Metabolic Syndrome Research Articles

Метаболічний синдром: механізми розвитку та експериментальні моделі

Metabolic syndrome is a condition characterized by the presence of insulin resis­tance and the presence of two of the following risk factors: obesity, hyperlipidemia (hypertriglyceridemia, decreased high-density lipoprotein cholesterol), hypertension, or microalbuminuria. The multifactorial nature of metabolic syndrome makes it difficult to create an adequate experimental model that would best represent the entire spectrum of the pathophysiology of this condition. This review aims to summarize current literature data on the pathophysiological mechanisms of metabolic syndrome in the context of the development of insulin resistance, obesity, dyslipidemia, impaired glucose tolerance, and inflammation. The article also summarizes modern approaches to the induction of metabolic syndrome in rodents, among which dietary manipulation, genetic modifications, and the use of pharmaceuticals are the most common. As genetic models of metabolic syndrome, rodents with leptin or leptin receptor deficiency are most often used, in particular leptin-deficient mice (ob/ob), leptin receptor-deficient mice (db/db), Zucker obese rats (ZF), diabetic rats lines Zucker with obesity (ZDF) and others. Pharmaceutical drugs that can be used to induce metabolic syndrome include endogenous glucocorticoids and antipsychotic drugs. Several dietary manipulations are used to induce metabolic syndrome in laboratory animals. In particular, one type of diet or a combination of diets can be used, such as diets high in fructose, sucrose and fat, or a diet characterized by a high content of both fructose and fat or sucrose and fat. Manipulations with the composition of products consumed by experimental animals make it possible to simulate the development of metabolic syndrome, since the diet affects the metabolism of the entire body, and has a regulatory effect on hormones, glucose and lipid metabolism pathways.

Impact of a Physical Exercise and Health Education Program on Metabolic Syndrome and Quality of Life in Postmenopausal Breast Cancer Women Undergoing Adjuvant Treatment with Aromatase Inhibitors

Background and Objectives: Adjuvant treatment with aromatase inhibitors (AIs) in breast cancer (BC) survivors can cause adverse effects such as metabolic syndrome (MS) (insulin resistance, central obesity, atherogenic dyslipidemia, and hypertension) associated with morbidity and premature mortality. We evaluate the effect of a multimodal program based on physical exercise and health education on MS and health-related quality of life (QoL) in postmenopausal women with BC under AIs. Methods: A total of 56 postmenopausal women, diagnosed with BC, aged 60 years or older (mean age 67.2 years) and on hormonal treatment with AIs, were included in the multimodal physical exercise and health education program, and evaluated before and after their participation. The assessment of the five criteria of the MS included the following: waist circumference, high blood pressure, fasting glucose, triglycerides, and high-density lipoprotein cholesterol. Two main instruments were used to evaluate the impact of the intervention on QoL: the EORTC QLQ C30 (questionnaire for cancers in general) and the EORTC QLQ BR23 (specifically for breast cancer patients). The EuroQol 5D (EQ-5D) was also used to compare these results. Results: The percentage of women meeting the MS criteria was 37.7% at baseline and fell to 15.1% at 3 months after the intervention (p = 0.02). The intervention significantly reduced hypertension (p < 0.001), central obesity (p < 0.001), and the concentration of triglycerides (p = 0.016). No significant changes were observed in fasting glucose and HDL concentration. A statistically significant improvement was found in QoL (on both the QLQ30 and BR23 scales). A multivariate regression model analysis identified marital status (being married) (95% CI: 1.728–131.615, p = 0.014), and percentage of attendance at health education sessions (95% CI: 1.010–1.211, p = 0.029) as positive predictive variables of improvement in MS. Conclusions: The implementation of multimodal, community-based programs of physical exercise and health education improve the prevalence of MS and specific criteria of MS and QoL in postmenopausal women with breast cancer receiving AI treatment.

High-Sensitivity C-Reactive Protein Levels in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD), Metabolic Alcohol-Associated Liver Disease (MetALD), and Alcoholic Liver Disease (ALD) with Metabolic Dysfunction

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a recently introduced term for steatotic liver disease (SLD). Although the inflammatory process is central to the pathogenesis of SLD, research investigating the differences in systemic inflammation across various SLD subtypes as well as sex differences is limited. This population-based, cross-sectional study investigated the association between SLD subtypes and high-sensitivity C-reactive protein (hs-CRP) levels among Korean adults (N = 20,141; mean age: 50.8 ± 16.7 years). The participants were classified into five groups that included no SLD, MASLD, metabolic alcohol-associated liver disease (MetALD), alcoholic liver disease with metabolic dysfunction (ALD with MD), and other SLDs. The median (Q1, Q3) value of the hs-CRP level was 0.54 mg/L (0.33, 1.04). Among men, compared to levels in the no SLD group, the MASLD, MetALD, and ALD with MD groups were associated with 41.9% (95% confidence interval [CI]: 35.1–49.1%), 46.8% (95% CI: 35.0–59.6%), and 51.8% (95% CI: 30.0–77.2%) increases in hs-CRP levels, respectively. The association between SLD subtypes and hs-CRP levels was stronger among women, and compared to the levels in the no SLD group, the MASLD, MetALD, and ALD with MD groups were associated with 81.5% (95% CI: 73.6–89.8%), 84.3% (95% CI: 58.1–114.8%), and 98.2% (95% CI: 38.0–184.8%) increases in hs-CRP levels, respectively. In conclusion, our findings indicate a varying profile of systemic inflammation across SLD subtypes, with more pronounced increases in hs-CRP levels in women with SLDs.

Cardiovascular status in endogenous cortisol excess: the prospective CV-CORT-EX study

Abstract Objective Cushing´s syndrome (CS) results in increased cardiovascular morbidity and mortality. Subtype-specific differences and possible reversibility after biochemical cure are not well investigated. Design Prospective cohort study evaluating the cardiovascular status in different forms of endogenous cortisol excess. Methods Patients with overt CS (n=40, 47±13 years, 75% women; 18 pituitary, 13 adrenal, 9 ectopic), biochemically cured CS (n=56, 53±12 years, 79% women; 30 pituitary, 21 adrenal, 5 ectopic), and adrenal incidentalomas with mild autonomous cortisol secretion (MACS) (n=18, 62±11 years, 56% women) underwent comprehensive biochemical, metabolic, and cardiovascular assessment. Results were compared with a representative sample of the general population of Würzburg (n=4965, 55±12 years, 52% women). Results Overt CS was associated with left ventricular (LV) remodeling along with hypertrophy and impaired longitudinal systolic/diastolic function at echocardiography. In 20 CS patients followed for a median of 8 (quartiles: 6, 11) months after biochemical remission, hypertension and hyperglycemia were better controlled, while cardiac alterations only partially improved. Patients with previous CS (median time of biochemical remission: 95 (36, 201) months) had worse diastolic function than the general population (LV relaxation velocity e´ 0.08 (0.07, 0.10) ms-1 vs 0.10 (0.08, 0.12) ms-1, p<0.001). In MACS, cardiac remodeling was even more pronounced than in individuals with metabolic syndrome. Conclusions In patients with overt CS, cured CS, and MACS, we found a sizable and significant deviation from the general population mean regarding cardiac structure and function. Even mild cortisol excess is associated with glucocorticoid-induced cardiac alterations which appear to persist despite long-term biochemical remission.

The association between metabolic syndrome and lung cancer risk: a Mendelian randomization study

The association between metabolic syndrome and lung cancer risk: a Mendelian randomization study

Assessing coronary artery stenosis exacerbated impact on left ventricular function and deformation in metabolic syndrome patients by 3.0 T cardiac magnetic resonance imaging

Abstract Background Metabolic syndrome (MetS) and coronary artery stenosis (CAS) independently increase the risk of cardiovascular events, while the impact of CAS on left ventricular (LV) function and deformation in MetS patients remains unclear. This study investigates how varying degrees of CAS exacerbate LV function and myocardial deformation in MetS patients. Methods One hundred thirty-one MetS patients who underwent CMR examinations were divided into two groups: the MetS(CAS−) group (n = 47) and the MetS(CAS+) group (n = 84). The MetS(CAS+) group was divided into MetS with non-obstructive CAS(NOCAS+) (n = 30) and MetS with obstructive CAS(OCAS+) group (n = 54). Additionally, 48 age- and sex-matched subjects were included as a control group. LV functional and deformation parameters were measured and compared among subgroups. The determinants of decreased LV global peak strains in all MetS patients were identified using linear regression. The receiver operating characteristic (ROC) curve and logistic regression model (LRM) evaluated the diagnostic accuracy of the degree of CAS for identifying impaired LV strain. Results Compared to MetS(CAS−), MetS(NOCAS+) showed a significantly increased LV mass index (p < 0.05). Global longitudinal peak strain was decreased gradually from MetS(CAS−) through MetS(NOCAS+) to MetS(OCAS+) (− 13.02 ± 2.32% vs. − 10.34 ± 4.05% vs. − 7.55 ± 4.48%, p < 0.05). MetS(OCAS+) groups showed significantly decreased LV global peak strain (GPS), PSSR and PDSR in radial and circumferential directions compared with MetS(NOCAS+) (all p < 0.05). The degree of CAS was independently associated with impaired global radial peak strain (GRPS) (β = − 0.289, p < 0.001) and global longitudinal peak strain (GLPS) (β = 0.254, p = 0.004) in MetS patients. The ROC analysis showed that the degree of CAS can predict impaired GRPS (AUC = 0.730) and impaired GLPS (AUC = 0.685). Conclusion Besides traditional biochemical indicators, incorporating CAS assessment and CMR assessment of the LV into routine evaluations ensures a more holistic approach to managing MetS patients. Timely intervention of CAS is crucial for improving cardiovascular outcomes in this high-risk population.

Trends in Hepatocellular Carcinoma Mortality Rates in the US and Projections Through 2040

ImportanceThe burden of liver cancer varies worldwide. An upward trend in both hepatocellular carcinoma (HCC) incidence and mortality in the past 2 decades has been observed.ObjectiveTo assess observed HCC-related age-standardized mortality rates (ASMRs) in the US for 2006 to 2022 and provide ASMR projections through 2040.Design, Setting, and ParticipantsThis cross-sectional study used data from the National Vital Statistics System, which is accessible through the Centers for Disease Control and Prevention Wide-Ranging Online Data for Epidemiologic Research website. Data on deaths attributed to HCC (from January 1, 2006, to December 31, 2022) were obtained for adults 25 years or older and were stratified by liver disease etiology, age, sex, and race and ethnicity. Etiologies included alcohol-associated liver disease (ALD), hepatitis B virus (HBV), hepatitis C virus (HCV), and metabolic dysfunction–associated steatotic liver disease (MASLD).Main Outcomes and MeasuresThe main outcomes were (1) observed ASMRs of HCC per 100 000 persons using Joinpoint regression (National Cancer Institute) to assess trends during 2006 to 2022 and (2) ASMRs projected for 2023 to 2040 using Prophet and AutoARIMA modeling.ResultsThis study included 188 280 HCC-related deaths from 2006 to 2022. Most deaths occurred among males (77.4%). The annual percentage change was 4.1% (95% CI, 2.2% to 7.7%) for 2006 to 2009 and decreased to 1.8% (95% CI, 0.7% to 2.0%) for 2009 to 2022, with an overall observed ASMR of 5.03 per 100 000 persons in 2022 and a projected ASMR of 6.39 per 100 000 persons by 2040, with consistent trends for both sexes. By etiology, ASMRs decreased for HCV- and HBV-related mortality but increased for ALD- and MASLD-related mortality. In 2022, MASLD surpassed HBV as the third-leading cause of HCC-related death and was projected to overtake HCV in 2032 as the second-leading cause; ALD was projected to be the leading cause of HCC-related death in 2026. In 2022, the ASMR was higher among individuals aged 65 years or older compared with those aged 25 to 64 years (18.37 vs 1.79 per 100 000 persons). The American Indian or Alaska Native population had the largest increase in projected ASMR by 2040 (14.71 per 100 000 persons) compared with the Asian population (3.03 per 100 000 persons).Conclusions and RelevanceIn this cross-sectional study, ASMRs for ALD- and MASLD-related HCC death increased rapidly from 2006 to 2022; ALD-related HCC was projected to be the leading cause by 2026, with MASLD as the second-leading cause by 2032. These findings may serve as a reference for public health decision-making and timely identification of groups at high risk of HCC death.

Artificial Intelligence and Image Analysis-Assisted Diagnosis for Fibrosis Stage of Metabolic Dysfunction-Associated Steatotic Liver Disease Using Ultrasonography: A Pilot Study

Purpose: Elastography increased the diagnostic accuracy of liver fibrosis. However, several challenges persist, including the widespread utilization of equipment, difficulties in measuring certain cases, and the influence of viscosity factors. A rough surface and a blunted hepatic margin have long been acknowledged as valuable characteristics indicative of hepatic fibrosis. The objective of this study was to conduct an image analysis and quantitative assessment of the contour of the sagittal section of the left lobe of the liver. Methods: Between February and October 2020, 486 consecutive outpatients underwent ultrasound examinations at our hospital. A total of 214 images were manually annotated by delineating the liver contour to create annotation images. U-Net was employed for liver segmentation, with the dataset divided into training (n = 128), testing (n = 42), and validation (n = 44) subsets. Additionally, 43 Metabolic Dysfunction Associated Steatotic Liver Disease (MASLD) cases with pathology data from between 2015 and 2020 were included. Segmentation was performed using the program developed in the first step. Subsequently, shape analysis was conducted using ImageJ. Results: Liver segmentation exhibited high accuracy, as indicated by Dice loss of 0.044, Intersection over Union of 0.935, and an F score of 0.966. The accuracy of the classification of the liver surface as smooth or rough via ResNet 50 was 84.6%. Image analysis showed MinFeret and Minor correlated with liver fibrosis stage (p = 0.046, 0.036, respectively). Sensitivity, specificity, and AUROC of Minor for ≥F3 were 0.571, 0.862, and 0.722, respectively, and F4 were 1, 0.600, and 0.825, respectively. Conclusion: Deep learning segmentation of the sagittal cross-sectional contour of the left lobe of the liver demonstrated commendable accuracy. The roughness of the liver surface was correctly judged by artificial intelligence. Image analysis showed the thickness of the left lobe inversely correlated with liver fibrosis stage.

Concentration and composition of circulating vesicles of adipocytic origin in patients with colon polyps and colorectal cancer

Extracellular vesicles (EVs) are a heterogeneous population of membrane particles less than 1 μm in size, secreted by various cell types. Most EVs circulating in human blood are particles of platelet, leukocyte, erythrocyte and endothelial origin. The composition of circulating adipocyte EVs in various pathological conditions has been virtually unknown. Small EVs from the blood plasma of patients with colorectal cancer (CRC) and colon polyps with obesity or metabolic syndrome were isolated by ultrafiltration with double ultracentrifugation. To study the composition of adipocyte EVs, immunoprecipitation in combination with Western blotting and flow cytometry were used. Vesicle fractions (FABP4- and CD11b-immunoprecipitated EVs, as well as EVs contained in the supernatant after removal of CD11b-positive EVs) contained a complex of adipocyte markers (FABP4, PPAR-γ and perilipin 1). EVs of monocyte-macrophage origin precipitated on CD11b-coated particles in CRC patients without obesity were characterized by combined overexpression of FABP4 and perilipin 1, while such overexpression was not typical for CRC patients with metabolic syndrome or obesity. The fraction of truly adipocyte vesicles (supernatant after removal of CD11b-positive EVs) was characterized by the presence in all patients of a complex of adipocyte markers with predominant expression of FABP4 in both patients with metabolic syndrome/metabolically healthy obesity and patients without metabolic disorders. To correctly characterize circulating EVs of patients without obesity, it is first necessary to remove the fraction of CD11b-positive monocyte-macrophage EVs from EV preparations by immunoprecipitation or similar methods, and in the supernatant after removal/sorption of precipitated EVs, the composition of adipocyte vesicles can be studied using a set of markers (FABP4, PPAR-γ, perilipin 1, etc.). Moreover, in patients with metabolic disorders, taking into account the insignificant expression of FABP4 in CD11b-immunoprecipitated EVs, preliminary depletion of vesicle preparations is apparently not so necessary.

Effects of multidisciplinary therapy on energy balance, inflammation, and metabolic diseases in adolescents with obesity: A narrative review.

Obesity is a consequence of multiple factors, including genetics, lifestyle and nutritional choices, physical activity, sleep duration, screen time, and mood disorders. These behavioral elements can impair the regulation of energy balance and obesity management that link obesity to a constellation of chronic conditions that lead to a high prevalence of cardiometabolic risk factors, metabolic syndrome, and nonalcoholic fatty liver disease. Multidisciplinary therapy is defined as an approach delivered by a multidisciplinary-trained health team covering at least two components of behavior, physical activity/exercise, dietary habits, and/or psychological counseling associated with clinical interventions. This narrative review summarizes the effects of multidisciplinary therapy on neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, metabolic syndrome, nonalcoholic fatty liver diseases, behavior, and quality of life. We found that multidisciplinary therapy, including medical, nutritional, exercise, and behavioral counseling, and/or education, was useful for addressing outcomes such as visceral adiposity, neuroendocrine regulation of energy balance, inflammatory biomarkers, cardiometabolic risk factors, nonalcoholic fatty liver disease, and metabolic syndrome. The effects were mediated by improvements in neuroendocrine regulation of energy balance, downregulation of the pro-inflammatory states, and a reduction in comorbidities. Multidisciplinary therapy also improved mood disorders and quality of life.

Psychoneuroimmunology of Mood Disorders.

Recent research has shed light on the intricate relationship between mood disorders, such as major depressive disorder (MDD) and bipolar disorder (BD), and inflammation. This chapter explores the complex interplay involving immune and metabolic dysfunction in the pathophysiology of these disorders, emphasizing their association with autoimmunity/inflammatory conditions, chronic low-grade systemic inflammation, T cell overactivation, and immunosenescence. This perspective underscores the notion that MDD and BD are not solely brain disorders, highlighting their nature as multi-system conditions.

The dietary phytochemical index and its relation to polycystic ovary syndrome: a case-control study.

Polycystic ovary syndrome (PCOS), a hormonal disorder affecting women of reproductive age, can be significantly impacted by diet. This study explores the relationship between a diet rich in phytochemicals, measured by the Dietary Phytochemical Index (DPI), and PCOS, along with associated health markers. A case-control study design was implemented with 480 individuals diagnosed with PCOS based on the Rotterdam criteria, paired with 480 controls matched in terms of age and BMI. The evaluation encompassed dietary intake, anthropometric measurements, and hormonal/metabolic markers. Additionally, the DPI score was determined based on the consumption of phytochemical-rich foods. The study also examined PCOS-related complications like acne and irregular menstrual cycles, as well as mental health using the Beck Depression Inventory (BDI-II) scores. Women with PCOS had significantly lower DPI scores (32.42 vs 43.87, p < 0.001) compared to the control group, indicating a less phytochemical-rich diet. The DPI scores coincided with higher levels of hormones typically associated with PCOS, including Luteinizing Hormone (LH), Dehydroepiandrosterone Sulfate (DHEA-S), and testosterone. Additionally, these scores were associated with markers of metabolic dysfunction such as C-reactive Protein (CRP), Fasting Blood Sugar (FBS), and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), while positively correlating with Sex Hormone-Binding Globulin (SHBG) (all p < 0.050).). Higher DPI scores were associated with a significantly reduced risk of PCOS (OR: 0.13, 95% CI: 0.08, 0.23, P for trend: 0.001) and its complications, including acne and irregular menstrual cycles. Interestingly, a positive association emerged, suggesting better mental health (lower BDI-II scores) with higher DPI scores. In conclusion, this study indicates that lower DPI scores are associated with a higher incidence and severity of PCOS, suggesting that a phytochemical-rich diet could potentially benefit the management of PCOS by enhancing hormonal profiles, metabolic health, and mental well-being in women.

Role of metabolic syndrome and lifestyle factors in endometrial cancer risk and prevention

Introduction: The incidence of endometrial cancer, the sixth most common cancer among women, has been rising, especially in developed countries, possibly due to the obesity and diabetes pandemic. The aim of this review is to investigate the connection between metabolic syndrome, its individual components and endometrial cancer risk and to explore the role of lifestyle factors in endometrial cancer prevention. Materials and methods: For this review, we included studies regarding endometrial cancer and metabolic syndrome, obesity, diabetes and hyperglycemia, hypertension, dyslipidemia and several lifestyle factors, from 1994 to 2024. State of knowledge: This paper reviews existing literature on the relationship between metabolic syndrome and endometrial cancer, highlighting the significant role of central obesity, hyperglycemia and diabetes, dyslipidemia, and hypertension as risk factors. Evidence consistently demonstrates that individuals with metabolic syndrome, and its components individually, are at a heightened risk of developing endometrial cancer compared to those without metabolic abnormalities. Biological mechanisms linking metabolic syndrome’s components to endometrial cancer involve complex interplays between metabolic, hormonal or inflammatory factors and signalling pathways. Lifestyle interventions focusing on weight management, physical activity, and eating habits play an important role in reducing endometrial cancer risk and improving overall health outcomes. Conclusion: An understanding of the relationship between metabolic syndrome and endometrial cancer is crucial for improving risk stratification, early detection, and prevention strategies. Addressing metabolic abnormalities and promoting healthy lifestyle behaviours are essential actions against the rising incidence and burden of endometrial cancer.

Insulin resistance has closer correlation with the occurrence of metabolic dysfunction associated steatotic liver disease diagnosed by liver biopsy

ObjectiveTo explore any correlation between serum urate (SU) level or insulin resistance (IR) and metabolic dysfunction associated steatotic liver disease (MASLD) in patients with metabolic syndrome (MS).MethodsData from all MASLD patients, diagnosed by liver biopsy, were enrolled and divided into MASLD alone group and MASLD with MS group. They were subdivided into hyperuricemia group and normal SU group to find correlation between SU/IR and MASLD in patients with MS and independent risk factors for MASLD.ResultsData from 539 MASLD patients were analyzed. Body mass index (BMI) (p = 0.000), waist circumference (WC) (p = 0.004), and low-density lipoprotein (LDL) (p = 0.000) were dramatically higher in MASLD with MS group than those with MASLD alone; MASLD with MS patients had significantly more family history of diabetes (p = 0.000) and hypertension (p = 0.000) than patients with MASLD alone. Height (p = 0.000), weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.001), and LDL (p = 0.007) were dramatically higher in hyperuricemia patients than those with normal SU. SU was inversely associated with age (p = 0.000) and high-density lipoprotein (HDL) (p = 0.003), and positively correlated with weight (p = 0.000), BMI (p = 0.000) and WC (p = 0.000), TG (p = 0.000), and LDL (p = 0.000). Logistic Regression analysis showed that age (p = 0.031), TG (p = 0.002), LDL (p = 0.010), HbA1c (p = 0.026), and family history of hypertension (p = 0.000) may be independent risk factors for MASLD in patient with MS.ConclusionInsulin resistance (IR) in MASLD patients with MS, but not higher SU levels, has closer correlation with the occurrence of MASLD in patients with family history of hypertension and diabetes having higher BMI, LDL, HbA1c.

Serum urea concentration and risk of 16 site-specific cancers, overall cancer, and cancer mortality in individuals with metabolic syndrome: a cohort study.

The relationship between serum urea concentration and cancer in patients with metabolic syndrome (MetS) remains unclear. This study aimed to investigate the association between serum urea concentration and 16 site-specific cancers, overall cancer incidence, and cancer mortality in individuals with MetS. We analysed the data of 108,284 individuals with MetS obtained from the UK Biobank. The Cox proportional hazards model was used to determine the association between serum urea concentration at recruitment and cancer. The Benjamini-Hochberg correction was used to account for multiple comparisons. Over the median follow-up period of 11.86years, 18,548 new incident cases of cancer were documented. There were inverse associations of urea concentration with overall cancer incidence, and the incidence of oesophageal and lung cancers, with respective hazard ratios (95% confidence intervals) [HR (95% CI)] for the highest (Q4) vs lowest (Q1) urea quartiles of 0.95 (0.91-0.99), 0.68 (0.50-0.92), and 0.76 (0.64-0.90). However, high serum urea concentrations increased the male prostate cancer risk (HR 1.15; 95% CI 1.02-1.30). Although the Cox model indicated a protective effect of higher urea levels against stomach (HR 0.67; 95% CI 0.45-0.98; p = 0.040; FDR 0.120) and colorectal cancer (HR 0.86; 95% CI 0.74-0.99; p = 0.048; FDR 0.123), no strong evidence of association was found after applying the Benjamin-Hochberg correction. Moreover, across the median follow-up period of 13.77years for cancer mortality outcome, 5034 cancer deaths were detected. An "L-shaped" nonlinear dose-response relationship between urea concentration and cancer mortality was discovered (p-nonlinear < 0.001), and the HR (95% CI) for urea concentration Q4 vs Q1 was 0.83 (0.77-0.91). Serum urea concentration can be considered as a valuable biomarker for evaluating cancer risk in individuals with MetS, potentially contributing to personalised cancer screening and management strategies.

Skin as a mirror of metabolic syndrome: Do some dermatoses alarm internal metabolic sinister?

Metabolic syndrome is a group of abnormalities in metabolism including hypertension, central obesity, insulin resistance and dyslipidaemia. Etiopathogenesis is multifactorial including genetic and environmental factors. It is more prevalent in recent decade due to sedentary lifestyle with unhygienic food habits and cause increased prevalence in younger age group. This abnormal metabolism leads to oxidative stress in body involving multiple inflammatory pathways. There are so many dermatoses which are associated with metabolic syndrome due to common factors are involved in etiopathogenesis. These includes psoriasis, acne vulgaris, acanthosis nigricans, hidradenitis suppurativa, atopic dermatitis, androgenetic alopecia, lichen planus. There is increased risk of developing diabetes mellitus and damage to cardiovascular system. Early diagnosis and management are required to reduce risk of complications. These includes active lifestyle, dietary changes and medications.

Obesity, Metabolic Syndrome, and Obesity Paradox in Heart Failure: A Critical Evaluation.

Since the turn of the millennium, obesity has been on the rise worldwide, and particularly so throughout the United States. Even more concerning is the rate at which persons with severe obesity continue to trend upwards. Given the detrimental effects of obesity on cardiac structure and function, it is not surprising that obesity stands as one of the leading risk factors for developing heart failure (HF). This state-of-the-art article aims to review the updated literature on the obesity paradox to help further understand its relationship to body composition, weight loss, fitness, and exercise. An intriguing phenomenon appears to exist in which obesity is associated with a better prognosis in those with HF, compared to patients with lesser body mass. Recent studies suggest, however, that weight loss induced by pharmacologic strategies might be beneficial in patients with HF with preserved ejection fraction. Despite the presence of an obesity paradox, recent data suggest that obesity could be targeted in HF, however, long-term data are currently lacking. Consequently, definitive guidelines for managing obesity, and specifically the body composition of these patients, remain amiss.

Developmental Origins of Non-Communicable Chronic Diseases: Role of Fetal Undernutrition and Gut Dysbiosis in Infancy

There is an increasing prevalence of non-communicable chronic diseases (NCCDs) like obesity, metabolic syndrome, type 2 diabetes mellitus (T2DM), hypertension, allergic asthma, and neuro-developmental/psychiatric problems in many parts of the world. A suboptimal lifestyle as an adult is often blamed for the occurrence of NCCDs. This review discusses the developmental origin of health and disease theory and how suboptimal nutrition in intrauterine life and the establishment of a suboptimal gut microbiome during infancy can influence the predisposition to NCCDs.

Understanding the Role of Alcohol in Metabolic Dysfunction and Male Infertility

Purpose: Over the past 40–50 years, demographic shifts and the obesity epidemic have coincided with significant changes in lifestyle habits, including a rise in excessive alcohol consumption. This increase in alcohol intake is a major public health concern due to its far-reaching effects on human health, particularly on metabolic processes and male reproductive function. This narrative review focuses on the role of alcohol consumption in altering metabolism and impairing testicular function, emphasizing the potential damage associated with both acute and chronic alcohol intake. Conclusion: Chronic alcohol consumption has been shown to disrupt liver function, impair lipid metabolism, and dysregulate blood glucose levels, contributing to the development of obesity, metabolic syndrome, and related systemic diseases. In terms of male reproductive health, alcohol can significantly affect testicular function by lowering testosterone levels, reducing sperm quality, and impairing overall fertility. The extent of these effects varies, depending on the frequency, duration, and intensity of alcohol use, with chronic and abusive consumption posing greater risks. The complexity of alcohol’s impact is further compounded by individual variability and the interaction with other lifestyle factors such as diet, stress, and physical activity. Despite growing concern, research on alcohol’s effects remains inconclusive, with significant discrepancies across studies regarding the definition and reporting of alcohol consumption. These inconsistencies highlight the need for more rigorous, methodologically sound research to better understand how alcohol consumption influences metabolic and reproductive health. Ultimately, a clearer understanding is essential for developing targeted public health interventions, particularly in light of rising alcohol use, demographic changes, and the ongoing obesity crisis.

SGLT2 inhibition improves coronary flow velocity reserve and contractility: role of glucagon signaling.

SGLT2 inhibitors, a T2DM medication to lower blood glucose, markedly improve cardiovascular outcomes but the underlying mechanism(s) are not fully understood. SGLT2i's produce a unique metabolic pattern by lowering blood glucose without increasing insulin while increasing ketone body and glucagon levels and reducing body weight. We tested if glucagon signaling contributes to SGLT2i induced improvement in CV function. Cardiac contractility and coronary flow velocity reserve (CFVR) were monitored in ob/ob mice and rhesus monkeys with metabolic syndrome using echocardiography. Metabolic status was characterized by measuring blood ketone levels, glucose tolerance during glucose challenge and Arg and ADMA levels were measured. Baysian models were developed to analyse the data. Dapagliflozin improved CFVR and contractility, co-application of a glucagon receptor inhibitor (GcgRi) blunted the effect on CFVR but not contractility. Dapagliflozin increased the Arg/ADMA ratio and ketone levels and co-treatment with GcgRi blunted only the Dapagliflozin induced increase in Arg/ADMA ratio but not ketone levels. Since GcgRi co-treatment only reduced the Arg/ADMA increase we hypothesize that dapagliflozin via a glucagon-signaling dependent pathway improves vascular function through the NO-signaling pathway leading to improved vascular function. Increase in ketone levels might be a contributing factor in SGLT2i induced contractility increase and does not require glucagon signaling.