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The aim of the present study was to investigate the effects of multicomponent training on adropin, endothelial function, insulin resistance, and sleep quality in overweight older adults. In this randomized controlled study, 40 overweight older adults were randomly divided into training and control groups. The multicomponent training program including aerobic, resistance, and balance exercise was followed for 8 weeks, 3 days a week. Study variables were measured 48 hr before and after the intervention. After 8 weeks of multicomponent training, adropin (p =.01), nitric oxide (p =.01), and maximal oxygen uptake (VO2max; p =.002) increased, and glucose (p =.001), insulin (p =.001), insulin resistance (p =.01), systolic blood pressure (p =.01), and sleep disorders (p =.01) decreased significantly. Also, Pearson's test results showed a significant inverse relationship between adropin level (p =.01 and r = −.55) and glucose (p =.01 and r = −.51) with sleep disorders. It seems that multicomponent training increases adropin and improves insulin resistance, endothelial function, and sleep quality in older adults. [ABSTRACT FROM AUTHOR]

Background: Metabolic syndrome (MS) is a significant risk factor for cardiovascular and cerebrovascular diseases, primarily driven by insulin resistance (IR). Although the herbal compound Chaihu Shugan powder (CSP) has demonstrated the potential to improve IR in animal models of MS, its mechanism of action remains incompletely understood. Therefore, this study aimed to investigate the biological pathways through which CSP exerts its therapeutic effects on IR in MS using both in vitro and in vivo methods. Methods: The primary metabolites of CSP aqueous extract and CSP-containing serum were measured by LC-MS/MS. A mouse model of MS-related IR was induced by a high-fat, high-fructose diet combined with chronic immobilization stress. The CSP's therapeutic potential was evaluated through glucose and insulin tolerance tests and hepatic insulin signaling molecules (p-IRS-1, IRS-1, p-Akt, and Akt). The expression of lipid metabolism-related factors (FFA, DAG, LXRα, SREBP-1, FASN, and ACC) in the liver was also measured. Hepatocyte IR was modeled using high-glucose and high-insulin conditions, and CSP impact was evaluated using 2-NBDG uptake and insulin signaling molecule expression. The specific mechanism of CSP was explored using the LXRα agonist T0901317. Results: The MS-related IR model exhibited a decreased p-Akt/Akt ratio and increased fasting glucose, insulin, homeostatic model assessment of IR, and hepatic lipid metabolism factors. Treatment with CSP mitigated these effects. In the hepatocyte IR model, CSP-containing serum improved glucose uptake and modulated the expression of insulin signaling and lipid metabolism factors. Furthermore, T0901317 reversed the beneficial effects of CSP, indicating the role of LXRα in CSP's therapeutic action. Conclusion: The CSP ameliorated IR in MS by restoring fatty acid metabolism through the regulation of the LXRα/SREBP-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Time‐restricted feeding is known to ameliorate obesity in young mice. However, evaluation of its effect in old age is still lacking. The current work aims to investigate the effects of time‐restricted feeding on treating pre‐existing obesity in old animals. The study utilized middle‐aged and old high fat diet‐induced obese mice and subjected them to 8 h daily time‐restricted feeding. Aged obese mice did not lose fat mass but lost lean mass after 8 weeks of treatment. In addition, time‐restricted feeding reduced adiposity in brown adipose tissue, reversed excessive hepatic lipid accumulation, and improved glucose homeostasis in middle‐aged and old obese mice. Mechanistic studies show that these metabolic benefits were mediated by transcriptional downregulation of essential genes responsible for hepatic adipogenesis and adipose tissue chronic inflammation. These results demonstrate that time‐restricted feeding improves metabolic health and has beneficial effects in combating diet‐induced obesity in aged obese mice. Key points: Contrary to in young obese mice, in old obese mice time‐restricted feeding did not significantly reduce body fat but decreased lean mass.Time‐restricted feeding reduced adipose tissue inflammation, reversed fatty liver, and improved glucose homeostasis in aged mice with diet‐induced obesity.Time‐restricted feeding is effective in improving metabolic homeostasis in aged mice, but less effective in terms of reducing obesity. Future studies should investigate the underlying mechanism of how ageing impaired intermittent fasting induced fat loss. [ABSTRACT FROM AUTHOR]

Objective: An alternative metric for evaluating insulin resistance (IR) is the triglyceride glucose-body mass index (TyG-BMI). However, it is yet unclear how TyG-BMI and suicide attempts (SA) are related. The objective of this research was to explore the correlation between the TyG-BMI index and SA in individuals with untreated first-episode (UFE) major depressive disorder (MDD) in Shanxi Province. Methods: This cross-sectional study was conducted from September 2016 to December 2018 in the psychiatric outpatient clinic of Taiyuan General Hospital and included 1718 patients with UFE MDD, with a mean age of 34.9 ± 12.4 years. The relationship between TyG-BMI and SA was assessed using logistic regression modeling. We investigated threshold effects using a two-piecewise linear regression model. Results: Taking into consideration the potential influence of confounding variables, a comprehensive multivariate logistic regression analysis was conducted, which demonstrated the absence of a statistically significant association between the TyG-BMI index and the occurrence of SA, as evidenced by P-values that were all greater than 0.05. On the other hand, the visual analysis of the smoothed plots revealed a U-shaped relationship between the TyG-BMI index and the incidence of SA, with a notable inflection occurring at a TyG-BMI value of around 210. It was observed that the effect sizes flanking the inflection point, accompanied by their 95% confidence intervals, were 0.985 (95% CI: 0.972 to 0.999, P = 0.031) and 1.012 (95% CI: 1.003 to 1.047, P = 0.005), respectively. Conclusions: In UFE MDD patients, a U-shaped link was observed between TyG-BMI and SA, with the minimal SA incidence noted at a TyG-BMI level of 210, signifying that an augmented risk for SA might be connected to both diminished and augmented TyG-BMI levels. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) and insulin resistance (IR) increase the risk of adverse pregnancy outcomes. We aimed to examine the relationship of interstitial glucose assessed by continuous glucose monitoring (CGM) at early gestation, and the subsequent development of IR and GDM, and to determine 24-h interstitial glucose centile distributions in women with normal (non-IR and non-GDM) and suboptimal glycemic status (IR and/or GDM). Methods: CGM measurements were taken for 3–10 days at 18–24 weeks' gestation, followed by fasting serum insulin and oral glucose tolerance testing at 24–28 weeks' gestation. IR and GDM were determined by the updated Homeostasis Model Assessment of IR score of ≥ 1.22 and 2013 World Health Organization criteria, respectively. Risks of IR and GDM were estimated using modified Poisson models, and hourly interstitial glucose centiles determined using Generalized Additive Models for Location, Scale and Shape. Results: This prospective cohort study involved 167 pregnant women in Singapore, with a mean age of 31.7 years, body mass index of 22.9 kg/m2, and gestation of 20.3 weeks. 25% of women exhibited IR and 18% developed GDM. After confounders adjustment, women with suboptimal glycemic control, indicated by higher mean daily glucose (risk ratio 1.42; 95% confidence interval 1.16, 1.73), glucose management indicator (1.08; 1.03, 1.12), and J-index (1.04; 1.02, 1.06), as well as those with greater glycemic variability, indicated by higher standard deviation (1.69; 1.37, 2.09), coefficient of variation (1.03; 1.00, 1.06), and mean amplitude of glycemic excursions (1.4; 1.14, 1.35) derived from CGM in early gestation were associated with higher risks of developing IR in later gestation. These associations were similarly observed for the development of GDM. Centile curves showed that, compared to those with normal glycemic status, women with suboptimal glycemic status had higher glucose levels, with greater fluctuations throughout 24 h. Conclusions: In pregnant women who subsequently developed IR and GDM, interstitial glucose levels assessed by CGM were elevated and varied greatly. This supports the potential use of CGM to screen for glycemic changes early in pregnancy. [ABSTRACT FROM AUTHOR]

Although obesity-related asthma is associated with worse asthma outcomes, optimal treatment approaches for this complex phenotype are still largely unavailable. This state-of-the-art review article synthesizes evidence for existing and emerging treatment approaches for obesity-related asthma and highlights pathways that offer potential targets for novel therapeutics. Existing treatments targeting insulin resistance and obesity, including metformin and GLP-1 (glucagon-like-peptide 1) receptor agonists, have been associated with improved asthma outcomes, although GLP-1R agonist data in asthma are limited to individuals with comorbid obesity. Monoclonal antibodies approved for treatment of moderate to severe asthma generally appear to be effective in individuals with obesity, although this is based on retrospective or secondary analysis of clinical trials; moreover, although most of these asthma biologics are approved for use in the pediatric population, the impact of obesity on their efficacy has not been well studied in youth. Potential therapeutic targets being investigated include IL-6, arginine metabolites, nitro-fatty acids, and mitochondrial antioxidants, with clinical trials for each currently underway. Potential therapeutic targets include adipose tissue eosinophils and the GLP-1–arginine–advanced glycation end products axis, although data in humans are still needed. Finally, transcriptomic and epigenetic studies of "obese asthma" demonstrate enrichment of IFN-related signaling pathways, Rho-GTPase pathways, and integrins, suggesting that these too could represent future treatment targets. We advocate for further study of these potential therapeutic mechanisms and continued investigation of the distinct inflammatory pathways characteristic of obesity-related asthma, to facilitate effective treatment development for this unique asthma phenotype. [ABSTRACT FROM AUTHOR]

Background: The correlation between Alzheimer's disease (AD) and the glucose-triglyceride (TyG) index remains undetermined. Objective: This study aimed to investigate the relationship between the TyG index and AD, as well as the relationship between the TyG index and cerebrospinal fluid (CSF) AD biomarkers and cognition. Methods: Six hundred twenty-eight non-dementia participants were included. The TyG index, pathological markers, and cognitive measures were studied using multiple linear regression. Also calculated using a multivariate Cox regression model were the hazard ratio (HR) and its 95% confidence interval (CI). Ten thousand bootstrap iterative causal mediation analyses were performed to investigate the potential mediating effect of AD pathology on cognition. Results: The TyG index was linked to CSF AD biomarkers (βAβ42 = 0.880; βTau = −0.674; βpTau = −0.884; βAβ42/pTau = 1.764; βAβ42/Tau = 1.554; βpTau/Tau = −0.210) and cognitive measurements (βMEM = 0.570; βEF = 0.535; βADAS11 = −0.789). Mediation analysis revealed that the TyG index may influence cognition via CSF AD biomarkers, including Aβ42, tau, and pTau. Furthermore, each 1-unit increase in TyG index was associated with a 29.5% reduction in the risk of incident AD. Conclusions: A delayed rate of cognitive decline and a reduced risk of AD were found to be correlated with higher levels of the TyG index, but this does not mean increasing TyG index levels is beneficial for health. Through AD pathology, the TyG index may influence AD and cognitive changes. [ABSTRACT FROM AUTHOR]

Background: Data regarding the relation between serum myostatin level, type I interferon-inducible gene expression and insulin resistance in dermatomyositis patients are limited. This study aimed to assess serum myostatin level, homeostatic model assessment of insulin resistance (HOMA-IR) and type I interferon-inducible gene expression in dermatomyositis patients. We evaluated the role of serum myostatin level, and type I interferon-inducible gene expression in the pathogenesis of dermatomyositis as well as the relation of serum myostatin level and type I interferon-inducible gene expression to the occurrence of insulin resistance. We evaluated serum levels of myostatin and HOMA-IR utilizing ELISA as well as IFIT1 and Mx1(MxA) gene expression with RT-PCR in 25 dermatomyositis patients (group A) and 25 obviously sound subjects as controls (group B). Results: Among group A, body mass index, serum levels of myostatin, fasting insulin, HOMA-IR, IFN-inducible genes Mx1 and IFIT1 were more significantly increased as well as; serum level of myostatin was positively correlated with age, gender, fasting insulin level, body mass index, and HOMA-IR. Conclusions: Serum level of myostatin, Mx1 and IFIT1 gene expression act as hazard factors of insulin resistance in group A. [ABSTRACT FROM AUTHOR]

Background: Previous studies have demonstrated a relationship between prevalence of Osteoarthritis (OA) and insulin resistance (IR). The correlation between IR surrogates indices and gold standard tool for IR evaluation (Hyperinsulinemic-euglycemic clamp (HIEC)) have been well demonstrated. However, few studies evaluated the relationship between IR surrogates and OA. The aim of this study is to investigate the potential associations between different IR surrogates (the homeostatic model assessment of insulin resistance (HOMA-IR) index, the triglyceride glucose (TyG) index, the triglyceride glucose with body mass (TyG-BMI) index, the triglyceride glucose with waist circumference (TyG-WC) index, and the triglyceride glucose with the ratio of waist circumference divided by height (TyG-WtHR) index) and OA. Methods: This study used data from the National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression analysis was used to assess the associations of different IR surrogates with OA. Results: After adjusting for covariates, TyG-BMI index (OR = 1.006, 95% CI [1.004, 1.007], P < 0.0001), TyG-WC index (OR = 1.002, 95% CI [1.002, 1.003], P < 0.0001) and TyG-WtHR index (OR = 1.425, 95%CI [1.292,1.572], P < 0.0001) still showed robust positive correlation with IR. The risk of OA in the fourth quartile of the TyG-BMI index, TyG-WC index, and TyG-WtHR index are 2.634-fold, 2.651-fold, and 2.433-fold higher than that in the first quartile, respectively. Conclusions: Compared to the HOMA-IR index and the TyG index, the association between the TyG-BMI, TyG-WC, and TyG-WtHR indices and OA is closer and more stable. The TyG-WtHR index has the highest accuracy in predicting OA, followed by the TyG-WC and TyG-BMI index. [ABSTRACT FROM AUTHOR]

Background: To investigated the link between the systemic immunity-inflammation index (SII), a new inflammatory biomarker, and the risk of abnormal glucose regulation in non-diabetic population. Methods: Using data from the 2005–2016 National Health and Nutrition Examination Survey (NHANES), we conducted a cross-sectional study on non-diabetic adults with data on SII and glucose regulation markers. We analyzed the relationship between SII and indicators of glucose regulation, including fasting plasma glucose, fasting insulin, hemoglobin A1c, oral glucose tolerance test (OGTT), and states of abnormal glucose regulation like impaired glucose tolerance (IGT), insulin resistance, and prediabetes. Results: Adjusting for confounders, higher SII levels were significantly associated with a higher OGTT and a greater likelihood of IGT (OR = 2.673, 95% CI: 1.845, 3.873). In subgroup analysis, participants without hyperlipidemia in the highest SII quartile had a 240% higher odds of IGT compared to those in the lowest quartile (OR = 3.407, 95%CI: 1.995, 5.820), an association not observed in those with hyperlipidemia (p for interaction < 0.05). Conclusions: SII emerges as a useful biomarker for identifying IGT in non-diabetic individuals, specifically in those without hyperlipidemia. [ABSTRACT FROM AUTHOR]

Hypertriglyceridemia (HTG) is influenced by multiple genetic and environmental factors. Spontaneous, idiopathic HTG is common in the Miniature Schnauzer dog and presumed to have a strong genetic influence in this breed. To define genes that are differentially expressed in dogs with HTG, we performed RNA sequencing on peripheral blood of 13 Miniature Schnauzers with HTG and 18 controls. We identified 110 differentially expressed genes (DEGs). Pathway analysis suggests an ongoing pro-thrombotic, endothelial activation process in dogs with HTG. The gene with the largest fold change (5.4 ± 1.4, Padj = 4.4E-04), SERPINE1, encodes plasminogen activator inhibitor 1 (PAI-1), a known risk factor for atherosclerosis and thrombosis. Other top DEGs, including SHANK3, MMRN1, and FZD7, are involved in endothelial activation. Two of the top DEGs, ARHGAP29 and ARHGAP21, inhibit pro-thrombotic pathways and are potentially protective of disease sequelae. Top DEGs, including SERPINE1 and ARHGAP21, have also been linked to metabolic syndrome or its features (e.g. insulin resistance) in humans and animal models. Our findings indicate that HTG in the Miniature Schnauzer dog has similar features to HTG and metabolic syndrome in humans, highlighting the potential use of the dog as a spontaneous model for further research into the etiology and effects of HTG. [ABSTRACT FROM AUTHOR]

Background: G1, a specific agonist targeting the G protein–coupled receptor 30 (GPR30), has demonstrated significant involvement in combating obesity and regulating glucose homeostasis. Nevertheless, the beneficial effects of G1 treatment have solely been investigated in animal models under normal feeding conditions, leaving its therapeutic potential in high‐fat feeding scenarios unexplored. Material and Methods: To address this gap, our study employed an ovariectomized high‐fat diet mouse model to assess the therapeutic effects of G1 in combating obesity and metabolic dysfunction. Results: The findings revealed that G1 treatment resulted in weight loss, but concurrently led to increased blood glucose levels and insulin resistance. Treatment with G1 resulted in an amplification of fat mobilization and an enhancement of pyruvate carboxylase activity in mice fed a high‐fat diet. Moreover, the combined impact of G1 treatment and a high‐fat diet on pyruvate metabolism, as well as the regulation of crucial gluconeogenesis enzymes such as pyruvate dehydrogenase kinase 4 (PDK4), phosphoenolpyruvate carboxykinase (PEPCK), and glucose transporter 2 (GLUT2), expedites the elevation of blood glucose and the progression of insulin resistance. Conclusions: These findings indicate that G1 treatment is influenced by a high‐fat diet, potentially disrupting glucolipid metabolism and promoting insulin resistance alongside its antiobesity effects. Consequently, further investigation is imperative to thoroughly explore this potential toxic side effect of G1 therapy. [ABSTRACT FROM AUTHOR]

Background: The Metabolic Insulin Resistance Score (METS-IR) is a non-invasive proxy for insulin resistance (IR) that has been newly developed in recent years and has been shown to be associated with diabetes risk. Our aim was to assess the predictive value of METS-IR for the future development of diabetes and its temporal differences in people of different sex, age, and body mass index (BMI). Methods: The current study included 15,453 baseline non-diabetic subjects in the NAGALA cohort and then grouped according to the World Health Organization's (WHO) recommended criteria for age and BMI. Multivariate Cox regression and time-dependent receiver operator characteristics (ROC) curves were used to analyze the value of METS-IR in assessing and predicting the risk of diabetes in people of different sexes, ages, and BMIs. Results: 373 individuals developed diabetes during the observation period. By multivariate COX regression analysis, the development of future diabetes was significantly associated with increased METS-IR, and this positive association was stronger in women than in men and in individuals < 45 years than in individuals ≥ 45 years; while no significant differences were observed between non-obese and overweight/obesity individuals. Using time-dependent ROC analysis we also assessed the predictive value of METS-IR for future diabetes at a total of 11-time points between 2 and 12 years. The results showed that METS-IR had a higher predictive value for the future development of diabetes in women or individuals < 45 years of age compared to men or individuals ≥ 45 years of age for almost the entire follow-up period. Furthermore, across different BMI categories, we also found that in the short term (3–5 years), METS-IR had a higher predictive value for the development of diabetes in individuals with overweight/obesity, while in the medium to long term (6–12 years), METS-IR was more accurate in predicting the development of diabetes in non-obese individuals. Conclusions: Our study showed that METS-IR was independently associated with the development of future diabetes in a non-diabetic population. METS-IR was a good predictor of diabetes, especially for women and individuals < 45 years old for predicting the future risk of developing diabetes at all times. [ABSTRACT FROM AUTHOR]

Background: Gout stands as a prevailing manifestation of inflammatory arthritis. While it is linked to several well-established risk factors, the associations between lipid profiles and the risk of gout remain unclear. Methods: This research involved National Health and Nutrition Examination Survey data (2007–2018). The cardiometabolic index, which incorporates the Triglycerides (TG)/High-density lipoprotein cholesterol (HDL) ratio and waist to height ratio (WHtR), was used to assess lipid profiles and metabolic health. Multivariate logistic regression analysis, propensity score matching, and mediation analyses were utilized to evaluate the associations of lipid profiles and the cardiometabolic index with the risk of developing gout. Results: Among 11,032 participants, each 1-unit increase in TG levels was associated with a 65% increase in the odds of developing gout before matching [1.65 (1.15–2.38), P = 0.007] and a 155% increase in the odds of developing gout after matching [2.55 (1.59–4.09), P = 0.007]. Each 1-unit increase in the cardiometabolic index was linked to an 81% increase in the odds of developing gout before matching [1.81 (1.22–2.70), P = 0.004] and a 215% increase in the odds of developing gout after matching [3.15 (1.84–5.40), P < 0.001]. The participants with HDL levels in the third quartile presented a 35% reduction in gout risk relative to those with HDL levels in the first quartile before matching [0.65 (0.46–0.92), P = 0.014] and a 51% reduction in gout risk after matching [0.49 (0.32–0.75), P < 0.001]. Mediation analyses revealed that BMI, WHtR, and homeostatic model assessment for insulin resistance (HOMA-IR) mediated the relationships between TG levels and the risk of developing gout at 18.75%, 24.28%, and 5.35%, respectively. For the association between HDL levels and the risk of developing gout, the mediating effects of BMI, WHtR, leukocytes, γ-glutamyltransferase (in those with HDL < 56 mmol/L), and HOMA-IR were 57.98%, 69.03%, 8.77%, 5.18%, and 11.14%, respectively. Conclusion: This study reveals the relationship between lipid profiles and the risk of developing gout. Regularly checking TG and HDL levels and actively managing obesity, insulin resistance, oxidative stress and inflammation are important for lowering the risk of developing gout. [ABSTRACT FROM AUTHOR]

Background: Triglyceride–glucose (TyG) index, as an effective surrogate marker of insulin resistance, has shown predictive value in the risk of heart failure in patients with coronary artery disease (CAD). This study aims to investigate the correlation between TyG index and myocardial work measurements in CAD, and to explore its role in detecting early subclinical cardiac dysfunction. Methods: This cross-sectional study included 267 patients diagnosed with CAD and excluding left ventricular myocardial dysfunction in Beijing Hospital. Participants were divided into two groups according to the TyG index level, and myocardial work measurements were compared between groups. The correlation was explored between gradually increased TyG index and subclinical myocardial function in CAD patients. Results: We observed that TyG index was significantly correlated with the global waste work (GWW), and the value of GWW increased progressively with the elevation of TyG index. After adjusting for the effects of confounding factors, TyG index was still independently associated with GWW. Conclusion: An elevated TyG index was independently correlated with early subclinical myocardial dysfunction in CAD patients. Our study demonstrated that the strict control of TyG index may be conducive to forestall the progression of clinical heart failure in CAD patients. [ABSTRACT FROM AUTHOR]

Metabolic compromise is crucial in aggravating age-associated chronic inflammation, oxidative stress, mitochondrial damage, increased LDL and triglycerides, and elevated blood pressure. Excessive adiposity, hyperglycemia, and insulin resistance due to aging are associated with elevated levels of damaging free radicals, inducing a proinflammatory state and hampering immune cell activity, leading to a malfunctioning cardiometabolic condition. The age-associated oxidative load and redox imbalance are contributing factors for cardiometabolic morbidities via vascular remodelling and endothelial damage. Recent evidence has claimed the importance of gut microbiota in maintaining regular metabolic activity, which declines with chronological aging and cardiometabolic comorbidities. Genetic mutations, polymorphic changes, and environmental factors strongly correlate with increased vulnerability to aberrant cardiometabolic changes by affecting key physiological pathways. Numerous studies have reported a robust link between biological aging and cardiometabolic dysfunction. This review outlines the scientific evidence exploring potential mechanisms behind the onset and development of cardiovascular and metabolic issues, particularly exacerbated with aging. [ABSTRACT FROM AUTHOR]

Background: Insulin resistance (IR) is linked to an increased risk of neurological impairment following a stroke and may contribute to poor neurological prognosis in affected patients. The metabolic score for the insulin resistance index, shortened as the METS-IR, generally serves as a surrogate index for IR. However, its association with the severity of neurological impairment in patients with severe cerebral infarction (CI) in neurological intensive care units (ICU) has not been fully established. Methods: Patients with a diagnosis of CI, admitted to the neurological ICUs of Yangzhou University's Affiliated Hospital and Xuzhou Medical University's Affiliated Hospital, were included in the study. A multivariate logistic regression model and restricted cubic splines (RCS) were employed to explore the relationship between the METS-IR index and the severity of neurological impairment in these patients. The predictive capabilities of the METS-IR index and the triglyceride-glucose (TyG) index for outcome measures were compared through the ROC curve. Furthermore, a decision curve analysis was executed, and the integrated discrimination improvement (IDI) index was computed to evaluate the enhancements in predictive performance and clinical utility of various scoring systems with the inclusion of the METS-IR index. Subgroup analysis was conducted regarding age, BMI, and smoking status. Results: The study ultimately included 504 participants. Adjusted logistic regression and RCS results showed that as the METS-IR index increases, the risk of neurological impairment in patients with severe CI consistently grows (P for overall = 0.0146, P -nonlinear: 0.0689). The METS-IR index's predictive capability for neurological impairment (AUC = 0.669) was superior to that of the TyG index (AUC = 0.519). Conclusion: From the study results, the METS-IR index can serve as an important predictor for neurological impairment in ICU patients with severe CI. It can aid in the identification and early intervention of neurological impairment in these patients. [ABSTRACT FROM AUTHOR]

Objects: It remains unclear whether the triglyceride-glucose (TyG) index has correlations with gallstones. This study aimed to investigate the association between TyG index and gallstones. Methods: Data was obtained from the 2017-2020 National Health and Nutrition Examination Survey (NHANES). Participants who provided complete data about TyG index and gallstones were included in the analysis. Multivariable regression analysis and subgroup analysis were preformed to estimate the relationship between TyG index and gallstones. Restricted cubic splines (RSC) was employed to calculate the cut off value. Results: The TyG index was independently associated with gallstones and demonstrates a clear positive correlation (OR = 1.10; 95% CI: 1.01–1.21; p = 0.033). The threshold value is 8.98, showing a positive correlation between TyG index and gallstones when the TyG index is less than 8.98 (Log likelihood ratio P < 0.001). Subgroup analysis indicates that the correlation between TyG and gallstones is mainly observed in individuals with obesity, females, younger individuals, and those with normal blood sugar levels, with these subgroups all acting as mediators between TyG and gallstones. Conclusions: Higher TyG index was linked to a higher chance of developing gallstones. Managing insulin resistance (IR) could help reduce the risk of gallstones since the TyG index is an indicator of IR. [ABSTRACT FROM AUTHOR]

Background: The triglyceride–glucose (TyG) index has garnered recognition as a surrogate marker for insulin resistance, a pivotal factor in the pathogenesis of various metabolic disorders. Despite its emerging role, the empirical evidence delineating its association with prediabetes mellitus (Pre-DM) remains scant. This research aims to clarify the link between the TyG index and the likelihood of Pre-DM development within a Chinese demographic. Methods: This investigation was structured as a retrospective cohort analysis, encompassing a sample of 179,177 Chinese adults. These individuals underwent medical examinations at the Rich Healthcare Group over a period spanning from 2010 to 2016. To ascertain the relationship between the TyG index and the incidence of Pre-DM, this study employed Cox regression analysis complemented by sensitivity and subgroup assessments. Furthermore, Cox proportional hazards regression with cubic spline functions and smooth curve fitting was incorporated to explore the existence of any non-linear connection within this association. Results: Upon adjusting for a comprehensive array of confounding variables, a statistically significant positive correlation between the TyG index and the risk of Pre-DM was identified (HR: 1.60, 95%CI 1.56–1.65, P < 0.001). The analysis illuminated a non-linear relationship, with an inflection point at a TyG index value of 8.78. For TyG index values below and above this inflection point, the HR was calculated to be 1.94 (95%CI 1.86–2.03) and 1.26 (95%CI 1.20–1.33), respectively. Sensitivity analyses further fortified the reliability of these findings. Conclusions: This comprehensive examination delineated a significantly positive, non-linear correlation between the TyG index and the risk of Pre-DM within a Chinese population. Individuals with TyG index values below 8.78 have a significantly increased risk of developing prediabetes. These findings underscore the TyG index's potential efficacy as a predictive tool for assessing Pre-DM risk in clinical practice. [ABSTRACT FROM AUTHOR]

Background: Gestational diabetes mellitus (GDM) is a common pregnancy complication characterized by insulin resistance. A link has been suggested between insulin resistance and breast cancer, which is the most common cancer in women. Hence, women with previous GDM may be at increased risk of developing breast cancer, yet, the existing evidence is conflicting. This study explored the association between GDM and incident breast cancer, including age at cancer diagnosis. Additionally, we investigated the potential impact of severity of insulin resistance during pregnancy and of subsequent diabetes development on the breast cancer risk. Methods: We conducted a nationwide, register-based cohort study including all women giving birth in Denmark from 1997 to 2018. We defined GDM and breast cancer based on ICD-10 codes. Premenopausal and postmenopausal breast cancer was pragmatically defined as age at outcome < 50 years and ≥ 50 years, respectively. A proxy for severity of insulin resistance during pregnancy was based on insulin treatment; subsequent diabetes was defined as presence of ICD-10 codes and/or antidiabetic medication after pregnancy. The statistical analyses included Cox regression, logistic regression and t-test. Results: Of 708,121 women, 3.4% had GDM. The median follow-up period was 11.9 years (range 0-21.9). The overall breast cancer risk was comparable in women with and without previous GDM (adjusted hazard ratio 0.96 [95% CI 0.83–1.12]). Premenopausal and postmenopausal breast cancer risk also did not differ; however, women with previous GDM had a breast cancer diagnosis at younger age (42.6 vs. 43.5 years, p-value 0.01). All-cause mortality was similar regardless of GDM history. Severity of insulin resistance during pregnancy and subsequent diabetes did not affect breast cancer risk. Conclusions: This large, population-based cohort study showed no higher risk of incident breast cancer in women with previous GDM compared to women without previous GDM after a median of almost 12 years of follow-up. This was evident irrespective of menopausal state. The breast cancer risk was not influenced by the severity of insulin resistance during pregnancy and by subsequent diabetes development. Regardless of GDM history, attention towards prevention, early detection and treatment of breast cancer should be prioritized. [ABSTRACT FROM AUTHOR]

Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder characterized by hyperandrogenism, prolonged anovulation and polycystic ovaries. However, there are no effective interventions to treat this disorder. As previously shown, mangiferin modulated the AMPK and NLRP3 signal pathways to alleviate nonalcoholic fatty liver disease (NAFLD). In recent years, mangiferin has emerged as a promising drug candidate for treating metabolic diseases. In this study, we evaluated the effects of mangiferin on a letrozole (LET) combined with high-fat diet (HFD)-induced PCOS rat model through estrous cycle detection, serum/tissue biochemical analysis, and hematoxylin and eosin (HE) staining of ovarian tissue. The mechanisms of mangiferin's effects on PCOS rats were analyzed using 16S rRNA sequencing, RNA-seq, western blotting (WB), and immunohistochemical (IHC) staining. Our results displayed that mangiferin showed a promising effect in PCOS rats. It improved lipid metabolism, glucose tolerance, insulin resistance, hormonal imbalance, ovarian dysfunction, and adipocyte abnormalities. RNA-seq analysis indicated that mangiferin may be involved in several signal pathways, including apoptosis, necrosis, and inflammation. Furthermore, western blot and immunohistochemical staining demonstrated that mangiferin regulates Caspase-3 and Cytc, exhibiting anti-apoptotic activity in the ovaries. Additionally, mangiferin significantly altered the gut microbiota community of PCOS rats, changing the abundance of firmicutes, bacteroidota, proteobacteria, and actinobacteria at the phylum level and the abundance of Blautia , Coprococcus , Roseburia, and Pseudomonas at the genus level. In conclusion, mangiferin is a promising and novel therapeutic agent for PCOS as it ameliorates insulin resistance, gut microbiota and ovarian cell apoptosis. [ABSTRACT FROM AUTHOR]

Background: Polycystic ovary syndrome (PCOS) is a complex heterogenous disorder manifesting with various reproductive, endocrine, and metabolic derangements such as insulin resistance and hyperglycemia. The arginine vasopressin peptide (AVP), also called or antidiuretic hormone (ADH), modulates metabolic functions such as glucose hemostasis, insulin sensitivity, and lipid metabolism via binding to two central and peripheral receptors (AVPR1A and AVPR1B). In the present study, we aimed to detect whether the AVPR1A and AVPR1B genes confer risk for PCOS. Methods: In peninsular Italian families, we tested 7 variants in the AVPR1B gene and 2 variants in the AVPR1A gene via Pseudomarker for linkage and linkage joint to association (i.e.., linkage disequilibrium) with PCOS. Results: We identified two risk variants in each gene, significantly associated with the risk of PCOS. Conclusion: To the best of our knowledge, this is the first study to report risk variants in AVPR1A and AVPR1B genes in association with PCOS. However, replication in other ethnic groups as well as functional studies are needed to confirm these results. [ABSTRACT FROM AUTHOR]

FAM20C, a member of the family with sequence similarity 20, is involved in many physiological functions. Obesity, characterized by excessive accumulation of adipose tissue, has attracted more and more attention as a worldwide health problem. Here we generated adipocyte‐specific FAM20C knockout mice to investigate the role of FAM20C in adipose tissue expansion and obesity. Our results demonstrate that knockout mice are protected against high fat diet‐induced obesity, adiposity, and fatty liver disease. Additionally, knockout mice exhibited improved metabolic phenotypes, including enhanced glucose tolerance and insulin sensitivity compared with control mice. Furthermore, we observed reduced inflammatory infiltration and collagen deposition in the adipose tissues of knockout mice. Taken together, our results indicate that targeting FAM20C in adipocytes may be a promising strategy for the treatment of obesity and associated metabolic disorders. [ABSTRACT FROM AUTHOR]

The association of serum N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP) with insulin resistance (IR), as measured by homeostasis model assessment of insulin resistance (HOMA‐IR), in the general population is unclear. Our study aimed to characterize its relationship in a large community‐based population. Subjects were recruited from the Danyang city between 2017 and 2019. Serum NT‐proBNP was measured using an enhanced chemiluminescence immunoassay. IR was defined by a HOMA‐IR in the highest sex‐specific quartile. Categorical and continuous analyses were performed with sex‐specific NT‐proBNP tertiles and naturally logarithmically transformed NT‐proBNP (lnNTproBNP), respectively. The 2945 participants (mean age 52.8 years) included 1728 (58.7%) women, 1167 (39.6%) hypertensive patients, 269 (9.1%) diabetic patients, and 736 (25.0%) patients with IR. In simple and multivariate‐adjusted regression analyses, serum lnNTproBNP were both negatively associated with HOMA‐IR (β = −0.19 to −0.25; p < 0.0001). Similar results were also obtained in multiple subgroup analyses. In multiple logistic regression analyses, elevated serum NT‐proBNP was associated with lower risks of IR (odds ratios: 0.68 and 0.39; 95% confidence intervals: 0.61–0.74 and 0.30–0.50 for lnNTproBNP and top vs. bottom tertiles, respectively; p < 0.0001). In conclusion, increased serum NT‐proBNP level was strongly associated with a lower risk of IR in Chinese. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the relationship between the triglyceride-glucose (TyG) index, a recently proposed marker of insulin resistance, and the occurrence of diabetic retinopathy (DR), a complication associated with cardiovascular risk. This systematic review and meta-analysis aimed to evaluate the association between the TyG index and DR. To achieve the objective of the meta-analysis, an extensive search was conducted on databases such as PubMed, Embase, and Web of Science to identify observational studies with longitudinal follow-up. Random-effects models were employed to combine the findings, taking into account the potential influence of heterogeneity. Twelve observational studies from 11 reports were included in the meta-analysis, which involved 16 259 patients with type 2 diabetes (T2D). Among them, 4302 (26.5%) were diagnosed as DR. Pooled results showed that a higher TyG index was associated with a higher risk of DR [odds ratio (OR) for the fourth versus the first quartile of TyG index: 1.91, 95% confidence interval (CI): 1.44 to 2.53, p<0.001; I2=72%]. Meta-analysis of TyG index analyzed in continuous variable showed consistent results (OR for per 1 unit increment of TyG index: 1.41, 95% CI: 1.08 to 1.86, p=0.01; I2=82%). Subgroup analysis showed that adjustment of HbA1c or the duration of diabetes did not significantly affect the results (p for subgroup difference all>0.05). In conclusion, a high TyG index was associated with the risk of DR in T2D patients. [ABSTRACT FROM AUTHOR]

Insulin acts on different organs, including the brain, which helps it regulate energy metabolism. Insulin signaling plays an important role in the function of different cell types. In this review, we have summarized the key roles of insulin and insulin receptors in healthy brains and in different brain disorders. Insulin signaling, as well as insulin resistance (IR), is a major contributor in the regulation of mood, behavior, and cognition. Recent evidence showed that both peripheral and central insulin resistance play a role in the pathophysiology, clinical presentation, and management of neuropsychiatric disorders like Cognitive Impairment/Dementia, Depression, and Schizophrenia. Many human studies point out Insulin Resistance/Metabolic Syndrome can increase the risk of dementia especially Alzheimer's dementia (AD). IR has been shown to play a role in AD development but also in its progression. This review article discusses the pathophysiological pathways and mechanisms of insulin resistance in major neuropsychiatric disorders. The extent of insulin resistance can be quantified using IR biomarkers like insulin levels, HOMA-IR index, and Triglyceride glucose–body mass index (TyG–BMI) levels. IR has been shown to precede neurodegeneration. Human trials showed current treatment with certain antidiabetic drugs, as well as life style management, like weight loss and exercise for IR, have shown promise in the management of cognitive/neuropsychiatric disorders. This may pave the pathway to the development of new therapeutic approaches to these challenging disorders of dementia and psychiatric diseases. Recent clinical trials are showing some encouraging evidence for these pharmacological and nonpharmacological approaches for IR in psychiatric and cognitive disorders, even though more research is needed to apply this evidence into clinical practice. Early identification and management of IR may help as a strategy to potentially alter neuropsychiatric disorders onset as well as its progression [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus is a complex metabolic disorder characterized by insulin resistance and, subsequently, decreased insulin secretion. This condition is closely linked to obesity, a major risk factor that boosts the development of chronic systemic inflammation, which, in turn, is recognized for its crucial role in the onset of insulin resistance. Under conditions of obesity, adipose tissue, particularly visceral fat, becomes an active endocrine organ that releases a wide range of pro-inflammatory mediators, including cytokines, chemokines, and adipokines. These mediators, along with cluster of differentiation (CD) markers, contribute to the maintenance of systemic low-grade inflammation, promote cellular signaling and facilitate the infiltration of inflammatory cells into tissues. Emerging studies have indicated the accumulation of a new cell population in the adipose tissue in these conditions, known as myeloid-derived suppressor cells (MDSCs). These cells possess the ability to suppress the immune system, impacting obesity-related chronic inflammation. Given the limited literature addressing the role of MDSCs in the context of type 2 diabetes, this article aims to explore the complex interaction between inflammation, obesity, and MDSC activity. Identifying and understanding the role of these immature cells is essential not only for improving the management of type 2 diabetes but also for the potential development of targeted therapeutic strategies aimed at both glycemic control and the reduction in associated inflammation. [ABSTRACT FROM AUTHOR]

Prenatal adipose tissue development affects body composition and growth trajectory in early infancy, therefore it is a key determinant of adiposity in childhood. Childhood overweight and obesity increase the probability of being obese as an adult. After birth and in adulthood, adipose tissue macrophages (ATMs) are relevant constituents of the fat depots, and they are necessary for physiological adipose tissue development and fat metabolism. In obesity, however, ATMs may induce chronic inflammation leading to insulin resistance, pancreatic beta cell damage and self-immunity. Despite being relevant regulators of adipose tissue development and functioning, it is unknown whether ATMs are present in the fetal adipose tissue, therefore it is elusive whether they may affect the prenatal establishment of fat depots. Here we studied the distribution of ATMs in the human fetus between gestational weeks 17 and 38 and labeled ATMs in the early postnatal life. We found that CD45+/CD14+/CD68+ ATMs infiltrated the fetal adipose tissue from the 17th week of gestation and remained persistent throughout the second and third trimesters. ATMs were phagocytic in the neonate and expressed interleukin-6, along with other pro-inflammatory gene products. These findings show that ATMs colonize the adipose tissue early in gestation, raising the possibility that intrauterine ATM–adipocyte communication may exist, eventually allowing ATMs to affect prenatal adipose tissue development. [ABSTRACT FROM AUTHOR]

In postmenopausal women, due to endocrine changes, there is an increase in oxidative stress (OS) that predisposes them to cardiovascular and metabolic alterations. Sixty-one percent of women in this stage require a primary therapeutic strategy to decrease OS. This study aimed to evaluate the effect of resveratrol and vitamin C on OS in postmenopausal women. A randomized, double-blind clinical trial was carried out. Forty-six postmenopausal women with insulin resistance (HOMA-IR > 2.5) were included and divided into three treatment groups: group A: resveratrol, n = 13; group B: resveratrol + vitamin C, n = 15; and group C: vitamin C, n = 14. Between before and after the antioxidants, group B showed a decrease of 33% in lipohydroperoxides (p = 0.02), and malondialdehyde (MDA) decreased by 26% (p = 0.0007), 32% (p = 0.0001), and 38% (p = 0.0001) in groups A–C, respectively. For protein damage, group B is the most representative, with a decrease of 39% (p = 0.0001). For total antioxidant capacity (TAC), there were significant increases of 30% and 28% in groups B and C, respectively. For HOMA-IR, there were no significant differences among the study groups. Supplementation with this combination of antioxidants significantly decreases markers of OS in postmenopausal women. In addition, it increases TAC by up to 30%. [ABSTRACT FROM AUTHOR]

Background/Objectives: An inappropriate intake of dietary fats can disrupt the homeostasis of intestinal microbiota, affect the host's metabolic status, and increase the risk of chronic diseases. The impact of dietary fat types on the composition and metabolic functionality of the intestinal microbiota has become a research focus over recent years. The objective of this study was to explore the effects of regular peanut oil (PO) and high-oleic-acid peanut oil (HOPO) on the composition and metabolic function of the intestinal microbiota. Methods: A dietary intervention test was conducted on SD rats fed a high-fat/high-fructose (HFF) diet. The composition and metabolic functionality of the intestinal microbiota of the experimental rats were investigated by 16S rRNA gene sequencing and fecal metabolomics. Results: Compared with saturated fat, PO and HOPO enhanced the diversity of intestinal microbiota in HFF diet-fed rats. Compared with PO, HOPO significantly increased the relative abundance of Lachnospiraceae_NK4A136_group and Harryflintia (p < 0.05), which are able to generate butyrate and acetate. Compared with saturated fat, 318 and 271 fecal biomarkers were identified in PO and HOPO groups, respectively. In contrast, 68 fecal biomarkers were identified between the PO and HOPO groups. The inhibition of harmful proteolytic fermentation in the colon may represent the main regulatory mechanism. With regard to metabolic status, HOPO provided better control of body weight and insulin sensitivity than PO. Conclusions: Compared with saturated fat, peanut oils better regulated the composition and metabolic function of the intestinal microbiota. In addition, HOPO exhibited better regulatory effects than PO. [ABSTRACT FROM AUTHOR]

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a disorder characterized by insulin resistance, hyperglycemia, and dyslipidemia. Myricetin, a flavonoid found in various plants, has shown potential anti-diabetic effects in murine studies. This meta-analysis aimed to evaluate the impact of myricetin supplementation on glucose metabolism and lipid profiles in mouse models of metabolic diseases. Methods: A systematic review and meta-analysis were conducted in accordance with PRISMA guidelines (PROSPERO: CRD42024591569). Studies involving mice with metabolic disease models and exclusively using myricetin supplementation were checked across four databases (Embase, Scopus, PubMed, and WoS) until 23rd September 2024. The primary outcomes assessed were blood glucose (BG), insulin levels, triacylglycerol (TAG), total cholesterol (TC), HDL, and LDL. A random-effects model was applied to estimate standardized mean differences (SMD), and SYRCLE's risk-of-bias tool for animal studies was used. Results: Twenty-one studies with 514 mice met the inclusion criteria. Myricetin supplementation significantly reduced BG (SMD = −1.45, CI: −1.91 to −0.99, p < 0.00001, I2 = 74%), insulin (SMD = −1.78, CI: −2.89 to −0.68, p = 0.002, I2 = 86%), TAG (SMD = −2.60, CI: −3.24 to −1.96, p < 0.00001, I2 = 81%), TC (SMD = −1.86, CI: −2.29 to −1.44, p < 0.00001, I2 = 62%), and LDL (SMD = −2.95, CI: −3.75 to −2.14, p < 0.00001, I2 = 74%). However, the effect on HDL was not statistically significant (SMD = 0.71, CI: −0.01 to 1.43, p = 0.05, I2 = 83%). Conclusions: Myricetin supplementation improved glucose metabolism and lipid profiles in mouse models, suggesting its potential as a therapeutic agent for managing T2DM. However, further research is needed to confirm these findings in human studies. [ABSTRACT FROM AUTHOR]

Skeletal muscle is one of the predominant sites involved in glucose disposal, accounting for ∼80% of postprandial glucose uptake, and plays a critical role in maintaining glycemic homeostasis. Dysregulation of energy metabolism in skeletal muscle is involved in developing insulin resistance and type 2 diabetes (T2D). Transcriptomic responses of skeletal muscle to exercise found that the expression of Klf3 was increased in T2D Goto-Kakizaki (GK) rats and decreased after exercise with improved hyperglycemia and insulin resistance, implying that Klf3 might be associated with insulin sensitivity and glucose metabolism. We also found that knockdown of Klf3 promoted basal and insulin-stimulated glucose uptake in L6 myotubes, whereas overexpression of Klf3 resulted in the opposite. Through pairwise comparisons of L6 myotubes transcriptome, we identified 2,256 and 1,988 differentially expressed genes in Klf3 knockdown and overexpression groups, respectively. In insulin signaling, the expression of Slc2a4, Akt2, Insr, and Sorbs1 was significantly increased by Klf3 knockdown and decreased with Klf3 overexpression; Ptprf and Fasn were markedly downregulated in Klf3 reduced group and upregulated in Klf3 overexpressed group. Moreover, downregulation of Klf3 promoted the expression of glucose transporter 4 (GLUT4) and protein kinase B (AKT) proteins, as well as the translocation of GLUT4 to the cell membrane in the basal situation, and enhanced insulin sensitivity, characterized by increased insulin-stimulated GLUT4 translocation and AKT, TBC1 domain family member 1 (TBC1D1) and TBC1 domain family member 4 (TBC1D4) phosphorylation, whereas overexpression of Klf3 showed contrary results. These results suggest that Klf3 affects glucose uptake and insulin sensitivity via insulin signal transduction and intracellular metabolism, offering a novel potential treatment strategy for T2D. NEW & NOTEWORTHY: The knockdown of Klf3 increased glucose uptake and improved insulin sensitivity in L6 myotubes, whereas its overexpression had the opposite effect. To explore the underlying mechanisms, we evaluated the transcriptional profiles of L6 myotubes after Klf3 knockdown and overexpression and revealed that metabolism and insulin-related pathways were significantly impacted. Klf3 also influenced the expression or modification of glucose transporter 4 (GLUT4), protein kinase B (AKT), TBC1 domain family member 1 (TBC1D1), and TBC1 domain family member 4 (TBC1D4) in the insulin signaling pathway, affecting insulin sensitivity and glucose uptake. [ABSTRACT FROM AUTHOR]

Key Points: Question: Are differing trajectories of low-grade inflammation throughout childhood and adolescence associated with an increased risk of developing certain mental and related cardiometabolic health conditions in early adulthood? Findings: This longitudinal cohort study found that having persistently raised levels of inflammation as measured by C-reactive protein throughout childhood and adolescence, peaking at age 9 years, was associated with an increased risk of developing psychosis disorder, severe depression, and higher levels of insulin resistance. Meaning: Increased inflammation in childhood may be an important predisposing risk factor to the development of both mental and cardiometabolic disorders in early adulthood. Importance: Research suggests that low-grade, nonresolving inflammation may predate adult mental and physical illness. However, evidence to date is largely cross-sectional or focuses on single disorder outcomes. Objectives: To examine trajectories of inflammation as measured by C-reactive protein (CRP) levels in a large sample of children and adolescents, and to explore associations between different identified trajectories and mental and related cardiometabolic health outcomes in early adulthood. Design, Setting, and Participants: In a longitudinal cohort study using data from the large UK-based Avon Longitudinal Study of Parents and Children (ALSPAC), latent class growth analysis (LCGA) was used to explore different trajectories of inflammation, with logistic regression exploring association with mental and physical health outcomes. Participants with measurable CRP data and associated mental and cardiometabolic health outcomes recorded were included in the analysis. Data analysis was performed from May 1, 2023, to March 30, 2024. Exposures: Inflammation was assessed via CRP levels at ages 9, 15, and 17 years. LCGA was used to identify different trajectories of inflammation. Main Outcomes and Measures: Outcomes assessed at age 24 years included psychotic disorders, depressive disorders, anxiety disorders, hypomania, and, as a measure of insulin resistance, Homeostasis Model Assessment (HOMA2) score. Results: A total of 6556 participants (3303 [50.4%] female) were included. Three classes of inflammation were identified: persistently low CRP levels (reference class, n = 6109); persistently raised CRP levels, peaking at age 9 years (early peak, n = 197); and persistently raised CRP levels, peaking at age 17 years (late peak, n = 250). Participants in the early peak group were associated with a higher risk of psychotic disorder (odds ratio [OR], 4.60; 95% CI, 1.81-11.70; P =.008), a higher risk of severe depression (OR, 4.37; 95% CI, 1.64-11.63; P =.02), and higher HOMA2 scores (β = 0.05; 95% CI, 0.01-0.62, P =.04) compared with participants with persistently low CRP. The late peak group was not associated with any outcomes at age 24 years. Conclusions and Relevance: Low-grade systemic inflammation peaking in midchildhood was associated with specific mental and cardiometabolic disorders in young adulthood. These findings suggest that low-grade persistent inflammation in early life may be an important shared common factor for mental-physical comorbidity and so could be relevant to future efforts of patient stratification and risk profiling. This longitudinal cohort study using data from the Avon Longitudinal Study of Parents and Children (ALSPAC) examines trajectories of inflammation in childhood and their associations with mental and related cardiometabolic health outcomes in early adulthood. [ABSTRACT FROM AUTHOR]

White adipose tissue (WAT) and the gut are involved in the development of neuroinflammation when an organism detects any kind of injury, thereby triggering metainflammation. In fact, the autonomous nervous system innervates both tissues, although the complex role played by the integrated sympathetic, parasympathetic, and enteric nervous system functions have not been fully elucidated. Our aims were to investigate the participation of inflamed WAT and the gut in neuroinflammation. Firstly, we conducted an analysis into how inflamed peripheral WAT plays a key role in the triggering of metainflammation. Indeed, this included the impact of the development of local insulin resistance and its metabolic consequences, a serious hypothalamic dysfunction that promotes neurodegeneration. Then, we analyzed the gut–brain axis dysfunction involved in neuroinflammation by examining cell interactions, soluble factors, the sensing of microbes, and the role of dysbiosis-related mechanisms (intestinal microbiota and mucosal barriers) affecting brain functions. Finally, we targeted the physiological crosstalk between cells of the brain–WAT–gut axis that restores normal tissue homeostasis after injury. We concluded the following: because any injury can result not only in overall insulin resistance and dysbiosis, which in turn can impact upon the brain, but that a high-risk of the development of neuroinflammation-induced neurodegenerative disorder can also be triggered. Thus, it is imperative to avoid early metainflammation by applying appropriate preventive (e.g., lifestyle and diet) or pharmacological treatments to cope with allostasis and thus promote health homeostasis. [ABSTRACT FROM AUTHOR]

Alzheimer's disease (AD) presents a public health challenge due to its progressive neurodegeneration, cognitive decline, and memory loss. The amyloid cascade hypothesis, which postulates that the accumulation of amyloid-beta (Aβ) peptides initiates a cascade leading to AD, has dominated research and therapeutic strategies. The failure of recent Aβ-targeted therapies to yield conclusive benefits necessitates further exploration of AD pathology. This review proposes the Mitochondrial–Neurovascular–Metabolic (MNM) hypothesis, which integrates mitochondrial dysfunction, impaired neurovascular regulation, and systemic metabolic disturbances as interrelated contributors to AD pathogenesis. Mitochondrial dysfunction, a hallmark of AD, leads to oxidative stress and bioenergetic failure. Concurrently, the breakdown of the blood–brain barrier (BBB) and impaired cerebral blood flow, which characterize neurovascular dysregulation, accelerate neurodegeneration. Metabolic disturbances such as glucose hypometabolism and insulin resistance further impair neuronal function and survival. This hypothesis highlights the interconnectedness of these pathways and suggests that therapeutic strategies targeting mitochondrial health, neurovascular integrity, and metabolic regulation may offer more effective interventions. The MNM hypothesis addresses these multifaceted aspects of AD, providing a comprehensive framework for understanding disease progression and developing novel therapeutic approaches. This approach paves the way for developing innovative therapeutic strategies that could significantly improve outcomes for millions affected worldwide. [ABSTRACT FROM AUTHOR]

Neuregulin 4 (Nrg4) is an adipokine that belongs to the epidermal growth factor family and binds to ErbB4 tyrosine kinase receptors. In 3T3-L1 adipocytes, the downregulation of Nrg4 expression enhances inflammation and autophagy, resulting in insulin resistance. Here, we searched for the causes of this phenotype. Nrg4 knockdown (Nrg4 KD) adipocytes showed a significant reduction in mitochondrial content and elongation, along with a lower content of the mitochondria fusion protein mitofusin 2 (MFN2), and increased H2O2 production compared to the control scrambled cells (Scr). The antioxidant N-acetylcysteine reversed the oxidative stress and reduced the gene expression of the pro-inflammatory cytokine tumor necrosis factor α (TNFα). Nrg4 KD adipocytes showed enhanced lipolysis and reduced lipogenesis, in addition to a significant reduction in several intermediates of the Krebs cycle. In summary, Nrg4 downregulation in adipocytes affects mitochondrial content and functioning, causing impaired cellular metabolism, which in turn results in oxidative stress, inflammation, and insulin resistance. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus (GDM) is a common complication during pregnancy with an increasing prevalence worldwide. Early prediction of GDM and its associated adverse outcomes is crucial for timely intervention and improved maternal and fetal health. The objective of this review is to provide a comprehensive summary of contemporary evidence on biomarkers, focusing on their potential to predict the development of GDM and serve as predictors of maternal, fetal, and neonatal outcomes in women with GDM. A literature search was conducted in the PubMed database using relevant terms. Original research articles published in English between 1 January 2015, and 30 June 2024, were included. A two-stage screening process was employed to identify studies on biomarkers for GDM diagnosis and prognosis and to evaluate the evidence for each biomarker's diagnostic performance and its potential prognostic correlation with GDM. Various biochemical markers, including adipokines, inflammatory markers, insulin resistance markers, glycemic markers, lipid profile markers, placenta-derived markers, and other related markers, have shown promise in identifying women at risk of developing GDM and predicting adverse pregnancy outcomes. Several promising markers with high predictive performance were identified. However, no single biomarker has demonstrated sufficient accuracy to replace the current diagnostic criteria for GDM. The complexity of multiple pathways in GDM pathogenesis highlights the need for a multi-marker approach to improve risk stratification and guide personalized management strategies. While significant progress has been made in GDM biomarker research, further studies are required to refine and validate these markers for clinical use and to develop a comprehensive, evidence-based approach to GDM prediction and management that can improve maternal and child health outcomes. [ABSTRACT FROM AUTHOR]

Gestational diabetes (GD) is a metabolic disorder characterized by glucose intolerance during pregnancy, significantly impacting maternal and fetal health. Its global prevalence is approximately 14%, with risk factors including obesity, family history of diabetes, advanced maternal age, and ethnicity, which are linked to cellular and molecular disruptions in glucose regulation and insulin resistance. GD is associated with short- and long-term complications for both the mother and the newborn. For mothers, GD increases the risk of developing type 2 diabetes, cardiovascular diseases, and metabolic syndrome. In the offspring, exposure to GD in utero predisposes them to obesity, glucose intolerance, and metabolic disorders later in life. This review aims to elucidate the complex cellular and molecular mechanisms underlying GD to inform the development of effective therapeutic strategies. A systematic review was conducted using medical subject headings (MeSH) terms related to GD's cellular and molecular pathophysiology. Inclusion criteria encompassed original studies, systematic reviews, and meta-analyses focusing on GD's impact on maternal and fetal health, adhering to PRISMA guidelines. Data extraction captured study characteristics, maternal and fetal outcomes, key findings, and conclusions. GD disrupts insulin signaling pathways, leading to impaired glucose uptake and insulin resistance. Mitochondrial dysfunction reduces ATP production and increases reactive oxygen species, exacerbating oxidative stress. Hormonal influences, chronic inflammation, and dysregulation of the mammalian target of rapamycin (mTOR) pathway further impair insulin signaling. Gut microbiota alterations, gene expression, and epigenetic modifications play significant roles in GD. Ferroptosis and placental dysfunction primarily contribute to intrauterine growth restriction. Conversely, fetal macrosomia arises from maternal hyperglycemia and subsequent fetal hyperinsulinemia, resulting in excessive fetal growth. The chronic inflammatory state and oxidative stress associated with GD exacerbate these complications, creating a hostile intrauterine environment. GD's complex pathophysiology involves multiple disruptions in insulin signaling, mitochondrial function, inflammation, and oxidative stress. Effective management requires early detection, preventive strategies, and international collaboration to standardize care and improve outcomes for mothers and babies. [ABSTRACT FROM AUTHOR]

Gestational diabetes mellitus is characterised by an insufficient insulin response to hyperglycaemia and the development of insulin resistance. This state has adverse effects on the health outcomes of the mother and child. Existing hyperglycaemia triggers a state of inflammation that involves several tissues, including the placenta. In this study, we analysed the putative pathomechanism of GDM, with special emphasis on the role of chronic, sterile, pro-inflammatory pathways. The expression and regulation of the elements of IL-1β and Toll-like receptor (TLR) pathways in GDM maternal blood plasma, healthy placental explants and a choriocarcinoma cell line (BeWo cell line) stimulated with pro-inflammatory factors was evaluated. Our results indicate elevated expression of the IL-1β and TLR pathways in GDM patients. After stimulation with IL-1β or LPS, the placental explants and BeWo cell line showed increased production of pro-inflammatory IL-6, TNFa and IL-1β together with increased expression of the elements of the signalling pathways. The application of selected inhibitors of NF-ĸB, MAPK and recombinant interleukin 1 receptor antagonist (IL1RA) proved the key involvement of the IL-1β pathway and TLRs in the pathogenesis of GDM. Our results show the possible existence of loops of autocrine stimulation and a possible inflammatory pathomechanism in placentas affected by GDM. [ABSTRACT FROM AUTHOR]

Type 2 diabetes (T2D), characterized by insulin resistance and β-cell dysfunction, requires continuous advancements in management strategies, particularly in controlling postprandial hyperglycemia to prevent complications. Current antidiabetics, which have α-amylase and α-glucosidase inhibitory activities, have side effects, prompting the search for better alternatives. In addition, diabetes patients are particularly vulnerable to yeast infections because an unusual sugar concentration promotes the growth of Candida spp. in areas like the mouth and genitalia. Asphodelus microcarpus contains bioactive flavonoids with potential enzyme inhibitory properties. This study investigates α-amylase and α-glucosidase inhibitory activities and antioxidant and antimycotic capacity of ethanolic extracts from different parts of A. microcarpus. Results show that extracts significantly inhibit α-glucosidase, with the IC50 value being up to 25 times higher than for acarbose, while exerting low α-amylase activity. The extracts also demonstrated strong antioxidant properties and low cytotoxicity. The presence of phenolic compounds is likely responsible for the observed biological activities. Molecular docking analysis of 11 selected compounds identified emodin and luteolin as significant inhibitors of α-glucosidase. Additionally, the extracts demonstrated significant antibiofilm action against an MDR strain of Candida albicans. These findings suggest that A. microcarpus is a promising source of natural compounds for T2D management. [ABSTRACT FROM AUTHOR]

Metabolic syndrome (MetS) is a group of risk factors in the form of central obesity, insulin resistance, dyslipidemia, and hypertension, increasing oxidative stress. This pathological event leads to the development of cardiovascular disease, for instance, atherosclerosis. Besides modifiable risk factors, non-modifiable risk factors such as genetic factors also play a role in the formation of atherosclerosis in MetS conditions such as THOC5, AIF1, CNN1, and ACTA2. Recently, natural compound derivatives, such as epigallocatechin-3-gallate (EGCG), chlorogenic acid (CGA), and turmeric, have shown beneficial effects in MetS improvement. This study aimed to investigate the effect of green tea, green coffee, and turmeric extract on the expression of THOC5, AIF1, CNN1, and ACTA2 genes that contributed to atherosclerotic vasculopathy development in the MetS rat model. Twenty-five MetS rat models were grouped into 4 groups (n = 5): Standard control (SC), MetS (MetS), a combination of green tea, green coffee, and turmeric extract with treatment doses: 300/100/150 mg/BW(C1) and 400/200/250 mg/BW(C2) group. The THOC5, AIF1, CNN1, and ACTA2 expression were measured at the end of treatment periods. This study found that administering green tea, green coffee, and turmeric extract can lower the expression of THOC5, AIF1, CNN1, and ACTA2. The correlation test showed that there is a strong correlation between THOC5 and AIF1 gene expression, with positive value. In summary, the combined effects of green tea, green coffee, and curcumin extract show significant promise as a potential anti-atherosclerosis treatment by improve the THOC5 and AIF1, but not ACTA2 and CNN1 gene expression in the aortic tissue of metabolic syndrome model. [ABSTRACT FROM AUTHOR]

Obesity-induced insulin resistance (IR) can precipitate metabolic disorders such as diabetes. Zeaxanthin, a crucial member of the carotenoid family, has been found to mitigate the damage caused by obesity. However, reports on the effects of zeaxanthin on obesity-induced IR are lacking. Our objective was to examine the metabolic regulatory impacts of zeaxanthin on mice subjected to a high-fat diet (HFD) that triggered IR and to explore their influence on gut microbiota regulation. This study constructed a mouse model of metabolic dysfunction caused by lipid-rich nutritional patterns to investigate physiological and biochemical indices, liver pathway expression, and the intestinal microbiota. The mechanisms by which zeaxanthin improved both IR and glucose metabolic disorders were elucidated. The results demonstrate that zeaxanthin effectively suppressed obesity. The fasting blood glucose, area under curve of oral glucose tolerance test and insulin tolerance test, and homeostatic model assessment–insulin resistance (HOMA-IR) indices in the HFDZEA group decreased by 14.9%, 25.2%, 28.9%, and 29.8%. Additionally, zeaxanthin improved the lipid metabolism and alleviated damage to the liver and pancreas while also activating the PI3K/Akt pathway, regulating hepatic gluconeogenesis and the glycogen metabolism. The number of OTUs in the HFDZEA group increased by 29.04%. Zeaxanthin improved the structure and profile of the gastrointestinal microbiome and enhanced its diversity, increasing probiotics abundance, decreasing pathogen abundance, and thereby ameliorating the dysbiosis of enteric microbial communities in rodents with obesity resulting from excessive fat consumption. The outcomes of our analysis provide a rational basis for advancing zeaxanthin-based nutritional products. [ABSTRACT FROM AUTHOR]

Objective Secreted frizzled-related protein 1 (SFRP1) is an adipokine whose production is significantly altered in metabolic disorders. Considering the relationship between dysfunction of Wnt/β-catenin signaling and metabolic disorders as well as the inhibitory effects of SFRP1 on this signaling pathway, the present work aimed to investigate the correlation between serum SFRP1 levels and type 2 diabetes mellitus (T2DM) and its developing risk factors for the first time. Methods This case-control study measured serum levels of SFRP1, tumor necrosis factor (TNF)-α, interleukin (IL)-6, adiponectin, and fasting insulin using enzyme-linked immunosorbent assay kits in 80 T2DM patients and 80 healthy individuals. Biochemical parameters were determined using the AutoAnalyzer instrument. Results The T2DM group had higher levels of SFRP1 compared with the controls (146.8100 ± 43.61416 vs 81.9531 ± 32.78545 pg/mL; P <.001). There was a positive correlation between SFRP1 and insulin (r = 0.327, P =.003), TNF-α (r = 0.420, P <.001) as well as homeostatic model assessment for insulin resistance (r = 0.328, P =.003) in the T2DM group. In addition, 10-unit changes in SFRP1 levels showed the risk of T2DM in both the unadjusted (odds ratio [OR] [95% CI] = 1.564 [1.359-1.800]) and adjusted models accounting for age, gender, and body mass index (OR [95% CI] = 1.564 [1.361-1.799]; P <.001). A cut-off value of SFRP1 (105.83 pg/mL) was identified to distinguish between the T2DM patients and the healthy subjects, with sensitivity of 75.0% and specificity of 80.0%. Conclusion According to our research, there was a significant and positive link between the amount of SFRP1 and the likelihood of developing T2DM as well as the related factors like insulin resistance index and TNF-α. These results indicated that SFRP1 might have a potential role in the development of T2DM. [ABSTRACT FROM AUTHOR]

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

Aim: To thoroughly investigate the impact of sustained neuropeptide Y4 receptor (NPY4R) activation in obesity‐associated diabetes. Methods: Initially, the prolonged pharmacodynamic profile of the enzymatically stable pancreatic polypeptide (PP) analogue, [P3]PP, was confirmed in normal mice up to 24 h after injection. Subsequent to this, [P3]PP was administered twice daily (25 nmol/kg) for 28 days to high‐fat‐fed mice with streptozotocin‐induced insulin deficiency, known as HFF/STZ mice. Results: Treatment with [P3]PP for 28 days reduced energy intake and was associated with notable weight loss. In addition, circulating glucose was returned to values of approximately 8 mmol/L in [P3]PP‐treated mice, with significantly increased plasma insulin and decreased glucagon concentrations. Glucose tolerance and glucose‐stimulated insulin secretion were improved in [P3]PP‐treated HFF/STZ mice, with no obvious effect on peripheral insulin sensitivity. Benefits on insulin secretion were associated with elevated pancreatic insulin content as well as islet and beta‐cell areas. Positive effects on islet architecture were linked to increased beta‐cell proliferation and decreased apoptosis. Treatment intervention also decreased islet alpha‐cell area, but pancreatic glucagon content remained unaffected. In addition, [P3]PP‐treated HFF/STZ mice presented with reduced plasma alanine transaminase and aspartate transaminase levels, with no change in circulating amylase concentrations. In terms of plasma lipid profile, triglyceride and cholesterol levels were significantly decreased by [P3]PP treatment, when compared to saline controls. Conclusion: Collectively, these data highlight for the first time the potential of enzymatically stable PP analogues for the treatment of obesity and related diabetes. [ABSTRACT FROM AUTHOR]

Aim: To evaluate the efficacy and safety of dapagliflozin versus placebo as an add‐on in patients with type 2 diabetes who did not achieve adequate glycaemic control with evogliptin and metformin combination. Patients and Methods: In this multicentre, randomized, double‐blind, placebo‐controlled Phase 3 trial, patients with glycated haemoglobin (HbA1c) levels ≥7.0% (≥53 mmol/mol) and ≤10.5% (≤91 mmol/mol) who had received stable‐dose metformin (≥1000 mg) and evogliptin (5 mg) for at least 8 weeks were randomized to receive dapagliflozin 10 mg or placebo once daily for 24 weeks. Participants continued treatment with metformin and evogliptin. The primary endpoint was change in HbA1c level after 24 weeks of treatment from baseline level. Results: In total, 198 patients were randomized, and 195 patients were included in the efficacy analyses (dapagliflozin: 96, placebo: 99). At Week 24, dapagliflozin significantly reduced HbA1c levels. The least squares mean difference in HbA1c level change from baseline after 24 weeks of treatment was −0.70% (−7.7 mmol/mol) (p < 0.0001). The proportion of participants achieving HbA1c <7.0% (≥53 mmol/mol) was higher in the dapagliflozin group than in the placebo group. Compared to placebo, dapagliflozin significantly reduced fasting plasma glucose, mean daily glucose, 2‐h postprandial plasma glucose, fasting insulin, uric acid and gamma‐glutamyl transferase levels, homeostatic model assessment for insulin resistance index, body weight, hepatic steatosis index, and albuminuria. Adiponectin level significantly increased from baseline level after 24 weeks of dapagliflozin treatment. Adverse event rates were similar in the two groups. Conclusion: Dapagliflozin add‐on to evogliptin plus metformin improved glycaemic control and was well tolerated by the target patients. [ABSTRACT FROM AUTHOR]

Identifying biomarkers can help in the early detection of muscle loss and drive the development of new therapies. Research suggests a potential link between retinol-binding protein 4 (RBP4) and muscle mass, particularly in postmenopausal women. This study aimed to examine the association between baseline RBP4 levels and changes in appendicular lean mass (ALM), an indicator of muscle mass, in postmenopausal women. A 12-month follow-up period (n = 153) included baseline and 12-month ALM assessments using DXA. ALM was normalized to squared height (ALMI). Baseline evaluations encompassed insulin resistance via HOMA-IR and immunoassay magnetic bead panel measurements of RPB4, IL-6, TNF-α, and IL-10. Postmenopausal women were categorized into higher (n = 77) and lower (n = 76) RPB4 groups based on baseline RPB4 values. Their changes in ALMI were compared using Mann–Whitney tests. General linear model was employed to evaluate the predictive power of baseline RBP4 for ALMI changes, adjusting for confounding variables: age, physical activity, smoking status, body fat, HOMA-IR, inflammatory markers (TNF-α and IL-6), and anti-inflammatory factor (IL-10). The higher RBP4 group exhibited a more pronounced reduction in ALMI compared to the lower RBP4 group (Higher RBP4 = −0.39 kg/m2, 95% CI: −0.48 to −0.31 kg/m2vs. Lower RBP4 = −0.24 kg/m2, 95% CI: −0.32 to −0.15 kg/m2, P = 0.011). After adjusting for confounding factors, the association between baseline RBP4 changes and ALMI remained (b = −0.008, SE = 0.002, P < 0.001), indicating higher baseline RBP4 values linked to greater ALMI reduction. Our findings support RBP4 as a potential biomarker for changes in muscle mass in postmenopausal women. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: A newly developed technique, the Triglyceride-glucose (TyG) index, supplies a more straightforward method to identify IR than the HOMA-IR (Homeostasis Model Assessment of Insulin Resistance). Yet no methodical analysis has looked into the link involving the TyG index and low muscle mass (LMM), low muscle strength (LMS), and sarcopenia within the US. Thus, this study intended to find any connection concerning the TyG index and LMM, LMS, and sarcopenia. Methods: Between 2011 to 2014, data from the NHANES were used to conduct a nationally representative study involving 2,504 participants. LMM, LMS, and sarcopenia were the outcome variables. Moreover, this positive correlation persists irrespective of age and gender. Results: The TyG index revealed a significant correlation with the prevalence of developing LMM (OR = 1.63(1.26–2.11), p=0.001), LMS (OR = 1.61(1.36–1.91), p<0.001) and sarcopenia (OR = 1.59 (1.23–2.07), p<0.001), after correcting for all variables. Utilizing smooth curve fitting alongside two-piecewise linear regression models, an inverted U-shaped correlation between the TyG index and the prevalence of LMM, LMS, and sarcopenia. Finally, subgroup analysis revealed that the association between the TyG index and LMM, LMS, and sarcopenia was particularly evident in all gender, age subgroups, and individuals with a normal BMI of 25. Conclusion: Sarcopenia and the TyG index reveal an essential positive link. It highlights the potential utility of the TyG index as a screening tool for identifying individuals at risk of sarcopenia earlier. [ABSTRACT FROM AUTHOR]

Background: This study aimed to determine the correlation of plasma asprosin with anthropometric and metabolic parameters in Korean children and adolescents. Methods: This single-center study included 109 Korean children and adolescents: 62 (56.9%) obese participants with a body mass index (BMI) ≥95th percentile and 47 (43.1%) healthy controls with BMI between the 15th and 85th percentile. Metabolic parameters were measured, including fasting blood glucose, fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride and glucose (TyG) index, and lipid profiles. Results: Plasma asprosin levels were higher in the obese group than in the control group (mean 87.0 vs. 69.3 ng/mL; p = 0.001) and in the IR group than in the non-IR group (mean 98.6 vs. 70.2 ng/mL; p < 0.001). Plasma asprosin levels were not associated with sex or pubertal stage. Plasma asprosin levels were positively correlated with BMI SDS (r = 0.34; p = 0.002), glycated hemoglobin (HbA1c) (r = 0.25; p = 0.02), glucose (r = 0.33; p = 0.002), insulin (r = 0.44; p < 0.001), HOMA-IR (r = 0.47; p < 0.001), triglyceride (TG) (r = 0.33; p = 0.003), high-density lipoprotein (HDL) cholesterol (r = -0.29; p = 0.008), and TyG index (r = 0.38; p < 0.001). Multiple linear regression analysis indicated that plasma asprosin levels were independently associated with HOMA-IR (p < 0.001) and TG/HDL cholesterol ratio (p < 0.001). Conclusions: This study demonstrated an association between plasma asprosin levels and obesity and insulin resistance in Korean children and adolescents. [ABSTRACT FROM AUTHOR]