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Background: To determine whether obesity and markers of lipid metabolism are associated with radiological hand osteoarthritis (OA) in the Halland County Osteoarthritis (HALLOA) cohort., Methods: In this cross-sectional study, we included 231 participants aged 30-65 from the HALLOA cohort, which began in 2017 and is ongoing. Hand OA was defined as ≥ 2 joint groups (distal interphalangeal, proximal interphalangeal, and carpometacarpal I) with Kellgren-Lawrence grade ≥ 2. The severity of hand OA was classified in terms of the number of affected joint groups (moderate hand OA 2-4 joint groups, severe hand OA 5-6 joint groups). Metabolic profile, including body mass index (BMI), bioimpedance, waist circumference, blood pressure, serum leptin, total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and triglycerides, were obtained. Multicollinearity was assessed with Pearson's correlation and associations with logistic regression analyses adjusting for age, HDL-cholesterol, and central obesity., Results: Two-thirds of the participants were women, and 91 (39%) had hand OA. We found a relationship between LDL-cholesterol and prevalent hand OA in women with an odds ratio of 1.7 (95% CI 1.1-2.6) and an association between LDL-cholesterol and severity of hand OA in women; odds ratio for no hand OA vs. moderate hand OA was 1.6 (95% CI 1.0-2.4) and for no hand OA vs. severe hand OA 2.5 (95% CI 1.2-4.9). There were no significant relationships between hand OA and obesity or serum leptin levels., Conclusion: Circulating LDL-cholesterol levels were associated with the prevalence and severity of hand OA in women but not men., Trial Registration: ClinicalTrials. Gov (NCT04928170), Date of registration: 2017-12-20., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved, in accordance with the Declaration of Helsinki, by the Regional Ethical Review Board, Faculty of Medicine, University of Lund, Sweden (2016/229, 2017/253, and 2020–03866). All individuals gave their informed consent to participate in the study and to publish results on a group level. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Background: Insulin resistance coexist with many metabolic disorders, whether these disorders were promotors or pathway-factors for the association of insulin resistance and cardiovascular disease (CVD) remained unclear. We aimed to investigate the pathways related to elevated the triglyceride-glucose (TyG) index and pathways through elevated TyG index to the occurrence of CVD in Chinese adults., Methods: A total of 96,506 participants were enrolled from the Kailuan study. Bayesian network model with the max-min hill climbing algorithm and maximum likelihood estimation was applied to identify factors and pathways related to the TyG index, and quantitatively infer the impact of associated factors on elevated TyG index and the occurrence of CVD by computing conditional probabilities., Results: A final Bayesian network was constructed with 14 nodes and 25 arcs, creating 28 pathways related to elevated TyG index and 8 pathways from elevated TyG index to CVD. Elevated TyG index was causally associated with CVD, the condition probability was 11.9%. Pathways to elevated TyG index were mainly through unhealthy lifestyles and the subsequent increase in lipid profiles, especially smoking and low-density lipoprotein cholesterol. The most important pathway from elevated TyG index to CVD was through overweight/obesity, hypertension, and chronic kidney disease, with a condition probability of 18.5%. The maximum relative change rate related to elevated TyG index was observed for overweight/obesity (64.3%)., Conclusions: Elevated TyG index was causally associated with the risk of CVD, a combined control of lifestyles and metabolic factors may contribute to the reduction of TyG index and the prevention of CVD., Competing Interests: Declarations. Ethics approval and consent to participate: The study was performed according to the guidelines of the Helsinki Declaration and was approved by the Ethics Committee of Kailuan General Hospital (approval number: 2006-05). All participants were agreed to take part in the study and provided informed written consent. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests. Disclosure: None., (© 2024. The Author(s).)

Polycystic ovary syndrome (PCOS) is one of the most prevalent obesity-related diseases in women of reproductive age. Linkage between diet and PCOS are still controversial. Dietary obesity prevention score (DOS) is one of the new indicators of diet evaluation which have been previously linked to obesity. To the best of our knowledge, this study was the first to investigate the relationship between DOS and PCOS. In this case-control study, 100 newly diagnosed women with PCOS and 100 age-matched women without PCOS were assayed from clinics affiliated to Kashan university of medical sciences, Kashan, Iran. A validated semi-quantitative food frequency questionnaire was used to evaluate food intakes. DOS was calculated based on previous published guideline. Anthropometric measurements were carefully measured by a trained nutritionist. A 10-houres fasting plasma blood sample was collected for all participants. Fasting blood sugar (FBS), triglyceride (TG), total cholesterol (CHOL), High density lipoprotein (HDL), Low density lipoprotein (LDL) and C - reactive protein (CRP) were measured based on laboratory methods. The mean age and BMI of study participants was 23.6 year and 24.9 kg/m 2 respectively. After adjustment for potential confounders, adherence to DOS score was inversely associated with CRP levels. People in the top tertile of DOS had lower CRP level compared to people in the bottom tertile (3.71 compared to 4.48 mg/dl) (P = 0.04). In addition, participant in the top tertile of DOS had marginally significant higher level of FBS compared to participants in the bottom tertile (92.3 vs. 88.9 mg/dl, P = 0.051). After adjustment for all confounding factors people in the highest tertile of DOS had a 46% non-significant lower odds for PCOS compared to people in the lowest tertile (95% CI: 0.23-1.25; P-trend = 0.15). In the present study, an inverse significant association was seen between adherence to DOS and inflammation. However, no significant relationship was observed between DOS and odds of having PCOS. Further longitudinal studies are suggested to investigate the association between DOS and PCOS., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Since sarcopenic obesity (SO) impacts negatively on our health, early detection of SO is essential. However, prevalence of SO in an apparently healthy population has not been well examined. This study aimed to elucidate the prevalence and related factors of SO in middle-aged women, and to investigate useful diagnostic criteria for SO. Body component analyses were conducted on 432 female Osaka University employees aged 30-59 during their health checkups. Healthy (H) and SO groups were defined using cutoff values of 5.7 kg/m 2 for skeletal muscle mass index and 30% for percent body fat. Serum myostatin and insulin levels were additionally measured. Among 432 participants, the prevalence of SO was 6.3%. Grip strength (P < 0.0001) was lower and triglyceride (P = 0.0004) and low-density lipoprotein cholesterol (P = 0.0105) levels, and Homeostatic Model Assessment of Insulin Resistance (P = 0.0262) were higher in the SO group than in the H group. Serum myostatin levels in the SO group were lower than in the H group (3,107 pg/mL vs. 3,957 pg/mL, P = 0.0003). Myostatin levels may be suppressed in individuals with SO without any pre-existing conditions. Our diagnostic criteria for SO could reveal the risks for metabolic-related diseases and may be useful for the early detection of SO., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Background: Existing researches have predominantly focused on the implications of dynamic alterations in the triglyceride-glucose (TyG) index and traditional obesity measures for cardiovascular disease (CVD) risk. However, the application of the weight-adjusted waist index (WWI), which incorporates the dynamically changing body composition factors of weight and waist circumference, alongside the TyG index for predicting CVD risk, remains unexplored. This study explores the relationships between baseline TyG-WWI index and its dynamic changes with CVD risk., Methods: Subjects were drawn from the China Health and Retirement Longitudinal Study. Logistic regression analyses were conducted to determine the relationships between baseline and longitudinal changes in the TyG-WWI index and CVD risk, quantified through odds ratios (ORs) and 95% confidence intervals (CIs). The robustness of results was confirmed via subgroup analyses and E-values. Additionally, restricted cubic spline and quartile-based methods evaluated the relationships between baseline and cumulative TyG-WWI indices and CVD risk., Results: Over two survey waves, 613 CVD events were recorded. Analysis using adjusted multivariable models demonstrated a significant relationship between the cumulative TyG-WWI index and increased CVD risk, with an adjusted OR (95% CI) of 1.005 (1.000, 1.009). Class 2 of the TyG-WWI index change showed greater risk of CVD compared to Class 1, with ORs of 1.270 (1.008, 1.605). However, no significant connection was observed between the baseline TyG-WWI index and CVD risk (OR = 1.007, 95% CI: 0.996, 1.019). These findings were corroborated through extensive sensitivity analyses., Competing Interests: Declarations Ethics approval and consent to participate Ethical approval for this program was granted by the Biomedical Ethics Review Board of Peking University, with approval numbers IRB00001052-11015 and IRB00001052-11014. All participants provided informed consent before inclusion in this program. Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Objective: To extract exosomes from obese and non-obese mice, screen specifically expressed microRNAs by high-throughput sequencing and explore their roles., Methods: An animal obesity model was constructed, and the successful construction of the obesity model was verified by HE staining, Western Blot and RT-qPCR. In addition, exosomes were extracted and verified by Western Blot. High-throughput sequencing was performed on the extracted serum exosomes to screen for differentially expressed microRNAs. fluorescence quantitative RT-PCR (RT-qPCR) was used to validate the differentially expressed miRNAs and explore their functions., Results: 8 microRNAs were up-regulated and 11 microRNAs were down-regulated. mmu-miR-674-5p and X&#95;28316 were significantly down-regulated and had the greatest impact on protein pathways. 8&#95;13258 was significantly up-regulated and affected multiple protein pathways. GO enrichment analysis suggested that the differentially expressed microRNAs were mainly involved in the cleavage of microtubule activity, transferase activity/transferase pentameric acid. GO enrichment analysis suggested that differentially expressed microRNAs were mainly involved in the processes of cleavage microtubule activity, transferase activity/transfer pentamer, and threonine phosphatase/threonine kinase activity.KEGG pathway enrichment analysis showed that differentially expressed microRNAs were mainly involved in the processes of regulating the phosphorylation of TP53 activity, the G2/M DNA damage checkpoint, and the processing of the ends of DNA double-strand breaks. Protein interaction networks were enriched for Stat3, Fgr, Camk2b, Rac1, Asb6, and Ankfy1. Suggesting that they may be mediated by differential genes to participate in the process of insulin resistance. qRT-PCR results showed that the expression trend of mmu-miR-674-5p was consistent with the sequencing results. It suggests that it may be able to participate in the regulation of insulin resistance as a target gene., Conclusion: microRNAs were differentially expressed in serum exosomes of obese and non-obese mice and might be involved in the specific regulation of insulin resistance. mmu-miR-674-5p was differentially expressed significantly and the validation trend was consistent with it, suggesting that it might be able to participate in the regulation of insulin resistance as a target gene., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Obesity and adverse lipid profile leads to female infertility. The cardiometabolic index (CMI) is a promising indicator for predicting obesity-related diseases. The correlation between CMI and female infertility merits further investigation., Methods: The data for this study were acquired from the 2013-2020 National Health and Nutrition Examination Survey (NHANES), with 2333 women enrolled. The cardiometabolic index (CMI) of each participant was calculated as the ratio of triglycerides and high-density lipoprotein cholesterol multiplied by waist-to-height ratio. Weighted multivariate logistic regression models were used to assess the independent correlation between the log-transformed CMI and infertility. Subgroup analyses were carried out to assess the reliability of the findings. Interaction tests were employed to determine whether variables affected infertility by interacting with log CMI., Results: A total of 2333 participants aged 18-45 years were enrolled, 274 of whom were infertile. Log CMI of the infertility group was significantly higher than that of the non-infertility group (P < 0.001). After adjustment for potential confounders, women with higher CMI were at an increased risk of infertility (OR = 2.411, 95% CI: 1.416-4.112), and this correlation was still consistent in subgroups aged under 35 years (P < 0.001). Furthermore, restricted cubic spline analysis showed a positive non-linear relationship between log CMI and infertility., Conclusions: Cardiometabolic index levels are positively correlated with increased risk of infertility in American females. Our study demonstrates the predictive capacity of CMI for female infertility., Competing Interests: Declarations Consent for publication Not applicable. Competing interests The authors declare no competing interests. Ethics approval and consent to participate All data obtained from NHANES were reviewed and approved by National Center for Health Statistics (NCHS) Ethics Review Board and all participants agreed on the survey and signed written consent. The NHANES was conducted in compliance with local laws and institutional guidelines. Since NHANES is a publicly accessible database, no additional ethical approvals are required., (© 2024. The Author(s).)

The aim of this study was to investigate the relationship between red blood cell distribution width and albumin ratio (RAR) levels and mortality in adult patients with sarcopenic obesity in the United States. The study included 1,361 adult patients with sarcopenic obesity from the National Health and Nutrition Examination Survey (1999-2006). The X-tile was used to determine the optimal subgroup thresholds for RAR values, and propensity score matching (PSM) was employed to reduce baseline bias. Cox regression analysis, Kaplan-Meier survival curves, and restricted cubic spline analysis were utilized to assess the relationship between RAR levels and all-cause and cardiovascular mortality. Subgroup analysis and the Subpopulation Treatment Effect Pattern Plot were employed to determine survival advantages across different subgroups. Time-dependent ROC analysis to evaluate the accuracy of RAR level in predicting survival outcomes at different time points. Post-PSM multifactorial Cox regression analyses revealed that RAR was a significant independent predictor of all-cause mortality (HR 1.487, 95% CI: 1.259-1.756) and an independent risk factor for cardiovascular mortality (HR 1.487, 95% CI: 1.260-1.758) in patients with sarcopenic obesity. The survival advantage was consistent across subgroups. Restricted cubic spline analysis indicated an approximate S-shaped association between RAR levels and mortality. Time-dependent ROC curves demonstrate that the areas under the all-cause mortality curves at the RAR level for 1-year, 3-year, 5-year, and 10-year are 0.79, 0.66, 0.64, and 0.63, respectively. The areas under the cardiovascular mortality curve are 0.80, 0.70, 0.66, and 0.61, respectively. Moreover, in comparison to the baseline model lacking covariates, the AUC values of the joint model exhibited heightened levels at various time points. Therefore, We demonstrated that the RAR level is an independent prognostic factor for mortality risk in the American population with sarcopenic obesity, and it is reasonable to consider the RAR level as a simple and effective risk prediction tool., Competing Interests: Declarations Competing interests The authors declare no competing interests., (© 2024. The Author(s).)

Introduction: Preclinical evidence suggests that host obesity is associated with tumor progression due to immuno-metabolic dysfunction, but the impact of obesity on immunity and clinical outcomes in patients is poorly understood, with some studies suggesting an obesity paradox. We recently reported that high-adiposity and low-muscle body composition phenotypes are associated with striking increases in epithelial ovarian cancer (EOC) mortality and we observed no evidence of an obesity paradox. However, whether at-risk versus optimal body composition phenotypes are associated with distinct immuno-metabolic milieus remains a fundamental gap in knowledge. Herein, we defined differentially abundant circulating immuno-metabolic biomarkers according to body composition phenotypes in EOC., Methods: Muscle and adiposity cross-sectional area (cm 2 ) was assessed using CT images from 200 EOC patients in The Body Composition and Epithelial Ovarian Cancer Survival Study at Roswell Park. Adiposity was dichotomized as low versus high; patients with skeletal muscle index (SMI) <38.5 (muscle cm 2 /height m 2 ) were classified as low SMI (sarcopenia). Joint-exposure phenotypes were categorized as: Fit (normal SMI/low-adiposity), Overweight/Obese (normal SMI/high-adiposity), Sarcopenia/Obese (low SMI/high adiposity), and Sarcopenia/Cachexia (low SMI/low-adiposity). Treatment-naïve serum samples were assessed using Biocrates MxP Quant 500 for targeted metabolomics and commercially available Luminex kits for adipokines and Th1/Th2 cytokines. Limma moderated T-tests were used to identify differentially abundant metabolites and cytokines according to body composition phenotypes., Results: Patients with 'risk' phenotypes had significantly increased abundance of metabolites and cytokines that were unique according to body composition phenotype. Specifically, the metabolites and cytokines in increased abundance in the at-risk phenotypes are implicated in immune suppression and tumor progression. Conversely, increased abundance of lauric acid, IL-1β, and IL-2 in the Fit phenotype was observed, which have been previously implicated in tumor suppression and anti-tumor immunity., Conclusion: In this pilot study, we identified several significantly differentially abundant metabolites according to body composition phenotypes, confirming that clinically significant joint-exposure body composition phenotypes are also biologically distinct. Although we observed evidence that at-risk phenotypes were associated with increased abundance of immuno-metabolic biomarkers indicated in immune suppression, additional confirmatory studies focused on defining the link between body composition and immune cell composition and spatial relationships in the EOC tumor microenvironment are warranted., 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 Davis, Hsiao, Barone, Rosario and Cannioto.)

Background: Obesity is a complex, diverse and multifactorial disease that has become a major public health concern in the last decades. The current classification systems relies on anthropometric measurements, such as BMI, that are unable to capture the physiopathological diversity of this disease. The aim of this study was to redefine the classification of obesity based on the different H-NMR metabolomics profiles found in individuals with obesity to better assess the risk of future development of cardiometabolic disease., Materials and Methods: Serum samples of a subset of the Di@bet.es cohort consisting of 1387 individuals with obesity were analyzed by H-NMR. A K-means algorithm was deployed to define different H-NMR metabolomics-based clusters. Then, the association of these clusters with future development of cardiometabolic disease was evaluated using different univariate and multivariate statistical approaches. Moreover, machine learning-based models were built to predict the development of future cardiometabolic disease using BMI and waist-to-hip circumference ratio measures in combination with H-NMR metabolomics., Results: Three clusters with no differences in BMI nor in waist-to-hip circumference ratio but with very different metabolomics profiles were obtained. The first cluster showed a metabolically healthy profile, whereas atherogenic dyslipidemia and hypercholesterolemia were predominant in the second and third clusters, respectively. Individuals within the cluster of atherogenic dyslipidemia were found to be at a higher risk of developing type 2 DM in a 8 years follow-up. On the other hand, individuals within the cluster of hypercholesterolemia showed a higher risk of suffering a cardiovascular event in the follow-up. The individuals with a metabolically healthy profile displayed a lower association with future cardiometabolic disease, even though some association with future development of type 2 DM was still observed. In addition, H-NMR metabolomics improved the prediction of future cardiometabolic disease in comparison with models relying on just anthropometric measures., Conclusions: This study demonstrated the benefits of using precision techniques like H-NMR to better assess the risk of obesity-derived cardiometabolic disease., (© 2024. The Author(s).)

Background: Iron is an essential element for thyroid function. However, no study focuses on the association between iron and thyroid in individuals with obesity. Our research aimed to investigate the iron status in relation to baseline thyroid hormone levels and after laparoscopic sleeve gastrectomy (LSG)., Methods: A total of 216 subjects with obesity were enrolled and divided into low and high iron groups depending on the median value. The association between iron and thyroid hormone was analyzed and compared before and after LSG at the 6-month follow-up in patients who underwent LSG., Results: 1) In all, Total Triiodothyronine (TT3) was significantly higher in high iron than low iron group (P = 0.008). TT3 and thyroid stimulating hormone (TSH) were significantly higher in high iron than low iron group (1.92 ± 0.61 vs. 1.69 ± 0.28 nmol/l, P = 0.029; 2.93 ± 1.66 vs. 1.88 ± 1.03 mU/l, P = 0.002) in females while not in males (all P > 0.05). 2) Iron was significantly positively associated with free triiodothyronine (FT3), free thyroxine (FT4), TT3 and TSH (all P < 0.05). Adjusted for body mass index (BMI), total cholesterol (TCH), high-density lipoprotein cholesterol (HDL-C), fasting insulin (FINS) and homeostatic model assessment of insulin resistance (HOMA-IR), FT3, FT4 and TSH were still significantly associated with iron (all P < 0.05). 3). Regression analysis showed that iron was significantly associated with FT4 (β = 0.338, P = 0.038). 3) LSG led to decreased FT3, FT3, TT3, total thyroxine (TT4) and TSH at 6 months follow-up (all P < 0.05). Changed FT4 was significantly associated with changed iron (r = 0.520, P = 0.009). Subjects with iron decreased had more significant decreased TT4 than subjects without iron decreased (P = 0.021)., Conclusion: Serum iron overload is significantly associated with impaired thyroid function in subjects with obesity. LSG led to improved thyroid function which is associated with a change in iron., Trial Registration: NCT04548232 registration date is on October 9, 2022, registered in https://register., Clinicaltrials: gov/ ., (© 2024. The Author(s).)

The aim of this study was to explore the intricate relationship between serum metabolomics and lifestyle factors, shedding light on their impact on health in the context of breast cancer risk. Detailed metabolic profiles of 2283 female participants in the Trøndelag Health Study (HUNT study) were obtained through nuclear magnetic resonance (NMR) spectroscopy and mass spectrometry (MS).We show that lifestyle-related variables can explain up to 30% of the variance in individual metabolites. Age and obesity were the primary factors affecting the serum metabolic profile, both associated with increased levels of triglyceride-rich very low-density lipoproteins (VLDL) and intermediate-density lipoproteins (IDL), amino acids and glycolysis-related metabolites, and decreased levels of high-density lipoproteins (HDL). Moreover, factors like hormonal changes associated with menstruation and contraceptive use or education level influence the metabolite levels.Participants were clustered into three distinct clusters based on lifestyle-related factors, revealing metabolic similarities between obese and older individuals, despite diverse lifestyle factors, suggesting accelerated metabolic aging with obesity. Our results show that metabolic associations to cancer risk may partly be explained by modifiable lifestyle factors., (© 2024. The Author(s).)

Objective: This study aimed to assess the effects of multi-strain probiotics on anthropometric and biochemical measures in Saudi adults with overweight or obesity., Design: Single-centre, double-blind, placebo-controlled, randomised clinical trial., Setting: Occupational Health Clinics at King Saud University Medical City, Riyadh, Saudi Arabia., Participants: Ninety-three Saudi participants with overweight or obesity were randomly assigned to receive twice-daily doses of either placebo ( n 49) or 30 × 10 9 CFU/g of HEXBIO® containing three Lactobacillus and three Bifidobacterium species ( n 44) in a double-blind manner over a 12-week period, respectively. Both groups adhered to a hypoenergetic diet. Anthropometric measurements, glycaemic indices and lipid profiles were evaluated at baseline and post-intervention., Results: Following the 12-week intervention, no statistically significant differences were found in all between the probiotic group and placebo group comparisons, except for fat intake, where the group*time interaction showed a significant decrease in favour of the probiotic group ( P = 0·02). However, significant within-group reductions were observed in the probiotic group: body weight (-0·9 kg, P = 0·02), HC (-1·5 cm, P = 0·002), energy intake (-387·3 kcal/d, P = 0·002), fasting glucose (-0·7, P = 0·002) and LDL-cholesterol (-0·7, P = 0·02)., Conclusion: Consumption of multi-strain probiotic supplementation over 12 weeks significantly decreased fat intake in Saudi adults with overweight or obesity, with the probiotic group highlighting improved anthropometric and biochemical parameters. Further research is needed to evaluate the long-term clinical significance of this dietary practice and whether it has a meaningful impact on overall health beyond the placebo effect.

Background: Branched-chain amino acid (BCAA) has been reported to be associated with obesity, the association of BCAA with visceral fat area (VFA) and subcutaneous fat area (SFA) remained unclear in patients with type 2 diabetes., Methods: This cross-sectional study was conducted in 284 patients with type 2 diabetes mellitus. Enzyme-linked immunospecific assay was used to measure levels of serum BCAA and branched-chain keto acid (BCKA). VFA and SFA were measured with bio-impedance analysis method. The association between BCAA and VFA was calculated using Pearson correlation and multivariable linear regression analysis., Results: There were significant differences in the means of body mass index, waist circumstance, SFA and VFA among the three groups divided by total BCAA tertiles (all p < 0.05). Compared to patients with lower levels of serum BCAA (the lower tertile group), the means of VFA and SFA were significantly larger in the middle and upper tertile groups (all p < 0.05). However, the differences in above obesity parameters were nonsignificant according to various BCKA tertiles. Pearson correlation analysis also demonstrated that BCAA levels were positive associated with each obesity parameter (p < 0.05). Nevertheless, multivariable linear regression analysis showed that levels of serum BCAA were correlated with VFA, BMI and WC (all p < 0.05) rather than SFA after adjusted for other confounders., Conclusions: levels of serum BCAA were more closely correlated with VFA than SFA, prospective studies should be warranted to further explore the mechanism mediating BCAA and visceral fat accumulation in Human beings., Clinical Trial Number: Not applicable., (© 2024. The Author(s).)

Background: Obesity is a serious health problem with increasing incidence. worldwide and remains one of the most important causes of preventable deaths. We aimed to examine the relationship between Vitamin B12 and Folic acid, which have an important role for human life, and homocysteine is widely recognized for its association with the development of cardiovascular disease, although its role as an independent risk factor remains a topic of ongoing debate., Materials and Methods: We evaluated 126 patients who underwent bariatric metabolic surgery between September 2019-September 2020. In addition to demographic characteristics of the patients, weight, Vitamin B12, folate, HbA1c, cholesterol, triglyceride, ferritin, serum iron, albumin levels at preoperative, postoperative 1st month, 6th month, 12th month follow-ups were analyzed., Results: Patients with the desired biochemical parameters at the determined follow-up points were identified and two groups were formed as RYGB(n = 43) and SG(n = 7) patients. When biochemical parameters were analyzed between the groups, homocysteine, HbA1c, HDL Cholesterol, VLDL Cholesterol, Total Cholesterol, Triglycerides, Ferritin, Serum Iron levels showed a statistical difference (p < 0.001). Folate (p = 0.064) and albumin (p = 0.257) did not show a significant difference over time. The change in vitamin B12 (p = 0.409) over time was not significant in the SG group, whereas a significant difference was observed in the RYGB group (p < 0.001). When we established a marginal model to determine the factors affecting the change in homocysteine over time, vitamin B12 and folate values., Conclusions: The relationship between Vitamin B12, folate and homocysteine is important in order to better understand the complications that develop in bariatric metabolic surgery patients, to prevent possible complications and to better manage the process., (© 2024. The Author(s).)

Background: Glycated albumin (GA) has shown promise in predicting risk of adverse neonatal outcomes (ANO) in pregnant women with type 2 diabetes (T2DM) and gestational diabetes (GDM). However, previous studies showing a negative correlation between GA and body mass index (BMI) suggest that lower predictive cutoffs may be needed in populations with elevated BMI., Methods: We performed a case-control study of prospectively enrolled pregnant women with T2DM or GDM and BMI ≥25 kg/m2 matched to biobanked controls without diabetes. Serum collected during the second and/or third trimesters was used to measure the percentage of GA (% GA). Receiver operating characteristic (ROC) curves were used to examine % GA to predict an ANO composite, including macrosomia, hypoglycemia, respiratory distress syndrome, and/or hyperbilirubinemia for the second and third trimesters., Results: The median BMIs for cases and controls were 34.0 and 31.0 kg/m2, respectively. The area under the ROC curve to predict the ANO composite was significant for second trimester values but ambiguous for third trimester due to its wide 95% CI. A cutoff of 12.3% GA during second trimester showed 100% sensitivity and 73% specificity. Transference of previously published reference ranges did not validate, suggesting lower ranges are needed for women with overweight/obesity., Conclusions: In this pilot study, % GA shows promise to stratify pregnant patients with diabetes and obesity into risk categories for ANO with excellent predictive ability in the second trimester. If this holds in larger studies, using second trimester % GA could allow additional intervention to improve blood glucose control and minimize ANO., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objective: Type 1 diabetes mellitus (DM1) and obesity represent two chronic pediatric diseases characterized by increased risk for renal impairment and cardiovascular disease. The potential usefulness of neutrophil gelatinase-associated lipocalin (NGAL) and matrix metalloproteinase-9 (MMP-9), two novel biomarkers, for predicting early kidney injury or increased cardiovascular risk in children and adolescents with DM1 or obesity, was investigated in this cross-sectional study., Patients and Methods: Serum samples were obtained from children and adolescents aged 12.7 ± 3.8 years old with DM1 (n = 38) or obesity (n = 34) and normal renal function, as well as from healthy controls (n = 24). NGAL and MMP-9 concentrations were measured using commercially available sandwich ELISA kits (NGAL: DY1757-05, MMP-9: DMP900; R&D systems, Minneapolis, MN, USA)., Results: NGAL serum values were found significantly higher in patients with obesity but not in those with DM1. A positive correlation was found in patients with DM1 with diabetes duration, and in the total population with body mass index (BMI) z-score. Also, serum MMP-9 levels were significantly increased in patients with DM1 and in patients with obesity compared to controls., Conclusions: Circulating NGAL and MMP-9 levels may prove useful as surrogate biomarkers to creatinine, glomerular filtration rate (GFR), and albumin excretion rate for early detection of kidney injury and cardiovascular complications in children and adolescents with DM1 or obesity.

Background: In heart failure patients, obesity is associated with better outcomes as compared to normal weight, a phenomenon called the obesity paradox., Objective: To examine if obesity modifies the relationship between NT-proBNP and all-cause and cause-specific mortality in adults without coronary artery disease or heart failure history., Methods: We used the National Health and Nutrition Examination Survey (NHANES) data from 1999 to 2004 and linked it with mortality through December 31, 2019. Participants > 18 years were categorized into normal weight (BMI ≤ 25 kg/m 2 ), overweight (BMI > 25-29.9 kg/m 2 ) and obese (BMI > 29.9 kg/m 2 ). NT-proBNP levels were categorized as low (< 126 pg/mL) or high (≥ 126 pg/mL). Using Cox proportional hazard models, we examined effect modification by obesity using interaction, without and with adjusting for potential confounders., Results: Of the 12 621 participants, 2794 (22%) died during 202 859 person-years follow-up. In adjusted models, normal-weight participants with high NT-proBNP had 2 times higher all-cause mortality risk than those with low NT-proBNP (HR = 2.05; 95%CI = 1.74, 2.41; p < 0.001); however, this mortality risk was 27% lower in obese participants (HR interaction = 0.73; 95%CI = 0.59, 0.92; p = 0.008). Similarly, in normal-weight participants, the difference in other-cause mortality risk between high and low NT-proBNP participants was significant in adjusted models (HR = 2.27; 95%CI = 1.81, 2.85; p < 0.001) and obese participants had 48% lower other-cause mortality risk between those with high and low NT-proBNP (interaction HR = 0.52; 95%CI = 0.36, 0.77; p = 0.001). Conversely, obesity did not modify the relationship between NT-proBNP and cardiovascular or cancer mortality., Conclusions: In patients free of heart failure or coronary artery disease, obesity may be protective against mortality associated with high NT-proBNP., (© 2024 The Author(s). Clinical Cardiology published by Wiley Periodicals LLC.)

Background: This study aimed to evaluate the relationships of conventional and calculated lipid indices with obesity or overweight in patients with type 2 diabetes (T2D)., Methods: In this cross-sectional study, all participants were categorised into three groups: normal weight (18 ≤ BMI < 25), overweight (25 ≤ BMI < 30) and obese (BMI ≥ 30). Conventional lipid indices, including triglyceride (TG), total cholesterol, LDL-C and HDL-C, were measured. Lipid indices, including the atherogenic index of plasma (AIP), non-HDL-C, TC/HDL-C, LDL-C/HDL-C, non-HLD-C/HDL-C (atherogenic index, AI) and lipoprotein combine index (LCI), were calculated. The associations of these lipid indices with obesity and overweight status were evaluated using univariate and multivariate multinomial logistic regression analyses., Results: In this study, 2661 patients with T2D, including 651 patients with normal weight, 1144 with overweight, and 866 with obesity, were recruited. According to a multinomial logistic regression analysis after adjustment for multiple confounders, the odds ratio (OR) was greater for the AIP than for other conventional and calculated lipid indices in overweight and obese patients with T2D. The AIP had a significant relationship with overweight, with an OR of 4.79 (95% CI: 1.65-13.85), and it had a significant relationship with obesity, with an OR of 13.64 (95% CI: 3.96-47.04). According to the ROC curve, with a cut-off value of 0.68, AIP could predict obesity with 82% sensitivity and 55% specificity (AUC = 0.770, 95% CI: 0.729-0.812, p < 0.001)., Conclusion: Compared with other conventional and calculated lipid markers, the AIP is most strongly associated with obesity and overweight in patients with T2D., (© 2024 The Author(s). Endocrinology, Diabetes & Metabolism published by John Wiley & Sons Ltd.)

Background and Objective: The triglyceride-glucose (TyG) index, a surrogate marker for insulin resistance, has been proposed as a predictor of cardiovascular events. However, the combined impact of the TyG index and obesity indicators, such as body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR), on stroke risk was not fully understood. This study aimed to investigate the association between the TyG index combined with these obesity indicators and stroke risk in the Chinese population., Materials and Methods: Data on 17,708 participants aged 45 years or older for this study were collected from the China Health and Retirement Longitudinal Study (CHARLS) from baseline (2011) to the Wave 5 follow-up (2020). Cox proportional hazards model, restricted cubic spline (RCS) and receiver operating characteristic (ROC) analysis were employed to examine the association between the TyG index and its combined obesity-related indicators with stroke. Mediation analysis was conducted to explore the mutual potential mediating role of TyG and obesity indicators in the above relationships., Results: A total of 8,207 participants with an average age of 58.2 years were investigated, of which 11.0% were stroke individuals, 44.80% were men and 84.6% were from rural areas. TyG, TyG-BMI, TyG-WHtR, TyG-WC were significantly higher in stroke subjects than in the non-stroke subjects (P < 0.001), and were significantly and positively associated with stroke in all 3 models (P < 0.05). Restricted cubic spline models revealed nonlinear associations between TyG and TyG-BMI with stroke (P-overall < 0.001, P-nonlinear = 0.003 for TyG, and P-overall < 0.001, P-nonlinear = 0.028 for TyG-BMI), while TyG-WC and TyG-WHtR (P-overall < 0.001 and P-nonlinear > 0.05) demonstrated linear associations with stroke after adjusting for covariates. TyG-WHtR, TyG-BMI and TyG-WC had more robust predictive power than TyG for risk of stroke. TyG-WHtR or TyG-WC had the highest predictive power for stroke (AUC:0.696, 95% CI 0.677-0.715), slightly higher than the other indicators. Associations between TyG, TyG-WC, TyG-WHtR, and TyG-BMI with stroke were found to be stronger among individuals who were ≥ 55 years of age, male. The relationship between TyG and stroke was significantly mediated by BMI, WHtR and WC (15.79%, 21.72%, and 24.06% respectively), while the relationship between these obesity measures and stroke was significantly mediated by TyG (18.48%, 14.45%, and 14.70% respectively)., Conclusion: The combination of TyG and obesity-related indicators was significantly associated with stroke risk, and could improve predictive power for stroke compared to the single TyG. Obesity indicators and TyG mediated each other in their respective associations with stroke risk., (© 2024. The Author(s).)

Background: Sarcopenic obesity (SO) and osteoarthritis (OA) are highly prevalent musculoskeletal conditions that significantly impair health-related quality of life., Aim: This study investigated the association between SO and OA, and explored the potential mediating role of insulin resistance in this relationship. We utilized data from the National Health and Nutrition Examination Survey (NHANES) 1999-2018., Methods: This cross-sectional analysis employs NHANES data collected from 1999 to 2018, including participants aged 18 years and older. SO was assessed using dual-energy X-ray absorptiometry (DXA) measurements. Insulin resistance was estimated using the triglyceride-glucose (TyG) index. OA status was based on self-reported physician diagnosis. Statistical analyses included weighted logistic regression, restricted cubic spline (RCS) interaction analysis, mediation analysis using structural equation modeling (SEM), and receiver operating characteristic (ROC) curve analysis. Subgroup analyses were conducted based on age, sex, and diabetes status., Results: The sarcopenic obese group demonstrated the highest prevalence of OA (23.4 %), hypertension (47.8 %), and diabetes (12.0 %). Additionally, they exhibited elevated levels of triglycerides, cholesterol, glucose, blood urea nitrogen (BUN), creatinine, and uric acid. Logistic regression revealed significant positive associations between sarcopenic obesity, the TyG index, and OA risk. RCS analysis identified significant non-linear relationships and interactions of the TyG index with age, sex, and diabetes status on OA risk. Mediation analysis indicated that the TyG index mediated approximately 4.9 % of the effect of sarcopenic obesity on OA risk. ROC curve analysis demonstrated moderate diagnostic accuracy for the TyG index (AUC = 0.65), which improved when incorporated into the multivariate model (AUC = 0.78). Subgroup analyses confirmed significant associations between the TyG index and sarcopenic obesity with OA risk across different age, sex, and diabetes status categories., Conclusion: Our findings suggest a significant correlation between insulin resistance, as measured by the TyG index, and elevated OA risk in individuals with sarcopenic obesity. Targeting insulin resistance through future research may be a promising avenue to lower OA risk in this population., 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 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: To test the efficacy of time-restricted eating (TRE) in comparison to dietitian-led individualised dietary guidance to improve HbA1c in people with Type 2 diabetes mellitus., Methods: In a parallel groups design, 51 adults (35-65 y) with Type 2 diabetes mellitus and overweight/obesity (HbA1c ≥6.5% (48 mmol/mol), BMI ≥25-≤40 kg/m 2 ) commenced a six-month intervention. Following baseline, participants were randomised to TRE (1000-1900 h) or DIET (individualised dietetic guidance) with four consultations over four months. Changes in HbA1c (primary), body composition, and self-reported adherence (secondary) were analysed using linear mixed models. A non-inferiority margin of 0.3% (4 mmol/mol) HbA1c was set a priori., Results: Forty-three participants (56 ± 8 y, BMI: 33 ± 5 kg/m 2 , HbA1c: 7.6 ± 0.8%) completed the intervention. HbA1c was reduced (P=0.002; TRE: -0.4% (-5 mmol/mol), DIET: -0.3% (-4 mmol/mol)) with no group or interaction effects; TRE was non-inferior to DIET (-0.11%, 95%CI: -0.50% to 0.28%). Body mass reduced in both groups (TRE: -1.7 kg; DIET: -1.2 kg) via ∼900 kJ/d spontaneous energy reduction (P<0.001). Self-reported adherence was higher in TRE versus DIET (P<0.001)., Conclusions: When individualised dietary guidance is not available, effective, and/or suitable, TRE may be an alternative dietary strategy to improve glycaemic control in people with Type 2 diabetes mellitus., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Evelyn B. Parr reports financial support was provided by Diabetes Australia. Evelyn B. Parr reports financial support was provided by Australian Catholic University. If there are other authors, they 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 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG) are effective procedures to treat and manage type 2 diabetes (T2D). However, the underlying metabolic adaptations that mediate improvements in glucose homeostasis remain largely elusive. The purpose of this study was to identify metabolic signatures associated with biochemical resolution of T2D after medical therapy (MT) or bariatric surgery., Research Design and Methods: Plasma samples from 90 patients (age 49.9 ± 7.6 years; 57.7% female) randomly assigned to MT (n = 30), RYGB (n = 30), or SG (n = 30) were retrospectively subjected to untargeted metabolomic analysis using ultra performance liquid chromatography with tandem mass spectrometry at baseline and 24 months of treatment. Phenotypic importance was determined by supervised machine learning. Associations between change in glucose homeostasis and circulating metabolites were assessed using a linear mixed effects model., Results: The circulating metabolome was dramatically remodeled after SG and RYGB, with largely overlapping signatures after MT. Compared with MT, SG and RYGB profoundly enhanced the concentration of metabolites associated with lipid and amino acid signaling, while limiting xenobiotic metabolites, a function of decreased medication use. Random forest analysis revealed 2-hydroxydecanoate as having selective importance to RYGB and as the most distinguishing feature between MT, SG, and RYGB. To this end, change in 2-hydroxydecanoate correlated with reductions in fasting glucose after RYGB but not SG or MT., Conclusions: We identified a novel metabolomic fingerprint characterizing the longer-term adaptations to MT, RYGB, and SG. Notably, the metabolomic profiles of RYGB and SG procedures were distinct, indicating equivalent weight loss may be achieved by divergent effects on metabolism., (© 2024 by the American Diabetes Association.)

Aims: To investigate circulating angiogenic cells in adults with prediabetes and the effect of a structured exercise program., Methods: A cohort of adults with overweight/obesity and either normal glucose (NG) or prediabetes were randomised to receive exercise (Exercise) (as twice weekly supervised combined high intensity aerobic exercise and progressive resistance training, and once weekly home-based aerobic exercise) or an unsupervised stretching intervention (Control) for 12 weeks. Circulating angiogenic T cells, muscle strength, and cardiovascular disease risk factors, including blood lipids, arterial stiffness, central haemodynamic responses, and cardiorespiratory fitness (VO 2 peak) in those with prediabetes (n = 35, 16 Control, 19 Exercise) and NG (n = 37, 17 Control, 20 Exercise) were analysed at baseline and after the 12-week intervention., Results: At baseline, compared with NG those with prediabetes demonstrated reduced VO 2 peak, angiogenic CD31 + CD8 + T cells and VEGFR2 + CD4 + T cells, and increased systolic blood pressure. CD31 + T cells were negatively correlated with cardiovascular disease (CVD) risk. Compared with Control, exercise training increased muscle strength, VO 2 peak, and CD31 + CD4 + and CD31 + CD8 + T cells in NG and prediabetes., Conclusions: Circulating angiogenic CD31 + T cells are decreased in people with prediabetes and are enhanced with exercise training. Exercise increases CD31 + T cells, and through this mechanism it is proposed that it may reduce CVD risk., Trial Registration: Australian New Zealand Clinical Trials Registry number: ACTRN12617000552381., 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 Inc.)

Systemic inflammation is reported in normal-weight obesity (NWO) and metabolically healthy obesity (MHO), which may be linked to their increased cardiovascular disease (CVD) risk. Yet, drivers of this inflammation remain unclear. We characterized factors known to influence inflammatory status (i.e., intestinal permeability, adipose tissue, diet quality, microbiota), and their relationships with measured inflammation, in NWO and MHO, healthy control subjects (CON), and metabolically unhealthy obesity (MUO; N = 80; n = 20/group). Serum indicators of intestinal permeability and inflammation were assessed by ELISA and/or multiplex. Total, visceral, and percent body fat were measured with dual-energy X-ray absorptiometry (DXA). Fecal microbiota composition was assessed via 16S rRNA sequencing ( n = 9-10/group). For C-reactive protein (CRP), MUO > NWO > CON ( P < 0.0001). In MHO, CRP was intermediate and similar to both MUO and NWO. Lipopolysaccharide binding protein (LBP) and the ratio of LBP to soluble CD14 (sCD14) were higher in MHO and MUO vs. CON/NWO ( P < 0.0001). Across correlation and regression analyses, LBP consistently displayed the strongest relationships with CRP in the entire sample ( r = 0.78; β = 0.57; P < 0.0001) and in MHO ( r = 0.74; P < 0.01) but not NWO ( r = 0.37; P = 0.11). Shannon index was higher in CON compared with MUO ( P < 0.05) and inversely correlated with CRP in the full sample ( r = -0.37; P < 0.05). These data are consistent with the notion that intestinal permeability is associated with low-grade inflammation in MHO, which could be implicated in this population's reported CVD risk. NEW & NOTEWORTHY This is the first study to our knowledge to examine biomarkers of intestinal permeability in normal-weight obesity and one of few assessing microbiota compositions in this population. Additionally, we report that individuals with metabolically healthy obesity and metabolically unhealthy obesity displayed similar evidence of intestinal permeability, which was more strongly associated with systemic inflammation than total and visceral adipose tissue mass.

Background: Glucocorticoid metabolites are associated with body composition measures and are altered with weight status. Metabolic and bariatric surgery (MBS) results in significant changes in weight and body composition. However, MBS effects on glucocorticoid metabolites are unknown. Objective: To evaluate (i) changes in the cortisol/cortisone ratio in youth with obesity 12 months after sleeve gastrectomy (SG) compared with nonsurgical controls with obesity (NS), and (ii) associations of these changes with body composition changes. Methods: A total of 38 participants 13-25 years old with obesity (29 female) were followed for 12 months. Half underwent SG, and the other half were followed with routine care (nonsurgical, NS). Fasting blood was assessed for cortisol and cortisone using liquid chromatography-mass spectroscopy as part of metabolomic analysis, and the cortisol/cortisone ratio was calculated. A single-slice MRI of the abdomen was performed to assess subcutaneous and visceral adipose tissue (SAT, VAT ) . Hepatic steatosis was assessed by computed tomography (CT). Results: SG did not differ from NS for baseline clinical characteristics, other than the mean age (SG 18.0 ± 0.46 vs. NS 16.6 ± 0.50 years, P = 0.041), BMI (BMI, 47.23 ± 1.5 vs. 41.32 ± 1.1 kg/m 2 , P = 0.003) weight and VAT, which were higher in SG. Significant reductions were noted over 12 months in BMI, BMI z-score, VAT, and SAT within the SG versus NS groups ( P ≤ 0.001). Over 12 months, groups did not differ for changes in cortisol/cortisone ratio after controlling for age at baseline ( P = 0.293). The ratio trended to decrease within the SG group [-1.40 (-5.08, 0.06), P = 0.080], particularly among those that had completed puberty ( P = 0.048). No associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Conclusions: The cortisol/cortisone ratio trended to decrease 12 months following SG. However, no associations were found between changes in the cortisol/cortisone ratio and changes in body composition. Studies with larger numbers of participants are necessary to confirm these findings.

Aims/hypothesis: The temporal suppression of insulin clearance after glucose ingestion is a key determinant of glucose tolerance for people without type 2 diabetes. Whether similar adaptations are observed after the ingestion of a mixed-macronutrient meal is unclear., Methods: In a secondary analysis of data derived from two randomised, controlled trials, we studied the temporal responses of insulin clearance after the ingestion of a standardised breakfast meal consisting of cereal and milk in lean normoglycaemic individuals (n=12; Lean-NGT), normoglycaemic individuals with central obesity (n=11; Obese-NGT) and in people with type 2 diabetes (n=19). Pre-hepatic insulin secretion rates were determined by the deconvolution of C-peptide, and insulin clearance was calculated using a single-pool model. Insulin sensitivity was measured by an oral minimal model., Results: There were divergent time course changes in insulin clearance between groups. In the Lean-NGT group, there was an immediate post-meal increase in insulin clearance compared with pre-meal values (p<0.05), whereas insulin clearance remained stable at baseline values in Obese-NGT or declined slightly in the type 2 diabetes group (p<0.05). The mean AUC for insulin clearance during the test was ~40% lower in the Obese-NGT (1.3 ± 0.4 l min -1 m -2 ) and type 2 diabetes (1.4 ± 0.7 l min -1 m -2 ) groups compared with Lean-NGT (1.9 ± 0.5 l min -1 m -2 ; p<0.01), with no difference between the Obese-NGT and type 2 diabetes groups. HOMA-IR and glucagon AUC emerged as predictors of insulin clearance AUC, independent of BMI, age or insulin sensitivity (adjusted R 2 =0.670). Individuals with increased glucagon AUC had a 40% reduction in insulin clearance AUC (~ -0.75 l min -1 m -2 ; p<0.001)., Conclusions/interpretation: The ingestion of a mixed-macronutrient meal augments differing temporal profiles in insulin clearance among individuals without type 2 diabetes, which is associated with HOMA-IR and the secretion of glucagon. Further research investigating the role of hepatic glucagon signalling in postprandial insulin kinetics is warranted., Trial Registration: ISRCTN17563146 and ISRCTN95281775., (© 2024. The Author(s).)

Introduction: Female hormones and obesity have an impact on women with asthma. We aimed to describe how these components affect asthma inflammatory processes., Methods: Sex hormones [FSH, LH, estradiol (E2), estrone (E1), testosterone and Δ4 androstenedione (A4)] and serum IL1β, IL13, IL17a, IL-5, IL6, TNF-a were measured from 11 to18 pre- and postmenopausal women with asthma., Results: Premenopausal normal weight women revealed higher levels of IL5 and IL17a than obese women on both days of the menstrual cycle (IL5: D1: 6.4 vs 1.4 pg/ml, p  = .036 and D14: 3 vs 1.4 pg/ml, p  = .045 and IL17a: D1: 13.7 pg/ml vs 10.6 pg/ml and D14: 12.4 pg/ml vs 10.6 pg/ml, p  = .009, respectively). In premenopausal women on D1, Δ4 Androstenedione was positively correlated with IL1β ( p  = .016, r  = 0.733), whereas on D14, Estradiol with IL1β ( p  = .009, r = -.768) and TNF-a with Testosterone ( p  = .004, r = -0.816), and Δ4 Androstenedione ( p  = .002, r = -0.841) negatively. In postmenopausal women, TNF-a was negatively associated with FSH ( p  = .004, r = -0.638), but positively with Testosterone ( p  = .025, r  = 0.526) and IL10 also positively with Estradiol ( p  = .007, r  = 0.610)., Conclusion: Obesity shows a protective role in asthma through the suppression of IL5 and IL17. Estrogens seem to inhibit Th1 and Th2 inflammation, while androgens have a dual role with negative and positive correlations with neutrophilic biomarkers.

Objectives: This study was designed to evaluate the association of four surrogate indexes of IR with NASH in patients with obesity., Methods: A total of 270 patients who underwent bariatric surgery, were included in this cross-sectional study. NASH was diagnosed based on liver biopsies. Binary logistics regression analyses were performed to assess the associations of four surrogate indexes of IR (HOMA-IR, Matsuda index, TyG, and TG/HDL-C) with NASH in patients with obesity. The restricted cubic spline was used to assess the dose-response associations of surrogate indexes of IR with NASH after adjusting for confounding factors., Results: NASH was diagnosed in 136 patients, with a prevalence of 50.37%. Compared with tertile 1, the fully adjusted ORs (95% CIs) of NASH for tertile 3 were 2.711(1.113-6.608) and 0.297 (0.152-0.579) for TyG and Matsuda index. Consistently, per SD increment of TyG were still significantly associated with 64% increased risks of NASH, and per SD increment of Matsuda index were still significantly associated with 38% decreased risks of NASH. In contrast, no significant associations were found between HOMA-IR and TG/HDL-C and the risk of NASH in patients with obesity (all P > 0.05). After adjusting covariates in restricted cubic splines, the risk of NASH decreased with the increment of Matsuda Index levels (P-nonlinear = 0.442, P-overall = 0.007) and with the decrement of TyG levels (P-nonlinear = 0.004, P-overall = 0.001)., Conclusions: In patients with obesity, TyG and Matsuda index were independently related to the risk of NASH after adjustment for traditional risk factors. In addition, compared with HOMA-IR and TG/HDL-C, the Matsuda index and TyG may be more suitable for NASH prediction in patients with obesity., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: Obesity and its associated metabolic disorders, such as T2DM and MeS, are a growing public health problem worldwide. Our goal was the identification of protein patterns that are uniquely characteristic of higher BMI, MeS, and T2DM in a Brazilian population., Experimental Design: Saliva and plasma proteomes, clinical parameters were analyzed in a population from the state of Rio de Janeiro, Brazil, a mixed-race population. Volunteers were sorted by their BMI into normal (n = 29), overweight (n = 25), and obese (n = 15) and were compared with individuals with MeS (n = 23) and T2DM (n = 11)., Results: The Random Forest (RF) predictive model revealed that three clinical variables, BMI, HOMA-IR, and fasting blood glucose, are most important for predicting MeS and T2DM. A total of six plasmatic proteins (ABCD4, LDB1, PDZ, podoplanin, lipirin-alpha-3, and WRS) and six salivary proteins (hemoglobin subunit beta, POTEE, T cell receptor alpha variable 9-2, lactotransferrin, cystatin-S, carbonic anhydrase 6), are enhanced in T2DM and in MeS., Conclusions and Clinical Relevance: Our data revealed similar alterations in protein composition across individuals with abnormal weight gain, T2DM, and MeS. This finding confirms the close link between these conditions at the molecular level in the studied population, potentially enhancing our understanding of these diseases and paving the way for the development of novel diagnostic tools., (© 2024 Wiley‐VCH GmbH.)

Objective: Obesity is often accompanied by insulin resistance (IR) and diabetes. We explored the association between vitamin D levels and IR in non-diabetic obesity., Methods: We conducted a cross-sectional study based on the data of National Health and Nutrition Examination Survey (NHANES) from 2001 to 2018. Non-diabetic individuals (aged ≥20 years) with obesity (BMI ≥ 30kg/m 2 ) were included in the study. And HOMA-IR ≥ 2.5 was defined as IR. The multivariable linear regression models were constructed to evaluate the associations between levels of 25(OH)D and HOMA-IR. We calculated the odds ratio (OR) and 95% confidential intervals (CIs) for associations between 25(OH)D deficiency and IR in obesity using multivariable logistic regression models., Results: Overall, a total of 3887 individuals were included in this study. Serum vitamin D level was significant lower in obesity participants with IR than that of non-IRs. The linear regression models showed that vitamin D level was inversely associated with HOMA-IR in obesity after adjusting for covariables (β=-0.15, 95%CI (-0.28, -0.02), p  = 0.028). And the multivariable logistic regression models indicated an association between vitamin D deficiency and IR in obesity ((OR= 1.38, 95%CI (1.09-1.73), p  = 0.007)). The further stratified regression analyses among different BMI demonstrated that vitamin D deficiency (OR = 1.4, 95%CI (1.05,1.86), p  = 0.022) only contributed to developing IR in class I obesity., Conclusion: This study suggested an association of vitamin D levels with IR in obesity. And vitamin D deficiency contributed to IR in class I obesity.

Nonsoy legumes offer many health benefits, including improved arterial function, reduced cholesterol levels, and better management of cardiovascular diseases and type 2 diabetes. This systematic review and meta-analysis aim to clarify the inconclusive findings from randomized controlled trials (RCTs) by comprehensively evaluating the effects of nonsoy legumes consumption on serum levels of inflammatory biomarkers and Adiponectin. The search encompassed databases up to January 2024, including PubMed, EMBASE, MEDLINE, Scopus, Web of Science, and Cochrane CENTRAL to retrieve all RCTs examining the effects of nonsoy legumes on inflammatory biomarkers or Adiponectin. The effect sizes quantified as mean differences (MD) and standard deviations (SD) of outcomes, and an overall effect estimate was derived using a random-effects model. RCTs examining serum levels of C-reactive protein (CRP), Interleukin-6 (IL-6), Tumor Necrosis Factor-alpha (TNF-α), Interleukin-1β (IL-1β), and Adiponectin were included in the final meta-analysis. Results revealed that consumption of nonsoy legumes increased Adiponectin serum levels (P=.0017) and reduced IL-1β serum levels (P<.0001). However, it may not significantly affect CRP (P=.2951), IL-6 (P=.2286), and TNF-α (P=.6661) levels. Subgroup analyses showed that nonsoy legumes consumption significantly decreased TNF-α serum levels in studies involving healthy participants. Additionally, sensitivity analysis using the leave-one-out method suggested a potential significant reduction in serum levels of IL-6. This study indicates that consuming nonsoy legumes can increase levels of Adiponectin and decrease serum levels of IL-1β in overweight or obese adults., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Numerous studies have shown that vitamin D may play an important role in modulating the inflammatory process. This study aimed to evaluate the effect of vitamin D supplementation on inflammatory markers in patients with orthopedic disorders and obesity. Thirty-three obese subjects were included in the study and were divided into two groups based on their medical condition: acute orthopedic diseases and chronic orthopedic diseases. Inclusion criteria for the research included age 18-75 years, BMI > 30 kg/m 2 , vitamin D deficiency, and no previous vitamin D supplementation. Samples were collected before and after 3 months of 4000 IU/day vitamin D supplementation. The study used enzyme-linked immunosorbent assay (ELISA) and measured serum levels of markers such as chitinase-3-like protein 1 (YKL-40), interleukin 6 (IL-6), interleukin 17 (IL-17), tumor necrosis factor (TNF-α), and adiponectin. After 3 months of vitamin D supplementation, a statistically significant increase in vitamin D and IL-17 levels was observed in the group with acute orthopedic diseases. Similarly, after supplementation, a statistically significant increase in vitamin D, IL-6 and TNF-α levels was observed in the group with chronic orthopedic diseases. Moreover, after vitamin D supplementation, statistically significantly higher adiponectin levels were observed in the chronic orthopedic group than in the acute orthopedic group. Despite high-dose vitamin D supplementation, inflammatory markers increased in acute and chronic orthopedic conditions. Based on our study, vitamin D does not reduce inflammation in patients with orthopedic conditions and obesity.

Introduction: Background: the relationship between vitamin D deficiency and carotid intima-media thickness (CIMT) in children and adolescents with obesity is unknown. The aim of this study was to investigate the correlation between vitamin D levels and CIMT in children and adolescents with obesity. Methods: a total of 440 children and adolescents aged 6-16 with obesity were included in the study. Anthropometric measurements, blood pressure measurements, blood lipids, blood glucose, and vitamin D levels were measured. Bilateral carotid ultrasound was performed to assess CIMT. The relationships between vitamin D levels and CIMT were assessed using multivariate linear regression with Generalized Linear Models and restricted cubic splines. Binary logistic regression analyses were conducted to explore the association between vitamin D status and the risk of abnormal CIMT. Results: vitamin D levels were inversely correlated with CIMT in subjects with serum 25-hydroxyvitamin D [25(OH)D] levels less than or equal to 50 nmol/L (ß = -0.147, 95 % CI [-0.263, -0.030], p = 0.013), but this correlation was not significant in subjects with serum 25(OH)D levels above 50 nmol/L. After correcting for various confounders, the risk of abnormal CIMT was significantly higher in the vitamin D deficiency group (OR = 2.080, 95 % CI [1.112, 3.891], p = 0.022). Conclusions: vitamin D deficiency is an independent risk factor for abnormal CIMT, and vitamin D deficiency may play a promoting role in the atherosclerotic process in children and adolescents with obesity.

Introduction: Introduction: a relationship has been observed between elevated levels of liver enzymes and uric acid with the presence of metabolic syndrome (MS) in the pediatric population. Objective: to compare serum liver enzyme and uric acid levels between adolescents with and without MS. Methods: a cross-sectional study was carried out in adolescents with obesity between 10 and 18 years old. Somatometric data, serum insulin, lipid profile, uric acid levels and liver enzymes (aspartate aminotransferase [AST], alanine aminotransferase [ALT] and gamma-glutamyl transferase [GGT]) were analyzed. Statistical analysis: Student's t test or the Chi-square test was used to evaluate differences between groups. Results: a total of 1095 adolescents with obesity were included (444 with MS and 651 without MS). The group with MS had a higher BMI (with MS 2.28 vs without MS 2.11 p < 0.001), with no difference in body fat (42.9 % vs 42.9 %, p = 0.978). The MS group had significantly higher levels of AST (34.4 vs. 29.5, p = 0.013), ALT (42.2 vs. 34.6, p = 0.003), and uric acid (6.17 vs. 5.74, p = 0.002). comparison to the group without MS. The proportion of ALT (40.5 % vs 29.5 %, p = 0.029) and altered uric acid (58.1 % vs. 45.6 %, p = 0.019) was higher in the MS group. Conclusions: serum levels of ALT, AST and uric acid in adolescents with obesity and MS were higher compared to those without MS. Altered ALT was a risk factor for SM.

Background and Aims: Active Surveillance (AS) is a favored strategy for the management of indolent prostate cancers (PCs). Overweight and obese men harbor an increased risk of cancer progression during AS. We aim to prospectively evaluate the feasibility and outcomes of a ketogenic diet (KD) weight-loss intervention in overweight men with PC., Materials and Methods: Men with PC and a BMI > 25 kg/m 2 undergoing AS were placed on an 8-week ad libitum KD program before a scheduled surveillance biopsy to assess the impact on clinical grade group (CGG). Blood ketone levels were tracked to ensure compliance. BMI, PSA, and inflammatory marker data (TNF-α, TNFR1, TNFR2, sICAM-1, sVCAM-1, IL-6, IL1-RA, CRP, and SAA) were collected before and after the KD intervention. A Shapiro-Wilk test was performed to assess the normality of all continuous study variables. Paired t-tests and Wilcoxon rank sum tests were utilized to compare normally and non-normally distributed study outcomes, respectively., Results: Ten AS patients aged 62.1 (±5.4) years were enrolled with an average BMI of 31.7 kg/m 2 (±11.8). Post-KD intervention mean blood ketone levels were 0.32 (±0.12) mmol/L with a mean BMI reduction of 7.4% ( p < 0.0003). There were no meaningful changes in PSA or inflammatory biomarkers ( p > 0.05). Nine patients completed re-biopsy following a KD with four patients showing no evidence of cancer; one downgraded to a lower CGG; two had unchanged CGG scores; and two had higher CGG scores compared to baseline., Conclusions: Short-term KD interventions for BMI reduction are feasible in men undergoing AS for PC and may result in favorable pathological effects without inflammatory marker changes. Larger studies with longer follow-up are needed to explore whether KD-induced weight loss can improve clinical outcomes with AS in PC.

Background: Numerous studies have indicated a growing prevalence of hyperuricemia. Elevated levels of serum uric acid (SUA) have been established as influential factors in conditions such as obesity, metabolic syndrome, diabetes mellitus, gout, and cardiovascular disease. Overweight and obesity are closely related to an increase in SUA. Our objective is to demonstrate the mediating role of liver enzyme in the correlation between body mass index (BMI) and SUA., Methods: A total of 5925 adults aged 18 to 65 were included in this cross-sectional study. Logistic regression and mediation analysis were used to investigate the relationship between BMI and hyperuricemia as well as liver enzyme levels. Standard methods were used to determine the biochemical indexes, including SUA, liver enzymes, and blood lipids in the collected samples., Results: The study revealed that the prevalence of hyperuricemia was 28.0%. Furthermore, the prevalence of overweight and obesity was as high as 48.5%, with 70.7% of this subgroup presenting with hyperuricemia. There was a positive correlation between BMI and hyperuricemia, and elevated levels of liver enzymes (ALT, AST, GGT) were associated with a higher risk of hyperuricemia. The study also observed a positive correlation between BMI and liver enzymes (ALT, AST, GGT). The study findings suggested that ALT, AST, and GGT played significant mediating roles in the relationship between BMI and SUA. Specifically, the unadjusted model revealed that ALT and GGT accounted for 22.12% and 18.13% of the mediation effects, respectively., Conclusions: The study found that BMI is associated with hyperuricemia, where liver enzyme abnormalities may have a mediating role. It is suggested that being overweight or obese may affect liver enzyme levels, leading to increased SUA levels. Controlling weight and liver enzyme levels may help prevent and treat hyperuricemia., (© 2024. The Author(s).)

Chronic systemic inflammation is a hallmark of obesity. This cross-sectional study aimed to investigate the association between metabolic obesity phenotypes and inflammatory markers in Korean adults ( N = 21,112; mean age: 50.9 ± 16.6). Metabolic obesity phenotypes were categorized into metabolically healthy non-obesity (MHNO), metabolically unhealthy non-obesity (MUNO), metabolically healthy obesity (MHO), and metabolically unhealthy obesity (MUO) based on body mass index and the presence of any metabolic abnormalities. High-sensitivity C-reactive protein (hs-CRP) levels were measured. Multiple linear regression was used to determine the association between obesity phenotypes and hs-CRP levels. In the male sample, compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 22.3% (95% confidence interval; CI: 14.7-30.3%), 15.8% (95% CI: 2.6-30.7%), and 12.5% (95% CI: 3.0-22.9%) increase in the hs-CRP levels, respectively. The association between metabolic obesity types and hs-CRP levels was stronger among the female sample; compared to the MHNO type, the MUNO, MHO, and MUO types were associated with a 30.2% (95% CI: 22.8-38.2%), 16.0% (95% CI: 6.5-26.4%), and 22.8% (95% CI: 13.6-32.8%) increase in the hs-CRP levels, respectively. Our findings indicate a varying profile of systemic inflammation across different metabolic obesity phenotypes.

ApoB insertion/deletion (ins/del) genetic variant (rs11279109) is thought to be related to cardio-metabolic markers and obesity. This association has the potential to be modified by dietary patterns. Since the majority of studies concerned the role of dietary acid load (DAL) or ApoB in type 2 diabetes mellitus (T2DM) and its complications independently, and due to the insufficient data regarding the possible interactions between ApoB genetic variants and DAL on anthropometric and metabolic markers, we aimed to study the interaction between this genetic variant and dietary acid load (DAL) on cardio-metabolic markers, along with leptin among Iranian individuals with T2DM. 700 T2DM patients were randomly recruited. A validated semi-quantitative food frequency questionnaire was used for DAL calculation including potential renal acid load (PRAL) and net-endogenous acid production (NEAP). The polymerase chain reaction was used for genotyping the ApoB ins/del (rs11279109). The general linear model was applied to find the interactions in the crude and adjusted models. Patients with del/del genotype (rs11279109) with high PRAL intake have lower low-density lipoprotein cholesterol (LDL-C) (P interaction = 0.004), LDL/HDL ratio (P interaction = 0.02), total cholesterol (TC) (P interaction = 0.04), triglyceride (TG) (P interaction = 0.04), leptin (P interaction = 0.04) and interleukin-18 (IL-18) (P interaction = 0.04). Moreover, the interaction of gene and DAL in the PRAL method on TG concentration (P = 0.04), waist circumference (WC) (P = 0.04), and LDL/HDL ratio (P = 0.04) were significant. Eventually, a positive relationship was observed between the presence of the del/del genotype (rs11279109) and higher levels of TG, TC, LDL-C, IL-18, and LDL/HDL, in individuals with lower adherence to DAL, after adjusting for various covariates. Further studies are needed to investigate and confirm these findings., (© 2024. The Author(s).)

Background & Objectives: Obesity is a common comorbidity in heart failure, yet effective pharmacological options for weight loss in these patients are limited. Semaglutide, a glucagon-like peptide 1 receptor agonist, has shown promise for weight reduction in obese adults. This study aims to evaluate semaglutide's impact on weight loss, functional status, and clinical outcomes in obese patients with heart failure., Methods: A retrospective analysis was conducted on all consecutive obese (BMI > 30 kg/m²) patients with heart failure at the University Hospital Bonn outpatient clinic from July 2019 to July 2022. Propensity score matching paired patients receiving semaglutide as an add-on therapy (SEMA) with those on medical therapy alone (Control)., Results: Among 1,942 patients with heart failure screened, 26 matched pairs were identified. At one year, the SEMA group exhibited significant weight loss, with a mean BMI reduction of -2.91 kg/m² (95% CI: -4.27 to -1.55; p < 0.001), while the control group showed a non-significant mean change of -0.41 kg/m² (95% CI: -1.08 to 0.26; p = 0.22). The difference in BMI between the two groups was statistically significant (mean difference: 3.42 kg/m², 95% CI: 1.43 to 5.42; p = 0.001). Improvements by at least one NYHA class were observed in 65% of the SEMA group (p < 0.001) compared to 15% of the control group (p = 0.18). The SEMA group also showed a significant increase in 6-minute walk distance (6MWD), with a mean difference of 75 m between the groups at one year (95% CI: 0.53 to 150.02; p = 0.049). NT-proBNP levels significantly decreased in the SEMA group (p < 0.001) compared to the control group (p = 0.78), with a statistically significant difference in NT-proBNP between the groups (p = 0.048). Both improvements in 6MWD and reductions in NT-proBNP were significantly correlated with BMI percentage reductions., Conclusions: Semaglutide was associated with significant weight reduction in obese patients with heart failure, accompanied by improved NYHA classification and 6-minute walk distance. Larger, multi-center trials and prospective, randomized controlled trials are warranted. These studies should focus on assessing long-term outcomes, optimizing dosage, and exploring the potential cardiovascular benefits beyond weight reduction., (© 2024. The Author(s).)

Testosterone deficiency has been recognized as a significant health concern and is closely related to obesity. The weight-adjusted-waist index (WWI) is an innovative adiposity parameter that is superior to BMI in certain aspects, but its relationship with testosterone levels has not been elucidated. The aim of this study was to investigate the relationships of the WWI with total testosterone levels and testosterone deficiency. Data from the National Health and Nutrition Examination Survey (NHANES, 2011-2016) were utilized. The WWI was calculated as waist circumference (cm) over the square root of weight (kg), and a total testosterone level of less than 300 ng/dL was defined as testosterone deficiency. Weighted multivariable regression models were used to assess the associations. A total of 6859 participants were included, 26.28% of whom were testosterone deficient. The WWI was inversely related to total testosterone levels (β = -49.93, 95% CI: -60.07, -39.78, P < 0.001) and positively associated with testosterone deficiency (OR = 1.46, 95% CI: 1.23, 1.72, P < 0.001) in the fully adjusted model. A significant nonlinear relationship was also detected between WWI and testosterone deficiency (P for nonlinearity = 0.004) with an inflection point of 9.486 cm/√kg. The associations were consistent in the subgroup analysis (all P > 0.05), except for the participants with eGFR < 60 mL/(min*1.73m 2 ) and hypertension. A higher WWI was linked to lower total testosterone levels and a greater risk of developing testosterone deficiency, especially among those who had an eGFR ≥ 60 mL/(min*1.73m 2 ) and were nonhypertensive., (© 2024. The Author(s).)

Erectile dysfunction (ED) is a common male sexual health problem that can be associated with obesity. This study aimed to identify serum metabolic differences and pathways related to ED in obese men using non-targeted metabolomics techniques. We included 54 obese male patients with (n = 27) and without (n = 27) ED. We collected 5 mL of fasting elbow vein blood and analyzed serum metabolites using ultra-high-performance liquid chromatography-mass spectrometry. Multivariate statistical methods (principal component analysis and orthogonal partial least squares discriminant analysis) were used to identify differential metabolites between the groups. Finally, pathway analysis using the Kyoto encyclopedia of genes and genomes database identified 4 differential metabolic pathways in obese men with ED compared to obese men without ED. A total of 77 differential metabolites were identified in obese men with ED compared to the control group (obese men without ED) using a threshold of variable importance in the projection > 1 and P < .05. Pathway analysis revealed 4 main differences: glycine, serine and threonine metabolism, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and D-glutamine and D-glutamate metabolism. Specific metabolites associated with these pathways included betaine aldehyde, choline, L-threonine, phosphatidylcholine, L-serine, and D-glutamine. Our findings suggest abnormalities in fatty acid metabolism, phospholipid metabolism, and amino acid metabolism between obese men with and without ED. Metabolites such as betaine aldehyde, choline, L-threonine, phosphatidylcholine, L-serine, and D-glutamine may be potential biomarkers for distinguishing obese men with ED., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study investigates the impact of habitual late calorie intake on glucose metabolism in adults with overweight or obesity and diet or metformin-controlled prediabetes or type 2 diabetes independently of body weight, fat mass, energy intake or diet composition. Participants (n = 26) were classified as Later Eaters (LE) if ≥45% daily calories were consumed after 5 pm and Early Eaters (EE) if not, based on daily caloric intake assessed over 2-wk. EE and LE did not differ in anthropometrics or daily energy intake, but LE consumed more carbohydrates (p = 0.038) and fats (p = 0.039) after 5 pm. Fasting glucose, insulin, and C-peptide did not differ between groups but LE exhibited higher glucose concentrations after an oral glucose tolerance test (p = 0.001), even after adjusting for body weight, fat mass, energy intake and diet composition (p < 0.05). Glucose results remained when participants with T2D were excluded (p = 0.031). After diabetes status adjustment, differences in glucose concentrations were higher in LE for time 30 (p = 0.028) and 60 min (p = 0.036). LE, compared to EE, had poorer glucose tolerance, independent of body weight, fat mass, daily energy intake and diet composition. ClinicalTrials.gov: NCT04465721., (© 2024. The Author(s).)

Background: Obesity is a predisposing risk factor for type 2 diabetes mellitus (T2DM). Actually, not only obese/overweight but also nonobese/lean individuals may be prone to T2DM. This study is aimed at identifying the contribution of adipose tissue to the development of nonobese diabetes (NOD) and obese diabetes (OD). Methods: Serum samples from the nonobese nondiabetes (NOND, n = 47, age = 46.8 ± 8.4, BMI ≤ 23.9 kg/m 2 ) controls, NOD ( n = 48, age = 50.7 ± 6.5, BMI ≤ 23.9 kg/m 2 ) and OD (n = 65, age = 49.8 ± 10.2, BMI ≥ 28 kg/m 2 ) patients were utilized to measure the expression of metabolic indicators, adipocytokines, inflammatory factors. Different adipose depots from offspring with corresponding blood glucose and obesity levels of a spontaneously diabetic gerbil line with various degrees of diabetic penetrance and body weights were examined for adipocytokines and inflammation factors detected by ELISA and western blot. Adipose tissue volume and fat cell size of the gerbils were evaluated by magnetic resonance imaging and immunohistochemistry, respectively. Results: The study yielded four key findings. Firstly, in comparison to the NOD group, the OD group exhibited more severe insulin resistance (IR) and metabolic dysfunction in both patients and gerbils, attributed to higher visceral adipose tissue mass and larger fat cell sizes. Secondly, in gerbils, gonadal fat deposition was linked to obesity development, whereas kidney fat deposition correlated with obesity and diabetes occurrence. Thirdly, in both patients and gerbils, the interplay between adiponectin and leptin levels in serum may significantly influence the development of obesity and diabetes. Lastly, heightened expression of MCP3 in gerbils' kidney adipose tissue may serve as a pivotal factor in initiating obesity-associated diabetes. Conclusions: Our study, which may be considered a pilot investigation, suggests that the interaction of adipocytokines and inflammation factors in different adipose depots could play diverse roles in the development of diabetes or obesity., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2024 Hongjuan Fang et al.)

Objective: The objective of the present study was to examine the effect of calorie restricted diet (CRD) plus inulin supplementation on serum levels of tryptophan (Trp), kynurenine (Kyn) and Trp/Kyn ratio in obese women with major depressive disorder (MDD)., Results: In this double-blind placebo-controlled randomized clinical trial, 51 obese women (BMI = 30-40 kg/m 2 ) with mild MDD were assessed for depression level using Hamilton depression rating scale (HDRS). The patients were randomly allocated into either "Prebiotic group" (received 10 g/day inulin) or "Placebo group" (received 10 g/day maltodextrin). All participants also received individualized CRD. Fasting serum levels of Trp, Kyn, and Trp/Kyn ratio were assessed at baseline and after 8 weeks. Results showed slightly greater increases in serum levels of Trp and Trp/Kyn ratio as well as reductions in serum level of Kyn and HDRS score in prebiotic group than placebo group. However, between group differences in these parameters as well as HDRS score were not statistically significant after adjusting for baseline variables at the end of the trial. Results indicates that CRD accompanied by inulin supplementation (10 g/day) did not influence serum levels of Trp, Kyn and Trp/Kyn ratio as well as HDRS score after 8 weeks., Trial Registration: The trial was registered in the Iranian registry of clinical trials at 2018-08-02 ( https://www.irct.ir/ ; registration number: IRCT20100209003320N15)., (© 2024. The Author(s).)

Background: Mice experiments have underscored the efficacy of pharmacological inhibition of advanced glycation endproducts (AGEs) through the use of soluble receptors for advanced glycation endproducts (sRAGE) in mitigating obesity-linked metabolic disruptions and insulin resistance. However, human studies have presented conflicting findings regarding the correlation between circulating sRAGE levels and insulin resistance, as well as glucose tolerance. Here, we aimed to delve deeper into the relationship between sRAGE levels and systemic insulin sensitivity., Methods: Plasma sRAGE levels, hyperinsulinemic-euglycemic clamp, and continuous glucose monitoring were measured in two independent cross-sectional case-control studies [cohort 1 (n = 180) and cohort 2 (n = 124)]. In addition, a subgroup of 42 participants with obesity were followed for 12 months. In 14 of these participants, weight loss was achieved through bariatric surgery intervention., Results: Our results revealed a significant association between plasma sRAGE levels and both insulin sensitivity and glycemic control parameters, even after adjustments for age, sex, and BMI. Furthermore, longitudinal analysis demonstrated that interventions aimed at weight loss led to reductions in fasting glucose and HbA1c levels, concurrently with increases in sRAGE levels., Conclusions: These findings underscore that sRAGE levels were strongly associated with insulin sensitivity and glycemic control, suggesting a possible role of sRAGE in preserving insulin sensitivity and maintaining glycemic control, which should be confirmed in further studies., (© 2024. The Author(s).)

Background: Hyperuricaemia is common among obese children and adolescents, and is closely related to insulin resistance. The aim of this study was to explore the relationships between youth insulin resistance and hyperuricaemia, as well as their relationships with lifestyle factors in youths, to provide early guidance on the risk factors for hyperuricaemia in adolescents., Methods: This study included 233 adolescents aged 10 to 20 years. Insulin resistance was evaluated via the homeostasis model assessment-insulin resistance (HOMA-IR) method. Binary logistic regression analysis was used to assess the associations of HOMA-IR with hyperuricaemia status and serum uric acid (UA) levels. The participants were subsequently divided into two groups, the noninsulin resistant group (HOMA-IR ≤ 3.2) and the insulin resistant group (HOMA-IR > 3.2), to further explore the factors that may affect the serum UA level. Finally, the predictive ability of different indicators of hyperuricaemia was evaluated via the ROC curve., Results: Binary logistic regression analysis revealed a significant increase in the risk of developing hyperuricaemia for individuals with elevated HOMA-IR (p < 0.001) and insulin resistance (p < 0.01). Spearman's correlation analysis revealed a significant positive linear correlation between HOMA-IR and serum UA levels (r = 0.4652, p < 0.001). Among insulin-resistant adolescents, UA levels were positively correlated with weight ratings, frequency of staying up late, and sugary beverages intake. Notably, individuals who engaged in 1-3 h of weekly exercise had the lowest UA levels. The area under the ROC curve for HOMA-IR was 0.847 (cut-off value = 2.165, p < 0.001), and the optimal prediction model included HOMA-IR, BMI z-score, and other lifestyle factors (AUC: 0.870, p < 0.001))., Conclusion: HOMA-IR was identified as an independent risk factor for the development of hyperuricaemia and could be used as a sensitive indicator for the prediction its development in adolescents. In insulin-resistant adolescents with hyperuricaemia, maintaining normal weight, engaging in physical exercise for 1-3 h per week, avoiding staying up late and limiting sugary beverages intake are recommended to reduce the prevalence of hyperuricaemia among adolescents., (© 2024. The Author(s).)

Introduction: Obesity is characterized by low-grade chronic inflammation, which can be modulated by lipid mediators derived from omega-3 ( n -3) polyunsaturated fatty acids (PUFA). Obesity is a multifactorial disease, where genetic and environmental factors strongly interact to increase its development. In this context, the FADS1 gene encodes the delta-5 desaturase protein, which catalyzes the desaturation of PUFA. The rs174547 genetic variant of FADS1 has been associated with alterations in lipid metabolism, particularly with decreases in eicosapentaenoic acid (EPA) and arachidonic acid (AA) concentrations., Objective: To analyze the effect of an n -3-supplemented diet on the fatty acid profile and composition in red blood cells (RBCs) of obese subjects carrying the rs174547 variant of the FADS1 gene., Methodology: Seventy-six subjects with obesity were divided into two groups: omega-3 (1.5 g of n -3/day) and placebo (1.5 g of sunflower oil/day). The dietary intervention consisted of a four-month follow-up. Anthropometric, biochemical, and dietary variables were evaluated monthly. The total fatty acid profile in RBC was determined using gas chromatography. The rs174547 variant was analyzed through allelic discrimination., Results: The n -3 index (O3I) increased at the end of the intervention in both groups. Subjects carrying the CC genotype showed significant differences (minor increase) in n -6, n -3, total PUFA, EPA, DHA, and the O3I in RBCs compared to TT genotype carriers in the n -3 group., Conclusions: The diet supplemented with EPA and DHA is ideal for providing the direct products that bypass the synthesis step affected by the FADS1 rs174547 variant in subjects carrying the CC genotype. The O3I confirmed an increase in n -3 fatty acids in RBCs at the end of the intervention.

Introduction: Several blood markers of inflammation are elevated in prostate cancer (PCa) and have prognostic value. Little is known about the relationship between these markers, PCa, and other factors associated with chronic inflammation, such as smoking and obesity. We analyzed the interaction between neutrophil and platelet counts indexed to lymphocyte count (NLR and PLR, resp.) and clinically significant PCa (csPCa), accounting for the potential confounding factors of systemic inflammation., Methods: NLR and PLR were evaluated in a multicenter prospective study in 443 patients. CsPCa was defined as a Gleason ≥ 4 + 3. Differences between patients with csPCa and non-csPCA were evaluated using the chi-square test, analysis of variance or the Kruskal-Wallis test. Multivariable logistic regression analysis adjusted for smoking, hypertension, diabetes, and cardiovascular disease, and in separate models, either body mass index or waist-to-hip ratio was used to characterize the relationship between inflammation and csPCa., Results: None of the factors such as plateletcrit, NLR, and PLR were significantly different between patients with csPCa or non-significant PCa. After adjustment, there was no association between PLR, NLR, plateletcrit or platelet count and csPCa. In an exploratory analysis, there was no association between markers of inflammation and PSA levels > 10 ng/mL. When testing different NLR cutoffs to predict csPCa in ROC analysis, none reached a clinically meaningful value., Conclusion: In contrast to previous studies, we found no significant association between easily available blood markers of inflammation and indices of PCa aggressiveness. Further research is required to determine whether inflammation promotes PCa. (ClinicalTrials.gov: NCT03127631. Date of registration: April 25, 2017., (© 2024. The Author(s).)

Background: Fasting glucose is higher in pregnancies with obesity (OB); less is known about postprandial (PP) and nocturnal patterns when the diet is eucaloric and fixed or about the continuous-glucose-monitor (CGM) metrics that predict neonatal adiposity (NB%fat). We hypothesized that continuous glucose monitors (CGMs) would reveal higher glycemia in OB vs. normal weight (NW) during Early (14-16 weeks) and Later (26-28 weeks) gestation despite macronutrient-controlled eucaloric diets and elucidate unique predictors of NB%fat., Methods: In a prospective, parallel-group comparative study, a eucaloric diet (NW: 25 kcal/kg; OB: 30 kcal/kg) was provided (50% carbohydrate [20% simple/30% complex; of total calories], 35% fat, 15% protein) to Early and Later gestation groups wearing a blinded CGM for three days. CGM metrics (mean fasting; 1 h and 2 h PP; daytime and nocturnal glucose; percent time-in-range (%TIR: 63-140 mg/dL); PP excursions; and area-under-the-curve [AUC]) were interrogated between groups and as predictors of NB%fat by dual X-ray absorptiometry(DXA)., Results: Fifty-four women with NW (BMI: 23 kg/m 2 ; n = 27) and OB (BMI: 32; n = 27) provided their informed consent to participate. Early, the daytime glucose was higher in OB vs. NW (mean ± SEM) (91 ± 2 vs. 85 ± 2 mg/dL, p = 0.017), driven by 2 h PP glucose (95 ± 2 vs. 88 ± 2, p = 0.004). Later, those with OB exhibited higher nocturnal (89 ± 2 vs. 81 ± 2), daytime (95 ± 2 vs. 87 ± 2), 1 h (109 ± 3 vs. 98 ± 2), and 2 h PP (101 ± 3 vs. 92 ± 2) glucose (all p < 0.05) but no difference in %TIR (95-99%). Postprandial peak excursions for all meals were markedly blunted in both the Early (9-19 mg/dL) and Later (15-26 mg/dL). In OB, the Later group's 24 h AUC was correlated with NB%fat (r = 0.534, p = 0.02). Despite similar weight gain, infants of OB had higher birthweight (3528 ± 107 vs. 3258 ± 74 g, p = 0.037); differences in NB%fat did not reach statistical significance (11.0 vs. 8.9%; p > 0.05)., Conclusions: Despite macronutrient-controlled eucaloric diets, pregnancies with OB had higher glycemia Early and Later in gestation; the Later 24 h glucose AUC correlated with NB%fat. However, glycemic patterns were strikingly lower than current management targets.