This study examines how sitting for a long time affects the prevalence of multiple metabolic diseases early in life, focusing on differences between men and women. Researchers analyzed data from over 21,000 young adults aged 18 to 45, finding that men who sat for more than 6 h a day showed a higher prevalence of metabolic diseases like obesity, high blood pressure, and diabetes. Specifically, sitting 6–8 h daily was associated with a 22

The rising prevalence of unhealthy lifestyles characterized by chronic sleep deprivation (SD) combined with a high-fat diet (HFD), represents a significant health concern. However, the synergistic effects of these factors on metabolic disorders remain poorly understood. To address this, we developed a model of 'Unhealthy Lifestyles Zebrafish' (UHL) to investigate the interaction between chronic SD and HFD. We demonstrated that SD synergistically exacerbated HFD-induced obesity, lipid accumulation, and the progression of Metabolic Dysfunction-Associated Fatty Liver Disease (MAFLD). Compared to zebrafish exposed to HFD alone, the UHL zebrafish exhibited more severe metabolic dysregulation, including elevated cholesterol levels, metabolic inflammation, and bile acid imbalance. Mechanistically, this synergy was driven by melatonin deficiency resulting from SD, which triggered NF-κB activation. This activation led to the upregulation of pro-inflammatory cytokines (TNF-α, IL-6, IL-1β). Crucially, exogenous melatonin supplementation reversed these detrimental effects by inhibiting NF-κB activation and restoring metabolic homeostasis. Conversely, pharmacological activation of NF-κB antagonized melatonin's protective effects. This study confirms the critical role of the melatonin/NF-κB axis in mediating the synergistic impact of sleep deprivation and a high-fat diet on obesity and MAFLD. These findings advocate for integrated lifestyle interventions targeting both sleep quality and dietary habits in metabolic health management.

Purpose:This study aims to investigate changes in interleukin-1β (IL-1β) and pancreatic function before and after weight loss in obese individuals undergoing lifestyle interventions, as well as the relationship between these two factors, thereby providing scientific evidence for the comprehensive management of obesity and related metabolic disorders. Patients and Methods:This observational study included 36 obese patients who completed a lifestyle intervention program, along with 18 healthy controls. Glucose metabolism parameters and IL-1β levels were measured at baseline and after intervention. Normally distributed variables were analyzed using independent or paired samples t-tests, while non-normally distributed variables were analyzed using Mann-Whitney U and Wilcoxon signed-rank tests. Spearman correlation analysis was performed to assess bivariate relationships. Subsequently, multivariate linear regression models were employed to adjust for potential confounders and to evaluate the independent associations between ΔIL-1β and pancreatic function indices. Results:IL-1β levels were significantly correlated with both obesity indicators and insulin resistance parameters. Notably, after adjusting for confounding factors, changes in IL-1β levels (ΔIL-1β) showed significant independent associations with changes in the modified beta cell function index (ΔMBCI), homeostatic model assessment of insulin resistance (ΔHOMA-IR), and Stumvoll metabolic clearance rate of glucose (ΔStumvoll MCR120). Conclusion:The reduction in IL-1β levels is independently associated with improvements in pancreatic β-cell function and insulin resistance, suggesting a potential role of IL-1β in the metabolic benefits of weight loss. However, the study's small sample size limits the statistical power, warranting validation in larger cohorts.

The fasting insulin to high-density lipoprotein cholesterol ratio (FINS/HDL-C) is a newly identified insulin resistance (IR) marker. And the correlation between FINS/HDL-C and metabolic dysfunction-associated steatotic liver disease (MASLD) has not yet been explored, our study investigated the association between FINS/HDL-C and MASLD severity. This cross-sectional study included 330 participants with overweight/obesity and MASLD. Demographic information and biochemical indicators were collected, and IR markers including FINS/HDL-C, homeostatic model assessment for insulin resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), and triglyceride glucose index (TyG), were calculated. MASLD severity was assessed using the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) determined by FibroScan. The relationship between FINS/HDL-C and MASLD severity was evaluated and compared with that of other IR markers. Participants with higher CAP and LSM exhibited significantly higher FINS/HDL-C (P < 0.05). Even in the fully adjusted linear regression model, FINS/HDL-C remains positively correlated with CAP (β = 0.28, 95

Background:Obesity is an established contributor to hepatic steatosis. Despite weight control efforts, the incidence of steatosis and its associated hepatic complications continues to increase, highlighting the critical need to identify obesity-related pathogenic mechanisms for developing effective therapeutic strategies. Aim:This study aims to explore the association between thyroid hormone sensitivity indicators and hepatic steatosis assessed by controlled attenuation parameter (CAP) values in euthyroid individuals with overweight/obesity. Methods:Sensitivity to THs, was evaluated using TFQIFT3, TFQIFT4, TSHI, TT4RI, TT3RI, and FT3/FT4 ratio. Hepatic steatosis was diagnosed via Vibration-controlled Transient Elastography (VCTE). Linear regression, binary logistic regression, and restricted cubic spline regression (RCS) were used to analyze the associations between these composite indices and CAP levels. Bayesian mediation analysis was performed to assess the mediation effect of liver enzymes and lipids on the relationship between sensitivity parameters to THs and CAP. Results:Compared to the non-severe hepatic steatosis group, the severe hepatic steatosis group exhibited significantly higher levels of TFQIFT3, and FT3/FT4 ratio (all P < 0.05). After adjustment for multiple risk factors, TFQIFT3 (β = 25.38, 95% CI 10.21-40.55) and the FT3/FT4 ratio (β = 210.92, 95% CI 116.37-305.47) increased with CAP (P<0.001), but not in TFQIFT4 (p = 0.071). These associations remained significant in binary logistic regression analysis and RCS. Further mediation analysis and subgroup analysis showed that the correlation was not mediated by blood lipid and liver enzyme impairment, and remained stable across all subgroups. Conclusion:The correlation between TH sensitivity and hepatic steatosis was significantly stronger in TFQIFT3 than in TFQIFT4. TFQIFT3 and the FT3/FT4 ratio can be used as new indicators for predicting hepatic steatosis in individuals with overweight/obesity.

Lifestyle modification is the cornerstone of metabolic dysfunction-associated steatotic liver disease (MASLD) management, but effective adjunctive therapies are lacking. We examined the association between serum 25-hydroxyvitamin D [25(OH)D] and non-invasive parameters of MASLD severity and evaluated whether vitamin D3 supplementation, as an adjunct to lifestyle modification, influenced these parameters in adults with overweight or obesity and MASLD. A cross-sectional analysis of 505 adults with overweight or obesity and MASLD assessed associations between serum 25(OH)D and non-invasive liver parameters. In a subsequent 24-week randomized controlled trial (RCT), 132 participants were randomly assigned 1:1 to the vitamin D3 group (14,000 IU/week plus lifestyle modification) or the control group (lifestyle modification alone). In the cross-sectional analysis, serum 25(OH)D levels were independently and inversely associated with controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) (both P < 0.001). In the RCT, the vitamin D3 group showed a greater reduction in CAP than the control group [adjusted difference = -41.2 dB/m; 95 https://www.chictr.org.cn/showproj.html?proj=123441 .

This study aimed to explore the effects of hypoglycemic agents with weight loss effect plus a high protein diet and moderate exercise on weight loss and diabetes remission in adults with obesity and newly diagnosed prediabetes/type 2 diabetes (T2D). Participants with obesity and newly diagnosed prediabetes or T2D (n = 61) were randomly allocated to standard treatment group (conventional medication and lifestyle guidance for 12 months) and intensive treatment group (in addition to conventional medication, a high protein diet and moderate exercise were given for 12 months). By month 12, 60 (98.4

BACKGROUND AND AIM:The joint effects of longitudinal changes in body mass index (BMI) and estimated glomerular filtration rate (eGFR), on hyperuricemia risk remain unclear. We aimed to investigate this relationship and identify high-risk trajectories for hyperuricemia prediction. METHODS AND RESULTS:In this prospective community-based cohort (2018-2023), we enrolled 5329 Chinese adults ≥18 years with serial measurements of BMI, eGFR, and serum urate. Restricted cubic splines (RCS) nested in the Cox regression framework were applied to assess dose-response relationships between BMI, eGFR and hyperuricemia risk. Group-based trajectory modeling identified distinct BMI/eGFR patterns, with multivariable-adjusted Bayesian Cox proportional hazards models quantifying their associations with incident hyperuricemia. Over an average follow-up period of 3.25 years, 489 individuals developed hyperuricemia, resulting in an incidence rate of 15.05 per 100 person-years. Each unit increase in BMI during follow-up was associated with a 21 % (95 % CI: 14 %-30 %) increased risk for hyperuricemia. Similarly, each 10-unit decrease in eGFR correlated with a 12 % (95 % CI: 5 %-19 %) elevation in hyperuricemia risk. The RCS curves indicated linear associations between changes in BMI and eGFR and hyperuricemia risk (all p values < 0.001). The low eGFR trajectory showed a marginal HR of 1.52 (95 % CI: 1.02-2.37). The HRs for the high BMI trajectory group was 3.89 (95 % CI: 2.35-6.38). Notably, the influence of eGFR variability was more pronounced in men, while that of BMI was stronger in women. CONCLUSIONS:Longitudinal patterns of rising BMI and declining eGFR synergistically predict hyperuricemia development, with clinically relevant sexual difference.

Background Insulin therapy is still the most important treatment for T2DM, but the discussion about whether insulin brings more benefits or harms to T2DM patients has not stopped. Therefore, we used high-throughput RNA sequencing to investigate the role of insulin in T2DM and its molecular changes. Method We collected peripheral blood samples from 16 patients with T2DM, and performed RNA-seq on peripheral blood mononuclear cells. Bioinformatics analysis and machine learning were uesd to identify the key differential genes and transcription factor networks. In addition, we performed the flow cytometry and staining to observe ROS level and endothelial-monocyte adhesion in PBMCs of both groups. Results A total of 529 differential genes were identified by bioinformatics analysis. 8 genes were identified as key genes, among which IL-6 had high importance in the random forest model. In transcription factor analysis, IL-6, RETN, CTSG and ELANE have abundant transcriptional regulatory relationships. Flow cytometry showed that ROS production, phagocytosis, leukocyte adhesion in insulin treatment group were lower than that in non-insulin treatment group. Conclusion Insulin therapy is bidirectional, it can cause islet B cell damage and vascular complications, but also can reduce the level of inflammation and oxidative stress.

Background:Hyperinsulinemia (HI) is a common endocrine metabolic disorder in obesity and is closely associated with cardiovascular disease. Aim:This study aims to investigate the effects of progressive weight reduction on HI and cardiovascular risk factors. Methods:We enrolled 68 patients with overweight or obesity. Body composition assessments, clinical indicator sampling and a 75g-oral glucose tolerance test were conducted at baseline and after 12-month weight loss to assess HI and insulin sensitivity. And the people were divided into four groups based on the percent of weight loss (<10%, ~20%, ~30%, >30%) to study the remission of HI and changes in body composition and cardiovascular risk factors. Results:A total of 66 participants were studied at the end. Progressive weight loss significantly reduced plasma glucose and insulin (P<0.001, P for trend <0.001) and did not progressively reduce cardiovascular risk factors (P for trend <0.001). The greater the percentage of weight loss, the greater the remission rate of insulin resistance and hyperinsulinemia (P for trend <0.001), which reaches 100% when weight loss exceeds 30%. After adjusting for factors such as age, gender, and medication usage, remission of HI was still associated with progressive weight loss. Conclusion:With progressive weight loss, people with overweight or obesity experienced further improvements in glycemic outcomes, body compositions, HI and insulin resistance.

BACKGROUND:Adiposity, insulin resistance, and lipid metabolism abnormalities are established risk factors for hyperuricemia; however, the impact of exercise on these factors remains unclear. Moreover, there is a lack of prospective data regarding the predictive value of these risk factors concerning the timing of hyperuricemia onset. METHODS:From 2017 to 2023, data were prospectively collected from annual health checkups and questionnaires. The primary outcome was the incidence of hyperuricemia, stratified into early-onset (age < 40 years) and late-onset (age > 60). Key predictive indicators included the systemic immune-inflammation index (SII), systemic inflammation response index (SIRI), non-high-density lipoprotein cholesterol/high-density lipoprotein cholesterol ratio (NHHR), triglyceride-glucose index (TyG), and body mass index (BMI). The effects of various exercise types on these indicators were analyzed using multivariate quantile regression models. Cox regression analyses were conducted to assess the hazard ratios (HRs) and their 95% confidence intervals (CIs) of these inflammation and metabolic indictors on hyperuricemia risk. Mediation analyses were performed to explore the roles of these indicators. RESULTS:Out of 23,534 participants free of hyperuricemia at baseline, 2,555 developed hyperuricemia. Regular exercise was linked to lower inflammation and metabolic indicators, particularly in their higher quantiles. SIRI, BMI, NHHR, and TyG were associated with increased hyperuricemia risk (log-rank p < 0.001), with stronger effect in the early-onset group. For early-onset hyperuricemia, HRs of the highest quantile (Q4) for NHHR, TyG, and BMI > 30 were 1.64 (95% CI, 1.27-2.12), 1.70 (1.32-2.29), and 1.84 (1.29-2.63), respectively. SIRI and SII at Q3 also indicated increased risk. NHHR mediated 5.63% of the overweight/obesity effect on overall hyperuricemia, increasing to 10.86% in early-onset cases, while TyG mediated 12.01%, which was similar to the early-onset group (11.85%). CONCLUSIONS:Higher systemic inflammation, adiposity, and impaired lipid and glucose metabolism significantly increase hyperuricemia risk, particularly in early-onset cases. Exercise as interventions may reduce the levels of these risk factors, especially among individuals in higher quantiles.

To observe the effect of glucagon-like peptide-1 receptor agonists (GLP-1RA) combined with metformin and metformin monotherapy on proinsulin changes in patients with obesity following weight loss. To explore whether the changes of proinsulin were related to GLP-1RA or secondary to weight reduction. 100 adults with obesity (BMI ≥ 28 kg/m2) were randomized to 24-week treatment with liraglutide plus metformin (GLP-1RA group, n = 50) or metformin alone (1500 mg/day; control group, n = 50). All participants received standardized lifestyle interventions, including a 500 kcal/day energy-deficit diet and 150 min/week moderate intensity aerobic exercise. Visceral fat area (VFA) and body fat percentage (PBF) were measured using multifrequency bioelectrical impedance analysis (InBody770; Biospace Inc., Korea). Proinsulin levels were quantified via a chemiluminescent enzyme-linked immunosorbent assay (Human Proinsulin ELISA Kit, BayBio). Multiple regression analyses were applied to adjust for age, gender, baseline BMI, and treatment allocation, isolating weight loss effects from direct drug actions. The weight, blood lipids and glucose metabolism indexes of two groups were significantly improved, and the effects were more significant in the GLP-1RA group. Correlation analysis showed that proinsulin change was positively correlated with body weight change and VFA change, which persisted after adjusting for confounding factors such as age, gender, baseline body mass index (BMI), and GLP-1RA medication. GLP-1RA demonstrate superior weight loss effects and improvements in lipid and glucose metabolism in patients with obesity. However, the reduction in proinsulin levels is primarily attributed to the magnitude of weight loss itself, independent of GLP-1RA use.

Abstract Background Hepatic controlled attenuation parameter (CAP) is a novel marker for quantifying hepatic fat accumulation. Insulin resistance (IR) plays a major role in the pathogenesis and natural history of hepatic steatosis. This study aimed to investigate the possible relationship between CAP value and IR. Methods This study included a total of 420 patients with overweight or obesity who came to the obesity clinic at Tianjin Union Medical Center. Vibration-controlled transient elastography examination was conducted to detect CAP and liver stiffness measurement (LSM) values. Body composition, including visceral fat area (VFA), and body fat mass (BFM), was evaluated by the direct segmental multi-frequency bioelectrical impedance analysis (BIA). The associations between CAP value, body mass index (BMI), VFA, BFM and homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed. Results CAP value was positively associated with HOMA-IR (r = 0.568, P < 0.001), the strength of which was much stronger than BMI, VFA, and BFM. In multivariate linear regression, CAP value and HOMA-IR showed a significant positive association (adjusted β = 0.015, 95% CI 0.007–0.022, P < 0.001). Subgroup analysis suggested no significant interaction between CAP value and HOMA-IR across age, BMI, LSM, hypertension, and sex groups (all P for interaction > 0.05). Conclusions Hepatic CAP value is more remarkably than other obesity markers associated with HOMA-IR in individuals with overweight or obesity, regardless of age, BMI, LSM, hypertension, and sex.

Background: Growing evidence has demonstrated the important roles of gut microbiota and short chain fatty acids, especially acetate, propionate and butyrate, in the development of obesity and metabolic diseases.To date, the effects of acetate, propionate and butyrate on human adiposity and glucose metabolism remain controversial.This study aimed to explore the associations of systemically acetate, propionate and butyrate with obesity and glucose homeostasis in patients with type 2 diabetes (T2D) and obesity.Methods: A total of 12 patients with T2D and obesity and 8 age-and sex-matched healthy individuals with BMI <24 kg/m 2 were enrolled in this study.Height, weight, body composition, blood pressure, biochemical indices, a 75-g oral glucose tolerance test, and plasma acetate, propionate and butyrate were measured at baseline.Then, participants in T2D group were given a weight control therapy, in addition to conventional medication, and all the measurements were repeated 12 months from baseline.The direct segmental multi-frequency bioelectrical impedance analysis was used to assess body composition.Acetate, propionate and butyrate levels were determined by liquid chromatography coupled to tandem mass spectrometry.Results: Butyrate concentration significantly increased from baseline after obvious weight loss (P<0.05).Correlation analysis showed that propionate was negatively correlated with percent of body fat (PBF) and 2-h plasma glucose (2-h PG) (P<0.05), and butyrate was negatively associated with body mass index, visceral fat area, PBF and 2-h PG (P<0.05).No association was found between acetate and obesity.Conclusion: Butyrate and propionate are negatively correlated with obesity and glucose levels in patients with T2D and obesity.

OBJECTIVE:Interleukin-27 (IL-27), a potential mediator linking obesity to inflammatory diseases, is considered an important candidate for regulating obesity. The present study evaluated the relationship of IL-27 with obesity and insulin resistance (IR) and further investigated the changes in IL-27 levels after weight loss. METHODS:The study analyzed 405 participants, of whom 62 with overweight or obesity completed one year of lifestyle intervention. The body compositions, including percent of body fat (PBF), visceral fat area (VFA), skeletal muscle mass (SMM), and visceral fat area to skeletal muscle mass ratio (VSR), were assessed using the bioelectrical impedance analysis method. Serum IL-27 levels were measured using the enzyme-linked immunosorbent assay (ELISA). RESULTS:IL-27 levels increased significantly with the increase in body mass index (BMI) (P < 0.001). Moreover, IL-27 levels were positively correlated with PBF, VFA, and VSR. Homeostatic model assessment for insulin resistance (HOMA-IR), the inverse of hepatic insulin sensitivity (1/HISI), adipose tissue insulin resistance (Adipo-IR), and homeostasis model assessment-adiponectin (HOMA-AD) increased significantly with each quartile of IL-27 levels (all P < 0.001). IL-27 levels significantly decreased after weight loss (P < 0.001). CONCLUSIONS:IL-27 was positively correlated with obesity, HOMA-IR, 1/HISI, Adipo-IR, and HOMA-AD. IL-27 levels significantly decreased after weight loss.

Objective:To investigate the impact of sarcopenia on the 10-year risk of atherosclerotic cardiovascular disease (ASCVD) among individuals with type 2 diabetes mellitus (T2DM).Methods:This study included the clinical, laboratory, and body composition data of 1491 patients with T2DM who were admitted to the Department of Endocrinology and Metabolism at Tianjin Union Medical Center from July 2018 to July 2023. The China-PAR model was utilized to evaluate cardiovascular disease risk. Associations between ASCVD risk and various clinical parameters were analyzed, and the relationship between body composition parameters and ASCVD risk was assessed using logistic regression.Results:The analysis revealed that T2DM patients with sarcopenia had a higher 10-year ASCVD risk compared to those without sarcopenia, with reduced muscle mass independently predicting an increased risk of cardiovascular disease. This association was significant among female T2DM patients, while male T2DM patients with sarcopenia showed a marginally higher median ASCVD risk compared to their non-sarcopenic counterparts. ASCVD risk inversely correlated with body muscle parameters and positively correlated with fat content parameters. Specifically, height- and weight-adjusted fat mass (FM, FM%, FMI) were identified as risk factors for ASCVD. Conversely, muscle parameters adjusted for weight and fat (ASM%, SMM%, FFM%, ASM/FM, SMM/FM, FMM/FM) were protective against ASCVD risk. These findings highlight the critical role of sarcopenia in influencing cardiovascular disease risk among Chinese patients with T2DM, as predicted by the China-PAR model.Conclusion:This study highlights the importance of sarcopenia in T2DM patients, not only as an indicator of ASCVD risk, but possibly as an independent risk factor in this demographics.

BACKGROUND:While short sleep duration is linked to higher risk of non-alcoholic fatty liver disease (NAFLD), the combined effects of sleep timing and sleep duration on NAFLD are less explored. METHODS:In this cross-sectional study of 39,471 participants from Beijing-Tianjin-Hebei region of China, self-reported sleep information and ultrasonography-diagnosed NAFLD were obtained from Jan 2018 to Jan 2020. Sleep timing was categorized based on sleep midpoint: early-type (before 2:00 AM), intermediate-type (2:00-2:30 AM), and late-type (after 2:30 AM). We used multivariable logistic regression to explore the relationship between sleep timing, duration, and NAFLD. We analyzed sleep midpoint and duration categorically and continuously, and conducted stratification analyses by age, sex, body mass index, hypertension, diabetes, and dyslipidemia. RESULTS:Intermediate-type (OR: 1.15, 95% confidence interval: 1.05-1.26) and late-type sleep timing (OR: 1.08, 1.00-1.16) were associated with higher NAFLD risk compared to early-type. Additionally, longer sleep duration was linked to lower risk (OR: 0.92, 0.90-0.95 per hour increase). Notably, intermediate to late-type sleepers with normal sleep duration (7 to <8 h) exhibited a 20% higher NAFLD risk compared to early-type sleepers with the same duration (OR: 1.20, 1.04-1.39). The increased NAFLD risk associated with intermediate to late sleep timing was particularly evident in men, hypertension, and prediabetes or diabetes participants. CONCLUSIONS:Intermediate to late sleep timing, even with normal sleep duration, is associated with increased NAFLD risk. These findings underscore the importance of considering both sleep timing and sleep duration for NAFLD prevention, especially in men and individuals with cardiometabolic conditions.

Aims: Insulin resistance (IR) is an important risk factor for obesity and cardiometabolic diseases, and our previous findings have demonstrated that visceral fat area to skeletal muscle mass ratio (VSR) is significantly and positively associated with the risk of cardiometabolic diseases. Hence, this study aimed to investigate the relationship between VSR and multiorgan IR, provide a new approach to improve body composition, and set the basis for VSR to increase the incidence of cardiometabolic diseases. Materials and Methods: The study included 398 patients who underwent anthropometric and biochemical measurements, and body composition assessment. Spearman correlation analysis was used to investigate the correlation between VSR and homeostatic model assessment for insulin resistance (HOMA-IR) as well as multiorgan IR, including homeostasis model assessment adiponectin (HOMA-AD), adipose tissue insulin resistance (ADIPO-IR), and hepatic insulin sensitivity (HISI). The new model that incorporated into the present study is made up of easily measured biochemical indicators and is used to predict IR. Logistic regression was used to analyze the odds ratio (OR) of VSR on the risk of multiorgan IR. The predictive value of VSR for HOMA-IR and new model was evaluated using the receiver operating characteristic (ROC) curve. Results: VSR was significantly associated with HOMA-IR, HOMA-AD, ADIPO-IR, 1/HISI, and new model (p < 0.001). With the increase of VSR, the OR increased significantly for HOMA-IR and new model (p < 0.001). Then, multiorgan IR indicators were quantified, compared to the lowest quartile group, and increased VSR exacerbated the risk of IR in the highest quartile (p trend < 0.001). The area under the curve for predicting IR using VSR for HOMA-IR and new model was 0.88 for men, 0.85 for women and 0.73 for men, 0.76 for women, respectively. Conclusions: There was significant correlation between VSR and multiorgan IR, and the risk of multiorgan IR increased with increasing VSR. Trial Registration: Clinical Trial Registry identifier: ChiCTR2100044305.