Metabolic Status Research Articles

Association between life’s essential 8 and hyperuricemia among adults in the United States: insights from NHANES 2005–2018

BackgroundHyperuricemia is a significant risk factor for various metabolic and cardiovascular conditions. Life’s Essential 8 (LE8), a comprehensive measure of cardiovascular health promoted by the American Heart Association, may have a protective role against hyperuricemia. This study aims to evaluate the association between LE8 scores and hyperuricemia in a representative sample of US adults.MethodsWe conducted a cross-sectional study using data from the National Health and Nutrition Examination Survey (NHANES) 2005–2018, encompassing 26,885 adults. LE8 scores were calculated based on diet, physical activity, nicotine exposure, sleep health, body mass index, blood lipids, blood glucose, and blood pressure. Hyperuricemia was defined as serum uric acid levels ≥7.0 mg/dL in men and ≥ 6.0 mg/dL in women. Logistic regression and generalized additive models (GAMs) were used to analyze the relationship between LE8 scores and hyperuricemia, adjusting for potential confounders.ResultsHigher LE8 scores were significantly associated with lower odds of hyperuricemia (OR per 10-point increase: 0.73, 95% CI: 0.72–0.75, p < 0.001). Stratified analyses revealed consistent protective effects across subgroups defined by sex, age, race/ethnicity, PIR (poverty income ratio), education level, drinking status, eGFR, and CVD status. Logistic regression and GAM analyses both confirmed a linear relationship between increasing LE8 scores and reduced hyperuricemia risk. For example, in males, the OR was 0.81 (95% CI: 0.78–0.84), and in females, it was 0.66 (95% CI: 0.64–0.68).ConclusionThe findings suggest that higher LE8 scores are robustly associated with lower odds of hyperuricemia in US adults. These results support the promotion of comprehensive cardiovascular health behaviors encapsulated by LE8 to mitigate hyperuricemia risk. Further studies are needed to explore the causal pathways and potential interventions.

SQ31f is a potent non-tuberculous mycobacteria antibiotic by specifically targeting the mycobacterial F-ATP synthase.

Non-tuberculous mycobacteria (NTM) infection presents a growing global health problem and requires new antibiotics targeting enzymes that are essential for the pathogens under various metabolic conditions, with high target specificity, good solubility and with attractive combinatory potency. SQ31f was synthesized by a simplified synthesis protocol, and its effect on growth inhibition of fast- and slow-growing NTM and clinical isolates, whole-cell ATP depletion, ex vivo macrophages and its potency in combination with other antibiotics were evaluated. Molecular docking studies were employed to assess SQ31f's binding mode. We present- squaramide SQ31f as a novel anti-NTM inhibitor targeting the NTM F1FO-ATP synthase, essential for ATP formation, regulation of ATP homeostasis and proton motive force under multiple growth conditions. The potency of SQ31f in growth inhibition of fast- and slow-growing NTM and clinical isolates correlates with whole-cell ATP depletion, which is not caused by altered oxygen consumption. SQ31f's high aqueous solubility enables binding to the waterfilled cytosolic proton half channel in the subunits a-c interface of the FO domain. As presented for the fast-growing Mycobacterium abscessus, the compound is active against intracellular-residing M. abscessus. Importantly, SQ31f shows an additive effect of the anti-M. abscessus drugs clofazimine, rifabutin or amikacin, and an attractive potentiation of linezolid, clarithromycin, or the oral pair tebipenem and avibactam. SQ31f represents an attractive inhibitor to tackle the issues associated with NTM drug tolerance and toxicity. Its combinatory potency with anti-M. abscessus drugs holds potential for overcoming resistance, while also reducing intensive compound synthesis and associated costs.

Socio-ecological metabolism and rural livelihood conditions: Two case studies on forest litter uses in France and Poland (1875–1910)

Socio-ecological metabolism and rural livelihood conditions: Two case studies on forest litter uses in France and Poland (1875–1910)

Association between triglyceride-glucose index and in-hospital all-cause mortality under different glucose metabolism status among patients with coronary artery disease

BackgroundThis current study aimed to investigate the relationship between the triglyceride-glucose (TyG) index and in-hospital all-cause mortality of coronary artery disease (CAD) in patients with different glucose metabolic statuses.MethodsParticipants were divided into three groups according to tertiles of the TyG index. Glucose metabolic status was classified as normal glucose regulation, pre-diabetes mellitus, and diabetes mellitus (DM). The primary outcome was in hospital all-cause mortality.ResultsWe observed a significant relationship between the TyG index and in-hospital deaths of patients with CAD in this study. After adjusting for multiple factors in the logistic regression model, the TyG index was still an independent risk factor, and the T3 group (OR, 2.311; 95% CI = 1.237–4.317; P = 0.009) was correlated with a 2.311-fold risk compared with the T1 group. In the subgroup analysis of different glucose metabolic status, the T3 group (OR, 1.541; 95% CI: 1.013–2.344; P = 0.043) were associated with a significantly higher risk of in-hospital deaths in CAD patients with DM.ConclusionsAn increased TyG index was correlated with a higher risk of in-hospital all-cause mortality. Our study indicated that TyG index could be a valuable predictor of in-hospital death of CAD patients, especially for individuals with DM.

Transcriptomic profiling of 'Candidatus Liberibacter asiaticus' in different citrus tissues reveals novel insights into Huanglongbing pathogenesis.

'Candidatus Liberibacter asiaticus' (Las) is a gram-negative bacterial pathogen associated with citrus huanglongbing (HLB) or greening disease. Las is transmitted by the Asian citrus psyllid (ACP) where it colonizes the phloem tissue, resulting in substantial economic losses to citrus industry worldwide. Despite extensive efforts, effective management strategies against HLB remain elusive, necessitating a deeper understanding of the pathogen's biology. Las undergoes cell-to-cell movement through phloem flow and colonizes different tissues in which Las may have varying interactions with the host. Here, we investigate the transcriptomic landscape of Las in citrus seed coat vasculatures, enabling a complete gene expression profiling of Las genome and revealing unique transcriptomic patterns compared to previous studies using midrib tissues. Comparative transcriptomics between seed coat, midrib and ACP identified specific responses and metabolic states of Las in different host tissue. Two Las virulence factors that exhibit higher expression in seed coat can suppress callose deposition. Therefore, they may contribute to unclogging sieve plate pores during Las colonization in seed coat vasculature. Furthermore, analysis of regulatory elements uncovers a potential role of LuxR-type transcription factors in regulating Liberibacter effector gene expression during plant colonization. Together, this work provides novel insights into the pathogenesis of the devastating citrus HLB.

The impact of metabolic heterogeneity of obesity and transitions on cardiovascular disease incidence in Chinese middle-aged and elderly population: A nationwide prospective cohort study.

Previous studies indicated that metabolic heterogeneity of obesity would affect the risk of cardiovascular disease (CVD). However, the alterations in CVD risk associated with transitions between various metabolic health statuses influenced by obesity status remain unclear. We utilized data from the China Health and Retirement Longitudinal Study (CHARLS), a longitudinal cohort study involving Chinese residents aged 45 years and older. Baseline data were collected in 2011-2012, with follow-up surveys conducted up to 2020. Participants in the study were categorized into four body mass index-metabolic phenotypes: metabolically healthy normal weight (MHNW), metabolically healthy overweight/obesity (MHOO), metabolically unhealthy normal weight (MUNW) and metabolically unhealthy overweight/obesity (MUOO). Transitions in these phenotypes over 4 years were analysed. Cox regression models were used to assess the associations of these phenotypes and their transitions with CVD incidence. Among 7721 participants, 1353 (17.5%) developed CVD during the follow-up period. Both overweight/obese and metabolically unhealthy statuses were associated with increased CVD risk. The highest risk was observed in the MUOO group (hazard ratio [HR]: 1.74, 95% confidence interval [CI]: 1.50-2.09, p < 0.0001), followed by the MUNW (HR 1.35, 95% CI: 1.13-1.66, p < 0.001) and MHOO (HR: 1.29, 95% CI: 1.08-1.56, p = 0.002) groups compared to the MHNW group. The deteriorations of obesity and metabolic health status elevated the incidence of CVD, whereas improvements in these statuses reduced the risk of CVD. Additionally, alterations in metabolic health status conferred greater benefits in overweight/obese individuals compared to those with normal weight. The study highlights the importance of maintaining and promoting metabolic health, particularly in overweight/obese individuals, to reduce CVD risk. Metabolic health status plays a more crucial role than obesity status in predicting CVD incidence.

The relationship between the Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and metabolic health status in adolescents with overweight and obesity: results from a cross-sectional study in Iran.

Few studies investigated the association between Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet and metabolic health status, particularly among adolescents. The present study was designed to investigate the association of MIND diet with metabolic health status in Iranian adolescents with overweight/obesity. This cross-sectional study was done among 203 adolescents with overweight/obesity (12-18 years) in Isfahan, Iran. A validated FFQ was applied to collect dietary intakes. Anthropometric indices and blood pressure were also measured by standard procedures. Fasting blood samples were obtained to determine serum insulin, glucose and lipid profile. To categorise participants as being with metabolically healthy overweight/obesity (MHO) or metabolically unhealthy overweight/obesity (MUO), two methods including International Diabetes Federation (IDF) criteria and IDF plus Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) were applied. Participants had a mean age of 13·98 years and 50·2 % of them were girls. In fully adjusted models, participants with highest MIND diet adherence had lower odds of MUO status based on IDF (OR = 0·20; 95 % CI 0·08, 0·51) and IDF/HOMA-IR (OR = 0·22; 95 % CI 0·08, 0·59) criteria. Stratified analyses revealed that this association was stronger among girls and was only significant among individuals with overweight. An inverse association was also found between MIND diet score and odds of hyperglycaemia and insulin resistance (IR). Higher MIND diet adherence was associated with lower odds MUO in adolescents with overweight/obesity. Inverse associations were also found between MIND diet and odds of hyperglycaemia and IR. Future longitudinal prospective studies are necessary to confirm our results.

Triglyceride-glucose index is associated with heart failure with preserved ejection fraction in different metabolic states in patients with coronary heart disease

BackgroundThe triglyceride-glucose (TyG) index is a surrogate indicator of insulin resistance. Therefore, we aimed to determine the association between TyG index and heart failure (HF) with preserved ejection fraction (HFpEF) in patients with coronary heart disease (CHD) and to explore whether such associations would be modified by different metabolic states.MethodsAmong 107,301 CHD patients, 62,794 were included to analyze the relationship between the TyG index and HF. Among them, 8,606 patients who had undergone echocardiography were included to identify different types of HF, including HF with reduced ejection fraction (HFrEF), HF with intermediate-range ejection fraction (HFmrEF), and HFpEF. Among them, 1896 patients were diagnosed with HFpEF. Logistic regression was used to analyze the relationship between the TyG index and HFpEF in CHD patients. In addition, the association between TyG index and HFpEF according to sex, age, blood lipids, and blood pressure was assessed.ResultsA baseline analysis of CHD patients divided into four groups according to the tertile level of the TyG index showed significant differences in the related parameters between the groups. In the multi-adjusted models, the TyG index was significantly associated with the risk of HFpEF (odds ratio [OR]: 1.17; 95% confidence interval [CI]: 1.09–1.25). After adjustment for multivariates, TyG index levels for T2 (OR: 1.33; 95% CI: 1.16–1.52) and T3 (OR: 1.52; 95% CI: 1.32–1.74) were associated with increased OR in HFpEF. In addition, the TyG index of CHD patients was significantly associated with HFpEF in older adults aged &amp;gt; 60 years (OR: 1.20; 95% CI: 1.11–1.29), hypertension (OR: 1.27; 95% CI: 1.17–1.37), and dyslipidemia (OR: 1.15; 95% CI: 1.08–1.24). Moreover, the OR (OR: 1.23; 95% CI: 1.11–1.36) in women is higher than in men (OR: 1.17; 95% CI: 1.02–1.22, indicating a stronger association between TyG index and HFpEF in women.ConclusionsOur findings demonstrated a significant association between TyG index and HFpEF in CHD patients. Furthermore, TyG index was independently associated with HFpEF in hypertension, dyslipidemia, and older patients (aged &amp;gt; 60 years). In addition, the association between the TyG index and HFpEF in CHD patients differed according to sex.

Impact of Dietary Fatty Acid Composition on the Intestinal Microbiota and Fecal Metabolism of Rats Fed a High-Fructose/High-Fat Diet.

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.

Investigating the role of dietary glycemic factors and antioxidant capacity, metabolic status, and oxidative stress in seborrheic dermatitis: A case-control study.

The etiopathogenesis of seborrheic dermatitis (SD) remains unexplained, although several factors have been considered in this regard. The aim of this study is to investigate diet, metabolic status, and oxidative stress in SD patients. This prospective, single-center, case-control study included 49 SD patients and 40 gender- and age-matched healthy controls. Dietary total antioxidant capacity values ​​were significantly lower in SD patients than among the controls (7.16 ± 2.66 vs. 12.85 ± 4.26; p < 0.001). Glycemic load (GL) values ​​were significantly higher in SD patients (187.2 ± 57.2 vs. 110.6 ± 46.5; p < 0.001). The glycemix index (GI) and GL values ​​of patients with severe SD were significantly higher than those with mild SD (p = 0.014, p = 0.017; respectively). The cross-sectional design, small sample size, and the relatively short duration of questioning dietary habits are the limitations of the study. A diet rich in antioxidants and with low GI/GL content may be beneficial in the treatment of SD.

Sex- and metabolic-specific association between cumulative body mass index and incident chronic kidney disease: a prospective community-based cohort study

Background and AimDifference in metabolic status may cause inconsistent association between body mass index (BMI) and chronic kidney disease (CKD) in men and women. This study aimed to quantify sex-specific association between cumulative BMI (cumBMI) and incident CKD by different metabolic status. Methods and ResultsParticipants free of CKD from the Kailuan Study were followed biennially from baseline (June 2006 to October 2007) to December 2019. cumBMI was calculated by use of follow-up BMI and follow-up time and was divided into low weight (<18.5 kg/m2), normal weight (18.5 to 23.9 kg/m2), overweight (24 to 27.9 kg/m2), and obesity (≥28 kg/m2) according to Chinese criteria. Metabolic health was defined as the absence of hypertension, dyslipidemia, and diabetes at baseline. CKD was defined as having estimated glomerular filtration rate <60 mL/min/1.73m2. This study included 76984 participants, with a mean age of 50.0 ± 11.6 years and 80.0% of men. Overweight (HR=1.24, 95% CI: 1.16–1.31) and obesity (HR=1.94, 95% CI: 1.77–2.12) were associated with higher risk of incident CKD in men regardless of metabolic status. Corresponding population attributable risk percentages for overweight and obesity were 10.3% (95%CI: 7.1–12.9) and 12.7% (95%CI: 10.6–14.7), respectively. However, low weight (HR=1.56, 95% CI: 1.05–2.30) and obesity (HR=1.32, 95% CI: 1.01–1.73) were associated with higher risk of incident CKD in metabolically healthy women but not in metabolically unhealthy women. ConclusionsThis study demonstrated sex- and metabolic-specific associations between BMI and CKD occurrence and advocates an individualized weight management strategy.

The Effects of Vitamin D Supplementation on Glycemic Indices, Lipid Profile and Blood Pressure of Pregnant Women with Vitamin D Deficiency: A Single Arm Clinical Trial

Introduction: Vitamin D Deficiency (VDD) is a global problem among pregnant women in many populations. There is an association between VDD and some pregnancy outcomes, as well as gestational diabetes mellitus (GDM) and pre-eclampsia. We aimed to evaluate the effect of vitamin D supplementation on metabolic status (Fasting Blood Sugar (FBS), insulin, Homeostasis model of assessment-insulin resistance (HOMA-IR) and lipid profile) and blood pressure (BP) among pregnant women with VDD. Methods: A clinical trial was carried out on 30 pregnant women with VDD referring to the Gynecology &amp; Obstetrics Clinic of Baqiyatallah Hospital, Tehran, Iran. The present study had two phases of vitamin D3 supplementation (50000 IU / week for 12 weeks and then 50000 IU / month for three months). Serum total cholesterol, triglyceride, Low Density Lipoprotein (LDL), High Density Lipoprotein (HDL), 25-hydroxyvitamin D (25(OH) D) level, insulin, Fasting Blood Sugar (FBS) and both systolic and diastolic blood pressure were measured. Homeostasis model of assessment-insulin resistance (HOMA-IR) was also determined. Results: The results showed that mean levels of Insulin (p=0.010), HOMA-IR (p=0.020), 25(OH) D level (p=0.001), cholesterol (p=0.001), triglyceride (p=0.001) and LDL (p=0.001) significantly increases during study period. However, Diastolic and systolic blood pressure, FBS, and HDL levels did not change significantly over time. Conclusion: The results of this investigation showed that weekly and monthly vitamin D3 supplementation in pregnant women with VDD had beneficial effects on glycemic status, lipid profile and blood pressure.

Obesity is highly associated with a non-home discharge following total ankle arthroplasty

Studies have shown that non-home discharge following orthopedic procedures is associated with a higher risk of 30-day complications and significantly increases medical costs. The purpose of this study was to identify risk factors for being discharged to a non-home destination following total ankle arthroplasty (TAA).We included patients undergoing TAA from the American College of Surgeons National Surgical Quality Improvement Program database (NSQIP) between 2014 and 2019. TAA was identified using CPT codes 27702, 27703 and 27704. Logistic regression models were used to assess the association between discharge location (home versus non-home) and a series of exposure variables (e.g., patient demographics, patient health characteristics, and operative factors).A total of 1,704 patients were included, experiencing a 3.6% short term complication rate (61/1,704). 8.5% of the population were discharged to a non-home destination. In the final adjusted model, patients who were older [OR 1.11; 95%CI 1.08, 1.13], female [OR 2.94; 95%CI 2.04, 4.34], obese [OR 1.93; 95%CI 1.29, 2.89], had surgery in an inpatient setting [OR 5.73; 95%CI 1.78, 18.46], and ASA class IV [OR 10.65; 95%CI 1.03, 110.61] were at greater risk for a non-home discharge.People living with obesity experienced a nearly 2x greater likelihood of being discharged to a non-home destination after TAA despite their preoperative functional (e.g., ASA class) and metabolic status (i.e., diabetes). Opportunities to mitigate this risk will be needed to lessen the financial burden of TAA surgery as a growing number of obese patients become eligible for TAA in the US.

Metabolic Conditions and Organ Dysfunctions Risk Factors for Gastrointestinal Cancer in Hypertensive Patients: A Case-Control Study in China

Metabolic Conditions and Organ Dysfunctions Risk Factors for Gastrointestinal Cancer in Hypertensive Patients: A Case-Control Study in China

Subcutaneously transplanted xenogeneic protein recruits treg cells and M2 macrophages to induce browning of inguinal white adipose tissue.

To study whether subcutaneously embedding xenogeneic protein threads or synthetic polymer absorbable threads can improve obesity phenotypes and metabolic conditions, and to further explore its underlying mechanism. Thirty-six 8-week-old ob/ob mice were randomly allocated to three groups, respectively, receiving catgut embedding, PGA thread embedding or sham treatment bilaterally to the groin. Individual parameters including weight, food intake, and core temperature are recorded and metabolism assessment, energy expenditure analysis, and PET/CT scanning are also performed at fixed timepoints. After surgical incision, the inguinal white adipose tissue was histologically examined and its expression profile was tested and compared among groups 4 weeks and 12 weeks after operation. Catgut embedding reduced weight gain and improved metabolic status in ob/ob mice. Browning of bilateral inguinal WAT (white adipose tissue) was induced after catgut embedding, with massive infiltration of Treg cells and M2 macrophages in the tissue slices of fat pads. IL-10 and TGF-β released by Treg cells targeted macrophages and the induced M2 macrophages increased the expression of thermogenic and anti-inflammatory genes in fat. The secretion of catecholamines by polarized M2 macrophages led to the activation of β3-AR-related pathways in adipocytes and the browning of adipose tissue. Abdominal subcutaneous catgut embedding has the potential to combat obesity through the induction of WAT browning mediated by infiltrated Treg cells and macrophages.

Metabolic Checkpoints in Rheumatoid Arthritis

BackgroundRheumatoid Arthritis is a systemic autoimmune disease affecting 0.5-1% of the population. Despite a growing therapeutic armamentarium, RA remains incurable, and many patients suffer significant morbidity over time. The strongest genetic risk derives from HLA class II polymorphisms, implicating T cells as pathogenic drivers. Innate immune cells, e.g. monocytes and macrophages (Mⱷ) contribute to chronic tissue inflammation through an array of pro-inflammatory functions but also present antigen to autoreactive T cells. Differentiation, survival, and effector functions of both T cells and Mⱷ are ultimately controlled by their bioenergetic and biosynthetic programs, identifying cellular metabolism as a critical disease mechanism in RA. ObjectivesSummarize current knowledge about metabolic conditions in the RA joint and disease-relevant metabolic circuits shaping the effector repertoire of RA T cells and Mⱷ. ResultsThe rheumatoid joint is a glucose deplete tissue environment, selecting for invading immune cells that can survive on non-glucose fuel sources. Inflamed synovium instead offers the amino acid glutamine and RA CD4+ T cells and RA Mⱷ rely on glutamine and glutamate to support their pathogenic functions. The metabolic hallmark of RA T cells is their low mitochondrial performance, resulting in low ATP production, low generation of reactive oxygen species (ROS) and low availability of tricarboxylic acid (TCA) cycle intermediates, all shifting RA T cells towards autoreactivity. The underlying defect stems from insufficient repair of mitochondrial DNA (mtDNA). Functional consequences include reversal of the TCA cycle, accumulation of citrate and lack of malate production. Excessive citrate promotes cytoskeletal hyperacetylation, creating hypermigratory and tissue-invasive T cells. Surplus acetyl-CoA supports lipid droplet formation and lipotoxicity. Lack of malate production disrupts the malate-aspartate shuttle, restricts recovery of cytosolic NAD and drives the endoplasmic reticulum (ER) into expansion. The bioenergetically stressed ER accumulates TNF mRNA and turns RA T cells into TNF superproducers. ATP low production renders RA T cells susceptible to cell death, depositing highly inflammatory mtDNA in the tissue. Mitochondrial deficiency leads to a slowdown in glycolysis and pyruvate processing, such that RA CD4+ T cells shunt glucose towards the pentose phosphate pathway to support nucleotide synthesis and clonal proliferation. Metabolically deprived CD4+ T cells partner with Mⱷ that have highly functional mitochondria. A hallmark of RA Mⱷ is the high expression of the DNA binding protein RFX5, which co-ordinates adaptations to metabolic needs with function. RFX5 upregulates HLA-DR expression and induces the glutaminolytic enzyme glutamate dehydrogenase 1 (GLUD1), providing bioenergetic resources for antigen presentation and survival in the tissue. In essence, RA CD4+ T cells and Mⱷ function in a metabolically challenging environment and rewire their cellular metabolism to survive. Metabolic adaptations promote immunostimulation and tissue inflammation, triggering and sustaining rheumatoid synovitis.

Development and Validation of Machine Learning Models for Identifying Prediabetes and Diabetes in Normoglycemia.

Prediabetes and diabetes are both abnormal states of glucose metabolism (AGM) that can lead to severe complications. Early detection of AGM is crucial for timely intervention and treatment. However, fasting blood glucose (FBG) as a mass population screening method may fail to identify some individuals who are actually AGM but with normoglycemia. This study aimed to develop and validate machine learning (ML) models to identify AGM among individuals with normoglycemia using routine health check-up indicators. According to the American Diabetes Association (ADA) criteria, participants with normoglycemia (FBG≤5.6mmol/L) were collected from 2019 to 2023, and then divided into AGM and Normalgroups using glycosylated haemoglobin (HbA1c) 5.7% as the threshold. Data from 2019 to 2022 were divided into training and internal validation sets at a 7:3 ratio, while data from 2023 were used as the external validation set. Seven ML algorithms-including logistic regression (LR), random forest (RF), support vector machine (SVM), extreme gradient boosting machine, multilayer perceptron (MLP), light gradient boosting machine (LightGBM), and categorical boosting (CatBoost)-were used to build models for identifying AGM in normoglycemia population. Model performance was evaluated using the area under the receiver operating characteristic curve (auROC) and the precision-recall curve (auPR). The feature contributions to the optimal model was visualised using the SHapley Additive exPlanations (SHAP). Finally, an intuitive and user-friendly interactive interface was developed. A total of 59,259 participants were finally enroled in this study, and then divided into the training set of 32,810, the internal validation set of 14,060, and the external validation set of 12,389. The Catboost model outperformed the others with auROC of 0.806 and 0.794 for the internal and external validation set, respectively. Age was the most important feature influencing the performance of the CatBoost model, followed by fasting blood glucose, red blood cells, haemoglobin, body mass index, and triglyceride-glucose. A well-performed ML model to identify AGM in the normoglycemia population was built, offering significant potential for early intervention and treatment of AGM that would otherwise have been missed.

Antipsychotic-Treated Schizophrenia Patients Develop Inflammatory and Oxidative Responses Independently From Obesity: However, Metabolic Disturbances Arise From Schizophrenia-Related Obesity.

To define the impact of obesity on inflammatory and oxidative disturbances in antipsychotic-treated schizophrenia patients. Several cytokines, inflammatory, metabolic, and oxidative status markers were evaluated in obese (n=40) and non-obese (n=40) antipsychotic-treated patients and compared with age-and BMI-matched controls (n=80). Schizophreniapatients had higher leptin, TNF-α, adiponectin, visfatin, resistin, P-selectin, NPY, BDNF, CD40-L, MCP-1, and malondialdehyde, and lower IL-6, ghrelin, neopterin, and vitamin E levels compared to their respective controls (p<0.001). Total oxidant status was higher in non-obese patients compared to controls (p<0.001), total antioxidant capacity was higher in obese compared to non-obese patients (p<0.01), but vitamin A and paraoxonase levels were not different. High sensitive-CRP levels were higher in obsese controls relative to non-obese controls (p<0.05) and in obese patients relative to non-obese patients (p<0.001). Fasting glucose, insulin, HbA1c, HOMA-IR, uric acid, total cholesterol, and triglyceride concentrations were higher in obese patients compared to non-obese patients. Insulin concentrations and HOMA-IR were also higher in obese controls than in non-obese controls. Our results suggest that inflammatory responses and oxidative stress develop independently from obesity in antipsychotic-treated schizophrenia patients. However, schizophrenia-induced obesity causes metabolic disturbances; thereby, obese schizophrenia patients are more liable to cardiovascular events and progress of metabolic syndrome than non-obese patients.

Genetic aspects of major blood metabolites in the Italian Simmental cattle population

The Simmental breed is widely known for its resilience, robustness, and resistance to disease and therefore the incidence of ketosis in this breed is generally lower compared with Holsteins. Blood concentrations of nonesterified fatty acids (NEFA), BHB, and urea provide valuable information about the metabolic, health, and nutritional status of lactating animals. In the present study we estimated h2 of BHB, NEFA, and urea in blood predicted from milk mid-infrared spectra and assessed their genetic correlation with milk yield and composition traits in the Italian Simmental cattle breed using phenotypes of 3,549 cows in 207 herds. Two sets were considered: early (1,920 records - 1 per cow - between 5 and 35 DIM) and whole (14,378 records - at least 3 per cow - between 5 and 305 d in milk) lactation. In early lactation, h2 were 0.06 for blood BHB as is, 0.06 for log-transformed BHB, 0.18 for NEFA, 0.14 for log-transformed NEFA, and 0.05 for blood urea. In whole lactation, the h2 were 0.09 for blood BHB as is, 0.16 for log-transformed BHB, 0.03 for NEFA, 0.04 for log-transformed NEFA, and 0.04 for blood urea. As far as the genetic correlations were concerned, blood BHB was positively correlated with NEFA and blood urea. Blood BHB and NEFA were generally positively correlated with milk fat-to-protein ratio and milk BHB; blood BHB was negatively correlated with lactose content and positively with SCS. Sires' estimated breeding values for BHB (accuracy ≥0.60) were extrapolated for a-posteriori evaluation of the daughters' observed performance. The progeny of the top 5% of sires exhibited, on average, lower blood BHB, NEFA, and urea compared with the daughters of the bottom 5%. Overall, it is highly recommended to monitor the genetic variability of the metabolic traits in the dual-purpose Italian Simmental breed to monitor the metabolic diseases incidence in future generations.

Targeting Gut microbiota as a therapeutic target in T2DM: a review of Multi-target interactions of probiotics, prebiotics, postbiotics, and synbiotics with the Intestinal Barrier

The global epidemic of type 2 diabetes mellitus (T2DM) imposes a substantial burden on public health and healthcare expenditures, thereby driving the pursuit of cost-effective preventive and therapeutic strategies. Emerging evidence suggests a potential association between dysbiosis of gut microbiota and its metabolites with T2DM, indicating that targeted interventions aimed at modulating gut microbiota may represent a promising therapeutic approach for the management of T2DM. In this review, we concentrated on the multifaceted interactions between the gut microbiota and the intestinal barrier in the context of T2DM. We systematically summarized that the imbalance of beneficial gut microbiota and its metabolites may constitute a viable therapeutic approach for the management of T2DM. Meanwhile, the mechanisms by which gut microbiota interventions, such as probiotics, prebiotics, postbiotics, and synbiotics, synergistically improve insulin resistance in T2DM are summarized. These mechanisms include the restoration of gut microbiota structure, upregulation of intestinal epithelial cell proliferation and differentiation, enhancement of tight junction protein expression, promotion of mucin secretion by goblet cells, and the immunosuppressive functions of regulatory T cells (Treg) and M2 macrophages. Collectively, these actions contribute to the amelioration of the body's metabolic inflammatory status. Our objective is to furnish evidence that supports the clinical application of probiotics, prebiotics, and postbiotics in the management of T2DM.