Obesity is a global health concern that promotes chronic low-grade inflammation, leading to insulin resistance, a key factor in many metabolic diseases. Angiotensin 1-7 (Ang 1-7), a component of the renin-angiotensin system (RAS), exhibits anti-inflammatory effects in obesity and related disorders, though its mechanisms remain unclear. In this study, we examined the effect of Ang 1-7 on inflammation of white adipose tissue (WAT) in dietary-induced obese mice. Monocyte chemoattractant protein-1 (MCP-1) produced by white adipocytes and tumour necrosis factor-α (TNF-α) produced by macrophages are pro-inflammatory cytokines and interact to form a pathogenic loop to exacerbate obesity-induced inflammation. We found that Ang 1-7 reduced MCP-1 and TNF-α gene expressions and the number of crown-like structures, which are histological hallmarks of the pro-inflammatory process, in visceral epididymal WAT (eWAT) and reduced circulating MCP-1 and TNF-α levels, accompanied by improvement in insulin resistance, in dietary-induced obese mice. Furthermore, Ang 1-7 reduced MCP-1 and TNF-α secretions in 3T3-L1 white adipocytes and RAW 264.7 macrophages, respectively, which are in vitro experimental models mimicking obesity condition. Our results suggest that Ang 1-7 directly acts on WAT to mitigate obesity-induced inflammation. Thus, this study provides novel insights into the underlying mechanism of anti-obesity effects of Ang 1-7.

Diabetes Mellitus, characterized by insufficient insulin secretion, pancreatic beta cell damage, or insulin resistance, is the third most prevalent chronic metabolic disease worldwide. Polysaccharides, biocompatible natural macromolecules, have garnered significant attention for their potential in modulating diabetes through various mechanisms. Despite extensive studies, a comprehensive and impartial evaluation of anti-diabetic polysaccharides (ATDPs) research is still lacking. This study employs bibliometric and knowledge mapping techniques to analyze research trends and developments concerning ATDPs. A total of 3435 publications from 2001 to 2024 were examined, revealing a marked increase in publication volume and citation frequency, particularly since 2016. Network analysis indicates China as the leading contributor, with the highest number of publications and prominent institutions. The International Journal of Biological Macromolecules is identified as the most prolific journal in this field. Shaoping Nie stands out as a leading researcher with the highest citation frequency and h-index. Current research trends focus on the role of polysaccharides in regulating oxidative stress and inflammation, modulation of gut microbiota, and their structural characterization. Emerging studies investigate how these polysaccharides impact gut microbiota composition, enhance intestinal barrier functions, and modulate immune responses, representing cutting-edge areas in diabetes research. This research pioneers the use of bibliometric analysis to map ATDPs research trajectories, offering valuable insights into prevailing trends, emerging topics, and opportunities for future research and collaboration.

Retinoid X receptors (RXRs) are nuclear hormone receptors (NRs) functioning as transcription factors. There are three RXR isoforms: RXRA (NR2B1), RXRB (NR2B2), and RXRG (NR2B3). RXRs serve as master regulators of gene networks governing cell growth, differentiation, survival, and death. RXRs might affect insulin action, but very little data currently supports this relationship. The aim of the study was to analyze the relationship between the expression of RXRs in skeletal muscles and insulin sensitivity in young, normal-weight, overweight and obese people.

The research group consisted of 45 volunteers, 20 had normal body weight, 13 were overweight, and 12 were obese. Insulin sensitivity was measured with hyperinsulinemic-euglycemic clamp. Vastus lateralis muscle biopsies were taken before each clamp, and RXRs mRNA expression was analyzed.

RXRA expression was lower in overweight, obese subjects in comparison with normal-weight volunteers (P = 0.003, P = 0.002, respectively). RXRB and RXRG expression did not differ between the groups. RXRA expression in muscle was positively correlated with insulin sensitivity (r = 0.49, P = 0.001). The relationship between muscle tissue RXRA and insulin sensitivity was independent of BMI (β = 0.35, P = 0.02).

Our results indicate that RXRA expression in skeletal muscle is linked to insulin sensitivity. The data suggest that muscle-associated RXRs may play a role in modulating insulin action.

Ectopic fat deposition in skeletal muscle (SKM) due to obesity leads to biochemical and morphological alterations that deteriorate SKM quality and performance. Here, we show that impaired MPST-derived hydrogen sulfide (H2S) signaling contributes to obesity-related SKM dysfunction. Muscle tissues from obese db/db mice exhibit reduced MPST expression, correlating with decreased protein persulfidation and muscle performance in vivo. Mpst-/- mice show similar deficits as db/db mice, confirming the role of MPST. H2S supplementation improves locomotor activity in db/db mice and restores protein persulfidation, including SIRT-1. Myotubes placed in an "obese environment" display a downregulation of MPST, coupled with a reduced SIRT-1 persulfidation leading to an inflammatory state. Exogenous H2S exerts beneficial effects recovering SIRT-1 persulfidation/activity. Finally, muscle biopsies from obese individuals show reduced MPST expression, underscoring the translational relevance to human SKM health. Our study unveils a crucial role for MPST-derived H2S in obesity-associated SKM dysfunction via SIRT-1 persulfidation, highlighting the importance of the MPST/H2S pathway in maintaining healthy SKM function.

Metabolic dysfunction associated steatotic liver disease (MASLD) is a universal hepatic disease, and many recent randomized clinical trials (RCTs) have explored whether hypoglycemic agents may be beneficial for its treatment. This study aimed to assess the relative effectiveness of each hypoglycemic agent for MASLD.

China National Knowledge Infrastructure（CNKI）, WanFang, Weipu, PubMed, Embase, The Cochrane Library, and Web of Science Core Collection were searched for RCTs on the efficacy of hypoglycemic agents in MASLD published up to December 31, 2024. All statistical analyses were performed using R version 4.3.3. The network meta-analysis was conducted using Bayesian statistical methods.

A total of 26 hypoglycemic agents for treating MASLD in 37 studies with 2406 participants were included. Empagliflozin was most effective in improving liver stiffness measurement (LSM), whereas liraglutide showed significant benefits in body weight, body mass index (BMI), and waist circumference. Both sodium-glucose co-transporter 2 (SGLT-2) inhibitors (e.g., empagliflozin) and glucagon-like peptide-1 (GLP-1) receptor agonists (e.g., liraglutide) improved liver enzymes (alanine aminotransferase [ALT], aspartate aminotransferase [AST], gamma-glutamyltransferase [GGT]), glucose metabolism (fasting plasma glucose [FPG], and homeostasis model assessment of insulin resistance [HOMA-IR]), and lipid profiles. Pioglitazone had limited benefits in these outcomes. Secondary outcomes such as inflammatory markers and fibrosis showed minimal changes.

Several hypoglycemic agents can improve laboratory and imaging indicators in adult patients with MASLD. Liraglutide is more effective than other agents, whereas empagliflozin emerged as the most effective for reducing LSM. However, different agents have different effects on the indicators; therefore, the relevant agents must be selected according to the specific patient condition.

Chinese herbal medicine effectively treats recurrent pregnancy loss, though its mechanism is unclear. This study used RStudio 4.3.0 to collect successful cases for cluster analysis, identifying medication patterns and core formulas, and further researching key prescriptions. The prescription is frequently used for recurrent abortion patients with insulin resistance. UPLC-QTOF-MS identified components, and network pharmacology explored key prescription targets in recurrent abortion with insulin resistance, validated by molecular docking and in vitro experiments. Traditional Chinese medicine treatment for 177 recurrent abortion cases and 640 prescriptions was analysed using RStudio 4.3.0 to identify medication patterns. Chaige Kangyi Recipe (CGKYR) active components and targets were obtained from TCMNPAS, and a herb-ingredient-target gene network was constructed using Cytoscape 3.7.2. GeneCards provided RSA target genes, and Cytoscape visualised a drug-disease target PPI network. Metascape software performed GO and KEGG enrichment analyses. UHPLC-MS/MS identified active compounds in core prescriptions, and molecular docking evaluated the therapeutic effects and mechanisms of major chemical components on key targets. Key prescriptions were derived from RStudio 4.3.0 cluster analysis of the Chaige Kangyi Recipe (CGKYR), commonly used for recurrent miscarriages with insulin resistance. Sixty-seven active ingredients were identified via UPLC-QTOF-MS. Network pharmacology revealed 179 target genes related to CGKYR's effects on recurrent miscarriage with insulin resistance. PPI analysis indicated IL-6, AKT1, STAT3, and INS as potential targets. Molecular docking demonstrated strong binding activity of four compounds with IL-6.CCK-8 assays showed CGKYR promoted HDSC proliferation dose-dependently. In vitro experiments indicated CGKYR increased IL-6 mRNA expression in human decidual stromal cells. CGKYR employs a multifaceted therapy for RPL complicated by insulin resistance, enhancing endometrial receptivity and stimulating HDSC proliferation by upregulating IL-6 mRNA expression in human decidual stromal cells.

This pioneering genome-wide association study examined surrogate markers for insulin resistance (IR) in 147,880 Taiwanese individuals using data from the Taiwan Biobank. The study focused on two IR surrogate markers: the triglyceride to high-density lipoprotein cholesterol (TG:HDL-C) ratio and the TyG index (the product of fasting plasma glucose and triglycerides). We identified genome-wide significance loci within four gene clusters: GCKR, MLXIPL, APOA5, and APOC1, uncovering 197 genes associated with IR. Transcriptome-wide association analysis revealed significant associations between these clusters and TyG, primarily in adipose tissue. Gene ontology analysis highlighted pathways related to Alzheimer's disease, glucose homeostasis, insulin resistance, and lipoprotein dynamics. The study identified sex-specific genes associated with TyG. Polygenic risk score analysis linked both IR markers to gout and hyperlipidemia. Our findings elucidate the complex relationships between IR surrogate markers, genetic predisposition, and disease phenotypes in the Taiwanese population, contributing valuable insights to the field of metabolic research.

This study investigated the acute effects of cocoa flavanol (CF) supplementation on glucose homeostasis, aerobic performance, and lactate concentration in rats with type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), and normoglycemia (NORM).

The study included 28 male Wistar rats (220-290 g). Induction of T1DM (n = 8) was achieved through intraperitoneal injection of streptozotocin, while T2DM (n = 10) was induced using an ad libitum high-fat diet combined with a fructose-rich beverage. The rats in the NORM group (n = 10) received a standard diet for 30 days. Two experiments were conducted: (1) T1DM rats performed two successive 30-minute treadmill runs below the anaerobic threshold and (2) T2DM and NORM rats underwent two incremental maximal treadmill running tests, both after CF or placebo supplementation. Blood glucose concentrations were measured from pre-exercise to 60 minutes post-exercise.

Glycemic reduction at 60 minutes post-exercise was significantly potentiated by CF compared with placebo supplementation in T1DM, T2DM, and normoglycemic rats (p < 0.05 for all). In T2DM rats, CF induced a glycemic response comparable to the NORM placebo-supplemented condition. These effects of CF persisted despite variations in aerobic performance or lactate concentration after incremental exercise.

Supplementation with CF prior to physical exercise elicited a pronounced post-aerobic exercise glycemic reduction. This represents a promising strategy for mitigating the duration of hyperglycemia exposure after physical exercise.

Insulin resistance (IR) is a metabolic disorder characterized by an impaired response to insulin. This condition is associated with excess adiposity and metabolic inflammation, contributing to an increased risk for related chronic diseases. Single-nucleotide polymorphisms (SNPs) can affect genes related to metabolic pathways which are related to IR and the individual response to nutrients and dietary patterns, affecting metabolic inflammation and insulin sensitivity. This narrative review explores the current evidence on interactions between genetic variants and dietary factors, specifically their effects in modulating IR and metabolic inflammation. A comprehensive search of the literature was conducted in PubMed, Google Scholar, and Web of Science, and a total of 95 articles were reviewed. The key findings reveal that SNPs in the TCF7L2, ADIPOQ, and TNF genes significantly influence metabolic responses and modulate the effects of the Mediterranean diet on biomarkers of inflammation and IR. Genotype-dependent variations in IR and inflammation biomarkers were observed in the response to different diets for SNPs in the TCF7L2, ADIPOQ, and TNF genes. Additionally, polygenic risk scores (PRSs) can also predict the response to the intake of nutrients and specific diets, and offer a promising tool for assessing genetic predisposition to IR. This review underscores the pivotal role of an individual's genetic background in the effects of their nutrient intake and in the responses to dietetic interventions, thereby laying the foundation for personalized and effective nutritional strategies tailored to each individual's necessity in mitigating IR and its associated risk factors for chronic diseases.

A newly developed technique, Atherogenic Index of Plasma (AIP), is linked to numerous metabolic disorders. Prior researches have indicated strong correlation between AIP and waist circumference (WC), as well as between WC and infertility. Yet no investigation has examined link involving the AIP and infertility, as well as the potential mediating role of WC in this relationship.

The study included 1,322 women from the 2013-2018 NHANES. Infertility was the outcome variable. Moreover, mediation analysis explored the mediating role of WC in the above relationships.

There were 1,163 controls and 159 infertile participants among the 1,322 participants. The study demonstrated increased WC and elevated AIP among infertile women. Also, the AIP demonstrated an independent correlation with a higher likelihood of infertility, regardless of adjustments for confounding factors. Subgroup analysis indicated the AIP was related to the prevalence of infertility even among women aged 35 years or younger with no history of cardiovascular disease (CVD), pelvic infections, or use of female hormones. Finally, WC had a substantial mediating effect on correlation between AIP and infertility, accounting for 54.49% of the association. Yet, it appears that the various IR surrogates did not demonstrate variability in their predictive ability for infertility [AIP: 0.642 (95% CI: 0.599, 0.683) vs. WC 0.658 (95% CI: 0.618, 0.705) vs. HOMA-IR 0.637 (95% CI: 0.593, 0.686)].

A notable positive correlation exists between AIP and female infertility. It provides the first evidence to demonstrate the mediating role of WC in the above relationship. Managing abdominal obesity and monitoring AIP levels may contribute to reduce the likelihood of infertility.

The aim of this review is to discuss and evaluate diabetic sarcopenia (DS) and its relationship with nutrition by discussing the mechanisms of diabetic sarcopenia in detail and comprehensively reviewing the literature.

Type 2 diabetes (T2DM) affects approximately 25% of people aged 50 years and over and indicates a significant the cost of health for the elderly. Nutrition is an important part of these treatment approaches, and in this review, the literature was comprehensively reviewed, focusing on understanding the mechanisms of DS and discussing its relationship with nutrition. A comprehensive search was conducted on Web of Science, Google Scholar, Scopus, Science Direct, and PubMed from inception up to July 2024. The aim of nutritional treatment for DS is to improve muscle mass, muscle strength and physical performance while improving diabetes-related metabolic risk and glucose levels. In this context, it is important to determine energy intake in individuals with DS according to calorie intake exceeding 30 kcal/kg. For these individuals, a protein intake of at least 1-1.2 g/kg/day is recommended, with an emphasis on the number and timing of meals and a nutritional pattern rich in branched chain amino acids (BCAA). In addition, it is important to adopt a diet rich in antioxidants and to choose diet patterns that contain sufficient levels of macro and micronutrients. The Mediterranean diet model can be a good diet option for individuals with DS. Comprehensive studies in this field are needed so that clinicians can make specific dietary recommendations for DS.

This cross-sectional study analyzed National Health and Nutrition Examination Survey data from 2011 to 2018, focusing on individuals aged ≥20 years. The association between metabolic score for insulin resistance (METS-IR) and sarcopenia was examined using weighted multivariable logistic regression, with dose-response relationships characterized by restricted cubic spline analysis. Subgroup and sensitivity analyses were performed, and receiver operating characteristic curve analysis assessed METS-IR's ability to detect sarcopenia, with the area under the curve used for evaluation. The study included 4553 participants (mean age, 40 years; 49.4% male and 50.6% female). In the descriptive analysis, METS-IR levels in sarcopenia (mean, 52.39) were significantly higher than METS-IR levels in nonsarcopenia (mean, 41.94), indicating an association with sarcopenia. A univariate logistic regression analysis showed that sarcopenia and METS-IR were positively correlated. Even after accounting for all variables, METS-IR maintained a stable positive correlation with the prevalence of sarcopenia (odds ratio, 1.06 [95% CI, 1.06-1.08]). The results remained stable when METS-IR was categorized into quartiles. METS-IR was found to positively correlate with sarcopenia prevalence using restricted cubic spline analysis. According to subgroup analysis, there is a consistent and stable positive correlation between the prevalence of sarcopenia and METS-IR. Sensitivity analysis showed that METS-IR and sarcopenia continued to have a significant positive connection even after excluding extreme findings. The area under the curve value of METS-IR in the receiver operating characteristic curve analysis was 0.7217, suggesting that METS-IR could be a useful predictor of sarcopenia.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease, also considered a metabolic syndrome, and is associated with poor prognosis. eGDR (estimated glucose disposal rate) is a new biomarker to assessment insulin resistance (IR). The association between eGDR and MASLD and liver fibrosis is currently unclear.

The aim of this cross-sectional study is to appraise the association between eGDR and MASLD and liver fibrosis.

This study have enrolled 3,100 participants from the 2017-2018 National Health and Nutrition Examination Surveys (NHANES). Binary logistic regression analysis was used to assess the association between eGDR and MASLD and liver fibrosis. Receiver operating characteristic (ROC) was applied to estimate the ability of eGDR to identify MASLD.

The mean age of the subjects was 54.59 (17.29) years, and 49.26% were female. The prevalence of MASLD and liver fibrosis was 62.19% and 11.15%, respectively. In the fully adjusted models, there were negative associations of eGDR with the controlled attenuation parameter (CAP) and liver stiffness measurement (LSM), with βs of -15.18 and - 0.74 (all p < 0.01), respectively. There were negative associations of eGDR with MASLD and liver fibrosis, with odds ratios (ORs) and 95% confidence intervals of 0.53 (95% CI: 0.48-0.74) and 0.40 (95% CI: 0.28-0.57) (all p < 0.01). The area under the curve (AUC) of the eGDR for identifying MASLD and liver fibrosis is 0.74 and 0.75, respectively.

The study findings suggest a significant association between eGDR and MASLD as well as liver fibrosis. eGDR may serve as a biomarker for identifying MASLD.

Gestational diabetes mellitus (GDM) is characterized by an inadequate pancreatic β-cell response to pregnancy-induced insulin resistance, resulting in hyperglycemia. The pathophysiology involves reduced incretin hormone secretion and signaling, specifically decreased glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), impairing insulinotropic effects. Pro-inflammatory cytokines, including tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6), impair insulin receptor substrate-1 (IRS-1) phosphorylation, disrupting insulin-mediated glucose uptake. β-cell dysfunction in GDM is associated with decreased pancreatic duodenal homeobox 1 (PDX1) expression, increased endoplasmic reticulum stress markers (CHOP, GRP78), and mitochondrial dysfunction leading to impaired ATP production and reduced glucose-stimulated insulin secretion. Excessive gestational weight gain exacerbates insulin resistance through hyperleptinemia, which downregulates insulin receptor expression via JAK/STAT signaling. Additionally, hypoadiponectinemia decreases AMP-activated protein kinase (AMPK) activation in skeletal muscle, impairing GLUT4 translocation. Placental hormones such as human placental lactogen (hPL) induce lipolysis, increasing circulating free fatty acids which activate protein kinase C, inhibiting insulin signaling. Placental 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) overactivity elevates cortisol levels, which activate glucocorticoid receptors to further reduce insulin sensitivity. GDM diagnostic thresholds (≥92 mg/dL fasting, ≥153 mg/dL post-load) are lower than type 2 diabetes to prevent fetal hyperinsulinemia and macrosomia. Management strategies focus on lifestyle modifications, including dietary carbohydrate restriction and exercise. Pharmacological interventions, such as insulin or metformin, aim to restore AMPK signaling and reduce hepatic glucose output. Emerging therapies, such as glucagon-like peptide-1 receptor (GLP-1R) agonists, show potential in improving glycemic control and reducing inflammation. A mechanistic understanding of GDM pathophysiology is essential for developing targeted therapeutic strategies to prevent both adverse pregnancy outcomes and the progression to overt diabetes in affected women.

Increases in the prevalence of type 2 diabetes (T2D) pose significant challenges to its prediction and prevention.

We aimed to evaluate whether cumulative exposure to a high triglyceride to high-density lipoprotein-cholesterol (TG/HDL-C) ratio is associated with increased T2D risk in young adults.

We collected South Korean National Health Insurance Service data between 2009 and 2012 from 1,840,251 young adults without T2D aged 20 to 39 years who underwent 4 consecutive annual health checkups. Participants were classified into 5 groups based on exposure to a high TG/HDL-C ratio, defined as the highest TG/HDL-C ratio quartile. T2D risk was evaluated using a multivariate Cox proportional hazard model.

During the 6.53-year follow-up period, 40,286 participants (2.2%) developed T2D. The cumulative incidence of T2D increased with higher TG/HDL-C exposure scores. The adjusted hazard ratios of TG/HDL-C ratio exposure scores for T2D were 1.584 (95% CI, 1.488-1.686), 2.101 (95% CI, 1.980-2.228), 2.942 (95% CI, 2.787-3.106), and 4.962 (95% CI, 4.718-5.219) for groups with scores of 1 to 4, respectively, compared with those with a score of 0. Further subgroup analyses stratified by age, sex, and statin use revealed no significant differences in risk of T2D.

Cumulative exposure to high TG/HDL-C ratio was associated with increased risk of T2D in young Korean adults, suggesting its importance in prediction and prevention. Subgroup analysis revealed no significant differences in age, sex, or statin use. Further research is required to explore the underlying mechanisms and develop effective interventions.

Obesity and metabolic syndrome are significant contributors to infertility in women and are closely associated with insulin resistance (IR). The metabolic score for insulin resistance (METS-IR) is a new, non-insulin-based fasting index used to measure IR. However, the potential of METS-IR as a predictive indicator of female infertility risk has not been established. This study aimed to explore the association between METS-IR and the risk of female infertility.

This cross-sectional study used data from the National Health and Nutrition Examination Survey (NHANES) from 2013 to 2018. We conducted multivariate logistic regression, restricted cubic spline (RCS), and threshold effect analyses to investigate the relationship between METS-IR and female infertility.

According to the self-reported data, 188 (12.20%) participants were classified as infertile. A significantly higher proportion of participants with elevated METS-IR were found to have infertility. Multivariable logistic regression analysis revealed that METS-IR was significantly associated with increased risk of female infertility, irrespective of the independent variable analysis by continuous variables or tertiles in the fully adjusted model (Model 3, continuous variable: OR = 1.02, 95% confidence interval (CI):1.01-1.04, p = 0.005; tertile 3 vs. tertile 1: OR = 2.00, 95% CI = 1.21-3.28, p = 0.0128, p for trend =0.0126). RCS analysis indicated a linear correlation between METS-IR and the risk of infertility (p = 0.121), and threshold effect analysis further supported this linear association (p = 0.136). Moreover, above the inflection point of 32.94, the risk of infertility significantly increased with increasing METS-IR level (p < 0.0001).

Our results suggest that high levels of the METS-IR index are positively associated with infertility among reproductive-aged females in the United States.

The molecular mechanisms involved in bone metabolism abnormalities in individuals with type 2 diabetes mellitus (T2DM) are a prominent area of investigation within the life sciences field. Myostatin (MSTN), a member of the TGF-β superfamily, serves as a critical negative regulator of skeletal muscle growth and bone metabolism. Current research on the exercise-mediated regulation of MSTN expression predominantly focuses on its role in skeletal muscle. However, due to the intricate and multifaceted mechanical and biochemical interactions between muscle and bone, the precise mechanisms by which exercise modulates MSTN to enhance bone metabolic disorders in T2DM necessitate additional exploration. The objective of this review is to systematically synthesize and evaluate the role of MSTN in the development of bone metabolism disorders associated with T2DM and elucidate the underlying mechanisms influenced by exercise interventions, aiming to offer novel insights and theoretical recommendations for enhancing bone health through physical activity.

Relevant articles in Chinese and English up to July 2024 were selected using specific search terms and databases (PubMed, CNKI, Web of Science); 147 studies were finally included after evaluation, and the reference lists were checked for other relevant research.

Myostatin's heightened expression in the bone and skeletal muscle of individuals with T2DM can impede various pathways, such as PI3K/AKT/mTOR and Wnt/β-catenin, hindering osteoblast differentiation and bone mineralization. Additionally, it can stimulate osteoclast differentiation and bone resorption capacity by facilitating Smad2-dependent NFATc1 nuclear translocation and PI3K/AKT/AP-1-mediated pro-inflammatory factor expression pathways, thereby contributing to bone metabolism disorders. Physical exercise plays a crucial role in ameliorating bone metabolism abnormalities in individuals with T2DM. Exercise can activate pathways like Wnt/GSK-3β/β-catenin, thereby suppressing myostatin and downstream Smads, CCL20/CCR6, and Nox4 target gene expression, fostering bone formation, inhibiting bone resorption, and enhancing bone metabolism in T2DM.

In the context of T2DM, MSTN has been shown to exacerbate bone metabolic disorders by inhibiting the differentiation of osteoblasts and the process of bone mineralization while simultaneously promoting the differentiation and activity of osteoclasts. Exercise interventions have demonstrated efficacy in downregulating MSTN expression, disrupting its downstream signaling pathways, and enhancing bone metabolism.

Polysaccharides are very promising molecules in the field of pharmacotherapy. Knowing this, the aim of this study was to extract, characterize, and evaluate the action of the polysaccharides in noni juice, using biological models of Type 2 diabetes mellitus processes. In this study, one polysaccharide named NJSPd-1 was separated from fermented noni fruit juice. The characterization assay showed that NJSPd-1 had a molecular weight (Mw) of 18,545 Da. NJSPd-1 consisted of galacturonic acid, galactose, rhamnose, and arabinose, with a molar ratio of 28.79:20.34:19.80:18.84 according to HPGPC analysis, and the glycosidic bond mainly included →4)-α-D-GalAp-(1→, 4)-β-D-Glcp-(1→, →2)-α-L-Rhap-(1→, and →3)-α-L-Araf-(1→. The prevention of oxidative stress activities by NJSPd-1 was evaluated using high-glucose-induced oxidative stress in HepG2 cells. In vitro results showed that NJSPd-1 influenced the downregulation of the proteins and genes Nrf2, Keap1, HO-1, and NQO1 in HepG2 cells. These results suggest that NJSPd-1 exerted a protective effect against oxidative stress in HepG2 cells by activating the Nrf2/HO-1/NQO1 signaling pathway.

Periodontitis and diabetes mellitus are two highly prevalent chronic conditions that share a bidirectional relationship, significantly impacting public health. Periodontitis, a gum inflammation caused by microbial dysbiosis, aggravates glycemic control in diabetics, while uncontrolled diabetes heightens periodontitis severity. These conditions create a vicious cycle, where inflammation and microbial dysbiosis mutually drive disease progression, exacerbating systemic health. The underlying mechanisms involve inflammation, immune dysfunction, and microbial dysbiosis, with both diseases contributing to a chain of chronic inflammation that exacerbates systemic health. This relationship is significant because managing one condition can significantly impact the other. In diabetic individuals, interventions such as periodontal therapy have shown effectiveness in improving glycemic control, underscoring the potential of integrated strategies for managing these conditions simultaneously. In this review, we highlight the importance of a deeper understanding of the molecular and immunological interactions between these diseases is essential for developing integrated therapeutic approaches, with the potential to enhance the quality of life of the patient significantly.

The triglyceride-glucose (TyG) index and its related indexes (TyG-BMI, TyG-WC, TyG-WHtR) are effective markers for screening metabolic diseases like insulin resistance (IR). However, few studies have explored the relationship between the TyG and its related indexes with bone density (BMD), osteopenia, and osteoporosis. This is a cross-sectional study that involved 1,303 adults aged 50 years and above from the National Health and Nutrition Examination Survey 2007-2010, and 2013-2014. In the multivariable-adjusted model, linear regression analysis and logistic regression analysis demonstrated that TyG and its related indexes have a significant positive correlation with BMD and a negative correlation with osteopenia/osteoporosis in the femoral neck, lumbar spine, and total hip region. Trend analysis further confirms these associations (p < 0.05). Restricted cubic spline analysis showed a nonlinear relationship between these indexes with BMD and osteopenia/osteoporosis. Sensitivity analyses further confirmed the robustness of these associations. This study reveals the significant and complex correlation between the TyG and its related indexes with BMD and osteoporosis, indicating the potential link between IR and bone health. The TyG and related indexes offer a new perspective for the diagnosis, prevention, and treatment of osteoporosis.

Type 2 diabetes mellitus (T2DM) is a multifactorial metabolic disorder characterized by insulin resistance and beta cell dysfunction, resulting in hyperglycemia. Olive oil, a cornerstone of the Mediterranean diet, has attracted considerable attention due to its potential health benefits, including reducing the risk of developing T2DM. This literature review aims to critically examine and synthesize existing research regarding the impact of olive oil on the expression of genes relevant to T2DM. This paper also seeks to provide an immunological and genetic perspective on the signaling pathways of the main components of extra virgin olive oil. Key bioactive components of olive oil, such as oleic acid and phenolic compounds, were identified as modulators of insulin signaling. These compounds enhanced the insulin signaling pathway, improved lipid metabolism, and reduced oxidative stress by decreasing reactive oxygen species (ROS) production. Additionally, they were shown to alleviate inflammation by inhibiting the NF-κB pathway and downregulating pro-inflammatory cytokines and enzymes. Furthermore, these bioactive compounds were observed to mitigate endoplasmic reticulum (ER) stress by downregulating stress markers, thereby protecting beta cells from apoptosis and preserving their function. In summary, olive oil, particularly its bioactive constituents, has been demonstrated to enhance insulin sensitivity, protect beta cell function, and reduce inflammation and oxidative stress by modulating key genes involved in these processes. These findings underscore olive oil's therapeutic potential in managing T2DM. However, further research, including well-designed human clinical trials, is required to fully elucidate the role of olive oil in personalized nutrition strategies for the prevention and treatment of T2DM.

The effects of wheat and oat dietary fiber (DF) alone or combined on T2DM remain unclear. In this research, db/db diabetic mice were fed with diets containing 10% insoluble wheat dietary fiber (WDF), 10% insoluble oat dietary fiber (ODF), and 10% WODF (mixture of WDF and ODF, WDF : ODF = 1 : 1) for 8 weeks. The results showed that WDF, ODF, and WODF all reduced the body weight and fasting blood glucose (FBG) and improved oral glucose tolerance in db/db mice. WDF and ODF alone further relieved insulin resistance and decreased the levels of glycated hemoglobin A1c (GHbA1c), and glycosylated serum protein (GSP). In addition, WDF and ODF alone decreased the levels of TNF-α, IL-6, and IL-1β in serum. The colon function was improved and similar changes were observed in the gut microbiota structure and abundance in all the DF groups. The change of gut microbiota mainly manifested as reducing F/B ratio at the phylum level, while at the genus level as decreasing Enterococcus, Escherichia-Shigella, Erysipelatoclostridium, and unclassified_f_Lachnospiraceae and increase of norank_f_Muribaculaceae, Bacteroides, and Alistipes. Further testing of colonic bile acids (BAs) revealed that WDF, ODF, and WODF all significantly changed the composition of BAs, mainly reducing the levels of UDCA, HDCA, and 3β-UDCA. WODF further decreased DCA and increased β-MCA, LCA-3S, and 12-KCDCA. Importantly, WODF reduced the values of 12-OH-BAs/non-12-OH-BAs. Moreover, the TGR5 level was up-regulated in both the liver and colon, and the FXR level was up-regulated in the liver while down-regulated in the colon in all the DF groups. Furthermore, for the protein level, IRS-1, p-PI3K/PI3K, and AKT were up-regulated in the liver in all the DF groups, while for the mRNA expression level, GLUT4 was up-regulated, and FOXO1, GSK3β, PEPCK, and PGC-1α were down-regulated. WDF and WODF further up-regulated the mRNA expression levels of GYS and down-regulated that of G6Pase. These results suggested that WDF, ODF, and WODF all can alleviate T2DM through the gutmicrobiota-BAs-TGR5/FXR axis and liver IRS-1/PI3K/AKT pathway in db/db mice. WDF and ODF alone are beneficial for improving glucose metabolism and inflammation indicators, while WODF helps improve BAs' profile more in the colon.

Impaired insulin receptor signaling is strongly linked to obesity-related metabolic conditions like non-alcoholic fatty liver disease (NAFLD) and Type 2 diabetes (T2DM). However, the exact mechanisms behind impaired insulin receptor (INSR) signaling in obesity induced by a high-fat diet remain elusive. In this study, we identify an E3 ubiquitin ligase, tripartite motif-containing protein 32 (TRIM32), as a key regulator of hepatic insulin signaling that targets the insulin receptor (INSR) for ubiquitination and proteasomal degradation in high-fat diet (HFD) mice. HFD induces the nuclear translocation of SREBP-1c (Sterol Regulatory Element-Binding Protein 1c), resulting in increased expression of TRIM32 in hepatocytes. TRIM32 ubiquitylates INSR and facilitates its proteasomal degradation, leading to severe insulin resistance and fat accumulation within the liver of high-fat diet induced obese (DIO) mice. Conversely, liver-specific knockdown of TRIM32 enhances INSR expression and hepatic insulin sensitivity. Reduced AMPK signaling and phosphorylation of SREBP-1c at S372 in high-fat DIO mice promotes the nuclear translocation of SREBP-1c, leading to increased TRIM32 expression. In conclusion, our results demonstrate that TRIM32 promotes diet-induced hepatic insulin resistance by targeting the INSR to degradation.

In nondiabetic people, the long-term effects of insulin resistance (IR) on heart failure (HF) and all-cause mortality have not been studied.

To examine the association between IR trajectories and incident HF and all-cause mortality in a nondiabetic population.

We studied 7835 nondiabetic participants from the Atherosclerosis Risk in Communities (ARIC) Study. We estimated IR with several methods: Homeostatic Model Assessment-Insulin Resistance (HOMA-IR), triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C), triglyceride glucose Index (TyG Index), and metabolic score for insulin resistance (METS-IR). The latent class analysis identified two trajectories for HOMA-IR ('low level' and 'high level'), and three trajectories for TG/HDL-C, TyG index, and METS-IR ('low level', 'moderate level', and 'high level'). Cox proportional hazard models were employed to examine the association.

Participants in the 'high level' group of HOMA-IR trajectory patterns were more likely to have incident HF and all-cause mortality with HRs (95% CIs) of 1.29 (1.11-1.50) and 1.31(1.19-1.44), respectively, compared to the 'low level' group. Similarly, participants in the 'moderate level' and 'high level' groups of TG/HDL-C, TyG index, and METS-IR trajectories had elevated risks of incident HF and all-cause mortality. However, no increased risk was found for all-cause mortality for men in the 'moderate level' and 'high level' group of TG/HDL-C, TyG index, and METS-IR relative to the 'low level' group.

Long-term moderate and high IR levels were positively associated with increased risks of incident HF for both males and females. For all-cause mortality, however, consistent associations were found only in women.

Introduction Insulin resistance (IR) plays a key role in the development of metabolic syndrome (MetS), type 2 diabetes, and cardiovascular disease. The Homeostasis Model Assessment of Insulin Resistance (HOMA-IR) is widely used to estimate IR, but there is no consensus on the optimal cutoff values for identifying individuals at risk. This study aims to compare two methodologies, percentile distributions and receiver operating characteristic (ROC) curve analysis, for determining optimal HOMA-IR cutoff values in a population from Mexico City. Methods This cross-sectional study included 765 adults recruited from a hospital outpatient clinic in Mexico City. Participants were divided into two groups: a reference group of individuals with healthy weight and fasting plasma glucose and a MetS group of overweight or obese individuals classified based on the presence or absence of MetS. HOMA-IR values were analyzed using the 75th percentile in the reference group and ROC curve analysis in the MetS group. Optimal cutoffs were determined using the Youden index. Results We include a total of 765 patients, 218 subjects in the reference group and 547 for the ROC curve analysis. HOMA-IR percentiles 75th and 90th were 2.72 and 3.71, respectively. ROC curve analysis yielded higher cutoff values for MetS diagnosis than the percentile-based method. The percentile-based approach allowed for earlier identification of individuals at risk, including those without clinical manifestations of MetS. Conclusions This study highlights the variability in HOMA-IR cutoff values across methodologies and emphasizes the importance of population-specific reference values. A percentile-based approach proves effective for early detection of IR, facilitating preventive interventions during the preclinical stage. These findings support using percentile-based cutoffs as a practical tool for improving risk assessment and guiding clinical decision-making.

Insulin resistance (IR) is an important risk factor for multiple chronic diseases, increasing mortality and reducing life expectancy. The associations between emerging surrogates for IR, triglyceride-glucose index (TyG) and TyG-related indicators, with all-cause mortality and life expectancy in middle-aged and older patients in primary care are unclear.

This study originated from the Polish primary care cohort LIPIDOGRAM2015, including patients aged ≥45 years. Baseline fasting triglycerides and fasting glucose were used to derive TyG. Other TyG-related indicators included TyG-adjusted body mass index (TyG-BMI), TyG-adjusted waist circumference (TyG-WC), TyG-adjusted waist-to-hip, and TyG-adjusted waist-to-height. In this longitudinal analysis, we assessed associations between TyG-related indicators with total all-cause mortality, premature (age at death ≤75 years) all-cause mortality and years of life lost (YLL).

We included 10,688 patients (mean age 61.8 ± 9.3 years; 63.5% female). Cumulative total and premature all-cause mortality were 7.2% and 4.6%, respectively, during 5.7 years (IQR 5.6-5.7) of follow-up. Lowest (Q1) and highest quartile (Q4) of TyG-BMI and TyG-WC were associated with total all-cause mortality (second quartile [Q2]: reference; TyG-BMI: Q1: aHR 1.33, 95% CI 1.07-1.65, Q4: aHR 1.28, 95% CI 1.03-1.58; TyG-WC: Q1: aHR 1.44, 95% CI 1.14-1.82, Q4: aHR 1.29, 95% CI 1.04-1.59), similar results for premature all-cause mortality. Within age 45-80 years, compared with Q2 and third quartile, YLL were 4.49 and 5.46 years for TyG-BMI Q1 and Q4, respectively, 3.24 and 5.31 years for TyG-WC Q1 and Q4, respectively.

TyG-BMI and TyG-WC demonstrated a U-shaped association with total and premature all-cause mortality. Low and high levels of TyG-BMI and TyG-WC were associated with reduced life expectancy. Despite the relatively short follow-up period, significant associations were still observed, but longer follow-up studies are required to further explore these relationships.

Polish Lipid Association, College of Family Physician in Poland, Valeant in Poland.

Oxidative balance score (OBS) is a composite measures that assess the balance between pro-oxidant and antioxidant factors in an individual's diet and lifestyle, with higher scores indicating greater antioxidant exposure. Despite its potential significance, there is a limited body of research exploring the relationship between OBS and all-cause and cardiovascular disease (CVD) mortality specifically in younger patients with diabetes. We aimed to investigate the possible relationship between OBS and all-cause and CVD mortality in younger patients with diabetes. Data for this study were obtained from the 2003-2018 NHANES. This study enrolled 3501 participants. The endpoints were all-cause and CVD mortality, determined by the National Death Index (NDI). OBS, which consists of 16 dietary factors and 4 lifestyle factors, is categorized into pro-oxidants and antioxidants. The OBS was categorized into four quartiles (Q1-Q4). We used multivariable Cox proportional hazards regression models to examine the association between continuous and quartile measures of OBS, lifestyle OBS (lifestyle antioxidants such as physical activity, etc., and lifestyle pro-oxidants such as alcohol, smoking, etc.), and dietary OBS (dietary antioxidants such as fiber, β-carotene, riboflavin, etc., and dietary pro-oxidants, such as total fat, etc.) with all-cause and CVD mortality. Additionally, we explored restricted cubic spline (RCS) analysis and also performed subgroup analyses and interaction tests. The occurrence of 409 all-cause deaths (11.7%) and 108 CVD-related deaths (3.1%) was recorded during the follow-up period. Our results found that OBS, lifestyle OBS, and dietary OBS were negatively associated with patients' all-cause and CVD mortality. The RCS analysis further validated the association of a linear negative correlation between OBS and all-cause and CVD mortality. The results of our subgroup analyses revealed that the negative association between OBS and CVD mortality may be influenced by alcohol use. In conclusion, results from a nationally representative study of younger American patients with diabetes suggest a negative association between OBS, lifestyle OBS, and dietary OBS and all-cause and CVD mortality. Antioxidant-rich diets and lifestyle improvements are essential for reducing all-cause and CVD mortality in patients.

Severe sepsis is cognate with life threatening multi-organ dysfunction. There is a disturbance in endocrine functions with alterations in several hormonal pathways. It has frequently been linked with dysfunction in the hypothalamic pituitary-adrenal axis (HPA). Increased cortisol or cortisolemia is evident throughout the acute phase, along with changes in the hypothalamic pituitary thyroid (HPT) axis, growth hormone-IGF-1 axis, insulin-glucose axis, leptin, catecholamines, renin angiotensin aldosterone axis, ghrelin, glucagon, hypothalamic pituitary gonadal (HGA) axis, and fibroblast growth factor-21. These changes and metabolic alterations constitute the overall response to infection in sepsis. Further research is essential to look into the hormonal changes that occur during sepsis, not only to understand their potential relevance in therapy but also because they may serve as prognostic indicators.

Epidemiological studies prove that type II diabetes, characterized by insulin resistance (IR), may be caused by fine particulate matter 2.5 (PM2.5). However, underlying mechanisms whereby PM2.5, particularly during short-term exposure, induces liver dysfunction leading to IR remains poorly understood. In the present study, HepG2 cells and the BALB/c mouse model were used to explore how PM2.5 affects insulin sensitivity. The effects of subacute PM2.5 exposure on glucose metabolism were examined using commercial kits. Oxidative stress and inflammation were detected by fluorescent staining and RT-qPCR. The phosphorylation of PI3K/AKT was examined by Western blot. Subacute PM2.5 exposure induced IR, as reflected by increased glucose levels in cell supernatants, elevated insulin levels, and the impaired intraperitoneal glucose tolerance test in mice. PM2.5 induced oxidative stress, as evidenced by increased reactive oxygen species, cytochrome P450 2E1, and malondialdehyde, along with reduced superoxide dismutase 1/2 and silent information regulator 1. IL-6 and TNF-α were found to be upregulated using RT-qPCR. Western blot showed that PM2.5 inhibited the PI3K-AKT signaling pathway, indicated by the decreased phosphorylation of PI3K/AKT in HepG2 cells. Additionally, H&E staining showed only mild hepatic injury in mice liver. These results firmly suggest that subacute PM2.5 exposure induces insulin resistance through oxidative stress, inflammation, and the inhibition of the PI3K-AKT signaling pathway.

Gestational diabetes mellitus (GDM) is a global health concern with significant short and long-term complications for both mother and baby. Early prediction of GDM, particularly late-onset, is crucial for implementing timely interventions to mitigate adverse outcomes. In this study, we conducted a comprehensive metabolomic analysis to explore potential biomarkers for early GDM prediction.

Plasma samples were collected during the first trimester from 60 women: 20 with early-onset GDM, 20 with late-onset GDM, and 20 with normal glucose tolerance. Using advanced analytical techniques, including liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-mass spectrometry (GC-MS), we profiled over 150 lipid species and central carbon metabolism intermediates.

Significant metabolic alterations were observed in both early- and late-onset GDM groups compared to healthy controls, with a specific focus on glycerolipids, fatty acids, and glucose metabolism. Key findings revealed a 4.0-fold increase in TG(44:0), TG(46:0), TG(46:1) with p-values <0.001 and TG(46:2) with 4.7-fold increase and p-value <0.0001 as well as changes in several phospholipids as PC(38:3), PC(40:4) with 1.4-fold increase, p < 0.001 and PE(34:1), PE(34:2) and PE(36:2) with 1.5-fold change, p < 0.001 in late-onset GDM.

Observed lipid changes highlight disruptions in energy metabolism and inflammatory pathways. It is suggested that lipid profiles with distinct fatty acid chain lengths and degrees of unsaturation can serve as early biomarkers of GDM risk. These findings underline the importance of integrating metabolomic insights with clinical data to develop predictive models for GDM. Such models could enable early risk stratification, allowing for timely dietary, lifestyle, or medical interventions aimed at optimizing glucose regulation and preventing complications such as preeclampsia, macrosomia, and neonatal metabolic disorders. By focusing on metabolic disruptions evident in the first trimester, this approach addresses a critical window for improving maternal and fetal outcomes. Our study demonstrates the value of metabolomics in understanding the metabolic perturbations associated with GDM. Future research is needed to validate these biomarkers in larger cohorts and assess their integration into clinical workflows for personalized pregnancy care.

The relationship between nontraditional lipid profiles and type 2 diabetes mellitus (T2DM) remains ambiguous within the hypertension population. The objective of this study is to examine the association between nontraditional lipid profiles and T2DM in Chinese adults with hypertension. The current investigation encompassed 13 728 participants with hypertension from the China Hypertension Registry Study. Logistic regression analysis and smooth curve fitting were employed to evaluate the association between nontraditional lipid profiles and T2DM. The prevalence of T2DM was found to be 17.8%. In the fully adjusted model, atherogenic index of plasma (AIP) exhibited the highest odds ratios (ORs) for T2DM (OR: 2.71, 95% confidence interval [CI]: 2.26-3.26). Conversely, the fully adjusted ORs (95% CI) for total cholesterol (TC)/high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C)/HDL-C, and non-high-density lipoprotein cholesterol (Non-HDL-C) were 1.33 (1.25-1.41), 1.40 (1.29-1.51), and 1.41 (1.34-1.49), respectively. Additionally, the study demonstrated that AIP had a superior ability to identify T2DM. Subgroup analyses indicated that the relationship between AIP and Non-HDL-C with T2DM was more significant in the lighter weight population. In addition, the association of TC/HDL-C with LDL-C/HDL-C with T2DM was stronger in the lower homocysteine level population. Among the southern Chinese population with hypertension, all nontraditional lipid indices positively correlated with the risk of T2DM. Among these lipid indices, AIP exhibited superior discriminatory power in identifying T2DM compared to TC/HDL-C, LDL-C/HDL-C. Trial Registration: ChiCTR1800017274.

Skeletal muscle is one of the most complex and largest tissues that perform important processes in the body, including performing voluntary movements and maintaining body temperature. Disruption of muscle homeostasis results in the development of several disorders, including diabetes and sarcopenia. To study the developmental and regenerative dynamics of skeletal muscle and the mechanism behind muscle diseases, it is important to model skeletal muscle and diseases in vitro. Since skeletal muscle has a complex structure and interaction with other tissues and cells that are required to perform their function, conventional 2D cultures are not sufficient to model the skeletal muscle with their interactions. Advances in the field of organoids and assembloids will enable the establishment of more complex and realistic tissue or disease models which cannot be fully recapitulated in conventional 2D culture systems for use in several areas, including disease research, regenerative, and tissue biology. To overcome these limitations, 3D organoid systems and assembloid systems are promising because of their success in recapitulating the complex structural organization, function, and cellular interactions of skeletal muscle.

Insulin resistance (IR) is a pathogenic factor in numerous metabolic diseases. The gut microbiota plays a crucial role in maintaining the function of the intestinal barrier and overall human health, thereby influencing IR. Dysbiosis of the gut microbiota can contribute to the development of IR. Therefore, it is essential to maintain a balanced and diverse gut microbiota for optimal health. Akkermansia muciniphila, a widely present microorganism in the human intestine, has been shown to regulate gastrointestinal mucosal barrier integrity, reduce endotoxin penetration, decrease systemic inflammation levels, and improve insulin sensitivity. Reduced abundance of A. muciniphila is associated with an increased risk of IR and other metabolic diseases, highlighting its correlation with IR. Understanding the role and regulatory mechanism of A. muciniphila is crucial for comprehending IR pathogenesis and developing novel strategies for preventing and treating related metabolic disorders. Individual variations may exist in both the gut microbiota composition and its impact on IR among different individuals. Further investigation into individual differences between A. muciniphila and IR will facilitate advancements in personalized medicine by promoting tailored interventions based on the gut microbiota composition, which is a potential future direction that would optimize insulin sensitivity while preventing metabolic disease occurrence. In this review, we describe the physiological characteristics of A. muciniphila, emphasize its roles in underlying mechanisms contributing to IR pathology, and summarize how alterations in its abundance affect IR development, thereby providing valuable insights for further research on A. muciniphila, as well as new drug development targeting diabetes.

Uric acid (UA) and homeostatic model assessment of insulin resistance (HOMA-IR) are endogenous biomarkers implicated in metabolic disorders and dysfunction.

To investigate the structural associations between sugar-sweetened beverage intake (SSB), UA, HOMA-IR and adolescent latent MetS construct (MetsC) representing paediatric metabolic syndrome (MetS).

A population-based representative adolescent cohort (n = 1454) was evaluated for risk profiles of MetS. Structural equation modelling was performed to identify multifactor structural associations between study parameters and evaluate mediating effects.

Adolescents had a single-factor latent construct representing MetS. Increased SSB intake was associated with higher UA and HOMA-IR levels, and the two biomarkers were positively associated with the MetsC score. UA and HOMA-IR exerted three mediating effects on the association between fructose-rich tea beverage (FTB) intake of >500 mL/day and MetsC: adjusted standardized coefficient and mediating effect (%), FTB → UA → MetsC: 0.071, 23.1%; FTB → HOMA-IR → MetsC: 0.034, 11.0%; FTB → UA → HOMA-IR → MetsC: 0.010, 3.1%. The UA-associated pathways accounted for 31.1% of the overall mediation on the association between bottled sugar-containing beverage intake and MetsC. After accounting for the UA- and HOMA-IR-derived detrimental effects, the fructose-rich tea beverage intake of >500 mL/day had a tea-related beneficial effect on MetsC, with an adjusted standardized coefficient of -0.103.

UA and HOMA-IR individually and jointly mediate the adverse effects of high fructose-rich SSB intake on the mechanisms underlying paediatric MetS. Fructose-free tea-based beverages may have a beneficial effect on latent MetS structure in adolescents.

The objective of this study is to assess the impact of pomegranate supplements on insulin resistance (IR) and insulin sensitivity through a systematic review and meta-analysis of randomized controlled trials (RCTs). Additionally, we aim to analyze the differences in efficacy among various pomegranate extracts and the sensitivity of different diseases to pomegranate supplementation. We conducted searches in PubMed, Embase, Web of Science, and Cochrane Library up to October 30, 2023, for relevant studies published in English. The treatment group required the intake of pomegranate extract for a minimum of 4 weeks, with no restrictions on the extract type. The control group received a placebo or a treatment excluding pomegranate extract. The primary outcome was homeostatic model assessment for insulin resistance (HOMA-IR) and fasting insulin (FI), and the secondary outcome was quantitative insulin sensitivity check index (QUICKI). RoB 2 was used to assess the risk of bias in the original studies. We pre-specified subgroup analyses based on types of intervention, intervention duration, health condition, and intervention dose. Sensitivity analysis was conducted to validate result stability, utilizing Begg's test and Egger's test for publication bias. Data synthesis and analysis were performed using Stata 15.1 software. This study included a total of 15 RCTs with 673 participants conducted in 7 countries. Risk of bias results indicated an overall low risk of bias of the articles. Participants included healthy individuals, overweight and obese individuals, non-alcoholic fatty liver disease (NAFLD) patients, type 2 diabetes (T2DM) patients, polycystic ovary syndrome (PCOS) patients, metabolic syndrome (MS) patients, and individuals with hyperlipidemia. Pomegranate extract variations included pomegranate juice (PJ), pomegranate seed oil (PSO) capsule, pomegranate/pomegranate peel (PP) extract capsule, and pomegranate peel-added bread. The control groups primarily received placebo treatments with varying dosage and frequency. No adverse reactions were reported in any of the studies. The summary results showed that compared to the control groups, pomegranate extract had no significant impact on improving HOMA-IR levels in participants (WMD = -0.03, 95%CI: -0.37 to 0.31, and p = 0.851) and FI (WMD = -0.03, 95%CI: -0.42 to 0.36, and p = 0.862). Additionally, there was no significant advantage of pomegranate extract on QUICKI changes in T2DM and PCOS patients (WMD = 0.00, 95%CI: 0.00 to 0.01, and p = 0.002). Subgroup analysis results indicated that pomegranate extract could improve HOMA-IR levels in PCOS patients (WMD = -0.42, 95%CI: -0.54 to -0.29, and p < 0.001) and FI levels in T2DM, PCOS, and NAFLD patients. Our results indicate that pomegranate extract only improves HOMA-IR and FI levels in PCOS patients and FI levels in T2DM and NAFLD patients. No significant difference has been found for HOMA-IR, FI, or QUICKI in other metabolic diseases. The current evidence suggests that we should interpret the value of pomegranate extract in regulating IR and sensitivity cautiously. In the future, there is a need for more rigorously designed RCTs to specifically evaluate the impact of pomegranate supplementation on insulin sensitivity in patients with NAFLD, PCOS, and T2DM.

Although the association between heavy metals in human and the development of metabolic syndrome (MetS) have been extensively studied, the pathogenic mechanism of MetS affected by metals is not clear to date. In this study, a predictive model was developed with machine learning base on the large-scale dataset. These proposed models were evaluated via comparatively analysis of their accuracy and robustness. With the optimal model, two metals significantly correlated with MetS were screened and were employed to infer the pathogenicity mechanism of MetS via molecular docking. Significant associations between heavy metals and MetS were found. Molecular docking provided insights into the interactions between metal ions and key protein receptors involved in metabolic regulation, suggesting a mechanism by which heavy metals interfere with metabolic functions. Specifically, Ba and Cd affect the development of MetS thru their interactions with insulin and estrogen receptors. This study attempted to explore heavy metals' potential roles in MetS at the molecular level. These findings emphasize the importance of addressing environmental exposures in the prevention and treatment of MetS.