3.34; 95% CI= 0.25 - 6.44; P =0.038). Conversely, the correlation between the serum selenium concentrations and metabolic homeostasis imbalance in females was linear. When the selenium concentration exceeded 2.12 µM, the increase in selenium content was accompanied by increases in total cholesterol (TC, weighted β=0.54, 95% CI=0.32 - 0.76; P =0.000) and triglyceride (TG, weighted β=0.51, 95% CI=0.27 - 0.75; P =0.000) concentrations., Conclusions: The findings of our study indicate that selenium supplementation strategies for individuals with obesity should be tailored to the sex of the individual. In females, serum selenium concentration above the saturation threshold primarily facilitates the transition from MHO to MUO by influencing alterations in serum lipid metabolism. Maintaining selenium concentrations below the threshold levels is highly important for preventing the conversion of MHO to MUO. In males, serum selenium concentrations above the threshold were found to be effective in preventing an elevation in blood pressure, particularly in improving systolic blood pressure (SBP). Nevertheless, serum selenium concentrations below the threshold are linked to an increased risk of hypertension in obese individuals, particularly those with elevated diastolic blood pressure (DBP). Further research is needed to elucidate the optimal serum selenium concentration that exerts deleterious effects on blood pressure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Li, Chen, Ma, Yu, He and Yang.)

Introduction: Background: childhood obesity is one of the major health problem worldwide. Obesity is associated with low-level chronic inflammation resulting from inflammatory cytokine release in white adipose tissue. We aim to specify inflammatory markers tumor necrosis factor-alpha (TNF-alpha) and interleukin-10 (IL-10) in children and adolescents to determine their relationship with obesity. Materials and methods: forty obese patients and 46 controls were included in the study from the pediatric clinic. Blood samples from the study group were centrifuged, and the sera were stored at -80 °C after separation. Serum levels of TNF-alpha and IL-10 were determined using Human ELISA kits for TNF-alpha and IL-10. Results: serum samples from 86 children, including 45 girls (52.3 %) in the study group, were analyzed for TNF-alpha and IL-10 levels. TNF-alpha levels in the obese and control groups were 1.04 ± 0.79 and 0.60 ± 0.72 pg/ml, respectively (p = 0.010). Also, IL-10 levels in the obese and control groups were 0.76 ± 0.62 and 1.54 ± 0.71 pg/ml, respectively (p < 0.001). Gender was not identified as a factor for serum TNF-alpha and IL-10 levels (p = 0.281 and p = 0.477, respectively). Moreover, white blood cell (WBC) and serum C-reactive protein (CRP) levels were higher in the obese patient group than in the control group (p = 0.002 and p = 0.010, respectively). Conclusion: TNF-alpha levels were higher than control in obese patients and it was important in terms of showing that obesity triggers inflammation in the body. IL-10 levels, which inhibit inflammation, were lower in obese patients than controls.

Background: Insulin resistance (IR) is related with adverse outcomes of in vitro fertilization (IVF) in women with obesity, but little is known about the relationship between IR and unexpected poor ovarian response (uPOR) in non-obese subjects with sufficient ovarian parameters (classified as POSEIDON group 1). This research aims to explore the association between the homeostasis model assessment of insulin resistance (HOMA-IR) and uPOR in non-obese women with normal biomarkers of ovarian reserve., Methods: The retrospective cohort study was conducted at a fertility center. The main inclusion criteria were age < 35 years, body mass index (BMI) < 28 kg/m 2 , normal ovarian reserve (anti-Mullerian hormone ≥ 1.2 ng/ml, antral follicle count ≥ 5). Women undergoing the first oocyte retrieval cycle were included consecutively between 2018 until 2023. Patients who have ≤ 9 oocytes retrieved were defined as uPOR. The multivariable logistic model and subgroup analysis were conducted after adjusting confounders., Results: A total of 6977 cycles were included. The adjusted odds ratio was 1.25 (95% confidence interval [CI], 1.12-1.39) for the increment of Ln HOMA-IR which was taken as a continuous variable. Meanwhile, as a sensitivity analysis, elevated tertile of HOMA-IR exhibited an increase in risk of uPOR for the third tertile (≥ 2.75) when compared with the first tertile (< 1.75) with OR of 1.33 (95%CI, 1.15-1.54). In the subgroup analysis, the positive association remained consistent., Conclusion: Elevated HOMA-IR values is significantly associated with increased risk of uPOR in non-obese women classified as POSEIDON group 1. Our study provided evidence for the adverse influence of IR on the ovarian response during IVF and shed light on the importance of IR measurement at the time of pre-stimulation among non-obese women., (© 2024. The Author(s).)

Introduction: We previously documented the beneficial effects of rice bran oil (RBO) on cardiac function and atherogenic cardiometabolic factors in men with coronary artery disease. Therefore, the existing evidence in this area aims to be expanded by investigating the impact of adding RBO to a daily standard diet on emerging insulin resistance surrogate markers, lipid peroxidation, antioxidant status, and metabolic disturbances in individuals with metabolic syndrome (MetSyn) through an open-label controlled trial., Methods: A total of 50 overweight/obese adults (mean body mass index (BMI) = 31.08 kg/m2) with at least 3 MetSyn components were randomly allocated to either the control group, which received a standard diet plan, or the intervention group, which was supplemented with 30 g/d RBO for 8 weeks. BMI, MetSyn components, metabolic score for insulin resistance (METS-IR), triglyceride‒glucose‒BMI (TyG‒BMI), malondialdehyde (MDA), total antioxidant capacity (TAC), and plasma polyphenol levels were measured before and after this open-label trial., Results: Analysis of covariance (ANCOVA) adjusted for baseline values revealed that, compared with patients who received only a standard diet, those who were supplemented with 30 g/d RBO presented significantly lower total cholesterol (P value = 0.005; effect size (ES):-0.92), LDL-cholesterol (P value = 0.048; ES:-0.62), fasting blood glucose (P value = 0.014; ES:-0.77), MDA (P value = 0.002; ES: -1.01), METS-IR (P value < 0.001; ES: -1.24), and TyG-BMI (P value = 0.007; ES:-0.85) after 8 weeks. Additionally, RBO consumption resulted in significantly higher levels of HDL-C (P value = 0.004; ES:0.94) and TAC (P value < 0.0001; ES:2.05). However, no significant changes were noted in BMI, waist circumference, serum triglycerides, plasma polyphenols, or blood pressure., Conclusion: Although the current findings suggest that the hypocholesterolemic, antihyperglycemic, and antioxidative effects of 30 g/d RBO seem to be promising for MetSyn patients, they should be considered preliminary. Therefore, further well-designed clinical trials with larger sample sizes and longer durations are needed to confirm these findings., (© 2024. The Author(s).)

Objective: Exploring the relationship between the cardiometabolic index (CMI) and serum testosterone levels as well as testosterone deficiency in American adult males. Additionally, comparing the diagnostic value of the CMI with several common obesity and metabolism indices for identifying testosterone deficiency., Methods: This cross-sectional study was conducted using data from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2016. Serum testosterone levels and testosterone deficiency were used as dependent variables, with the cardiometabolic index as the independent variable. Multivariable regression was used to assess the relationship between the independent and dependent variables, while subgroup analyses were performed to ensure the stability of the results. Smooth curve fitting was utilized to evaluate the nonlinear relationship between the CMI and testosterone levels. Receiver operating characteristic curves (ROC) were plotted for several obesity and metabolism prediction indices and the area under the curve was calculated to compare the specificity and sensitivity of each diagnostic index in the diagnosis of testosterone deficiency., Results: Among 3541 adult male participants, CMI is negatively associated with serum testosterone levels and positively associated with testosterone deficiency. In the fully adjusted model, for every unit increase in CMI, serum testosterone decreased by 14.89 ng/dl. Comparing the highest quartile to the lowest quartile of CMI, each unit increase in CMI, serum testosterone decreased by 98.58 ng/dl. Furthermore, each unit increase in CMI was associated with a 16% increase in incidence of testosterone deficiency. By plotting the ROC curves, we found that the AUCs for Lipid Accumulation Product (LAP), Body Mass Index (BMI), Weight Adjusted Waist Index (WWI), CMI, Visceral Adiposity Index (VAI) and Triglyceride glucose index (TyG) were 0.73, 0.72, 0.71, 0.69, 0.66, and 0.66 respectively., Conclusion: Elevated levels of CMI are associated with lower testosterone levels and an increased risk of testosterone deficiency. The predictive value of the LAP was superior to that of CMI, while the predictive value of CMI was higher than VAI and TyG., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Huang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Glucose metabolic disorder is associated with the risk of heart failure (HF). Adiposity is a comorbidity that is inextricably linked with abnormal glucose metabolism in older individuals. However, the effect of adiposity on the association between glucose metabolic disorder and HF risk, and the underlying mechanism remain unclear., Methods: A total of 13,251 participants aged ≥ 60 years from a cohort study were categorized into euglycemia, prediabetes, uncontrolled diabetes, and well-controlled diabetes. Adiposity was assessed using body mass index (BMI), waist-to-hip ratio (WHR), and visceral fat area (VFA). Adiposity-associated metabolic activities were evaluated using adiponectin-to-leptin ratio (ALR), homeostatic model assessment of insulin resistance (HOMA-IR), and triglyceride-glucose index (TyG). The first occurrence of HF served as the outcome during the follow-up period., Results: A total of 1,138 participants developed HF over the course of an average follow-up period of 10.9 years. The rate of incident HF occurrence was higher in prediabetes, uncontrolled diabetes, and well-controlled diabetes participants compared to that in euglycemia participants. However, the high rates were significantly attenuated by BMI, VFA, and WHR. For WHR in particular, the hazard ratio for incident HF was 1.18 (95% confidence interval (CI): 1.03, 1.35, P adj. =0.017) in prediabetes, 1.59 (95% CI: 1.34, 1.90, P adj. <0.001) in uncontrolled diabetes, and 1.10 (95% CI: 0.85, 1.43, P adj. =0.466) in well-controlled diabetes. The population attributable risk percentage for central obesity classified by WHR for incident HF was 30.3% in euglycemia, 50.0% in prediabetes, 48.5% in uncontrolled diabetes, and 54.4% in well-controlled diabetes. Adiposity measures, especially WHR, showed a significant interaction with glucose metabolic disorder in incident HF (all P adj. <0.001). ALR was negatively associated and HOMA-IR and TyG were positively associated with BMI, WHR, VFA, and incident HF (all P adj. <0.05). ALR, HOMA-IR, and TyG mediated the associations for BMI, WHR and VFA with incident HF (all P adj .<0.05)., Conclusions: Adiposity attenuated the association of glucose metabolic disorder with incident HF. The results also showed that WHR may be an appropriate indicator for evaluating adiposity in older individuals. Adiposity-associated metabolic activities may have a bridging role in the process of adiposity attenuating the association between glucose metabolic disorder and incident HF., Trial Registration: retrospectively registered number: ChiCTR-EOC-17,013,598., (© 2024. The Author(s).)

Objective: Obesity is associated with an exacerbated metabolic condition that is mediated through impairing balance in the secretion of some adipo-myokines. Therefore, the objective of the present study was to explore the impact of astaxanthin supplementation in conjunction with a 12-week CrossFit training regimen on some selected adipo-myokines, insulin insensitivity, and serum lipid levels in obese males., Material and Methods: This study is a randomized control trial design; 60 obese males were randomly divided into four groups of 15, including the control group (CG), supplement group (SG), training group (TG), and combined training and supplement group (TSG). The participants were subjected to 12 weeks of astaxanthin (AST) supplementation [20 mg/d capsule, once/d] or CrossFit training or a combination of both interventions. The training regimen comprised 36 sessions of CrossFit, each lasting 60 min, conducted three times per week. The metabolic indices, body composition, anthropometrical, cardio-respiratory, and also some plasma adipo-myokine factors, including decorin (DCN), activin A, myostatin (MST), transforming growth factor (TGF)-β1, and follistatin (FST), were examined 12 and 72 h before the initiation of the main interventional protocols, and then 72 h after the final session of the training protocol., Results: There was no significant difference in the baseline data between the groups ( p > 0.05). There were significant interactions between group x time for DCN (η 2 = 0.82), activin A (η 2 = 0.50), FST (η 2 = 0.92), MST (η 2 = 0.75), and TGFB-1 (η 2 = 0.67) ( p < 0.001 for all the variables). Significantly changes showed for DCN in TSG compared to TG and SG and also TG compared to SG ( p = 0.0001); for activin A in SG compared to TG ( p = 0.01) and TSG ( p = 0.002); for FST in SG compared to TG and TSG ( p = 0.0001), also in TSG compared to TG ( p = 0.0001); for MST in SG, TG, and TSG compared to CG ( p = 0.0001) and also in TSG compared to SG ( p = 0.0001) and TG ( p = 0.001); for TGFB-1 in SG, TG, and TSG compared to CG ( p = 0.0001) and also TSG compared to SG ( p = 0.0001) and TG ( p = 0.001)., Conclusions: The 12-week CrossFit training concurrent with AST supplementation reduced anthropometric and metabolic factors and also serum lipid levels while producing positive changes in body composition and cardiovascular factors. Increased FST and DCN and reduced activin A, MST, and TGF-β1 were other affirmative responses to both interventions.

Objectives: An acidogenic diet, by disrupting the blood pH equilibrium, can contribute to metabolic acidosis and lead to inflammation. Therefore, we hypothesized that dietary acid load (DAL) increases disease activity and inflammation in psoriatic arthritis (PsA) patients., Methods: This study was conducted with 58 obese/overweight patients, aged 20-65 years. Dietary intake was assessed using a 3-consecutive-day 24-hour recall. The DAL was evaluated through the PRAL (potential renal acid load) and NEAP (net endogenous acid production) and divided into the low and high groups by their median values. The disease activity assessments, anthropometric measurements, dietary data, and blood parameters of patients were recorded and compared at the low and high DAL groups., Results: We observed that patients in the high NEAP and PRAL groups had worse PsA pattern scores (P < 0.05). Also, PRAL and NEAP scores were positively associated with Disease Activity Index for Psoriatic Arthritis, Health Assessment Questionnaire, and Psoriatic Arthritis Impact of Disease-12 (PSAID-12) scores. After adjusting age, sex, smoking, and body mass index, 1 mEq increase in PRAL and NEAP was associated with an elevation of Disease Activity Index for Psoriatic Arthritis (0.506 and 0.486 points, respectively)., Conclusions: These results showed a close relationship between DAL and PsA symptoms. An acidogenic diet may negatively affect PsA prognosis. Healthy eating recommendations should be part of the management of the disease., (© Japan College of Rheumatology 2024. Published by Oxford University Press.)

Sedentary behavior (SB) is an essential risk factor for obesity, cardiovascular disease, and type 2 diabetes. Though certain levels of physical activity (PA) may attenuate the detrimental effects of SB, the inflammatory and cardiometabolic responses involved are still not fully understood. The focus of this secondary outcome analysis was to describe how light-intensity PA snacks (LIPASs, alternate sitting and standing, walking or standing continuously) compared with uninterrupted prolonged sitting affect inflammatory and cardiometabolic risk markers. Seventeen young adults with overweight and obesity participated in this study (eight females, 23.4 ± 3.3 years, body mass index (BMI) 29.7 ± 3.8 kg/m 2 , glycated hemoglobin A1C (HbA 1c ) 5.4 ± 0.3%, body fat 31.8 ± 8.2%). Participants were randomly assigned to the following conditions which were tested during an 8 h simulated workday: uninterrupted prolonged sitting (SIT), alternate sitting and standing (SIT-STAND, 2.5 h total standing time), continuous standing (STAND), and continuous walking (1.6 km/h; WALK). Each condition also included a standardized non-relativized breakfast and lunch. Venous blood samples were obtained in a fasted state at baseline (T 0 ), 1 h after lunch (T 1 ) and 8 h after baseline (T 2 ). Inflammatory and cardiometabolic risk markers included interleukin-6 (IL-6), c-reactive protein (CRP), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TGs), visceral fat area (VFA), triglyceride-glucose (TyG) index, two lipid ratio measures, TG/HDL-C and TC/HDL-C, albumin, amylase (pancreatic), total protein, uric acid, and urea. We found significant changes in a broad range of certain inflammatory and cardiometabolic risk markers during the intervention phase for IL-6 ( p = 0.014), TG ( p = 0.012), TC ( p = 0.017), HDL-C ( p = 0.020), LDL-C ( p = 0.021), albumin ( p = 0.003), total protein ( p = 0.021), and uric acid ( p = 0.040) in favor of light-intensity walking compared with uninterrupted prolonged sitting, alternate sitting and standing, and continuous standing. We found no significant changes in CRP ( p = 0.529), creatinine ( p = 0.199), TyG ( p = 0.331), and the lipid ratios TG/HDL-C ( p = 0.793) and TC/HDL-C ( p = 0.221) in response to the PA snack. During a simulated 8 h work environment replacement and interruption of prolonged sitting with light-intensity walking, significant positive effects on certain inflammatory and cardiometabolic risk markers were found in young adults with overweight and obesity.

The topic of ragweed pollen (RW) versus house dust mites (HDMs) has often been deliberated, but the increasing incidence of co-sensitization between them has been scarcely addressed. Utilizing Sprague Dawley rats, we explored the effects of co-sensitization with the combination of HDMs and RW pollen extracts in correlation with high-fructose diet (HFrD) by in vitro tracheal reactivity analysis in isolated organ bath and biological explorations. Our findings unveiled interrelated connections between allergic asthma, dyslipidemia, and HFrD-induced obesity, shedding light on their compounding role through inflammation. The increased CRP values and airway hyperresponsiveness to the methacholine challenge suggest a synergistic effect of obesity on amplifying the existing inflammation induced by asthma. One of the major outcomes is that the co-sensitization to HDMs and RW pollen led to the development of a severe allergic asthma phenotype in rats, especially in those with HFrD. Therefore, the co-sensitization to these allergens as well as the HFrD may play a crucial role in the modulation of systemic inflammation, obesity, and airway reactivity.

Cardiometabolic co-morbidities, diabetes (DM), hypertension (HTN), and obesity contribute to cardiovascular disease. Circulating biomarkers facilitate prognostication for patients with cardiovascular disease. We explored the relation between cardiometabolic co-morbidity burden in patients with chronic coronary disease and biomarkers of myocardial stretch, injury, inflammation, and platelet activity. We analyzed participants from the International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trials biorepository with plasma biomarkers (N-terminal probrain natriuretic peptide, high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, soluble CD40 ligand, and growth differentiation factor-15) and clinical risk factors (hemoglobin A1c [HbA1c], systolic blood pressure [SBP], and body mass index [BMI]) at baseline. We defined cardiometabolic co-morbidities as DM, HTN, and obesity at baseline. Co-morbidity burden is characterized by the number and severity of co-morbidities. Controlled co-morbidities were defined as HbA1c <7% for those with DM, SBP <130 mm Hg for those with HTN, and BMI <30 kg/m 2 . Severely uncontrolled was defined as HbA1c ≥8%, SBP ≥160 mm Hg, and BMI ≥35 kg/m 2 . We performed linear regression analyses to examine the association between co-morbidity burden and log-transformed biomarker levels, adjusting for age, gender, estimated glomerular filtration rate controlled for hemodialysis, and left ventricular ejection fraction. A total of 752 participants (mean age 66 years, 19% women, 84% White) were included in this analysis. Self-reported Black race, current smokers, history of myocardial infarction, and heart failure had a greater cardiometabolic co-morbidity burden. The presence of ≥1 severely uncontrolled co-morbidity was associated with significantly higher baseline levels of high-sensitivity cardiac troponin T, high-sensitivity C-reactive protein, interleukin-6, and growth differentiation factor-15 than participants with no co-morbidities. In conclusion, increasing cardiometabolic co-morbidity burden in patients with chronic coronary disease is associated with higher levels of circulating biomarkers of myocardial injury and inflammation., Competing Interests: Declaration of competing interest Dr. Bangalore reports grants from National Heart, Lung, and Blood Institute during the conduct of the study; grants and personal fees from Abbott Vascular; personal fees from Biotronik, Pfizer, Amgen, and Reata outside the submitted work. Dr. Mavromatis reports grants from National Heart, Lung, and Blood Institute (NHLBI); grants from NHLBI (CV Inflammation Reduction Trial and GMCSF in PAD-3 Trial), grants from CSL Behring, St Jude's Medical, Medtronic, DalCor Pharmaceuticals, AstraZeneca, Novartis, Regeneron, and Member of American College of Cardiology and Society of Cardiovascular Angiography and Interventions. Dr. Newby reports grants from the National Institutes of Health/NHLBI, AstraZeneca Healthcare Foundation, Boehringer Ingelheim (Ingelheim, Germany), CSL, and Medtronic. Dr. Reynolds reports grants from NHLBI, during the conduct of the study, she receives support from Abbott Vascular (donation of optical coherence tomography catheters for an unrelated research study), Biotelemetry Inc. (donation of telemetry monitors for an unrelated research study), and Siemens. Dr. Hochman is principal investigators for the ISCHEMIA trial for which, in addition to support by National Heart, Lung, and Blood Institute grant, devices and medications were provided by Abbott Vascular; Medtronic, Inc.; Abbott Laboratories (formerly St. Jude Medical, Inc.); Royal Philips NV (formerly Volcano Corporation); Arbor Pharmaceuticals, LLC; AstraZeneca Pharmaceuticals, LP (Wilmington, Delaware); Merck Sharp & Dohme Corp.; Omron Healthcare, Inc, Sunovion Pharmaceuticals, Inc. Espero BioPharma; and Amgen, Inc; and financial donations from Arbor Pharmaceuticals LLC and AstraZeneca Pharmaceuticals LP. Dr. Hochman is also the PI for ISCHEMIA-EXTEND. Drs. Anthopolos, Maron, Newman, and Berger reports grants from the NHLBI during the conduct of the study. The remaining authors have no competing interests to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

To study the laser acupuncture (LA) effects on postmenopausal obese women's metabolic syndrome. Randomized controlled trial. Benha university hospital. Thirty postmenopausal women were randomized into two equal groups. Group A received a diet regimen and Group B received LA treatment for 30 min three times a week for two months beside the diet regimen. Included weight (W), body mass index (BMI), waist (WC), hip (HC), waist-hip ratio (WHR), systolic blood pressure (SBP), diastolic blood pressure (DBP), serum level of total cholesterol (TC), triglycerides (TG), high density lipoprotein (HDL), low density lipoprotein (LDL), fasting blood glucose (FBG), fasting blood insulin (FBI), homeostatic model assessment-insulin resistance (HOMA-IR) before and after the end of treatment. The study's findings showed that both groups experienced a highly statistically significant decrease in the post-testing mean value of W, BMI, WC, HC, WHR, SBP, DBP, TC, TG, LDL, FBG, FBI, and HOMA-IR, while both groups experienced a significant increase in the post-treatment mean value of HDL (p 0.0001). The posttreatment SBP, DBP, TC, TG, LDL, FBS, FBI and insulin resistance were significantly lower while HDL was significantly higher in women who received combined LA and diet regimen compared to those who received dietary regimen only. LA beside the nutritional intervention is a physical therapy technique that may be used safely, easily, and effectively to minimize metabolic syndrome features during menopause., (© 2024. The Author(s).)

Background: Empirical evidence has demonstrated associations between pre-pregnancy obesity and perinatal maternal depressive symptoms. Omega-3 is an essential fatty acid derived from dietary sources that is critical for fetal brain development. Pre-pregnancy obesity is associated with higher omega-3 intake, but a weaker association between dietary intake and respective maternal and cord blood omega-3 levels. Further, lower intake of omega-3 during pregnancy has been linked to higher depressive symptoms. Yet, prior studies have not examined the interactive effects of pre-pregnancy overweight or obesity (OWOB) and prenatal maternal mental health symptoms on infant cord blood omega-3 levels., Methods: Participants included 394 maternal-infant dyads from the NIH Environmental influences on Child Health Outcomes (ECHO) - Safe Passage Study in South Dakota. A pre-pregnancy body mass index (BMI) > 25 was used to dichotomize participants as OWOB (54%) vs. non-OWOB (46%). Prenatal maternal depressive symptoms were measured using the Edinburgh Postnatal Depression Scale (EPDS) and prenatal maternal anxiety symptoms were measured using the State-Trait Anxiety Inventory (STAI). We implemented linear regression models to examine the interaction term between pre-pregnancy BMI category and prenatal maternal mental health symptoms on cord blood omega-3 levels. Secondary analyses were stratified by pre-pregnancy BMI category., Results: We observed a significant interaction between pre-pregnancy BMI category and prenatal maternal depressive symptoms with cord blood omega-3 (F(4,379) = 6.21, p < .0001, adj. R 2  = 0.05). Stratified models revealed an association between prenatal maternal depressive symptoms with lower cord blood omega-3 levels only among individuals with pre-pregnancy OWOB (β = -0.06, 95% CI = -0.11, -0.02; F (2,208) = 4.00, p < .05, adj R 2  = 0.03). No associations were observed among non-OWOB participants., Conclusions: Findings suggest maternal-placental transfer of omega-3 may represent one pathway by which maternal metabolic and mental health impacts infant development., (© 2024. The Author(s).)

Context: The role of glucagon-like peptide-1 (GLP-1) in type 2 diabetes (T2D) and obesity is not fully understood., Objective: We investigate the association of cardiometabolic, diet, and lifestyle parameters on fasting and postprandial GLP-1 in people at risk of, or living with, T2D., Methods: We analyzed cross-sectional data from the two Innovative Medicines Initiative (IMI) Diabetes Research on Patient Stratification (DIRECT) cohorts, cohort 1 (n = 2127) individuals at risk of diabetes; cohort 2 (n = 789) individuals with new-onset T2D., Results: Our multiple regression analysis reveals that fasting total GLP-1 is associated with an insulin-resistant phenotype and observe a strong independent relationship with male sex, increased adiposity, and liver fat, particularly in the prediabetes population. In contrast, we showed that incremental GLP-1 decreases with worsening glycemia, higher adiposity, liver fat, male sex, and reduced insulin sensitivity in the prediabetes cohort. Higher fasting total GLP-1 was associated with a low intake of wholegrain, fruit, and vegetables in people with prediabetes, and with a high intake of red meat and alcohol in people with diabetes., Conclusion: These studies provide novel insights into the association between fasting and incremental GLP-1, metabolic traits of diabetes and obesity, and dietary intake, and raise intriguing questions regarding the relevance of fasting GLP-1 in the pathophysiology T2D., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Obesity is a common metabolic disease characterized by abnormal fat accumulation. It contributes to health issues, such as type 2 diabetes, cardiovascular disease, and dyslipidemia, necessitating continuous management through diet and physical activity. Probiotics, particularly Bifidobacterium lactis IDCC 4301 ( B. lactis Fit™), have shown promise in positively regulating the gut microbiota. Therefore, this study aimed to evaluate the anti-obesity effect of B. lactis IDCC 4301 ( B. lactis Fit™) in obese women. A randomized, double-blind, placebo-controlled, parallel-arm study was performed in 99 volunteers with a body mass index (BMI) of 25-30 kg m -2 . The participants were randomly assigned to probiotics ( n = 49, >5.0 × 10 9 CFU day -1 ) or placebo ( n = 50) groups. Body fat, lipid profiles, and adipokine levels were assessed at baseline and at 12 weeks. After 12 weeks, changes in total fat (placebo -0.16 ± 0.83 kg; probiotics -0.45 ± 0.83 kg; p = 0.0407), trunk fat (placebo -0.03 ± 0.50 kg; probiotics -0.22 ± 0.51 kg; p = 0.0200), and serum triglyceride concentration (placebo 13 ± 60 mg dL -1 ; probiotics -15 ± 62 mg dL -1 ; p = 0.0088) were significantly different between the groups. The difference in total fat mass change between groups among postmenopausal women was greater than that of all women. A significant positive correlation was found between the change in total fat mass and log leptin/adiponectin ratio ( R = 0.371, p = 0.0112) in the probiotics group. In addition, BMI (26.6 ± 1.9 kg m -2 to 26.4 ± 2.0 kg m -2 , p = 0.0009) and leg fat (42 ± 5% to 41 ± 5%, p = 0.0006) significantly decreased in the probiotics group after 12 weeks, but there was no difference in the placebo group. In conclusion, B. lactis IDCC 4301 ( B. lactis Fit™) may be associated with body fat loss through changes in metabolic health parameters, such as serum triglyceride and adipokine levels. The clinical trial registry number is KCT0007425 (https://cris.nih.go.kr).

The relationship of weight change has extended to accelerated ageing, yet little is known about the association between weight change and anti-aging protein α-Klotho. This study included 10,972 subjects from the National Health and Nutrition Examination Survey 2007-2016. Participants were measured body weight and height at baseline and recalled weight at young adulthood and middle adulthood. α-Klotho concentrations were quantified. Generalized linear regression models were used to assess the association between weight change and α-Klotho. Across adulthood, maximal overweight, non-obese to obese, and stable obesity were consistently associated with lower serum Klotho levels. Compared with participants who remained at normal weight, from middle to late adulthood, participants experiencing maximal overweight, moving from the non-obese to obese, and maintaining obesity had 27.97 (95% CI: - 46.57 to - 9.36), 39.16 (95% CI: - 61.15 to - 17.18), and 34.55 (95% CI: - 55.73 to - 13.37) pg/ml lower α-Klotho, respectively; similarly, from young to late adulthood, those had 29.21 (95% CI: - 47.00 to - 11.42) , 34.14 (95% CI: - 52.88 to - 15.40), and 36.61 (95% CI: - 65.01 to - 8.21) lower, respectively. Interestingly, from middle to late adulthood, the absolute weight change values of 590 participants who changed from obese to non-obese were negatively associated with serum α-Klotho. Each 1 kg of weight loss during the process of changing from obese to non-obese brought about a relative increase in α-Klotho levels of 3.03 pg/ml. The findings suggest the potential role of weight management across adulthood for aging., (© 2024. The Author(s).)

We investigated the effects of tobacco smoke exposure and abnormal body weight on selected peptide hormones and their association with metabolic and hormonal disorders in women with polycystic ovary syndrome (PCOS). The study group included 88 women with PCOS and 28 women without the disease. In women with PCOS, chemerin, lipocalin, and apelin concentrations were influenced by overweight and obesity status, with the highest concentrations observed in those with a body mass index (BMI) ≥ 30.0. Exposure to tobacco smoke significantly increased only lipocalin-2 concentration. The disease itself did not affect the concentrations of chemerin, lipocalin, and apelin. Additionally, we found a positive correlation between chemerin concentration and fasting glucose, fasting insulin, and triglycerides levels, while a negative correlation was observed with high-density lipoprotein (HDL-C) concentration. In the smoking subgroup, chemerin concentration was positively correlated with free testosterone concentration and the free androgen index and negatively associated with sex hormone-binding globulin concentration. Our findings indicate that abnormal body weight has a stronger impact than tobacco smoke exposure on metabolic and hormonal disorders in women with PCOS, highlighting the important role of weight control in such individuals. However, smoking appears to be an additional factor that intensifies hormonal disorders associated with adipose tissue.

Background: Exercise is known to provide multiple metabolic benefits such as improved insulin sensitivity and glucose control in individuals with type 2 diabetes mellitus (T2DM) and those at risk. Beyond the traditional exercise dose, exercise timing is perceived as a contemporary hot topic, especially in the field of T2DM; however, the number of intervention studies assessing exercise timing and glucose metabolism is scarce. Our aim is to test the effect of exercise timing (i.e., morning, afternoon, or evening) on the inter-individual response variability in glycemic control and related metabolic health parameters in individuals with T2DM and those at risk during a 12-week intervention., Methods: A randomized crossover exercise intervention will be conducted involving two groups: group 1, individuals with T2DM; group 2, age-matched older adults with overweight/obesity. The intervention will consist of three 2-week blocks of supervised post-prandial exercise using high-intensity interval training (HIIT). Between each training block, a 2-week washout period, where participants avoid structured exercise, will take place. Assessments will be conducted in both groups before and after each exercise block. The primary outcomes include the 24-h area under the curve continuous glucose monitoring-based glucose. The secondary outcomes include body composition, resting energy expenditure, insulin response to a meal tolerance test, maximal aerobic capacity, peak power output, physical activity, sleep quality, and insulin and glucose levels. All primary and secondary outcomes will be measured at each assessment point., Discussion: Outcomes from this trial will provide us additional insight into the role of exercise timing on the inter-individual response variability in glycemic control and other related metabolic parameters in two distinct populations, thus contributing to the development of more effective exercise prescription guidelines for individuals with T2DM and those at risk., Trial Registration: ClinicalTrials.gov NCT06136013. Registered on November 18, 2023., (© 2024. The Author(s).)

Background: Evidence from cohort studies indicates a bidirectional relationship between periodontal disease and type 2 diabetes (T2D), but the underlying mechanisms remain unknown. In this study, we aimed to (1) identify saliva, plasma, and multifluid metabolomic signatures associated with periodontal disease and (2) determine if these signatures predict T2D progression and cardiometabolic biomarkers at year 3., Methods and Results: We included participants from the SOALS (San Juan Overweight Adult Longitudinal Study) (n=911). Metabolites from saliva (k=635) and plasma (k=1051) were quantified using liquid chromatography-mass spectrometry. We applied elastic net regression with 10-fold cross-validation to identify baseline metabolomic signatures of periodontal disease. Multivariable Cox proportional hazards regression and linear regression were used to evaluate the association with T2D progression and biomarker concentrations. Metabolomic profiles included highly weighted metabolites related to lysine and pyrimidine metabolism. Periodontal disease or its 3 metabolomic signatures were not associated with T2D progression in 3 years. Prospectively, 1-SD increments in the multifluid and saliva metabolomic signatures were associated with higher low-density lipoprotein (multifluid: 12.9±5.70, P =0.02; saliva: 13.3±5.11, P =0.009). A 1-SD increment in the plasma metabolomic signature was also associated with Homeostatic Model Assessment for Insulin Resistance (2.67±1.14, P =0.02) and triglyceride (0.52±0.18, P =0.002)., Conclusions: Although metabolomic signatures of periodontal disease could not predict T2D progression, they were associated with low-density lipoprotein, triglyceride, and Homeostatic Model Assessment for Insulin Resistance levels at year 3.

Cardiometabolic risk factors increase the chance of developing cardiovascular disease (CVD) and type 2 diabetes. Most CVD risk factors are influenced by total and regional obesity. A higher risk of developing CVD may be linked to vitamin D deficiency, which is more prevalent in the older population. With the goal of evaluating the association between vitamin D and cardiometabolic risk factors and total and regional obesity in older adults, this research included 25 (OH) vitamin D3 concentrations and biochemical markers associated with cardiometabolic diseases, as well as total and regional adiposity, which was measured by DXA. A total of 1991 older participants in the PoCOsteo study were included. Overall, 38.5% of participants had vitamin D deficiency. After adjusting for confounders, the results of multiple linear and logistic regression suggested an inverse association between vitamin D and body mass index (P = 0.04), waist circumference (P = 0.001), total fat (P = 0.02), android fat (P = 0.001), visceral fat (P < 0.001), subcutaneous fat (P = 0.01), trunk fat (P = 0.006), arm fat (P = 0.03), high systolic blood pressure (P = 0.004), high total cholesterol (P < 0.001), high LDL-cholesterol (P < 0.001), high serum triglycerides (P = 0.001), and high fasting glucose (P < 0.001). Additionally, higher vitamin D concentrations decreased the risk of dyslipidemia by 2%. Our results showed a significant association between serum vitamin D and a number of cardiometabolic risk factors, including total and regional obesity., (© 2024. The Author(s).)

The co-occurrence of multiple chronic metabolic diseases is highly prevalent, posing a huge health threat. Clarifying the metabolic associations between them, as well as identifying metabolites which allow discrimination between diseases, will provide new biological insights into their co-occurrence. Herein, we utilized targeted serum metabolomics and lipidomics covering over 700 metabolites to characterize metabolic alterations and associations related to seven chronic metabolic diseases (obesity, hypertension, hyperuricemia, hyperglycemia, hypercholesterolemia, hypertriglyceridemia, fatty liver) from 1626 participants. We identified 454 metabolites were shared among at least two chronic metabolic diseases, accounting for 73.3% of all 619 significant metabolite-disease associations. We found amino acids, lactic acid, 2-hydroxybutyric acid, triacylglycerols (TGs), and diacylglycerols (DGs) showed connectivity across multiple chronic metabolic diseases. Many carnitines were specifically associated with hyperuricemia. The hypercholesterolemia group showed obvious lipid metabolism disorder. Using logistic regression models, we further identified distinguished metabolites of seven chronic metabolic diseases, which exhibited satisfactory area under curve (AUC) values ranging from 0.848 to 1 in discovery and validation sets. Overall, quantitative metabolome and lipidome data sets revealed widespread and interconnected metabolic disorders among seven chronic metabolic diseases. The distinguished metabolites are useful for diagnosing chronic metabolic diseases and provide a reference value for further clinical intervention and management based on metabolomics strategy.

Both cardiometabolic and chronic inflammatory diseases pose a significant challenge to global public health, particularly among older adults. Here, we investigated the interplay between systemic inflammatory status and the cardiometabolic index (CMI) in older men with adequate weight or obesity. In this observational cross-sectional study, older men (71.79 ± 7.35 years) were separated into groups with normal weight (NW, n = 34) and obesity (O, n = 32) to assess circulating levels of pro- and anti-inflammatory cytokines and CMI. Overall, the O group showed not only a higher inflammatory status but also increased CMI ( p < 0.0001) compared with the NW group. Interestingly, only positive correlations were found between pro- and anti-inflammatory cytokines in both groups. Through multivariate regression analysis, IL-6 (β = -0.2276, p = 0.0003) and IL-10 (β = 0.2023, p = 0.0030) significantly influenced CMI in the NW group. No significant results were found in the O group. Our findings reinforce the effects of obesity in inflammaging, as well as suggesting that the influence of cytokines in CMI occurs in older men with normal weight, since the elevated pro-inflammatory profile observed in older men with obesity can interfere in this effect.

Postmenopausal women often experience hormonal changes and shifts in fat composition, affecting weight gain and obesity. Understanding the link between hormones, especially estrogen and leptin, is key to managing weight and lowering disease risk in menopausal women. The aim of this study was to compare the levels of leptin and estrone in menopausal women with normal weight and obesity. A cross-sectional study was conducted on menopausal women, either normal body mass index (BMI) or obese, at H. Adam Malik General Hospital, Medan, Indonesia. Blood samples were collected to measure leptin and estrone levels using the enzyme-linked immunosorbent assay (ELISA) method. The differences in leptin levels between groups were analyzed using the Wilcoxon test, while the correlation between BMI and leptin was examined using the Pearson correlation test. The disparity in estrone levels in both groups was analyzed using the Mann-Whitney test and the correlations between variables were assessed using the Spearman or Pearson correlation tests as appropriate. The mean leptin levels in normal BMI and obesity groups were 17.73±4.96 and 25.46±12.95 ng/mL, respectively, and were statistically different ( p =0.006). The mean estrone levels in menopausal women with normal BMI and obesity were 943.23±391.79 and 851.38±282.23 ng/mol, respectively and were not statistically different ( p =0.564). A significant positive correlation was found between BMI and leptin level ( r =0.59; p <0.001), while BMI and estrone were not significantly correlated ( r =0.083; p =0.559). In conclusion, leptin level was significantly different between BMI groups and had a strong positive correlation with BMI. This finding could be an important insight in body weight management and disease risk prevention in menopausal women., Competing Interests: All authors affirm that they have no conflicts of interest., (© 2024 The Author(s).)

Aims: To conduct a pooled analysis of Phase 3 trials investigating the efficacy and safety of inclisiran across glycaemic and body mass index (BMI) strata., Materials and Methods: Participants were randomized 1:1 to receive 300 mg inclisiran sodium or placebo twice yearly, after initial and 3-month doses up to 18 months, with background oral lipid-lowering therapy. Analyses were stratified by glycaemic status (normoglycaemia, prediabetes, and diabetes) or BMI (<25, ≥25 to <30, ≥30 to <35, and ≥35 kg/m 2 ). Co-primary endpoints were percentage and time-adjusted percentage change in low-density lipoprotein (LDL) cholesterol from baseline. Safety was also assessed., Results: Baseline characteristics were balanced between treatment arms and across strata. Percent LDL cholesterol change (placebo-corrected) with inclisiran from baseline to Day 510 ranged from -47.6% to -51.9% and from -48.8% to -54.4% across glycaemic/BMI strata, respectively. Similarly, time-adjusted percentage changes after Day 90 and up to Day 540 ranged from -46.8% to -52.0% and from -48.6% to -53.3% across glycaemic/BMI strata, respectively. Inclisiran led to significant reductions in proprotein convertase subtilisin/kexin type 9 and other atherogenic lipids and lipoproteins versus placebo across the glycaemic/BMI strata. The proportions of individuals achieving LDL cholesterol thresholds of <1.8 mmol/L and <1.4 mmol/L with inclisiran increased with increasing glycaemic and BMI strata. Across the glycaemic/BMI strata, a higher proportion of individuals had mild/moderate treatment-emergent adverse events (TEAEs) at the injection site with inclisiran (2.8%-7.7%) versus placebo (0.2%-2.1%)., Conclusion: Inclisiran provided substantial and sustained LDL cholesterol lowering across glycaemic/BMI strata, with a modest excess of transient mild-to-moderate TEAEs at the injection site., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

This study aimed to investigate the levels of serum, gingival crevicular fluid (GCF), and salivary adipokines and their possible relationship with periodontitis and obesity. An electronic search was conducted in the following databases: PubMed/ Medline, Scopus, and EBSCOhost through February 2023. Two independent reviewers screened the titles, abstracts, and full text of all the studies. Studies comparing the levels of adipokines in GCF, serum, and/or saliva in subjects with obesity and periodontitis (group 1), subjects with normal weight and periodontitis (group 2), and subjects with obesity and gingival health (group 3) were included. Meta-analyses and meta-regression were performed on the data from included studies. Seventeen studies with study participants ranging from 30 to 120 were included with subjects in each group ranging from 10 to 40. There was a significant increase in levels of serum TNF-α, leptin, IL-6, and CRP between groups 1 and 2 (p < .05). In GCF, TNF-α and resistin levels were significantly higher (p < .05) in Group 1 vs. 2. Serum level of leptin was higher for group 1 vs. 3 (p < .05). Meta-regression analysis revealed that the obesity definition (body mass index (BMI) cut-off value >25 or >30) was significant for serum resistin (p < .05) and GCF resistin (p < .05) between group 1 and 2. The current analysis indicates that both periodontitis and obesity can modulate the pro-inflammatory cytokines at systemic and local levels. This bidirectional interaction of periodontitis and obesity via the inflammation pathway seems likely plausible. Further studies are required to elucidate this mechanism in more detail., (© 2024 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Aim: Fatty acid esters of hydroxy fatty acids (FAHFA) are a class of bioactive lipids with anti-inflammatory, antidiabetic and cardioprotective properties. FAHFA hydrolysis into its fatty acid (FA) and hydroxy fatty acid (HFA) constituents can affect the bioavailability of FAHFA and its subsequent biological effects. We aimed to investigate FAHFA levels and FAHFA hydrolysis activity in children with or without obesity, and in adults with or without coronary artery disease (CAD)., Materials and Methods: Our study cohort included 20 children without obesity, 40 children with obesity, 10 adults without CAD and 28 adults with CAD. We quantitated plasma levels of four families of FAHFA [palmitic acid hydroxy stearic acid (PAHSA), palmitoleic acid hydroxy stearic acid (POHSA), oleic acid hydroxy stearic acid (OAHSA), stearic acid hydroxy stearic acid] and their corresponding FA and HFA constituents using liquid chromatography-tandem mass spectrometry analysis. Surrogate FAHFA hydrolysis activity was estimated as the FA/FAHFA or HFA/FAHFA ratio., Results: Children with obesity had lower plasma PAHSA (p = .001), OAHSA (p = .006) and total FAHFA (p = .011) levels, and higher surrogate FAHFA hydrolysis activity represented by PA/PAHSA (p = .040) and HSA/OAHSA (p = .025) compared with children without obesity. Adults with CAD and a history of myocardial infarction (MI) had lower POHSA levels (p = .026) and higher PA/PAHSA (p = .041), POA/POHSA (p = .003) and HSA/POHSA (p = .038) compared with those without MI., Conclusion: Altered FAHFA metabolism is associated with obesity and MI, and inhibition of FAHFA hydrolysis should be studied further as a possible therapeutic strategy in obesity and MI., (© 2024 The Author(s). Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Chronic low-grade inflammation is a common feature of obesity and plays a crucial role in the progression of its complications. Vitamin D (VitD) plays an important role in modulating the immune response and regulating inflammation. Thus, this systematic review and meta-analysis aimed to evaluate the effects of isolated VitD supplementation on main inflammatory markers in overweight and obese individuals with no comorbidities and with VitD deficiency. We hypothesized that the increase in serum VitD concentrations after supplementation would significantly reduce the concentrations of inflammatory markers. The search was conducted in Medline/PubMed, SCOPUS, EMBASE, and Web of Science. Eleven randomized placebo-controlled studies were included in the final analysis, with a total of 504 participants and daily (1000-7000 international units) or bolus (100,000-200,000 international units) doses of VitD lasting from 2 to 26 weeks. The VitD supplementation did not influence C-reactive protein (mean difference [MD]: 0.01; 95% confidence interval [CI] -0.37, 0.39; P = .97), interleukin-6 (MD: -0.34; 95% CI -1.09, 0.42; P = .38), and tumor necrosis factor concentrations (MD: -0.02; 95% CI -0.23, 0.19; P = .85). In the analysis considering the studies with a significant increase in serum VitD concentrations, VitD supplementation also did not influence C-reactive protein (MD: -0.17; 95% CI -0.88, 0.54; P = .64), interleukin-6 (MD: -0.47; 95% CI -1.31, 0.37; P = .27), and tumor necrosis factor concentrations (MD: 0.01; 95% CI -1.34, 1.37; P = .98). This meta-analysis suggests that VitD supplementation does not significantly alter inflammatory markers in overweight and obese individuals., Competing Interests: Author Declarations 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 article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aims/hypotheses: Glucagon and glucagon-like peptide-1 (GLP-1) are derived from the same precursor; proglucagon, and dual agonists of their receptors are currently being explored for the treatment of obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). Elevated levels of endogenous glucagon (hyperglucagonaemia) have been linked with hyperglycaemia in individuals with type 2 diabetes but are also observed in individuals with obesity and MASLD. GLP-1 levels have been reported to be largely unaffected or even reduced in similar conditions. We investigated potential determinants of plasma proglucagon and associations of glucagon receptor signalling with metabolic diseases based on data from the UK Biobank., Methods: We used exome sequencing data from the UK Biobank for ~410,000 white participants to identify glucagon receptor variants and grouped them based on their known or predicted signalling. Data on plasma levels of proglucagon estimated using Olink technology were available for a subset of the cohort (~40,000). We determined associations of glucagon receptor variants and proglucagon with BMI, type 2 diabetes and liver fat (quantified by liver MRI) and performed survival analyses to investigate if elevated proglucagon predicts type 2 diabetes development., Results: Obesity, MASLD and type 2 diabetes were associated with elevated plasma levels of proglucagon independently of each other. Baseline proglucagon levels were associated with the risk of type 2 diabetes development over a 14 year follow-up period (HR 1.13; 95% CI 1.09, 1.17; n=1562; p=1.3×10 -12 ). This association was of the same magnitude across strata of BMI. Carriers of glucagon receptor variants with reduced cAMP signalling had elevated levels of proglucagon (β 0.847; 95% CI 0.04, 1.66; n=17; p=0.04), and carriers of variants with a predicted frameshift mutation had higher levels of liver fat compared with the wild-type reference group (β 0.504; 95% CI 0.03, 0.98; n=11; p=0.04)., Conclusions/interpretation: Our findings support the suggestion that glucagon receptor signalling is involved in MASLD, that plasma levels of proglucagon are linked to the risk of type 2 diabetes development, and that proglucagon levels are influenced by genetic variation in the glucagon receptor, obesity, type 2 diabetes and MASLD. Determining the molecular signalling pathways downstream of glucagon receptor activation may guide the development of biased GLP-1/glucagon co-agonist with improved metabolic benefits., Data Availability: All coding is available through https://github.com/nicwin98/UK-Biobank-GCG., (© 2024. The Author(s).)

Background and Aims: Cardiorespiratory fitness has been postulated to lower chronic inflammation in obesity. We assessed sex-specific associations of inflammation with cardiorespiratory fitness in overweight and obese persons., Methods and Results: Peak oxygen uptake (VO 2max ) was measured by treadmill in 566 participants (age 48 ± 9 years, 60% women) with body mass index >27.0 kg/m 2 in the FAT associated CardiOvasculaR dysfunction (FATCOR) study. Fitness was identified from age- and sex specific reference levels of VO 2max . The inflammatory markers C-reactive protein (CRP), serum amyloid A (SAA), kynurenine:tryptophan ratio (KTR) and pyriodoxic acid ratio (PAr) were measured by mass spectrometry. In the total study population 63% had obesity and 74% were cardiorespiratory unfit. Unfit women had the highest fat percentage and the highest serum levels of CRP and SAA (p < 0.05). In multivariable linear regression analyses in women, higher CRP (β -0.15, p = 0.001), SAA (β -0.10, p = 0.03) and PAr (β -0.09, p = 0.03) were associated with lower VO 2max after adjusting for confounders. In multivariable analyses in men, higher PAr (β -0.14, p = 0.02) was associated with lower VO 2max . In multivariable analyses in obese women, higher CRP and PAr remained associated with lower VO 2max (p < 0.05), while in obese men there was no significant association. When normalizing VO 2max for fat-free mass (VO 2maxFFM ) higher CRP, SAA and PAr index were associated with lower VO 2maxFFM in women, while only higher PAr index was associated with lower VO 2maxFFM in men., Conclusion: The association of inflammation with lower cardiorespiratory fitness was more pronounced in women than men, in particular when obesity was present., Clinical Trial Registration: URL: http://www., Clinicaltrials: gov NCT02805478., Competing Interests: Declaration of competing interest HM has received speaker honoraria from Bayer, Pfizer and Boehringer Ingelheim. DC has received speaker honoraria from Orion Pharma and Janssen-Cilag. EG has received speaker honoraria from Bayer and Novo Nordisk., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Rheumatoid arthritis can be classified according to ACPA and RF status. ACPA status may be associated with other pathophysiological differences, e.g., the cytokines driving inflammation. Obesity influences the course of RA, likely involving leptin; the exact mechanisms are not completely understood. This study investigates BMI influence on RA cytokine profiles and the possibility of predicting ACPA status and disease activity measured by Power-Doppler sonography (PDS)., Methods: Patients were examined using a multi-biomarker disease assay and PDS examination of wrists and MCP and PIP joints and stratified according to ACPA status and BMI, using prediction precision to determine BMI cutoff. Analysis was performed using elastic net regularization of logistic and multiple regression. We then attempted to predict ACPA status/PDS activity based on a bootstrap approach., Results: A total of 120 measurements from 95 patients were performed. ACPA status prediction peaked at BMI 26 kg/m 2 , with AUC 0.82. PDS activity prediction had a mean average error of < 1.6 PDS points for all groups. In obese patients, cytokine profiles appear to align in ACPA-positive and -negative patients, with leptin playing a greater role in predicting PDS activity, but with some remaining differences., Conclusion: When stratified according to BMI, cytokine patterns can predict ACPA status and PDS activity in RA with a high degree of precision. This indicates that studies into the pathophysiology of RA should take BMI into account, to differentiate between disease- and obesity-associated phenomena. The underlying pathological processes of ACPA-negative and -positive RA appear different. Multi-cytokine evaluations may provide a deeper understanding of disease processes. Key Points • A multi-cytokine approach combined with ultrasonography and modern mathematical methods can contribute to a deeper understanding of the relationship between systemic and joint inflammation. • BMI influences cytokine profiles in rheumatoid arthritis and appears to "override" disease-specific processes. • Using cytokines only, and adjusting for BMI, it is possible to predict the ACPA status and joint inflammation with considerable precision., (© 2024. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Animal studies showed a detrimental effect of dietary branched chain amino acids (BCAAs) on metabolic health, while epidemiological evidence on dietary BCAAs and obesity is limited and inconclusive. We hypothesized that high dietary and circulating BCAAs are unfavorably associated with obesity in community-dwelling adults. We evaluated the 1-year longitudinal associations of dietary BCAA intake and circulating BCAAs with body fat measures. Body weight, height, and circumferences of the waist (WC) and hip (HC) were measured at baseline and again after 1-year. Body composition and liver fat [indicated by controlled attenuation parameter (CAP)] were also assessed after 1-year. Serum BCAA concentrations at baseline were quantified by liquid chromatography mass spectrometry. Diet was collected using 4 quarterly 3-day recalls during the 1-year. The correlation coefficients between dietary and serum BCAAs were 0.12 (P = .035) for total dietary BCAAs, and ranged from -0.02 (soy foods, P = .749) to 0.18 (poultry, P = .001). Total dietary BCAA intake was associated with increase in body weight (β = 0.044, P = .022) and body mass index (BMI, β = 0.047, P = .043). BCAAs from animal foods were associated with increase in HC, while BCAAs from soy foods were associated with weight gain and higher CAP (all P < .05). Serum BCAAs were associated with higher WC, HC, BMI, body fat mass, visceral fat level, and CAP (all P < .05). These results support that dietary and circulating BCAAs are positively associated with the risk of obesity. More cohort studies with validated dietary assessment tools and long-term follow-up among diverse populations are needed to confirm our findings., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Aim: To investigate growth/differentiation factor 15 (GDF-15) levels in response to antiobesity medications, namely, liraglutide (Lira) and naltrexone/bupropion (N/B), in individuals with overweight or obesity., Materials and Methods: This was a prospective, non-randomized clinical trial with a two-arm, parallel design. A total of 42 individuals with overweight or obesity without type 1 or type 2 diabetes mellitus were enrolled. The participants received either Lira 3 mg or N/B 32/360 mg, along with diet and exercise, according to comorbidities, cost and method of administration. Participants underwent clinical and laboratory measurements at baseline, as well as at the 3- and 6-month time points. Anthropometric measurements and body composition analysis via bioelectrical impendence analysis were performed. Total blood samples for GDF-15 and H-specific GDF-15 were collected in the fasting state and every 30 min for 3 h after the consumption of a standardized mixed meal., Results: Overall, participants' weight was reduced by 9.29 ± 5.34 kg at Month 3 and 11.52 ± 7.52 kg at Month 6. Total and H-specific GDF-15 levels did not show significant changes during the mixed meal compared to values before the meal when all participants were examined at baseline, and at 3 and 6 month follow-ups. No statistical significance was found when participants were examined by subgroup (Lira vs. N/B). No significant differences between treatment groups in postprandial area under the curve (AUC) or incremental AUC values were found at baseline or in the follow-up months with regard to total and H-specific GDF-15 levels., Conclusion: Neither total nor H-specific GDF-15 levels are affected by Lira or N/B treatment in patients with overweight or obesity., (© 2024 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

Our objective was to investigate the relationship between zinc, selenium, and magnesium status and markers of metabolically healthy and unhealthy obesity phenotypes. This was a cross-sectional study with 140 women: metabolically healthy obese women (n = 35), metabolically unhealthy obese women (n = 28), and normal-weight women (n = 77). We have calculated the body mass index, waist-hip ratio, waist-height ratio and some adiposity indices. Additionally, we evaluated endocrine-metabolic parameters and estimated the dietary intake of energy, macronutrients, zinc, selenium, and magnesium. The mineral concentrations in plasma, erythrocytes, and urine were assessed. In obese patients, there was a significant decrease in dietary zinc, selenium, and magnesium intake per kilogram of body weight, as well as lower mineral concentrations in both plasma and erythrocytes. Additionally, these patients exhibited higher urinary mineral levels compared to the control group, regardless of whether they had healthy or unhealthy phenotypes. We observed a significant correlation between deficiencies in zinc, selenium, and magnesium and obesity-associated metabolic disorders, including dyslipidemias and redox status disturbances. This study highlights a connection between deficiencies in zinc, selenium, and magnesium and metabolic disorders linked to obesity, including dyslipidemias, alterations in redox status, and thyroid hormonal dysfunction., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder. VWD is characterized by an abnormal quantity or quality of von Willebrand Factor (VWF). Anemia is often found at presentation for a bleeding disorder evaluation due to chronic blood loss., Objectives/hypothesis: We hypothesized that anemia is associated with elevations in both VWF and factor VIII (FVIII) over baseline. We also hypothesized that obesity would be associated with increased levels of VWF., Methods: We conducted a single-center review of the electronic health record for patients that had proximal von Willebrand profiles and Hb data., Results: We identified 4552 unique subjects with VWF studies and a CBC within 24 h. We found that decreasing hemoglobin inversely correlated with VWF antigen, VWF ristocetin cofactor activity, and FVIII activity. We also found that obesity and Black race were independently associated with increased VWF antigen, activity, and FVIII activity. Hb, race, and body mass index (BMI) continued to be determinants of VWF and FVIII levels in multivariable analysis., Conclusion: Our study demonstrates that anemia, race, and BMI were found to be associated with elevation of VWF antigen, VWF activity, and FVIII levels. As many individuals with anemia present for evaluation for a bleeding disorder, these variables need to be considered., Key Points: - Anemia was found to be associated with elevation of VWF antigen, VWF activity and FVIII levels. - Testing von Willebrand factor at times of anemia may mask a diagnosis of von Willebrand Disease., 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 Ltd.)

Obesity has become a global health concern in recent decades. Utilizing biomarkers presents a promising approach to comprehensively monitor the progress of obesity and its associated health conditions. This review aims to synthesize the available evidence on the correlation between cfDNA level and obesity and to provide insights into the applicability of using cfDNA level as a tool for monitoring progression of obesity. Searches were performed in PubMed and Embase on April 1, 2022. Data and other relevant information were extracted and compiled into a structured table for further analysis. Among 1170 articles screened, 11 articles were included in this review and assessed qualitatively. The results demonstrated that existing evidence mainly focused on three populations, including healthy individuals, cancer patients and pregnant women. Majority of the studies on healthy individuals identified a significant association between cfDNA level and body weight status but not among cancer patients. Varying results were observed among pregnant women at different gestational trimesters. Our review summarized some preliminary evidence on the association between cfDNA level and obesity. More cohort studies in larger scale with comprehensive assessment have to be conducted to examine the applicability of cfDNA as a biomarker for severity and disease progression of obesity., (© 2024 The Authors. Obesity Reviews published by John Wiley & Sons Ltd on behalf of World Obesity Federation.)

The objective of the study was to identify different phenotypes of overweight in women with systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) based on body mass index (BMI) and serum leptin levels, as well as to determine the frequencies of various metabolic disorders, hypertension, and cardiovascular complications (CVCs) in individual phenotypes. The study included 50 women with RA and 46 with SLE aged 18 to 65 years without a history of diabetes and fasting hyperglycemia. In all patients, the concentration of leptin was determined by ELISA, the concentration of insulin was determined by electrochemiluminescence analysis, and the HOMA-IR index was calculated. Hyperleptinemia was diagnosed at leptin concentrations > 11.1 ng/mL; insulin resistance (IR), at HOMA-IR values ≥ 2.77. Three main phenotypes of overweight were distinguished: "classic" (BMI ≥ 25 kg/m 2 + hyperleptinemia), "healthy" (BMI ≥ 25 kg/m 2 , without hyperleptinemia), "hidden" or "latent" (BMI < 25 kg/m 2 + hyperleptinemia), as well as "normal weight" (BMI < 25 kg/m 2 , without hyperleptinemia). Patients with RA and SLE were similar in age (p = 0.4), disease duration (p = 0.2) and BMI (p = 0.5). Hyperleptinemia was found in 46% of women with RA and in 74% of women with SLE (p = 0.005), and IR was found in 10 and 22% of patients, respectively (p = 0.2). The "classic" phenotype of overweight was diagnosed in 30%, "healthy" in 8%, and "hidden" in 16% of cases with RA and in 44%, 0%, and 30% of cases with SLE, respectively. IR was found in 3% and hypertension in 6% of patients with "normal weight." With the "classic" phenotype, IR (29%) and hypertension (66%) were more common than with "normal weight" (p < 0.01 in all cases); with the "hidden" phenotype, significant differences were obtained only in hypertension frequency (45%; p = 0.0012), but not IR (18%). Three out of four women with a history of cardiovascular complications suffered from "classic" overweight, and one patient had a "normal weight." In women with SLE up to 65 years of age, the frequency of hyperleptinemia, but not IR, is higher than in patients with RA. In both diseases, the "classic" overweight phenotype is most common. In RA, a "hidden" phenotype was detected less often than in SLE, at the same time, a "healthy" phenotype is not characteristic of SLE. The frequency of metabolic disorders and hypertension is low with the "normal weight" and "healthy" phenotype, high with the "classic" phenotype, and intermediate with the "hidden" phenotype., (© 2024. Pleiades Publishing, Ltd.)

Objective: Moderate-to-vigorous physical activity (MVPA) improves glucose levels; however, whether its timing affects daily glycemic control remains unclear. This study aims to investigate the impact of lifestyle MVPA timing on daily glycemic control in sedentary adults with overweight/obesity and metabolic impairments., Methods: A total of 186 adults (50% women; age, 46.8 [SD 6.2] years) with overweight/obesity (BMI, 32.9 [SD 3.5] kg/m 2 ) and at least one metabolic impairment participated in this cross-sectional study. MVPA and glucose patterns were simultaneously monitored over a 14-day period using a triaxial accelerometer worn on the nondominant wrist and a continuous glucose-monitoring device, respectively. Each day was classified as "inactive" if no MVPA was accumulated; as "morning," "afternoon," or "evening" if >50% of the MVPA minutes for that day were accumulated between 0600 and 1200, 1200 and 1800, or 1800 and 0000 hours, respectively; or as "mixed" if none of the defined time windows accounted for >50% of the MVPA for that day., Results: Accumulating >50% of total MVPA during the evening was associated with lower 24-h (mean difference [95% CI], -1.26 mg/dL [95% CI: -2.2 to -0.4]), diurnal (-1.10 mg/dL [95% CI: -2.0 to -0.2]), and nocturnal mean glucose levels (-2.16 mg/dL [95% CI: -3.5 to -0.8]) compared with being inactive. This association was stronger in those participants with impaired glucose regulation. The pattern of these associations was similar in both men and women., Conclusions: These findings suggest that timing of lifestyle MVPA is significant. Specifically, accumulating more MVPA during the evening appears to have a beneficial effect on glucose homeostasis in sedentary adults with overweight/obesity and metabolic impairments., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)