Bone-eating (also known as osteophagia), found in wild animals, is primarily recognized as a means to supplement phosphorus and calcium intake. Herein, we describe a novel function of bone-eating in detoxifying heavy metal ions through the dissolution and co-precipitation of bone minerals as they travel through the gastrointestinal (GI) tract. In this study, cadmium (Cd), a heavy metal ion, served as a toxic model. We demonstrated that hydroxyapatite (HAp), the major calcium phosphate (CaP) in bone, dissolves in the stomach and acts as a co-precipitant in the intestine for Cd detoxification. We compared HAp to a common antidote, activated charcoal (AC), which did not precipitate within the GI tract. In vitro experiments showed that HAp dissolves under acidic conditions and, upon return to a neutral environment, efficiently re-sequesters Cd. Similarly, oral administration of HAp effectively prevented Cd absorption and accumulation, resulting in enhanced Cd excretion in the feces when compared to AC. A co-precipitating CaP in the GI tract could serve as an excellent detoxification system, as it helps prevent the accumulation of toxic substances and aids in developing appropriate strategies to reduce tissue toxicity. Moreover, understanding this detoxification system would be a valuable indicator for designing efficient detoxification materials.

The ever-increasing use of chemicals and the rising incidence of adverse reproductive effects in the modern environment have become an emerging concern. Several studies have shown that environmental contaminants, such as organophosphate flame retardants (OPFRs), negatively impact reproductive health. To evaluate the potential endocrine-related adverse reproductive effects of widely used and priority-listed compound 2-Ethylhexyl diphenyl phosphate (EHDPP), we characterized its effects on adrenal steroidogenesis in human adrenocortical (H295R) cells. The cells were exposed to EHDPP (1 and 5 μM) for 48 h, and the production of hormones, including progesterone, androstenedione, testosterone, estradiol, cortisol, and aldosterone, was measured. In addition, LC-MS/MS-based lipidomics analysis was done to quantify intracellular lipid profiles, and transcriptional assays were performed to examine the expression of genes related to corticosteroidogenesis, lipid metabolism, and mitochondrial dynamics. Our findings indicate that EHDPP disrupts hormone regulation in vitro, as evidenced by increased estradiol, cortisol, and aldosterone secretion. The expression of key corticosteroidogenic genes (CYP11B2, CYP21A1, 3β-HSD2, and 17β-HSD1) was upregulated significantly upon EHDPP exposure. Intracellular lipidomics revealed EHDPP-mediated disruption, including reduced total cholesterol ester, sphingolipids, and increased phospholipids, triglyceride species, and saturated-monounsaturated lipids subspecies. These alterations were accompanied by decreased ACAT2 and SCD1 gene expression. Moreover, a shift in mitochondrial dynamics was indicated by increased MF1 expression and decreased FIS1 expression. These data suggest that EHDPP disrupts adrenal steroidogenesis and lipid homeostasis, emphasizing its potential endocrine-disrupting effects.

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) are increasingly used for anti-obesity indications. However, little is known of the comparative effect of GLP-1 RAs and their glycemic impact across the different routes of administration, diabetic statuses and durations of prescription. PubMed, EMBASE and CENTRAL were searched from inception to 13 February 2024. Only randomised controlled trials were included in this systematic review and meta-analysis. Adults aged above 18 years old, who were in the overweight/obesity range, with or without type 2 diabetes mellitus (T2DM) were included. Baseline characteristics and changes in glycated haemoglobin (HbA1c) and fasting plasma glucose (FPG) were obtained. GLP1-RAs demonstrated an overall reduction in HbA1c of -0.72% (95% confidence interval [CI] -0.79 to -0.65, p < 0.01) and in FPG of -1.00 mmol/L (95% CI -1.16 to -0.84, p < 0.01). HbA1c reduction in pre-DM patients was -0.44% (95% CI -0.54 to -0.18, p < 0.01). Patients who were followed up for more than a year experienced a smaller reduction of HbA1c. Meta-regression showed that the GLP-1 RAs are more efficacious at higher HbA1c and lower body mass index. Overall, GLP-1 RAs consistently led to a significant reduction in HbA1c at -0.72% and FPG at -1.00 mmol/L. These effects may be equally efficacious in pre-DM patients with obesity and those at lower BMI. With pre-DM and obesity being risk factors for metabolic syndrome, these findings may provide newer perspectives in expanding indications for GLP-1 RA initiation.

This study examines the relationship between the TyG index and the risk of sudden cardiac death (SCD) in the patients with diabetic foot ulcer (DFU).

688 type 2 diabetes mellitus (T2DM) inpatients with DFU between January 2010 and December 2023 was included in this retrospective study. The 1:1 propensity score matching (PSM) method was applied. The relationship between TyG index and SCD risk was analyzed using the Kaplan-Meier (K-M) survival curve analysis, multivariate Cox proportional hazard regression model, Restricted cubic spline (RCS) model analysis and subgroup analyses.

Over a median follow-up period of 61 months, 38 cases of SCD were recorded. After PSM, 71 pairs of score-matched patients according to TyG index were generated. K-M survival curves revealed higher SCD rates in patients with TyG index ≥9.65. The Cox proportional hazard model, independently associated with the risk of SCD (HR: 75.98; 95 % CI: 9.16 ∼ 630.40; P < 0.001). RCS model showed that SCD risk was non-linearly correlated with gradual increases in TyG index levels. Stratified analyses indicated a consistent relationship between increasing TyG index and SCD risk across all subgroups.

Elevated TyG index independently confers an increased risk for SCD in individuals with DFU.

Survivors of childhood, adolescent, and young adult (CAYA) cancer have an increased risk of metabolic syndrome (MetS). MetS describes the clustering of cardiovascular risk factors including overweight or obesity, hypertension, (pre)diabetes, and dyslipidaemia. While associated cardiovascular sequelae can be serious, MetS is preventable, manageable, and potentially reversible with the appropriate pharmacological and/or behavioral interventions. To optimize health outcomes in CAYA cancer survivors, international, harmonized surveillance recommendations are essential.

Systematic review and guideline development.

A multidisciplinary guideline panel evaluated concordances and discordances across national guidelines for MetS surveillance and performed a systematic literature review. The Grading of Recommendations Assessment, Development and Evaluation methodology was used to grade the available evidence and formulate recommendations considering the strength of the underlying evidence as well as potential harms and benefits associated with MetS surveillance. In case evidence was lacking, recommendations were based on expert opinion. In addition, recommendations for surveillance modalities were derived from existing guidelines for MetS components where applicable.

The systematic literature review included 20 studies and highlighted 2 high-risk groups, namely CAYA cancer survivors treated with total body irradiation and those treated with cranial or craniospinal irradiation (moderate-quality evidence). Recommendations were formulated for MetS surveillance in these risk groups, covering preferred screening modalities, age at screening initiation, and surveillance frequency.

In this international surveillance guideline for MetS in CAYA cancer survivors, we provide evidence-based recommendations for clinical practice, with the aim of ensuring optimal MetS surveillance for CAYA cancer survivors.

Although metabolic syndrome (MetS) is associated with an increased risk of various cancers, the combined impact of MetS and healthy lifestyle factors (HLF) on cancer risk is unclear. This study aimed to investigate the independent and combined effects of MetS and HLF on the risk of 16 site-specific cancers in a large community-based cohort.

A total of 289,557 participants in the UK Biobank were analyzed. MetS was defined using a combination of metabolic factors, while HLF scores were evaluated based on lifestyle behaviors, such as smoking, alcohol consumption, physical activity, and diet. Cox proportional hazard models were used to investigate the relationship between MetS or HLF and cancer risk, adjusting for age, sex, ethnicity, education level, family history of cancer, and the Townsend Deprivation Index (TDI).

During a median follow-up of 11.69 years, 11,190 individuals developed cancer. MetS was associated with an increased risk of 9 cancers in men and 7 cancers in women. Compared with participants with unfavorable lifestyles, regardless of metabolic status, HLF was significantly associated with decreased risk of overall cancer (without MetS: HR: 0.812; 95% CI: 0.745-0.886 for intermediate lifestyle and HR: 0.757; 95% CI: 0.669-0.855 for favorable lifestyle; with MetS: HR: 0.702; 95% CI: 0.572-0.862 for favorable lifestyle) and oesophagus, stomach, liver, lung, bronchus, trachea cancers in men and of lung, bronchus, trachea cancers in women. Our analysis demonstrated that the protective association between HLF and reduced cancer risk was confined to subgroups without MetS. Specifically, this association was observed for cancers of the lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, bladder, and lymphoid leukemia in men, and for overall cancer in women(HR: 0.917; 95% CI: 0.862-0.975 for intermediate lifestyle and HR: 0.875; 95% CI: 0.817-0.938 for favorable lifestyle).

MetS elevates risks for multiple cancers, while adopting a healthy lifestyle reduces risks of oesophagus, stomach, and lung, bronchus, trachea cancers in men and lung, bronchus, trachea cancer in women, regardless of metabolic status. However, MetS counteracts lifestyle-mediated protection against specific cancers-including lip, oral cavity, pharynx, colon, rectum, pancreas, kidney, and bladder cancers in men, as well as pancreas and breast cancers in women. These findings underscore the necessity to develop metabolic status-stratified management strategies and implement proactive prevention of MetS.

To determine how clustered metabolic risk based on a validated continuous metabolic syndrome risk score is associated with objectively assessed time in sedentary behaviors (SB) in physically active and inactive older adults, while considering adherence to healthy eating habits.

Cross-sectional study SETTING AND PARTICIPANTS: The study comprises 871 community-dwelling older adults (age 65-79 years) recruited from four European countries.

Daily times spent in SB and physical activity (PA) were assessed by accelerometers (Actigraph GT3X) for a week. Waist circumference, triglycerides, HDL-cholesterol, mean arterial blood pressure, fasting glucose and insulin were determined, and a continuous metabolic syndrome risk score (cMSy) was generated using principal component analysis. Healthy eating habits were assessed by food record. General linear models stratified by adherence to PA guidelines (active/inactive) were used to examine differences in cMSy across tertiles of time in SB (Low, Medium, High) with adjustment for covariates, including healthy eating habits.

A significantly (p < 0.05) lower cMSy was observed among older adults in the low SB tertile compared to medium and high SB tertiles, with no difference between the latter tertiles. The favorable effect of low amounts of SB on cMSy was indicated in both active and inactive groups, and regardless of healthy eating habits. Further, being active was related to a more favorable cMSy across all SB tertiles.

Low amounts of time spent in SB are related to a lower metabolic syndrome risk regardless of adherence to PA guidelines and healthy eating habits in older adults, supporting guidelines targeting limited amounts of SB alongside engagement in moderate-to-vigorous PA for promotion of metabolic health.

Background and Objectives: Elevated blood sugar poses an increasingly significant challenge to healthcare systems worldwide. We aimed to assess the efficacy of the SGLT-2i class in achieving metabolic control in patients with T2DM within a real-world standard-of-care regimen. Material and Methods: A prospective analysis was conducted over 6 months including individuals receiving care in an outpatient department, with baseline assessments and follow-ups at 3 and 6 months. Results: A total of 280 patients were assessed, with a mean age of 63.69 ± 9.16, 53.9% of which were males, with a mean DM duration of 9.06 ± 5.64 years, and a DM duration varying from 6 months to 24 years. Discussion: Real-world evidence bridges the gap between guidelines and practice. It emphasizes the need to overcome clinical inertia in order to optimize patient outcomes and contributes to the body of evidence supporting the efficacy of fixed-dose SGLT-2i combinations in managing T2DM and associated comorbidities. Conclusions: We demonstrate the significant clinical and therapeutic impact of SGLT-2i in T2DM patients in a real-world setting. This class of medication not only positively influences glycemic and weight control but also reduces CV risk factors and visceral adiposity.

High doses of bisphenol AF (BPAF), a widely used chemical in many products, has been reported to exert adverse effects on lipid or glucose metabolism, but whether low-dose exposure, especially in combination with a high-sugar, high-fat diet (Western diet, WD), has unacceptable effects remains unexplored. Here, we investigated the effects of postnatal exposure to 50 μg/kg/d (low) BPAF on glycolipid homeostasis in mice receiving administration through drinking water under the WD stress after weaning or not, in comparison with the effects 5000 (high) BPAF without stress. After approximately 8-week exposure, blood tests of glucose metabolism revealed that high-dose BPAF caused insulin resistance and elevated insulin levels in a normal diet (ND)-fed mice; low-dose BPAF exerted slight effects in ND-fed mice but caused significant glucose metabolic impairment under the WD stress. Also, low-dose BPAF exerted limited effects on pancreas islets as well as hepatic histology and metabolic homeostasis in ND-fed mice, but aggravated pancreatic and hepatic impairments caused by the WD stress. We also conducted cell culture experiments using β-TC-6 and HepG2 cells to explore whether BPAF could directly interfere with pancreatic cells and hepatocytes. In vitro assays showed that BPAF affected insulin secretion of pancreatic β-TC-6 cells in a glucose-dependent manner and glucose sensitivity of HepG2 cells, with slight effects on lipid metabolism in HepG2 cells. All results collectively demonstrate that low-dose BPAF caused metabolic disorders under the WD stress, highlighting its health risks. Besides, in vitro data suggest that BPAF may directly affect glucose metabolism rather than lipid metabolism.

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 a prevalent liver disorder with limited treatment options. This review explores the role of post-translational modifications (PTMs) in MASLD pathogenesis, highlighting their potential as therapeutic targets. We discuss the impact of PTMs, including their phosphorylation, ubiquitylation, acetylation, and glycosylation, on key proteins involved in MASLD, drawing on studies that use both human subjects and animal models. These modifications influence various cellular processes, such as lipid metabolism, inflammation, and fibrosis, contributing to disease progression. Understanding the intricate PTM network in MASLD offers the potential for developing novel therapeutic strategies that target specific PTMs to modulate protein function and alleviate disease pathology. Further research is needed to fully elucidate the complexity of PTMs in MASLD and translate these findings into effective clinical applications.

Background/Objectives: This study aims to investigate the impact of obesity severity on the prevalence and outcomes of acute metabolic emergencies in the emergency department (ED) setting, with a specific focus on obesity class stratification and associated metabolic complications. Methods: This retrospective, single-center study analyzed data from 433 patients admitted to the ED of the Timisoara Municipal Emergency Hospital between January 2019 and March 2024. Patients were classified according to WHO obesity grades (Class I: BMI 30.0-34.9 kg/m2, Class II: 35.0-39.9 kg/m2, Class III: ≥ 40.0 kg/m2). The prevalence and severity of metabolic emergencies, including hyperglycemic crises, acute kidney injury (AKI), and severe electrolyte imbalances, were compared across obesity classes. Results: Obese patients (37.2%) exhibited a significantly higher prevalence of metabolic emergencies than non-obese individuals (p < 0.001). Hyperglycemia was present in 27.9% of obese patients vs. 11.0% of non-obese patients (p < 0.001). AKI incidence nearly doubled in obese patients (12.4% vs. 5.5%, p = 0.01). Logistic regression identified Class III obesity as an independent risk factor for metabolic emergencies (adjusted OR = 3.2, 95% CI: 2.1-4.9, p < 0.001). Conclusions: The severity of metabolic emergencies increases with increasing obesity class, emphasizing the need for obesity-specific risk stratification in ED settings. Routine monitoring of metabolic markers and early intervention strategies should be prioritized for high-risk obese patients.

Peripheral artery disease (PAD) is a globally prevalent atherosclerotic disease associated with an increased risk of cardiovascular and cerebrovascular diseases and a poor prognosis. Skeletal muscle loss (sarcopenia) is particularly common in patients with PAD and is closely associated with poor prognosis.

The aim of this study was to evaluate the area, density and fat infiltration of skeletal muscle in patients with PAD by CT, and to analyze their relationship with the degree of vascular stenosis.

A total of 233 PAD patients who underwent lower extremity CTA in Beijing Hospital were included in this study. Image segmentation was performed using Slice-O-Matic® software, and parameters such as skeletal muscle area, density, and fat infiltration were measured at L3, L4, mid-thigh, and maximum soft tissue cross section of the lower leg. At the same time, the degree of lower extremity arterial stenosis was evaluated by CTA. The lower extremity arterial stenosis severity was graded as 0 (0-30%), 1 (31-50%), 2 (51-70%), 3 (71-99%), or 4 (occlusion).Then the CTA-score was calculated by summing the stenosis scores of the abdominal aorta and the lower limb arteries.

Patients were categorized into high (n = 113) and low (n = 120) CTA score groups. Among males, those in the low score group had higher muscle indices at L3, though not statistically significant. However, thigh and calf muscle areas were significantly larger in low score males (P < 0.001). High score patients had greater intermuscular fat indices. Regression analysis indicated that vascular stenosis accounted for 5% of the variance in muscle mass, with SFA, PoA, and PTA stenosis having the strongest correlations.

Our study reveals how vascular stenosis affects muscle mass and composition in PAD patients, with the SFA, PoA, and PTA having the greatest impact due to their key role in lower limb blood supply. Severe stenosis leads to muscle mass reduction and increased fat infiltration, possibly due to chronic inflammation and oxidative stress. These findings highlight the need to address muscle health in PAD management, as targeting muscle atrophy and fat infiltration could enhance patient outcomes.

PAD severity had a significant effect on the muscles of the lower limbs, especially the stenosis of the SFA, PoA, and PTA. CT evaluation provides a new perspective for understanding muscle loss in patients with PAD.

Prior research has highlighted the significant roles of circulating retinol, retinol-binding protein 4 (RBP4), and apolipoprotein C (ApoC) in metabolic health. This study investigates the joint association of retinol and RBP4 with metabolic syndrome (MetS) and examines the potential mediating role of ApoCs in these relationships. This prospective study included 3,009 and 2,724 participants with baseline serum retinol and RBP4 data, respectively. Over a 9-year follow-up among 2,621 participants, 1,136, 127, 696, and 662 were categorized into MetS-free, recovered, incident MetS, and persistent MetS groups, respectively. Midway through the study, ApoC1-4 levels were measured in 2316 participants. Adjusted odds ratios (95% CIs) for the highest (vs. lowest) tertile of retinol and RBP4 levels were 3.63 (2.69-4.92) and 5.64 (4.05-7.92) for 9-year persistent MetS, respectively. The corresponding hazard ratios (95% CIs) were 1.67 (1.39-2.01) and 1.67(1.38, 2.03) for incident MetS, and 0.65 (0.41-1.03) and 0.44 (0.28, 0.70) for recovered MetS (all P-trends<.05). A synergistic association of retinol and RBP4 with MetS risk was observed for persistent MetS. Higher levels of retinol or RBP4 were associated with increased concentrations of ApoC1-4, which were linked to a greater risk of incident and persistent MetS. A newly developed composite score (ApoCS), derived from ApoC1-4 levels, explained 30.5% and 24.5% of the association between retinol or RBP4 and MetS, with ApoC2 and ApoC3 contributing predominantly to this connection. Our study identified notable positive correlations between serum retinol and RBP4 levels and MetS progression, explained by increases in circulating ApoC2 and ApoC3 within a Chinese cohort.

Individuals with spinal cord injury (SCI) experience alterations in metabolism that result in increased central obesity, insulin resistance, and dyslipidemia placing them at elevated risk for developing cardiometabolic disease (CMD). Increased exercise and dietary modifications are the primary interventions for preventing CMD. However, people with SCI face unique challenges that prevent them from increasing their physical activity and easily modifying their nutritional intake. Tirzepatide is a medication that has been approved by the Food and Drug Administration to be used in conjunction with lifestyle changes to treat obesity in adults with type 2 diabetes mellitus.

A male in his 40's with C6 American Spinal Injury Association Impairment Scale B SCI 15 years prior with a body mass index of 32 presented to his primary care provider for treatment of obesity. He previously worked with multiple dietitians and increased his physical activity to lose weight. Despite these interventions, he was unable to reduce his weight. He was started on tirzepatide. After 3 months of treatment, he lost 31 pounds and saw improvements in his lipid profile. The only adverse effect reported was heartburn.

The metabolic dysfunction associated with SCI and barriers to adequate exercise for weight loss place individuals with SCI at increased risk for obesity and developing CMD. Tirzepatide may be an effective adjunct therapy to lifestyle interventions to help prevent CMD in those with SCI. Further research is indicated to examine the long-term efficacy, benefits, and adverse effects that may be associated with tirzepatide.

Evidence regarding the relationship between serum trace element levels and immune-mediated inflammatory skin diseases (IMSDs) is inconsistent.

In this systematic review and meta-analysis we aimed to evaluate the association between selected serum trace element levels (zinc [Zn], copper [Cu], iron [Fe], selenium [Se], and calcium [Ca]) and IMSDs (psoriasis, vitiligo, atopic dermatitis [AD], alopecia areata [AA], hidradenitis suppurativa, and bullous diseases).

We conducted a comprehensive search on the PubMed, EMBASE, Scopus, China National Knowledge Infrastructure, and Web of Science databases from the database inception date to May 2, 2024. Studies measuring serum, plasma, or whole-blood levels of Zn, Cu, Fe, Se, or Ca in patients with IMSD compared to those in healthy controls were included.

This study followed the guidelines of the Meta-analysis of Observational Studies in Epidemiology and the Preferred Reporting Items for Systematic Review and Meta-analyses guidelines. Two authors (X.Y.S. and Y.O.) independently reviewed the titles and abstracts of the identified studies using a standardized collection form.

The primary outcome was the standardized mean difference with a 95% CI in serum trace element levels (Zn, Cu, Fe, Se, and Ca) between patients with IMSDs and healthy controls. Overall, 113 studies involving 7014 patients with IMSD were included in the meta-analysis. Compared with those in the healthy control group, serum Zn levels decreased in patients with vitiligo, psoriasis, and AA; serum Cu levels increased in patients with psoriasis, AD, and AA; serum Se and Fe levels decreased in patients with psoriasis and AD.

Serum trace element levels showed more significant changes in patients with IMSDs than in healthy controls. These findings suggest that alterations in trace element levels may be associated with the occurrence, development, and prognosis of IMSDs.

The investigation of prevalence trends of metabolic cardiovascular risk factors is important for appropriate planning of future health programs aiming to prevent cardiovascular morbidity and mortality. In a previous study, we demonstrated an increase in the prevalence of type 2 diabetes (T2D) between 2000 and 2010 in Northeast Germany. The purpose of this study is to investigate prevalence trends of T2D treatment, dyslipidemia and hepatic steatosis in Northeast Germany.

The baseline examinations of the first Study of Health in Pomerania (SHIP) project were carried out from 1997 to 2001 (SHIP-START-0, 4308 subjects). A second, independent random sample of the same region was enrolled between 2008 and 2012 (SHIP-TREND-0, 4420 subjects). All data were standardized with post-stratification weighting derived from the adult population of the German federal state of Mecklenburg-West Pomerania.

The prevalence of metformin intake increased from 2.1% to 4.1% and insulin use from 2.0% to 2.8%. While the prevalence of statin intake increased from 6.8% to 12.2%, the prevalence of dyslipidemia decreased slightly from 49.0% in SHIP-START-0 to 45.5% in SHIP-TREND-0. The prevalence of hepatic steatosis increased from 29.7% to 37.3%. This increase was most prominently observed in women and younger age groups.

T2D, dyslipidemia and hepatic steatosis are common and increasing health problems among adults in Northeast Germany. Reassuring healthy diet and controlling obesity may result in prevention of above-mentioned health problems.

The non-HDL-C to HDL-C ratio (NHHR) is a dependable lipid marker linked to atherosclerotic traits. This study examines the potential relationship between NHHR and both metabolic dysfunction-associated steatotic liver disease (MASLD) and advanced liver fibrosis.

This study investigated the relationship between NHHR levels and both MASLD and advanced liver fibrosis using data from the 2017-2020 National Health and Nutrition Examination Survey (NHANES) in the United States. First, we conducted a baseline characteristics analysis of the population based on NHHR quartiles. Second, we employed multivariable weighted linear regression models to examine the associations between NHHR and MASLD, as well as advanced liver fibrosis. Third, we utilized restricted cubic splines (RCS) to assess potential non-linear relationships. Fourth, we performed subgroup analyses. Finally, ROC curve analysis was conducted to evaluate the effectiveness of NHHR.

In the main analysis, this study included a total of 9,864 participants. Following multivariable logistic regression and comprehensive adjustments, elevated NHHR levels in the Q3 and Q4 groups were significantly linked to MASLD, with odds ratios of 1.59 (95% CI: 1.20-2.11) and 1.83 (95% CI: 1.40-2.39), respectively (P for trend < 0.0001). Elevated NHHR levels in the Q2 and Q3 groups remained significantly linked to a decreased risk of advanced liver fibrosis, with odds ratios of 0.61 (95% CI 0.40-0.94, P = 0.03) and 0.64 (95% CI 0.47-0.89, P = 0.01), respectively. RCS analysis revealed a U-shaped nonlinear association between NHHR and both MASLD (P = 0.000; P for nonlinear = 0.029) and advanced liver fibrosis (P = 0.0001; P for nonlinear = 0.000). In the subgroup analysis, we found that this relationship was significant only in certain subgroups. The ROC curve analysis revealed that NHHR exhibited the best predictive performance for diagnosing MASLD based on the fatty liver index (FLI). The optimal cutoff point for NHHR in predicting MASLD using FLI was determined to be 2.476, with sensitivity and specificity values of 0.589 and 0.698, respectively.

NHHR may serve as a predictive marker for MASLD and advanced liver fibrosis, highlighting its potential significance in risk assessment and prevention strategies.

As China's ageing process accelerates, the annual prevalence of Metabolic Syndrome (MetS) among older Chinese adults continues to rise. This study seeks to assess the relationship between inflammatory markers, walking pace, and MetS in old Chinese adults.

This study utilised a cross-sectional design, drawing on data from the 2011 and 2015 waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted by Peking University, encompassing 3587 older adults aged over 60. Data regarding inflammatory markers (CRP), walking speed, and variables associated with MetS (including waist circumference and blood pressure) were gathered. Multiple linear regression analysis was used to evaluate the relationship between CRP, walking speed, and MetS.

In a cohort of 3587 older Chinese adults, slower walking speed (β = 0.414) and elevated CRP levels (β = 0.209) were significantly correlated with MetS, with the association persisting after controlling for confounding variables. Furthermore, females, urban residents, individuals with a higher BMI, and smokers exhibited an increased risk of developing MetS.

Walking speed and CRP levels are critical determinants in evaluating the risk of MetS in older adults; improving walking speed and mitigating inflammation may contribute to a decreased risk of MetS.

Inflammasomes are protein complexes that trigger pro-inflammatory responses and promote many diseases, including adipose tissue dysfunction. Linagliptin (L), a DPP-4 inhibitor used for type 2 diabetes therapy, has putative anti-inflammatory effects. This work explores L effects on inflammasome regulation, inflammation, and adipose tissue dysfunction in obese mice. Male C57BL/6N mice were fed a normal chow (NC) diet, high-fat (HF) diet, or HF diet with L (HFL) for 15 weeks. Gene expression and histological examinations were performed on visceral (VAT) and subcutaneous (SAT) adipose tissue samples. Biomarkers were quantified on sera. Murine macrophages were utilized for in vitro analyses. L decreased HF-induced endotoxemia and circulating inflammatory indicators. Despite having no effect on body weight, L reduced VAT inflammation by decreasing endotoxemia-induced NLRC4 inflammasome, inflammation severity, and fat cell hypertrophy. Although SAT response differed from VAT, inflammation was slightly reduced in this tissue too. In vitro, L modulated inflammation by directly reducing the pro-inflammatory macrophage phenotype. In obesity, increased NLRC4 inflammasome expression links endotoxemia and VAT inflammation. L protected against endotoxemia, maybe by affecting gut permeability and VAT responses. The decreased polarization of macrophages toward a pro-inflammatory phenotype and the reduction in adipocyte hypertrophy are involved in the response to L.

In the United States, two out of every five adults have obesity. The obesity epidemic is a significant public health concern and a major risk factor for atherosclerotic cardiovascular disease (ASCVD), contributing to its development through a complex interplay of social, biologic and behavioral mechanisms. It exacerbates traditional cardiovascular risk factors such as dyslipidemia, hypertension, and type 2 diabetes, while visceral and epicardial fat deposition promotes inflammation and insulin resistance, thereby accelerating atherosclerosis. Beyond traditional pathophysiologic pathways, social determinants of health (SDoH) significantly contribute to obesity-related disparities, particularly among racial and ethnic minorities. SDoH factors such as socioeconomic status, access to health care, and limited availability of nutritious food and safe spaces for physical activity not only increase obesity prevalence but also exacerbate its psychological toll, including stress and anxiety, which further elevate cardiovascular risk. Environmental factors, such as limited green spaces and air pollution, further promote obesogenic behaviors and worsen cardiovascular outcomes. In this review, we explore the association between obesity and ASCVD and key mediating pathways including the role of SDoH and environmental risk factors. We also discuss potential strategies-including patient education, community engagement to address SDoH, and establishment of dedicated cardiometabolic and cardiovascular prevention clinics-to mitigate the population burden of obesity and improve downstream cardiovascular outcomes.

The significance of interrelated risk factors for Type 2 diabetes (T2D) is not easily demonstrated by conventional statistical methods. This study aims to investigate the principal components of T2D risk by employing exploratory factor analysis in Iranian cohort. The analysis encompasses a range of sociodemographic, lifestyle, and health-related variables to uncover clusters of factors associated with the risk of T2D.

Cross-sectional data of 1200 diabetic and 1200 nondiabetic Iranian adults was analyzed using STATA 14.2 (p < 0.05). Pearson's Chi-squared test was used to assess the difference between the two groups. Spearman correlation explored the relationships between variables. Separate factor analyses were conducted for diabetic, non-diabetic, and combined groups. Principal component analysis (PCA) identified the initial components. Crude and adjusted logistic regressions examined the associations between derived factors and T2D risk.

PCA identified eleven components with eigenvalues ≥ 1, accounting for 65.09% of the variance. Logistic regression analysis highlighted several significant associations with T2D risk. Positive associations were observed for PC1 ("drugs, smoking, and alcohol"), PC2 ("chronic diseases", including age, hypertension, dyslipidemia, and coronary heart disease), PC3 ("lipids", such as triglycerides, cholesterol, and low-density lipoprotein), PC4 ("body mass", including BMI, waist circumference, and waist-to-hip ratio), PC5 ("gestational-related risks", such as gestational diabetes and gestational hypertension), and PC6 ("glucose/lipid factors", including fasting glucose, triglycerides, and an inverse relationship with high-density lipoprotein). Conversely, negative associations with T2D risk were found for PC7 ("socioeconomic factors", such as socioeconomic status and education), PC8 (inverse association with age, along with fatty liver, thyroid disorders, and low waist-to-hip ratio), and PC10 (marital status, sleep duration, low fasting glucose, lower age, and an inverse association with fatty liver).

Key metabolic clusters, including "Lipids", "Body Mass", "Chronic Diseases", and "Glucose/Lipid" align with previous findings. These results underscore the multifactorial and interconnected nature of T2D risk, highlighting underlying physiological processes.

Metabolic diseases like obesity and diabetes are on the rise, and therapies with biomacromolecules (such as proteins, peptides, antibodies, and oligonucleotides) play a crucial role in their treatment. However, these drugs are traditionally injected. For patients with chronic diseases (e.g., metabolic diseases), long-term injections are accompanied by inconvenience and low compliance. Oral administration is preferred, but the delivery of biomacromolecules is challenging due to gastrointestinal barriers. In this article, we introduce the available biomacromolecule drugs for the treatment of metabolic diseases. The gastrointestinal barriers to oral drug delivery and strategies to overcome these barriers are also explored. We then discuss strategies for alleviating metabolic defects, including glucose metabolism, lipid metabolism, and energy metabolism, with oral biomacromolecules such as insulin, glucagon-like peptide-1 receptor agonists, proprotein convertase subtilisin/kexin type 9 inhibitors, fibroblast growth factor 21 analogues, and peptide YY analogues.

This meta-analysis aims to systematically investigate whether dietary anthocyanin supplementation can reduce metabolic syndrome (MetS)-related risk factors: abdominal obesity, dyslipidemia (low high-density lipoprotein cholesterol (HDL-C) and hypertriglyceridemia), hypertension, and hyperglycemia by conducting a meta-analysis of randomized controlled trials (RCTs).

A systematic search of 5 electronic databases (PubMed, Web of Science, Scopus, Cochrane Library, and Embase) was conducted from inception until April 25, 2024. A total of 1213 studies were identified, of which randomized controlled trials involving subjects with MetS-related factors, comparing dietary anthocyanin supplementation with placebo, and reporting results on anthropometric, physiological, and metabolic markers relevant to this study were selected. Depending on the heterogeneity of the included studies, a fixed-effect model was applied for low heterogeneity (I2 < 50%), whereas a random-effects model was employed when substantial heterogeneity was present (I2 ≥ 50%). The weighted mean difference (WMD) and 95% confidence intervals (CI) were calculated.

This meta-analysis included 29 randomized controlled trials with 2006 participants. The results showed that dietary anthocyanins significantly improved various lipid and glycemic markers: HDL-C: increased by 0.05 mmol/L (95% CI: 0.01 to 0.10, p = 0.026), LDL-C: decreased by 0.18 mmol/L (95% CI: -0.28 to -0.08, p = 0.000), Triglycerides (TGs): reduced by 0.11 mmol/L (95% CI: -0.20 to -0.02, p = 0.021), Total cholesterol (TC): lowered by 0.34 mmol/L (95% CI: -0.49 to -0.18, p = 0.000), Fasting blood glucose (FBG): reduced by 0.29 mmol/L (95% CI: -0.46 to -0.12, p = 0.001), Glycated hemoglobin (HbA1c): decreased by 0.43% (95% CI: -0.74 to -0.13, p = 0.005). Weight: (WMD: -0.12 kg, 95% CI: -0.45 to 0.21, p = 0.473), Body mass index (BMI): (WMD: -0.12 kg/m2, 95% CI: -0.26 to 0.03, p = 0.12), Overall WC: (WMD: 0.18 cm, 95% CI: -0.51 to 0.87, p = 0.613), Systolic blood pressure (SBP): (WMD: -0.12 mmHg, 95% CI: -1.06 to 0.82, p = 0.801), Diastolic blood pressure (DBP): (WMD: 0.61 mmHg, 95% CI: -0.03 to 1.25, p = 0.061), Insulin levels: (WMD: -0.02 mU/L, 95% CI: -0.44 to 0.40, p = 0.932), HOMA-IR: (WMD: -0.11, 95% CI: -0.51 to 0.28, p = 0.573). Additionally, a 100 mg/day dosage of anthocyanins significantly reduced: Waist circumference (WC): by 0.55 cm (95% CI: -1.09 to -0.01, p = 0.047). Subgroup analyses based on intervention duration, anthocyanin dosage, health status, formulation, dosage frequency, physical activity levels, and baseline levels of corresponding markers revealed varying significances, particularly in relation to blood pressure.

Dietary anthocyanins effectively improve low HDL cholesterol, hypertriglyceridemia, and hyperglycemia, making them a promising adjunct for managing MetS. However, it is important to note that dietary anthocyanin interventions may raise systolic blood pressure (SBP) and diastolic blood pressure (DBP) depending on intervention dose, duration, participant health status, and formulation. Clinicians should fully consider these effects when recommending anthocyanin supplementation. Further long-term, well-designed, large-scale clinical trials are needed to draw definitive conclusions.

To investigate the glucose profile of Chinese individuals with type 1 diabetes (T1D) who also have metabolic syndrome.

Type 1 diabetes participants from Peking University People's Hospital were recruited from Jan 2017 to Jan 2024. The diagnosis of metabolic syndrome was developed based on the updated National Cholesterol Education Program Adult Treatment Panel III (NCEP-ATPIII) criteria. Demographic data, anthropometric measurements, clinical information and continuous glucose monitoring (CGM) data were collected and compared between participants with metabolic syndrome and those without.

The median age of the participants was 50.0 years (IQR 35.0-63.3), and the median duration was 10.0 years (IQR 2.0-17.0). Compared to those without metabolic syndrome, participants with metabolic syndrome were older (63.0 years, IQR 41.0-69.0 vs. 48.5 years, IQR 35.0-60.0; P < 0.001) and had a longer duration (13.0 years, IQR 5.0-22.0 vs. 9.0 years, IQR 2.0-15.0; P = 0.011). The comparison of CGM metrics suggested significantly higher time above range (TAR, 48.9%, IQR 35.3-59.5 vs. 32.8%, IQR 16.1-47.6; P < 0.001), standard deviation (SD, 3.6 ± 0.9 mmol/L vs. 3.2 ± 1.0 mmol/L; P = 0.022) and interquartile range (IQR, 4.2 mmol/L, IQR 3.2-4.8 vs. 3.7 mmol/L, IQR 3.0-4.5; P = 0.046) in those with metabolic syndrome. And the Logistic regression analysis showed that TAR (OR 1.53, 95% CI 1.02-2.23, per 20% increase), SD ( OR 1.75, 95% CI 1.07-2.84, P = 0.025) and IQR (OR 1.50, 95% CI 1.03-2.19, P = 0.036) were positively associated with metabolic syndrome after adjusting for age, sex, diabetes duration, BMI and complication status.

Our findings suggested that in T1D participants, metabolic syndrome was associated with higher glucose level and glycemic variability. Personalized diabetes education including optimal meal planning and sufficient physical activity should be emphasized to improve glycemic control in T1D with metabolic syndrome.

Despite growing interest in circadian disturbances as potential triggers for dementia, the specific impact of circadian syndrome (CircS) on dementia incidence remains poorly understood. Moreover, the role of genetic susceptibility modulating these effects remains to be explored.

Dementia-free participants from the UK Biobank cohort were included in the analysis. To evaluate the association between CircS and the incidence of dementia, as well as the modifying influence of genetic susceptibility on this relationship, Cox proportional hazards models were utilized.

During a median follow-up period of 14.55 years, 3,965 incident dementia cases were documented. CircS was found to significantly increased the risk of incident dementia, with a hazard ratio (HR) of 1.401 (95 % confidence interval [CI]: 1.296, 1.516). Compared to a CircS score of ≤3, mild CircS (HR: 1.259, 95 % CI: 1.146-1.383), moderate CircS (HR: 1.667, 95 % CI: 1.461-1.903), and severe CircS (HR: 2.028, 95 % CI: 1.397-2.944) were all significantly associated with an elevated risk of dementia. There were significant multiplicative interactions between CircS and genetic susceptibility (Pinteraction<0.001). Participants with both a high polygenic risk score (PRS) and CircS had the highest risk of incident dementia (HR: 2.551, 95 % CI: 2.169, 3.001), compared to those with a low PRS and no CircS.

CircS was associated with an increased risk of dementia, which might be aggravated by genetic susceptibility.

Overweight and obesity can induce an inflammatory milieu in the oocyte microenvironment and are closely associated with reduced assisted reproductive outcomes.

How are immune cells, cytokines and lipid profiles altered in the pre-ovulatory microenvironment of overweight and obese women?

32 women undergoing in vitro fertilization (IVF) were included, with 14 overweight or obese (OW) and 18 normal weight (NW) participants. Serum was collected before ovulation induction, follicular fluid (FF) and aspirates were obtained during oocyte retrieval for flow cytometry, cytokines, hormone, and lipid profiles measurement. Clinical outcomes were recorded through a one-year follow-up.

The percentage of T cells in the pre-ovulatory follicular microenvironment, especially CD4+ T cells, increased significantly in the OW group, which positively related with BMI. Notably, type 2 cytokine IL4 and IL13 transcription level in OW group had significantly increased, while the type 1 cytokine IFNG only showed a non-statistically significant upward trend. Lipid profiles were screened, revealing no difference between the two groups, however, levels were higher in serum compared to FF. Additionally, the concentration gradient of TG between serum and FF was 22-fold in OW group (2.92 ± 3.66 vs. 0.13 ± 0.03), which was significantly higher than the 12-fold gradient observed in NW group (1.72 ± 0.95 vs. 0.14 ± 0.08). Furthermore, day 3 high quality embryos rate is negatively associated with BMI and exhibits a decreasing trend in OW group.

Overweight and obesity can disrupt immune hemostasis in the pre-ovulatory follicular microenvironment, potentially leading to adverse effects on assisted reproductive outcomes.

The aim of this study was to assess the association between the level of lactate dehydrogenase (LDH) and the severity of metabolic syndrome (MetS) and Metabolic Associated Fatty Liver Disease (MAFLD) and the potential diagnostic value of LDH for identifying at-risk metabolic associated steatohepatitis (MASH).

This cross-sectional, real-world retrospective study enrolled a total of 1118 obese patients in the department of bariatric surgery at the Second Affiliated Hospital of Anhui Medical University from January 1, 2018, to December 31, 2021. Of these, 855 were enrolled in the study cohort. MAFLD was defined as the presence or absence of fatty liver disease as suggested by histologic biopsy of liver or postoperative pathology slides, or even hematology, and meets one of the following three conditions: overweight or obesity, T2DM, and metabolic dysfunction (MetS). Serum LDH activity levels were measured in 885 patients, and logistic regression was used to analyze the relationship between LDH and metabolic syndrome and the severity of MAFLD.

In the study cohort of 855 obese patients, 604 (70.6%) had MetS. Patients with MetS (214.1[209.0-219.2]) had significantly higher serum LDH levels than those without MetS (188.7[181.6-195.9]). Particularly, serum LDH level was significantly higher in subjects with hypertension, central obesity, diabetes mellitus or hyperglycemia, elevated levels of triglycerides, or reduced levels of high-density lipoprotein than in those without. Moreover, LDH concentrations were grouped according to the total number of MetS components present in each patient, with Serum LDH levels gradually increase with the total number of MetS components. The MASH subjects had significantly higher LDH levels than the other three less severe non-MASH cohorts, including normal liver, simple fatty steatosis, and B.MASH. Logistic regression showed that LDH was significantly and positively correlated with MAFLD, B.MASH, MASH, at-risk MASH, fibrosis grade ≥1, fibrosis grade ≥2 and fibrosis grade ≥3.

Increased LDH levels were significantly and independently associated with the presence and severity of metabolic syndrome and MAFLD, indicating that LDH could be used as a novel biomarker and clinical predictor of severity of metabolic syndrome and MAFLD.

Previous studies have shown that frailty and metabolic syndrome (Mets) share common pathophysiological mechanisms. However, whether the observed association reflects causality requires clarification. We performed a bidirectional Mendelian randomization study to investigate the causal relationship between frailty, Mets, and their individual components.

Summary-level data from GWAS to identify genetic variants associated with frailty, Mets, and its components among individuals of European ancestry. Inverse variance weighting was utilized as the main method. Using bidirectional Mendelian randomization analysis, we found that the risk of frailty was causally associated with an increased risk of MetS (OR: 2.092, 95%CI: 1.564-2.799) and its components, including waist circumference (OR: 1.349, 95 % CI: 1.181-1.541), hypertension (OR: 1.099, 95 % CI: 1.075-1.125), triglycerides (OR: 1.297, 95 % CI: 1.179-1.428). Conversely, the risk of MetS was causally associated with an increased risk of frailty (OR: 1.048; 95 % CI: 1.024-1.073). however, when removing SNPs assocaited with BMI at the loci significance level and performed MVMR, Mets and frailty were not associated.

These findings suggest a bidirectional causal relationship between frailty and MetS, indicating that genetic factors contributing to frailty also increase the risk of MetS and its components, and vice versa. Furthermore, BMI-related SNPs may act as effect modifiers in the association between MetS and frailty. These insights into the shared pathophysiology of frailty and MetS have implications for the prevention and treatment strategies in elderly individuals with MetS.

To examine the associations of commonly-used serum lipid measures (high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC) and triglycerides (TG)) with glaucoma.

This prospective cohort study included 400 229 participants from the UK Biobank. Cox regression and restricted cubic spline models and polygenic risk scores were employed to investigate the associations between serum lipids and glaucoma.

Over a mean follow-up of 14.44 years, 6868 (1.72%) participants developed glaucoma. Multivariate Cox regression revealed that higher levels of HDL-C were associated with an increased risk of glaucoma (HR for 1-SD increase in HDL-C 1.05, 95% CI 1.02 to 1.08, p=0.001), while elevated levels of LDL-C (HR 0.96, 95% CI 0.94 to 0.99, p=0.005), TC (HR 0.97, 95% CI 0.94 to 1.00, p=0.037) and TG (HR 0.96, 95% CI 0.94 to 0.99, p=0.008) were all associated with reduced risk. The analysis examining the associations between polygenic risk score of serum lipids and glaucoma showed per 1-SD increment of HDL-C genetic risk was associated with a 5% greater hazard of glaucoma (HR 1.05, 95% CI 1.00 to 1.11, p=0.031). However, the polygenic risk score of LDL-C, TC, and TG did not show a significant association with glaucoma.

Elevated HDL-C is associated with an increased risk of glaucoma, while elevated LDL-C, TC, and TG levels are associated with a lower risk of glaucoma. This study enhances our understanding of the association between lipid profile and glaucoma and warrants further investigation of lipid-focused treatments in glaucoma management.

Background/Objectives: Obesity is a global health challenge linked to a higher risk of metabolic and cardiovascular complications. This study investigates the role of cardiovascular markers in predicting metabolic crises in obese patients, focusing on the prevalence and clinical implications of these markers. Methods: This retrospective cohort study included 433 patients presenting with metabolic crises at the Emergency Department of Timișoara Municipal Emergency Hospital between 2019 and 2024. Patients were classified into obese (n = 161) and non-obese (n = 272) groups, with obesity further stratified into four grades based on body mass index (BMI). Cardiovascular markers, including NT-proBNP, troponin I, CRP, CK-MB, and D-dimer, alongside metabolic parameters, were analyzed. Results: Metabolic crises were significantly more prevalent in obese patients in all metabolic emergencies: hyperglycemia (27.9% vs. 11.0%, p < 0.001), electrolyte imbalance (23.6% vs. 9.2%, p < 0.001), and acute kidney injury (AKI) (12.4% vs. 5.5%, p = 0.01). NT-proBNP levels independently predicted AKI in obese patients (adjusted OR: 1.14 per 1000 pg/mL, 95% CI: 1.10-1.19, p < 0.001), with excellent discriminatory power (AUC: 0.88). Troponin I and D-dimer were higher in hyperglycemia and electrolyte imbalance, respectively, emphasizing the role of cardiac stress and pro-thrombotic states. Inflammatory markers such as CRP were significantly associated with metabolic disturbances, supporting the contribution of systemic inflammation. Comorbidities, particularly heart failure and atrial fibrillation, further increased the risk of metabolic crises. Conclusions: Cardiovascular markers suggest potential utility for early risk stratification of metabolic crises in obese patients. However, further studies are needed to validate their clinical applicability and to establish standardized approaches for integrating these biomarkers into routine practice, especially in patients with advanced obesity grades.

This study aimed to evaluate the association between rheumatoid arthritis (RA) and subsequent migraine risk using the Korean National Health Insurance Service database.

Migraine may be related to immune dysfunction and previous studies have suggested an association with chronic inflammatory rheumatic diseases; however, the relationship between RA and migraine remains unclear.

This was a population-based, nationwide, retrospective, longitudinal cohort study. Participants were enrolled from 2010 to 2017 and followed up until 2019. A total of 42,674 patients who had undergone a health checkup within 2 years prior to the initial diagnosis of RA were included in the study, after applying the exclusion criteria (previous migraine, other rheumatic disease, missing variables of interest). A non-RA control was obtained by age and sex-matching (1:5). Finally, 42,644 patients with RA were enrolled, with 213,370 individuals without RA included as controls. Among the patients with RA, 29,744 had seropositive RA (SPRA), and 12,900 had seronegative RA (SNRA). SPRA was defined by the International Classification of Diseases 10th revision (ICD-10) code M05, prescription of disease-modifying anti-rheumatic drugs (DMARDs), and enrollment in a special copayment reduction program. SNRA was defined by the ICD-10 code M06 and prescription of any DMARD. The primary endpoint was the occurrence of migraine incidents, defined using the ICD-10 code of migraine (G43).

A total of 22,294 migraine cases (17,912/213,370 [8.3%] in controls and 4382/42,674 [10.2%] in RA) were reported during a mean follow-up of 4.4 years after a 1-year lag period. Patients with RA had a 1.2-fold higher risk of migraine compared with controls (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.17-1.26). Increased risk of migraine was found in both patients with SNRA and SPRA compared with controls (aHR 1.20, CI 1.15-1.24 in SPRA; aHR 1.26, CI 1.19-1.34 in SNRA). Compared to patients with SNRA, those with SPRA did not demonstrate a heightened risk (aHR 0.94, CI 0.88-1.01). A significant interaction was confirmed between covariates (male, current smoker, those with diabetes mellitus, and dyslipidemia) and the risk of migraine (p for interaction of <0.05).

RA was linked to a higher migraine risk, regardless of seropositivity.

Epigallocatechin gallate (EGCG), the predominant catechin in green tea, comprises approximately 50% of its total polyphenol content and has garnered widespread recognition for its significant therapeutic potential. As the principal bioactive component of Camellia sinensis, EGCG is celebrated for its potent antioxidant, anti-inflammatory, cardioprotective, and antitumor properties. The bioavailability and metabolism of EGCG within the gut microbiota underscore its systemic effects, as it is absorbed in the intestine, metabolized into bioactive compounds, and transported to target organs. This compound has been shown to influence key physiological pathways, particularly those related to lipid metabolism and inflammation, offering protective effects against a variety of diseases. EGCG's ability to modulate cell signaling pathways associated with oxidative stress, apoptosis, and immune regulation highlights its multifaceted role in health promotion. Emerging evidence underscores EGCG's therapeutic potential in preventing and managing a range of chronic conditions, including cancer, cardiovascular diseases, neurodegenerative disorders, and metabolic syndromes. Given the growing prevalence of lifestyle-related diseases and the increasing interest in natural compounds, EGCG presents a promising avenue for novel therapeutic strategies. This review aims to summarize current knowledge on EGCG, emphasizing its critical role as a versatile natural bioactive agent with diverse clinical applications. Further exploration in both experimental and clinical settings is essential to fully unlock its therapeutic potential.

An insulin resistant state is characteristic of patients with type 2 diabetes, polycystic ovary syndrome, and metabolic syndrome. Identification of insulin resistance (IR) is most readily achievable using formulae combining plasma insulin and glucose results. In this study, we have used data from the European Biological Variation Study (EuBIVAS) to examine the biological variability (BV) of IR using the Homeostasis Model Assessment for Insulin Resistance (HOMA-IR) and the Quantitative Insulin sensitivity Check Index (QUICKI).

Ninety EuBIVAS non-diabetic subjects (52F, 38M) from five countries had fasting HOMA-IR and QUICKI calculated from plasma glucose and insulin samples collected concurrently on 10 weekly occasions. The within-subject (CVI) and between-subject (CVG) BV estimates with 95 % CIs were obtained by CV-ANOVA after analysis of trends, variance homogeneity and outlier removal.

The CVI of HOMA-IR was 26.7 % (95 % CI 25.5-28.3), driven largely by variability in plasma insulin and the CVI for QUICKI was 4.1 % (95 % CI 3.9-4.3), reflecting this formula's logarithmic transformation of glucose and insulin values. No differences in values or BV components were observed between subgroups of men or women below and above 50 years.

The EuBIVAS, by utilising a rigorous experimental protocol, has produced robust BV estimates for two of the most commonly used markers of insulin resistance in non-diabetic subjects. This has shown that HOMA-IR, in particular, is highly variable in the same individual which limits the value of single measurements.

Osteoarthritis (OA) affects several joints but tends to be more prevalent in those that are weight-bearing, such as the knees, which are the most heavily loaded joints in the body. The incidence and disability rates of OA have continued to increase and seriously jeopardise the quality of life of middle-aged and older adults. However, OA is more than just a wear and tear disease; its aetiology is complex, and its pathogenesis is poorly understood. Metabolic syndrome (MetS) has emerged as a critical driver of OA development. This condition contributes to the formation of a distinct phenotype, termed metabolic syndrome-associated osteoarthritis (MetS-OA),which differs from other metabolically related diseases by its unique pathophysiological mechanisms and clinical presentation. As key mediators of MetS, metabolic adipokines such as leptin, lipocalin, and resistin regulate inflammation and bone metabolism through distinct or synergistic signaling pathways. Their modulation of inflammatory responses and bone remodeling processes plays a critical role in the pathogenesis and progression of OA. Due to their central role in regulating inflammation and bone remodeling, metabolic adipokines not only deepen our understanding of MetS-OA pathogenesis but also represent promising targets for novel therapeutic strategies that could slow disease progression and improve clinical outcomes in affected patients.

Background: Metabolic syndrome (MetS) is a syndrome that comprises central obesity, increased serum triglyceride (TG) levels, decreased serum HDL cholesterol (HDL) levels, raised blood pressure (BP), and impaired glucose regulation, including prediabetic and diabetic glycaemic levels. Recently, the association with endometrial cancer (EC) has been described but it is unclear if the risk associated with MetS is higher than the individual effect of obesity alone. This study investigates the association between MetS components and differing MetS definitions on EC risk and compares the risk of MetS with the risk posed by obesity alone. It also analyses how MetS affects the risk of EC development in the pre- and post-menopausal subgroups. Methods: A prospective cohort study was undertaken using data from the UK biobank. Multivariable Cox proportional risk models with the time to diagnosis (years) were used to estimate the hazard ratio (HR) and 95% confidence interval (CI) of MetS and its components on the risk of EC. A subgroup analysis was also undertaken for pre- and post-menopausal participants. Kaplan-Meier (KM) was undertaken to assess the difference in the risk of EC development in differing BMI classes, and in pre- and post-menopausal subgroups. Results: A total of 177,005 females from the UK biobank were included in this study. Of those participants who developed EC (n = 1454), waist circumference > 80 cm, BMI > 30 kg/m2, hypertension > 130/80 mmHg, hyperlipidaemia and diabetes (HbA1C > 48 mmol/L were significant predictors of EC development, with waist circumference being the strongest predictor (HR = 2.21; 95% CI: 1.98-2.47, p < 0.001). Comparing the pre- and post-menopausal subgroup, hypertriglyceridaemia and diabetes were the strongest predictors of EC in the pre-menopausal subgroup (HR = 1.53; 95% CI: 1.18-1.99 and HR = 1.51; 95% CI: 1.08-2.12, p < 0.05, respectively). Raised waist circumference was not a significant independent predictor in the pre-menopausal subgroup. A KM curve analysis showed a clear distinction between those with and without MetS in the pre-menopausal group, suggesting a benefit of testing for MetS components in pre-menopausal women with obesity. Conclusions: Components of MetS, both independently and in combination, significantly increase the risk of EC. Screening those with obesity for MetS in their pre-menopausal years may help to identify those at the highest risk.

Metabolic syndrome (MetS) patients have impaired hypothalamic regulatory functions involved in food intake and energy expenditure and suffer from a state of meta-inflammation. Pre-clinical studies demonstrated that ultramicronized palmitoylethanolamide (PEA) acts both on the adipose tissue and the central nervous system, while hydroxytyrosol (HTyr) counteracts several types of dysmetabolism.

The aim of our randomized crossover double-blind placebo-controlled pilot study was to evaluate the potential effects of a food supplement (FS) containing a co-micronized formulation of PEA and rutin along with HTyr, combined with a tailored calorie-controlled Mediterranean diet, in patients with MetS.

Nineteen patients were enrolled and block-randomized to an eight-week MD together with the FS or placebo. After a two-week washout period, the treatments were reversed. Data on laboratory parameters and those detected by capillary sampling, anthropometry, body composition analysis, ultrasound examination, blood pressure monitoring, the 36-Item Short-Form Health Survey questionnaire, handgrip strength test, and physical performance tests were collected at each time point (protocol code R.S. 262.22, registered on 20 December 2022).

At the end of the study, patients supplemented with the FS showed a significant reduction in body weight, body mass index, fat mass, and inflammation biomarkers (CRP and ESR), compared to placebo-supplemented patients. In contrast, the fat-free mass, phase angle, and body cell mass were increased in FS compared to placebo patients.

Although preliminary, the results of our clinical study suggest that co-micronized PEA-rutin and HTyr may be of help against adiposopathy in patients with MetS.