Zebrafish (Danio rerio) have become indispensable models for advancing our understanding of multiple metabolic disorders such as obesity, diabetes mellitus, dyslipidemia, and metabolic syndrome. This review provides a comprehensive analysis of zebrafish as a powerful tool for dissecting the genetic and molecular mechanisms of these diseases, focusing on key genes, like pparγ, lepr, ins, and srebp. Zebrafish offer distinct advantages, including genetic tractability, optical transparency in early development, and the conservation of key metabolic pathways with humans. Studies have successfully used zebrafish to uncover conserved metabolic mechanisms, identify novel disease pathways, and facilitate high-throughput screening of potential therapeutic compounds. The review also highlights the novelty of using zebrafish to model multifactorial metabolic disorders, addressing challenges such as interspecies differences in metabolism and the complexity of human metabolic disease etiology. Moving forward, future research will benefit from integrating advanced omics technologies to map disease-specific molecular signatures, applying personalized medicine approaches to optimize treatments, and utilizing computational models to predict therapeutic outcomes. By embracing these innovative strategies, zebrafish research has the potential to revolutionize the diagnosis, treatment, and prevention of metabolic disorders, offering new avenues for translational applications. Continued interdisciplinary collaboration and investment in zebrafish-based studies will be crucial to fully harnessing their potential for advancing therapeutic development.

This study investigates the associations between modified triglyceride-glucose (TyG) indices and the triglyceride-to-high-density lipoprotein (TG/HDL) ratio, which are recognized as simple surrogate indicators of insulin resistance, with all-cause and cause-specific mortality.

A cohort of 410,515 participants from the UK Biobank was analyzed. Cox proportional hazard models and restricted cubic spline regression analyses were employed to examine the relationships between the TyG index, TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), TG/HDL ratio, and all-cause and cause-specific mortality. Structural equation modeling was employed to elucidate the associations between the TyG index, TG/HDL ratio, inflammation, metabolism, and mortality.

The TyG index, TyG-WC, and TG/HDL ratio were associated with an increased risk of all-cause mortality by 3.7% (HR 1.037 [1.016, 1.059]), 0.1% (HR 1.001 [1.024, 1.031]), and 1.5% (HR 1.015 [1.006, 1.025]), respectively. Restricted cubic spline regression models revealed nonlinear trends in the TyG index, TyG-BMI, TyG-WC, and TG/HDL ratio in relation to both all-cause and cause-specific mortality (P for nonlinearity < 0.05). TyG index and TG/HDL ratio exhibited a J-shaped relationship with all-cause mortality as well as mortality from cancer, cardiovascular diseases, and respiratory diseases. Similarly, TyG-BMI demonstrated an L-shaped association with all-cause mortality and mortality due to cancer, cardiovascular diseases, and respiratory diseases. Additionally, TyG-WC was associated with a progressively increasing mortality risk once it exceeded a certain threshold. Structural equation modeling demonstrated that the TyG index and TG/HDL ratio influenced mortality through inflammation and lifestyle factors.

In conclusion, TyG, TyG-BMI, TyG-WC, and TG/HDL ratio are significantly associated with all-cause and cause-specific mortality in the general population.These associations appear to be linked to inflammation and lifestyle.

Estimated glucose disposal rate (eGDR) is a novel insulin resistance (IR) assessment surrogate. Although it has shown promising potential in other metabolic disease studies, no research has yet explored its relationship with osteoarthritis (OA). Therefore, this study aims to investigate the association between eGDR and OA in a cross-sectional observational cohort.

Data utilized in this cross-sectional study were drawn from the National Health and Nutrition Examination Survey (NHANES). Logistic regression models were used to evaluate the association between eGDR and OA, stratified analysis was applied to assess the stability of the results.

A total of 19,040 participants were included in the study, including 2,001 OA patients and 17,039 non-OA participants with an age distribution ranging from 20 to 85 years. The fully adjusted logistic regression model shows that eGDR were less likely associated with OA compared to those with non-OA (OR = 0.879, 95% CI = 0.846-0.914, P < 0.001). By dispersing the eGDR into quartiles, the correlation between eGDR and OA remained significant (P for trend < 0.0001).

This study suggests that eGDR is independently associated with OA, with lower eGDR values being linked to a higher risk of OA.

Not applicable.

Transcatheter aortic valve implantation (TAVI) has emerged as an effective treatment option for patients with severe aortic stenosis, particularly in those who are not suitable candidates for open-heart surgery. While diabetes is known to be associated with a higher risk of cardiovascular diseases, the impact of diabetes on the outcomes of TAVI remains controversial.

A systematic literature search was conducted across major databases, including PubMed, Web of Science (WOS), and Google Scholar, for studies published in English over the past 20 years, up until July 2024.

A total of 10 observational studies were analyzed, revealing that diabetic patients were generally younger than non-diabetic patients. The 30-day mortality rate was lower in non-diabetics (0.03 [0.02-0.04]) compared to diabetics (0.04 [0.03-0.05]). However, the hazard ratio for death beyond 30 days in diabetics was 2.05 (95% CI: 0.91-4.60, p = 0.08), and at one year, it was 1.04 (95% CI: 0.78-1.39, p = 0.77), with neither result reaching statistical significance. Meta-regression analysis showed that non-insulin-treated diabetes was significantly associated with an increased risk of acute kidney injury (AKI) compared to non-diabetics, with a log odds ratio (LogOR) of 0.3393 (p = 0.035) in one analysis and 0.3166 (p = 0.028) in another, confirming a statistically significant increase in AKI risk.

This review highlights that while diabetes slightly increases short-term mortality after TAVI, long-term survival remains comparable to non-diabetic patients. However, non-insulin-treated diabetes significantly raises the risk of acute kidney injury (AKI), emphasizing the need for enhanced renal protection and perioperative management.

Not applicable.

Insulin resistance (IR) is a significant factor in the development and progression of metabolic-related diseases like dyslipidemia, T2DM, hypertension, nonalcoholic fatty liver disease, cardiovascular and cerebrovascular disorders, and cancer. The pathogenesis of IR depends on multiple factors, including age, genetic predisposition, obesity, oxidative stress, among others. Abnormalities in the insulin-signaling cascade lead to IR in the host, including insulin receptor abnormalities, internal environment disturbances, and metabolic alterations in the muscle, liver, and cellular organelles. The complex and multifaceted characteristics of insulin signaling and insulin resistance envisage their thorough and comprehensive understanding at the cellular and molecular level. Therapeutic strategies for IR include exercise, dietary interventions, and pharmacotherapy. However, there are still gaps to be addressed, and more precise biomarkers for associated chronic diseases and lifestyle interventions are needed. Understanding these pathways is essential for developing effective treatments for IR, reducing healthcare costs, and improving quality of patient life.

To determine the prevalence of fatty pancreas disease (FPD) diagnosed by transabdominal ultrasound in Chinese elderly aged 65 years and above to explore the correlation between triglyceride glucose index (TyG index) and FPD and its severity, and to evaluate the ability of TyG index to identify FPD and its severity.

The study population was derived from the Thyroid Diseases in Older Population: Screening, Surveillance, and Intervention (TOPS) study conducted in the iodine-adapted areas of Jiangsu Province from May to July 2021. A total of 567 participants aged 65 years and above in rural areas were included in the final analysis. TyG index was calculated by the established formula: Ln [TG (mg/dL) × FBG (mg/dL)/2]. FPD and the degree of intra-pancreatic fat deposition (IPFD) were diagnosed by abdominal ultrasound. The logistic regression model was performed to determine the correlation between clinical parameters, including TyG index, and FPD and its severity. The diagnostic power of TyG index was assessed by receiver operating characteristic curve (ROC).

Overall, 72.66% (412/567) of subjects had FPD, of which over half had moderate to severe FPD. The proportions of overweight, obesity, NAFLD, and dyslipidemia were significantly higher in the moderate-to-severe FPD group than in the mild FPD group. Multivariate logistic regression showed that TyG index was independently associated with FPD in the elderly population, but was not significantly associated with the severity of IPFD. As the level of TyG index increased, the metabolic disorders in the population worsened and the prevalence of FPD increased significantly. TyG index had a good diagnostic performance for FPD. The combination of BMI or NAFLD and TyG index improved the diagnostic ability for FPD.

The prevalence of FPD diagnosed by abdominal ultrasound is high in the elderly aged 65 years and above in rural areas in China. TyG index has good identification of FPD but poor recognition of the severity of IPFD. TyG index, when combined with other clinical parameters, may have more diagnostic advantages.

To explore the relationship between constant exposure to phthalates (PAEs) and overweight/obesity and the role of lifestyle in children.

This study conducted five repeated follow-up visits with 829 children and analysed data from 740 children. Logistic regression models were used to evaluate the association between constant PAE exposure, lifestyle and overweight/obesity.

The study found that constant high levels of PAEs exposure may increase the risk of obesity in girls, and the risk is higher in girls with an unhealthy lifestyle. In the unhealthy lifestyle group of girls, compared with the constant low (CL) exposure group of PAEs, the odds ratios (ORs) for overweight/obesity and obesity in the constant high (CH) exposure group were 2.99 (1.11, 8.05) and 11.58 (1.38, 96.87), respectively. In addition, an interaction effect between constant exposure to PAEs and lifestyle was observed on obesity in girls.

These results suggest the importance of reducing constant exposure to high levels of PAEs to reduce the risk of obesity, especially in individuals with unhealthy lifestyles. The government should strengthen the formulation of regulations and standards for PAEs while guiding parents to use fewer plastic products.

The association between insulin resistance (IR), type 2 diabetes mellitus (T2DM), and cancer is increasingly recognized and poses an escalating global health challenge, as the incidence of these conditions continues to rise. Studies indicate that individuals with T2DM have a 10-20% increased risk of developing various solid tumors, including colorectal, breast, pancreatic, and liver cancers. The relative risk (RR) varies depending on cancer type, with pancreatic and liver cancers showing a particularly strong association (RR 2.0-2.5), while colorectal and breast cancers demonstrate a moderate increase (RR 1.2-1.5). Understanding these epidemiological trends is crucial for developing integrated management strategies. Given the global rise in T2DM and cancer cases, exploring the complex relationship between these conditions is critical. IR contributes to hyperglycemia, chronic inflammation, and altered lipid metabolism. Together, these factors create a pro-tumorigenic environment conducive to cancer development and progression. In individuals with IR, hyperinsulinemia triggers the insulin-insulin-like growth factor (IGF1R) signaling pathway, activating cancer-associated pathways such as mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PIK3CA), which promote cell proliferation and survival, thereby supporting tumor growth. Both IR and T2DM are linked to increased morbidity and mortality in patients with cancer. By providing an in-depth analysis of the molecular links between insulin resistance and cancer, this review offers valuable insights into the role of metabolic dysfunction in tumor progression. Addressing insulin resistance as a co-morbidity may open new avenues for risk assessment, early intervention, and the development of integrated treatment strategies to improve patient outcomes.

Type 2 diabetes mellitus (T2DM) is characterized by hyperglycemia and affects millions of people globally. Even after advancement and development in medical science, it is a big task to achieve victory over type 2 diabetes mellitus (T2DM). T2DM can be a reason for fatal events like stroke, cardiac failure, nephropathy, and retinopathy. Many advanced antidiabetic drugs have been introduced in the market in the past two decades, leading researchers to hunt for new target proteins and their potential modulators that can help develop newer antidiabetic drugs. This review article comprises a broad literature of the latest developments in the management of T2DM concerning new target proteins, their inhibitors, or drugs from the clinical arena employed for the successful management of symptoms of T2DM using mono, dual, or triple combination medication therapy. The review categorizes antidiabetic drugs into three general classes that include conventional drug targets, currently explored targets, and upcoming emerging targets. The review aims to merge information on the medicines affecting these targets, their mechanisms, followed by the chemical structures, and recent advancements.

Metabolic dysfunction-associated steatotic liver disease (MASLD) is an emerging global health concern with limited therapeutic options. Multivitamins, widely consumed dietary supplements, have been proposed to modulate oxidative stress and inflammation, potentially impacting MASLD progression. However, their efficacy in reducing mortality and other complications in MASLD remains unclear. Using data from the UK Biobank with 7 years of median follow-up period, this study assessed the association between multivitamin use and health outcomes, including all-cause mortality, liver-related mortality, cardio-cerebrovascular disease (CVD), and chronic kidney disease (CKD), in individuals with MASLD and those without steatotic liver disease. Inverse probability of treatment weighting (IPTW) was employed to adjust for confounders. Multivitamin users showed a significantly lower all-cause mortality risk in the MASLD cohort both before (HR: 0.88, 95% CI 0.81-0.95, P = 0.034) and after (HR: 0.94, 95% CI 0.88-1.00, P = 0.037) IPTW adjustment. Multivitamin use was also associated with the lower risk of CVD (HR: 0.72, 95% CI 0.68-0.76, P < 0.001) and CKD (HR: 0.73, 95% CI 0.67-0.81, P < 0.001) in the MASLD cohort. No significant reduction was found for liver-related mortality or liver cirrhosis incidence. These findings suggest that multivitamins might provide broader protective effects in populations with metabolic dysfunction. Further research is needed to clarify their role in liver-specific outcomes.

The development of insulin resistance (IR) is characterized by a series of metabolic disturbances, including, but not limited to, impaired glucose uptake, increased blood sugar levels, and disrupted lipid metabolism [...].

The increasing prevalence of overweight and obesity not only in adults but also among children and adolescents has become one of the most alarming health problems worldwide. Metabolic disorders accompanying fat accumulation during pathological weight gain induce chronic low-grade inflammation, which, in a vicious cycle, increases the immune response through pro-inflammatory changes in the cytokine (adipokine) profile. Obesity decreases life expectancy, largely because obese individuals are at an increased risk of many medical complications, often referred to as metabolic syndrome, which refers to the co-occurrence of insulin resistance (IR), impaired glucose tolerance, type 2 diabetes (T2D), atherogenic dyslipidemia, hypertension, and premature ischemic heart disease. Metabotropic G protein-coupled receptors (GPCRs) constitute the most numerous and diverse group of cell surface transmembrane receptors in eukaryotes. Among the GPCRs, researchers are focusing on the connection of G protein-coupled receptor 120 (GPR120), also known as free fatty acid receptor 4 (FFAR4), with signaling pathways regulating the inflammatory response and insulin sensitivity. This review presents the current state of knowledge concerning the involvement of GPR120 in anti-inflammatory and metabolic signaling. Since both inflammation in adipose tissue and insulin resistance are key problems in obesity, there is a rationale for the development of novel, GPR120-based therapies for overweight and obese individuals. The main problems associated with introducing this type of treatment into clinical practice are also discussed.

Chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2DM) are highly prevalent chronic conditions, frequently coexisting due to their shared pathophysiological mechanisms and risk factors. Epidemiological studies estimate that up to 30% of COPD patients have comorbid T2DM, contributing to worsened disease progression, more hospitalizations, and higher mortality rates. Systemic inflammation in COPD contributes to insulin resistance by increasing pro-inflammatory cytokines (TNF-α, IL-6, and CRP), which impair glucose metabolism and beta-cell function. Conversely, hyperglycemia in T2DM exacerbates oxidative stress, leading to endothelial dysfunction, reduced lung function, and impaired pulmonary repair mechanisms. A comprehensive narrative review was conducted to evaluate the interplay between COPD and T2DM, examining shared pathophysiological mechanisms, clinical consequences, and management strategies. The co-occurrence of COPD and T2DM accelerates disease development, elevates hospitalization rates, and deteriorates overall prognosis. Pharmacological interactions complicate illness treatment, requiring a multidisciplinary therapy strategy. Recent data underscore the need to integrate palliative care, facilitate shared decision-making, and provide psychological support to enhance patient outcomes. Efficient therapy of COPD-T2DM comorbidity necessitates a customized, interdisciplinary strategy that targets both respiratory and metabolic health. Preliminary prognostic dialogues, palliative care, and holistic lifestyle modifications can improve patient quality of life and clinical results.

Obesity prevalence has steadily increased over the past decades. Standard approaches, such as increased energy expenditure, lifestyle changes, a balanced diet, and the use of specific drugs, are the conventional strategies for preventing or treating the disease and its associated complications. Fermented foods and their subsequent bioactive constituents are now believed to be a novel strategy that can complement already existing approaches for managing and preventing this disease. Recent developments in systems biology and bioinformatics have made it possible to model and simulate compounds and disease interactions. The adoption of such in silico models has contributed to the discovery of novel fermented product targets and helped in testing hypotheses regarding the mechanistic impact and underlying functions of fermented food components. From the studies explored, key findings suggest that fermented foods affect adipogenesis, lipid metabolism, appetite regulation, gut microbiota composition, insulin resistance, and inflammation related to obesity, which could lead to new ways to treat these conditions. These outcomes were linked to probiotics, prebiotics, metabolites, and complex bioactive substances produced during fermentation. Overall, fermented foods and their bioactive compounds show promise as innovative tools for obesity management by influencing metabolic pathways and overall gut health.

Triglyceride glucose index (TyG) serves as an effective parameter for assessing metabolic status. However, it remains uncertain whether TyG and other metabolic parameters can predict clinical outcomes in people with metabolic syndrome (MetS). We investigated the association of TyG, triglyceride glucose-waist to height ratio (TyG-WHtR), and metabolic score for insulin resistance (METS-IR) with all-cause and cardiovascular mortality in the MetS cohort and determined whether this association changes with age.

Participants enrolled in the National Health and Nutrition Examination Survey (NHANES) between 2001 and 2018 were selected and categorized into two groups: younger individuals (age < 65 years) and older individuals (age ≥ 65 years). Three new metabolic indices of TyG, TyG-WHtR, and METS-IR were constructed. The weighted Cox proportional hazards model and restricted cubic spline (RCS) models were employed to evaluate the relation between three indices and mortality outcomes. The time-dependent receiver operating characteristic (ROC) curve assessed the ability of different indices to predict mortality. Sensitivity analysis was conducted to evaluate the robustness and reliability of the findings.

The study comprised a total of 8271 participants, including 5456 younger participants and 2815 older participants, and 1407 deaths were observed over a median follow-up period of 8.3 years. Compared with the first quartile (Q1), the fourth quartile's (Q4) TyG, TyG-WHtR, and METS-IR were linked to an increased risk of all-cause mortality (HR 1.63, 95% CI 1.12-2.39; HR 2.78, 95% CI 1.68-4.61; HR 1.36, 95% CI 1.12-2.02, respectively) and cardiovascular mortality (HR 2.04, 95% CI 1.15-4.90; HR 4.99, 95% CI 1.76-14.11; HR 2.69, 95% CI 1.89-8.15, respectively) in the younger group but not in the older group. The RCS results showed no significant non-linear associations between TyG, TyG-WHtR, METS-IR, and all-cause (P = 0.082; P = 0.712; P = 0.062, respectively) or cardiovascular mortality (P = 0.176; P = 0.793; P = 0.482, respectively) in the older age group. TyG-WHtR demonstrated the highest area under the curve for predicting 3-year mortality in the younger age group, with values of 0.653 for all-cause mortality and 0.688 for cardiovascular mortality.

Our results highlight the predictive value of TyG, TyG-WHtR, and METS-IR in the MetS population, providing new evidence for medical practice and public health.

Cognitive impairments are common clinical manifestation of Alzheimer's disease, vascular dementia, type 2 diabetes mellitus, and autoimmune diseases. Emerging evidence has suggested a strong correlation between peripheral chronic inflammation and cognitive impairments. For example, nearly 40% of individuals with inflammatory bowel disease also suffer from cognitive impairments. In this condition, NLRP3 inflammasome (NLRP3-I) generating pro-inflammatory cytokines like IL-1β serves as a significant effector, and its persistence exerts adverse effects to both periphery and the brain. Moreover, investigations on serum biomarkers of mild cognitive impairments have shown NLRP3-I components' upregulation, suggesting the involvement of peripheral inflammasome pathway in this disorder. Here, we systematically reviewed the current knowledge of NLRP3-I in inflammatory disease to uncover its potential role in bridging peripheral chronic inflammation and cognitive impairments. This review summarizes the molecular features and ignition process of NLRP3-I in inflammatory response. Meanwhile, various effects of NLRP3-I involved in peripheral inflammation-associated disease are also reviewed, especially its chronic disturbances to brain homeostasis and cognitive function through routes including gut-brain, liver-brain, and kidney-brain axes. In addition, current promising compounds and their targets relative to NLRP3-I are discussed in the context of cognitive impairments. Through the detailed investigation, this review highlights the critical role of peripheral NLRP3-I in the pathogenesis of cognitive disorders, and offers novel perspectives for developing effective therapeutic interventions for diseases associated with cognitive impairments. The present review outlines the current knowledge on the ignition of NLRP3-I in inflammatory disease and more importantly, emphasizes the role of peripheral NLRP3-I as a causal pathway in the development of cognitive disorders. Although major efforts to restrain cognitive decline are mainly focused on the central nervous system, it has become clear that disturbances from peripheral immune are closely associated with the dysfunctional brain. Therefore, attenuation of these inflammatory changes through inhibiting the NLRP3-I pathway in early inflammatory disease may reduce future risk of cognitive impairments, and in the meantime, considerations on such pathogenesis for combined drug therapy will be required in the clinical evaluation of cognitive disorders.

Triglyceride glucose (TyG) index and atherogenic index of plasma (AIP) are indicators of insulin resistance. However, inadequate evidence indicates that the TyG index, AIP, and chronic pain are linked.

Data from the National Health and Nutrition Examination Survey (NHANES) between 1999 and 2004 were used. Directed acyclic graphs were used to identify 11 potential confounders. The TyG index and AIP were treated as continuous variables in the multivariate logistic regression models to assess their association with chronic pain. Furthermore, the nonlinear relationships between these indices and outcomes were investigated using restricted cubic spline plots. Subsequently, subgroup analyses were conducted for the sensitive populations. Receiver operating characteristic curves were used to compare the relationships between indices and outcomes. Ultimately, two sensitivity analyses were performed.

This study identified nonlinear associations between the TyG index, AIP, and chronic pain in 16,996,513 Americans. The odds ratio and 95% confidence interval for the TyG index (per 1 standard deviation increase) was 1.17 (1.02, 1.33), and for AIP (per 1 standard deviation increase) was 1.19 (1.07, 1.34). According to the subgroup analyses, the relationships between exposure and outcome were more pronounced in the non-diabetic population. The TyG index and AIP performed similarly in assessing chronic pain in ROC curves. Additionally, the results of the two sensitivity analyses matched the conclusions of the main study.

Nonlinear correlations between the TyG index, AIP, and chronic pain were identified among adults in the United States. This demonstrated that the TyG index and AIP displayed similar effectiveness in predicting the risk of chronic pain.

The study aimed to investigate the relationship between the frequency of metabolic diseases (MetD) and dietary behaviors as well as health risk behaviors in various age groups.

This Cross-Sectional study involved 12,215 participants, and the relationship between MetD and health risk behaviors was discussed using Pearson chi-square tests and unordered binary logistics regression. The Apriori algorithm was used to explore and analyze the combination patterns of health risk behaviors.

Insufficient sleep as a risk factor for MetD (for young adults, odds ratio (OR): 1.31, 95% confidence interval (CI): 1.15, 1.50; for middle-aged adults, OR: 1.15, 95% CI: 1.01, 1.33). For young adults, maladaptive emotion was a risk factor (OR: 1.45; 95% CI: 1.18, 1.80), and their risk of MetD was 1.48 times higher with three health risk behaviors compared with those with no or only one health risk behavior (95% CI: 1.27, 1.72). As for dietary behaviors, meat-based diet, greasy and salty taste preferences were associated with MetD.

High-risk alcohol consumption is a risk factor for MetD in elderly adults. Insufficient sleep was a common risk factor for MetD in young and middle-aged groups. Young adults may also be affected by maladaptive emotion and the number of risk factors. Poor dietary behaviors such as meat-based diet, greasy and salty dietary taste, may increase risk, particularly among young adults. We should consider interventions systematically and comprehensively targeting modern lifestyles of different key age group populations such as young adults.

Abnormal glucose metabolism inevitably disrupts normal neuronal function, a phenomenon widely observed in Alzheimer's disease (AD). Investigating the mechanisms of metabolic adaptation during disease progression has become a central focus of research. Considering that impaired glucose metabolism is closely related to decreased insulin signaling and insulin resistance, a new concept "type 3 diabetes mellitus (T3DM)" has been coined. T3DM specifically refers to the brain's neurons becoming unresponsive to insulin, underscoring the strong link between diabetes and AD. Recent studies reveal that during brain insulin resistance, neurons exhibit mitochondrial dysfunction, reduced glucose metabolism, and elevated lactate levels. These findings suggest that impaired insulin signaling caused by T3DM may lead to a compensatory metabolic shift in neurons toward glycolysis. Consequently, this review aims to explore the underlying causes of T3DM and elucidate how insulin resistance drives metabolic reprogramming in neurons during AD progression. Additionally, it highlights therapeutic strategies targeting insulin sensitivity and mitochondrial function as promising avenues for the successful development of AD treatments.

The Systemic Immune-Inflammation Index (SII) is a novel biomarker of systemic inflammation. We explored the association between the SII and metabolic syndrome (MetS) and its components in middle-aged and older adults.

We included 2755 participants (1305 men) aged 45-84 years from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort from examination 5 (2010-2012). Logistic regression was employed to assess the relationship between the SII and MetS, as well as its components.

A total of 1082 participants (463 men) were diagnosed with MetS. On a continuous scale, the SII was positively associated with MetS (odds ratio (OR): 1.23, 95% confidence interval (CI): 1.05-1.46) and its components including hyperglycemia (1.23: 1.05-1.44) and elevated blood pressure (BP) (1.47: 1.14-1.89). When analyzed on a quartile scale, participants in the quartile 4 of SII had 32% and 63% higher prevalence of hyperglycemia and elevated BP, respectively, compared to those in the quartile 1 (P for trend: 0.021 and < 0.001, respectively). Additionally, we identified 40% higher prevalence of low HDL-C in quartile 2 of the SII compared to quartile 1 (1.40; 1.07-1.83) (P trend = 0.454). In subgroup analysis, general obesity status modified the relationship between SII and abdominal obesity, showing a positive association in obese individuals (1.72: 1.00-2.95) and a negative association (0.80: 0.66-0.97) in non-obese individuals (P for interaction = 0.009).

Higher SII scores were associated with an increased likelihood of MetS, hyperglycemia, and high BP among middle-aged and older adults. Longitudinal studies are needed to determine the causal relationships between SII and the development of MetS, as well as to assess the potential role of SII as a screening tool in clinical practice.

Diabetes mellitus represents a complicated metabolic condition marked by ongoing hyperglycemia arising from impaired insulin secretion, inadequate insulin action, or a combination of both. Mitochondrial dysfunction has emerged as a significant contributor to the aetiology of diabetes, affecting various metabolic processes critical for glucose homeostasis. This review aims to elucidate the complex link between mitochondrial dysfunction and diabetes, covering the spectrum of diabetes types, the role of mitochondria in insulin resistance, highlighting pathophysiological mechanisms, mitochondrial DNA damage, and altered mitochondrial biogenesis and dynamics. Additionally, it discusses the clinical implications and complications of mitochondrial dysfunction in diabetes and its complications, diagnostic approaches for assessing mitochondrial function in diabetics, therapeutic strategies, future directions, and research opportunities.

This study aimed to investigate the association between zinc deficiency (ZD) and the risks of all-cause mortality, major adverse cardiovascular events (MACEs), major adverse kidney events (MAKEs), and all-cause hospitalization in diabetic patients.

This retrospective cohort study utilized the TriNetX research network to identify adult patients with diabetes mellitus (DM) between January 1, 2010, and August 31, 2024. Propensity score matching was used to match patients with serum zinc levels below 70 µg/dL (ZD group) to those with serum zinc levels between 70 and 120 µg/dL (control group).

Each group comprised 11,698 matched patients with balanced baseline characteristics. During the 1-year follow-up period, the ZD group exhibited significantly higher risks of all-cause mortality (hazard ratio [HR]: 1.788, 95% confidence interval [CI]: 1.591-2.009), MACEs (HR: 1.641, 95% CI: 1.278-2.105), and MAKEs (HR: 1.534, 95% CI: 1.293-1.821), as well as a higher risk of hospitalization (HR: 1.272, 95% CI: 1.216-1.330).

Zinc deficiency in diabetic patients is associated with increased risks of all-cause mortality, MACEs, MAKEs, and all-cause hospitalization. These findings underscore the importance of assessing zinc status in the clinical management of patients with DM.

Obesity is a devastating worldwide metabolic disease, with the highest prevalence in children and adolescents. Obesity impacts neuronal function but the fate of functional hyperemia, a vital mechanism making possible cerebral blood supply to active brain areas, is unknown in organisms fed a high-caloric Western Diet (WD) since adolescence.

We mapped changes in cerebral blood volume (CBV) in the somatosensory cortex in response to whisker stimulation in adolescent, adult, and middle-aged mice fed a WD since adolescence. To this aim, we used non-invasive and high-resolution functional ultrasound imaging (fUS).

We efficiently mimicked the metabolic syndrome of adolescents in young mice with early weight gain, dysfunctional glucose homeostasis, and insulinemia. Functional hyperemia is compromised as early as 3 weeks of WD and remains impaired after that in adolescent mice. These findings highlight the cerebrovascular vulnerability to WD during adolescence. In WD, ω-6:ω-3 polyunsaturated fatty acids (PUFAs) ratio is unbalanced towards proinflammatory ω-6. A balanced ω-6:ω-3 PUFAs ratio in WD achieved by docosahexaenoic acid supplementation efficiently restores glucose homeostasis and functional hyperemia in adults.

WD triggers a rapid impairment in cerebrovascular activity in adolescence, which is maintained at older ages, and can be rescued by a PUFA-based nutraceutical approach.

Gestational Diabetes Mellitus (GDM) is an emerging maternal health problem with increasing incidences. The lack of complete understanding of its pathophysiological mechanisms and novel regulatory biomarkers makes early diagnosis difficult. High-throughput RNA sequencing and computational bioinformatics analyses were conducted to identify novel hub genes, and their regulatory mechanisms were validated through qRT-PCR, western blot, and siRNA-mediated knockdown studies. Intermediate metabolites and circulatory levels of amino acids in the serum of GDM patients and healthy controls were measured. Transcriptomic studies identified SNW1 as the most sensitive and specific biomarker, significantly up-regulated in GDM (fold change = 1.09; p < 0.001). Metabolomic studies indicated significantly elevated gluconeogenesis in GDM, evidenced by decreased levels of alanine and increased levels of pyruvate and glucose compared to controls. siRNA-mediated knockdown of SNW1 in PANC1 cells resulted in significant down-regulation of alanine aminotransferase (ALT/GPT) and insulin receptor substrate (IRS1), while glucose transporters (GLUT2/GLUT4) and insulin (INS) were significantly up-regulated at both mRNA and protein levels. This study identified SNW1 as a novel insulin-resistant gene that induces hyperglycemia by elevating gluconeogenesis and decreasing glucose uptake. SNW1 may be considered a potential therapeutic target with clinical utility for the management of GDM.

Myonectin, a novel muscle-derived peptide or myokine, has been implicated in glucose and lipid homeostasis through its autocrine, paracrine, and endocrine functions. This review aimed to explore the impact of structured exercise interventions on myonectin levels and insulin resistance indicators in healthy individuals and those living with overweight or obesity. We performed a search of PubMed, Science Direct, CINAHL, TRIP Database, Cochrane Library, and Google Scholar for studies published until July 2022. The key terms used were "prediabetes", "overweight", "obesity", "myonectin", "Complement 1q / tumor necrosis factor-related protein 5 (CTRP5 or C1qTNF5)", "erythroferrone", and "exercise". Eight studies investigated the effects of exercise on myonectin levels and insulin resistance, measured through the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), in individuals who were overweight or obese, while six studies focused on those without these conditions. After data extraction, narrative qualitative synthesis and risk of bias analysis were performed. Findings indicate that structured aerobic or combined aerobic and resistance training at moderate intensity over 8-12 weeks led to significant increases in myonectin levels and reductions in insulin resistance, particularly among women who were overweight or obese. However, data was limited by heterogeneous age and gender groups' metabolic profiles and variability in exercise protocols. Myonectin response to exercise in healthy adults remains unclear due to baseline metabolic variability, though some improvements in the glucose-insulin axis were noted. This review suggests that myonectin may serve as a valuable biomarker to assess the impact of exercise on insulin sensitivity in individuals at risk of diabetes with overweight or obesity.

Using NHANES data from 2003 to 2008, 2011 to 2012, and 2015 to 2020, we examined the relationship between urinary organophosphate pesticide (OPP) metabolites and the triglyceride glucose (TyG) index. The TyG index evaluates insulin resistance, a crucial factor in metabolic diseases. Linear regression analyzed urinary metabolites in relation to the TyG index and OPPs. An RCS (restricted cubic spline) model explored the nonlinear relationship of a single OPP metabolite to TyG. A weighted quantile regression and quantile-based g-computation assessed the impact of combined OPP exposure on the TyG index. XGBoost, Random Forest, Support Vector Machines, logistic regression, and SHapley Additive exPlanations models investigated the impact of OPPs on the TyG index and cardiovascular disease. Network toxicology identified CVD targets associated with OPPs. This study included 4429 participants based on specific criteria. Linear regression analysis indicated that diethyl thiophosphate was positively correlated with the TyG index. The positive correlation between OPP metabolites and the TyG index at low to moderate concentrations was confirmed by WQS and QGC analyses. The machine learning results aligned with traditional statistical findings. Network toxicology identified PTGS3, PPARG, HSP40AA1, and CXCL8 as targets influenced by OPPs. OPP exposure influences IR and cardiometabolic health, highlighting the importance of public health prevention.

Insulin resistance is major factor in the development of metabolic syndrome and type 2 diabetes (T2D). We extracted 430 genes from literature associated with both insulin resistance and inflammation. The highly significant pathways were Toll-like receptor signaling, PI3K-Akt signaling, cytokine-cytokine receptor interaction, pathways in cancer, TNF signaling, and NF-kappa B signaling. Among the 297 common genes in all datasets of various T2D patients' tissues including blood, muscle, liver, pancreas, and adipose tissues, 71% and 60% of these genes were differentially expressed in pancreas (GSE25724) and liver (GSE15653), respectively. A total of 169 genes contain highly conserved motifs for various transcription factors involved in immune response, thereby suggesting coordinated expression. Through co-expression analysis, we obtained three modules. The respective modules had 78, 158, and 55 genes, and TRAF2, HMGA1, and RGS5 as hub genes. Further, we used the BioNSi pathways simulation tool and identified the following five KEGG pathways perturbed in four or more tissues, namely Toll-like receptor signaling pathway, RIG-1-like receptor signaling pathway, pathways in cancer, NF-kappa B signaling pathway, and insulin resistance pathway. The genes NFKBIA and IKBKB are common to all these five pathways. In addition, using the NF-κB computational activation model, we identified that the reversal of NF-κB constitutive activation through overexpression of NFKB1 (P50 homodimer), PPARG, PIAS3 could reduce insulin resistance by almost half of its original value. To conclude, co-expression studies, gene expression network simulation, and NF-κB computational modeling substantiate the causal role of NF-κB pathway in insulin resistance. These results taken together with other published evidence suggests that the TNF-TRAF2-IKBKB-NF-κB axis could be explored as a potential target in combination with available metabolic targets in the management of insulin resistance.

The online version contains supplementary material available at 10.1007/s13205-024-04202-4.

Nanotechnology has witnessed remarkable advancements in recent years, capturing considerable attention in diverse biomedical applications. Using the green precipitation method, this study aims to synthesize and characterize chitosan/polyvinyl alcohol-copper oxide nanocomposites (CS/PVA/CuONCs) using Anacardium occidentale plant fruit extract. The CS/PVA/CuONCs were further evaluated in antioxidant, antibacterial and biological activities. In our study results, UV-Vis spectrum analysis of CS/PVA/CuONCs revealed a peak at 430 nm. FTIR analyses confirmed the presence of different functional groups, while the XRD study confirmed the crystalline structure of the synthesized nanocomposites. FESEM-EDAX analysis demonstrated that the CS/PVA/CuONCs exhibited a spherical and rod-like shape, with an average particle size of 48.6 to 96.2 nm. Notably, CS/PVA/CuONCs exhibited higher antioxidant activity, as evidenced by their ABTS activity (83.79 ± 1.57%) and SOD activity (86.17 ± 1.28%). In antibacterial assays, CS/PVA/CuONCs demonstrated inhibition in Escherichia coli at 20.52 ± 0.85 mm and Bacillus subtilis at 19.64 ± 0.87 mm, displaying a zone of inhibition. The CS/PVA/CuONCs exhibited excellent anti-inflammatory potency against COX-1 (67.10 ± 0.58%) and COX-2 (76.39 ± 0.65%). The antidiabetic assay revealed excellent α-amylase inhibition (80.25 ± 1.29%) and α-glucosidase inhibition (84.74 ± 1.42%) activities. Anti-cholinergic activity of AChE was 65.35 ± 0.98% and BuChE was 82.46 ± 1.15% are observed. CS/PVA/CuONCs was shown to have strong cytotoxicity against MCF-7 cell lines. It also had the highest cell viability inhibition, at 13.66 ± 0.58%. The hemolysis activity was found to be 5.38 ± 0.34%. Overall, the study demonstrated that CS/PVA/CuONCs possess remarkably excellent biological activities.

This article reviews the synergistic effects of antioxidant-enriched functional foods and exercise in improving metabolic health, focusing on the underlying molecular mechanisms. The review incorporates evidence from PubMed, SCOPUS, Web of Science, PsycINFO, and reference lists of relevant reviews up to 20 December 2024, highlighting the central role of the Nrf2 pathway. As a critical regulator of oxidative stress and metabolic adaptation, Nrf2 mediates the benefits of these interventions. This article presents an innovative approach to understanding the role of Nrf2 in the regulation of oxidative stress and inflammation, highlighting its potential in the prevention and treatment of various diseases, including cancer, neurodegenerative disorders, cardiovascular and pulmonary diseases, diabetes, inflammatory conditions, ageing, and infections such as COVID-19. The novelty of this study is to investigate the synergistic effects of bioactive compounds found in functional foods (such as polyphenols, flavonoids, and vitamins) and exercise-induced oxidative stress on the activation of the Nrf2 pathway. This combined approach reveals their potential to improve insulin sensitivity and lipid metabolism and reduce inflammation, offering a promising strategy for the management of chronic diseases. However, there are significant gaps in current research, particularly regarding the molecular mechanisms underlying the interaction between diet, physical activity, and Nrf2 activation, as well as their long-term effects in different populations, including those with chronic diseases. In addition, the interactions between Nrf2 and other critical signalling pathways, including AMPK, NF-κB, and PI3K/Akt, and their collective contributions to metabolic health are explored. Furthermore, novel biomarkers are presented to assess the impact of these synergistic strategies, such as the NAD+/NADH ratio, the GSH ratio, and markers of mitochondrial health. The findings provide valuable insights into how the integration of an antioxidant-rich diet and regular exercise can improve metabolic health by activating Nrf2 and related molecular pathways and represent promising strategies for the prevention and treatment of metabolic disorders. Further studies are needed to fully understand the therapeutic potential of these interventions in diseases related to oxidative stress, such as cardiovascular disease, neurodegenerative disease, diabetes, and cancer.

Background and Aims: Older adults are particularly susceptible to type 2 diabetes mellitus (T2DM) due to factors such as age-related insulin resistance, decreased physical activity, and deficiency of micronutrients, especially zinc. Studies have suggested that the risk allele of the zinc transporter 8 gene (SLC30A8) single-nucleotide poly-morphism (SNP) rs13266634 may contribute to T2DM susceptibility in addition to the complex protein interactions and alterations in the protein expressions and modifications associated with T2DM. This study was implemented to study the associations between SLC30A8 polymorphism, serum zinc levels, and the profiles of proteins differentially expressed in nondiabetic (n = 116) and prediabetic/diabetic (n = 149) subjects. Methods: SNP genotyping using TaqMan® assay and proteomic analysis by LC-MS/MS were performed in each group. Results: The results showed a higher risk of diabetes in individuals with the risk genotype CC accompanied by a low serum zinc level than in those with other genotypes. Profiles of proteins differentially expressed between the groups were identified and shown to be particularly associated with zinc-related functions, zinc transporter 8, and glucose metabolism. Proteins exclusively expressed in prediabetes/diabetes were assigned to a Reactome pathway related to zinc transporter and insulin processing. Conclusions: Our findings suggest that individuals carrying at least one copy of SLC30A8 rs13266634 accompanied by a low serum zinc level might be susceptible to T2DM, which could be due to alterations in insulin signaling and zinc metabolism. Understanding this relationship deepens our understanding of the genetic and molecular mechanisms underlying T2DM risk, offering potential targets for therapeutic intervention and prevention strategies.

Background/Objectives: Metabolic syndrome (MetS) is a combination of conditions including central obesity, high blood pressure, high glucose levels, and abnormal triglycerides and cholesterol, which together increase the chances of heart disease, diabetes, and even death. The rates of MetS are different around the world, with 20-30% in Europe and 21.8-23.9% in Kazakhstan. Because MetS changes over time, it is important to study the dynamics of their components to improve prevention and treatments. This work aims to obtain the incidence of MetS and to evaluate the specific components associated with the emergence of new MetS cases in this population. Methods: This is a longitudinal study with a 10-year follow-up in Turkestan city between 2012 and 2024. Information was collected through physical exams, blood tests, and anthropometric measurements. Logistic regression and ROC curve analysis were used to find which factors increase the incidence of MetS. Results: Among 434 participants analyzed (78.8% women, and mean age 40.87, 66% < 2 MetS components, 20% had MetS blood pressure, and 65.9% had MetS waist circumference), the incidence of MetS at follow-up was 40%. The key risk factors for newly diagnosed MetS included elevated blood pressure and increased waist circumference. Multivariate analyses highlighted these components as the strongest predictors of MetS, with significant associations observed for participants with two or more MetS components at baseline. Conclusions: Elevated blood pressure and central obesity were identified as pivotal contributors to MetS progression. Given the rising prevalence of Mets and its implications, these results show the need to start treatment and check these risks early to prevent serious health problems.

Impaired glucose intolerance (IGT) and impaired fasting glucose (IFG) are totally different. Lifestyle modification is effective in moving from prediabetes to normoglycaemia. There is a lack of information showing the effect of lifestyle modification according to each prediabetes and assessing its effect on the degree of reversibility to normoglycaemia and on cardiometabolic markers.

We searched for randomized controlled trials (RCT) that enrolled individuals with IGT or IFG. Meta-analysis was performed to compare the proportion of subjects progressing to type 2 diabetes mellitus (T2DM); proportion reversing to normoglycaemia and mean differences in glucose level and cardiometabolic parameters. Thirty-six RCTs were included. The proportion of subjects progressing from impaired glycaemia to T2DM was higher among those with IGT (16.3% vs. 10.9%), whereas reversion to normoglycaemia was higher in subjects with IFG (27.2% vs. 24.8%). The effect of lifestyle modification on glucose level was significant on those with IFG (mean difference [MD] = -1.56 mg/dL, 95% CI: -2.71, -0.40), but not on those with IGT of (MD = 1.47 mg/dL, 95% CI: -1.33, 4.28).

Diverse lifestyle modification interventions improved glucose levels in people with IFG, but not in those with IGT. Our findings imply that different non-pharmacological interventions are warranted for IGT and IFG.

Metabolic syndrome is a metabolic disorder characterized by hypertension, dyslipidemia, impaired glucose tolerance, and abdominal obesity. Impaired insulin action or insulin resistance initiates metabolic syndrome. The prevalence of insulin resistance is increasing all over the world. Insulin resistance results in the defective metabolism of carbohydrates and lipids, in addition to low-grade chronic inflammation. Insulin resistance is associated with metabolic syndrome, which is a risk factor for a number of pathological conditions, such as Type 2 diabetes (T2D), cardiovascular disease (CVD), nonalcoholic fatty liver disease (NAFLD), and polycystic ovarian syndrome (PCOS). Genome-wide association studies have increased our understanding of many loci linked to these diseases and others. In this review, we discuss insulin resistance and its contribution to metabolic syndrome and these diseases. We also discuss the genetic loci associated with them. Genetic testing is invaluable in the identification and stratification of susceptible populations and/or individuals. After susceptible individuals and/or populations have been identified via genetic testing or screening, lifestyle modifications such as regular exercise, weight loss, a healthy diet, and smoking cessation can reduce or prevent metabolic syndrome and its associated pathologies.

Identifying the risks of metabolic syndrome (MetS) can lead to early targeted interventions and thus contribute to improved quality of life by reducing the risk of developing MetS, diabetes or heart disease in the future. We aimed to develop a valid and reliable measurement tool to measure the MetS risk of the population.

In the methodological study, an item pool was created by reviewing the literature. Pre-application was performed after the weighting of the items whose content validity was ensured by taking expert opinions. Data were collected from 43 patients with MetS from a state hospital affiliated to the Ministry of Health and 405 individuals without MetS from the community, from a total of 448 individuals using the Individual Information Form, Finnish Diabetes Risk Scale (FINDRISC) and Metabolic Syndrome Index (MSI). The data obtained were evaluated using SPSS 22.0 and MedCalc 19.1 statistical programmes. Scale discrimination was analyzed by independent samples t-test between the upper and lower 27% groups. The cut-off point of the scale score in predicting the diagnosis of MetS was tested by ROC analysis. Correlation analysis was performed with the parallel form for criterion validity.

As a result of the ROC analysis, a perfectly compatible scale with a sensitivity of 100%, a specificity of 85.43% and a cut-off score of 48 was obtained. When the correlation analyses between MSI and FINDRISC scores were examined for criterion validity, a positive moderate (r = 0.632, p < 0.001) correlation was found between FINDRISC and MSI. When the discrimination of the scale was analysed, it was found that there was a significant difference between the lower 27% and upper 27% groups (p < 0.05) and it was revealed that the MSI made sensitive measurements to discriminate.

The MSI scale is a valid and reliable tool for early detection of MetS risk.

Parkinson's disease (PD), a chronic and common neurodegenerative disease, is characterized by the progressive loss of dopaminergic neurons in the dense part of the substantia nigra and abnormal aggregation of alpha-synuclein. Type 2 diabetes mellitus (T2DM) is a metabolic disease characterized by chronic insulin resistance and deficiency in insulin secretion. Extensive evidence has confirmed shared pathogenic mechanisms underlying PD and T2DM, such as oxidative stress caused by insulin resistance, mitochondrial dysfunction, inflammation, and disorders of energy metabolism. Conventional drugs for treating T2DM, such as metformin and glucagon-like peptide-1 receptor agonists, affect nerve repair. Even drugs for treating PD, such as levodopa, can affect insulin secretion. This review summarizes the relationship between PD and T2DM and related therapeutic drugs from the perspective of insulin signaling pathways in the brain.

This study aimed to explore the association between the triglyceride-Glucose Index (TyG) and its combination with obesity indicators in relation to the risk of hypertension among middle-aged and elderly individuals in China.

A total of 9,248 participants aged 45 and above were selected from the 2015 China Health and Retirement Longitudinal Study. Data on basic demographics, behavioral habits, medical history, physical examination results, and blood indicators were collected. The TyG and its obesity-related indicators, including TyG-BMI, TyG-WC, and TyG-WHtR were analyzed. These indicators were categorized into four groups based on quartiles, and the prevalence of hypertension within each group was assessed. Logistic regression analysis was conducted to evaluate the association between different TyG indices and obesity-related indicators with the risk of hypertension. Additionally, a restricted cubic spline model was employed to investigate the dose-response relationship between the TyG index, its combined obesity indicators, and the risk of hypertension. The receiver operating characteristic curve was utilized to determine the optimal predictive index for diagnosis.

This study included a total of 9,248 middle-aged and elderly individuals aged 45 and above, comprising 4,274 males (46.21%), with an average age of 61.38 ± 9.28 years. The prevalence of hypertension exhibited an increasing trend as the quartiles of TyG, TyG-BMI, TyG-WC, and TyG-WHtR rose. After fully adjusting for covariates, comparisons between the first quartile (Q1) and the fourth quartile (Q4) of TyG, TyG-BMI, TyG-WC, and TyG-WHtR revealed that all these metrics at Q4 level were associated with an increased prevalence of hypertension. The odds ratios were as follows: TyG: OR = 1.80 (95% CI: 1.48-2.19); TyG-BMI: OR = 5.09 (95% CI: 4.33-5.98); TyG-WC: OR = 3.96 (95% CI: 3.38-4.65); TyG-WHtR: OR = 3.91 (95% CI: 3.33-4.60). A linear correlation was observed between TyG and the risk of hypertension (P for non-linearity = 0.2267), while non-linear correlations were noted between TyG-BMI, TyG-WC, and TyG-WHtR with the risk of hypertension (P for non-linearity < 0.001). The receiver operating characteristic curve indicated that TyG-WC demonstrated the highest diagnostic performance for hypertension, with an area under the curve of 0.642 (95% CI: 0.631-0.654).

As the levels of TyG, TyG-BMI, TyG-WC, and TyG-WHtR increased, the risk of hypertension among middle-aged and elderly individuals aged 45 and above in my country rises significantly. Among them, TyG-WC can be a predictor of hypertension in middle-aged and elderly people.

The worldwide health system faces challenges from obesity and related metabolic disorders because they exhibit both rising rates of occurrence and intricate pathophysiological mechanisms. This work examines how adipokines interact with body composition during obesity to control important metabolic functions. Bioactive molecules produced by adipose tissue function as adipokines which regulate essential biological pathways that control inflammation response and insulin sensitivity alongside energy balance management and immune system operation. The disruption of adipokine secretion and function leads directly to metabolic disorders which include insulin resistance and persistent inflammation characteristic of obesity-related conditions. This article investigates the therapeutic possibilities of adipokine pathway manipulation through new pharmacological approaches and lifestyle changes alongside personalized medicine developments. Researchers analyze adipokines as important biomarkers for patient disease classification and their application in creating individualized treatment plans. The review highlights existing research deficiencies and obstacles that stand in the way of applying adipokine discoveries to clinical settings. This article integrates existing research to show how adipokine regulation helps prevent obesity-related metabolic issues and suggests directions for future studies to enhance treatment results.

Type 2 diabetes mellitus (T2DM) is a widespread metabolic condition characterized by elevated glucose levels followed by deficiency in insulin secretion. Metformin notably decreased the incidence of T2DM by 31% and it exerts its effects through various signaling pathways. Databases searched included PubMed, Google Scholar, and Scopus from 2000 to 2024. One of the primary mechanisms involves AMPK activation which causes reduced lipogenesis and improved fatty acid oxidation in the liver and muscles. Key molecules affected by metformin include acetyl-CoA carboxylase (ACC) and sterol regulatory element-binding protein 1c (SREBP-1c), both involved in lipid synthesis regulation. Aerobic exercise has also emerged as a crucial component in managing T2DM due to its improved effects on hyperglycemia and insulin sensitivity. Key signaling pathways affected in T2DM include the PI3K/Akt, AMP-activated protein kinase (AMPK), and MAPK/ERK pathways which play essential roles in regulating glucose homeostasis, glycogenesis, and insulin secretion. When comparing the mechanisms and efficacy of aerobic exercise and metformin, it becomes evident that aerobic exercise primarily enhances physical fitness and metabolic function, while metformin exerts its effects through biochemical pathways involving AMPK activation. Aerobic exercise and metformin are effective for managing T2DM, though they operate through different mechanisms. Regular aerobic exercise improves insulin sensitivity, enhances cardiovascular health, and promotes weight loss, while metformin primarily decreases hepatic gluconeogenesis and enhances insulin secretion. Understanding the intricate signaling pathways affected by metformin and aerobic exercise provides valuable insights into its mechanisms of action and clinical implications for treating diabetic patients effectively.

This study aimed to evaluate the effects of gastrointestinal digestion on the physicochemical properties and hypoglycemic activity of extracellular polysaccharides from Morchella esculenta (MEPS). The results showed that the MEPS digestibility was 22.57 % after saliva-gastrointestinal digestion and only partial degradation had occurred. Contrarily, after 48 h of fecal fermentation, its molecular weight and molar ratios of the monosaccharide composition varied significantly due to being utilized by human gut microbiota, and the final fermentation rate was 76.89 %. Furthermore, the MEPS-I, the final product of saliva-gastrointestinal digestion still retained significant hypoglycemic activity, it alleviated insulin resistance and increased the IR cells glucose consumption by activating PI3K/AKT signaling pathway. MEPS-I treatment reduced the proportion of Firmicutes to Bacteroidetes, and the relative abundance of beneficial bacteria that enhanced insulin sensitivity and glucose uptake was promoted. This research can provide a theoretical basis for the further development of Morchella esculenta as a health functional food.

Diabetes is a medical condition that belongs to the group of chronic diseases that affect how the body processes glucose, the primary source of energy for cells. Glucose comes indirectly from the consumed food and is carried by bloodstream to various cells in the body. Insulin, a hormone synthesized by the pancreas plays a vital role in the conversion of glucose to energy. Managing diabetes involves regular monitoring of blood sugar levels, adopting a healthy diet, engaging in regular physical activity, and taking medications or insulin as prescribed by a healthcare provider. Proper management of diabetes may lead to the prevention or delay of diabetic complications may further sever other diseases associated impediment. Drug delivery in the management of diabetes is designed to administer insulin or other diabetes medications in a controlled and convenient manner. Recently nanotechnology has emerged as a transformative approach in the management of diabetic complications, particularly through carrier-mediated nano-biomedicine. Several natural products have been studied and reported for their potential role in managing diabetes. While they may not replace standard medical treatments, some of these natural products could complement existing therapies and support overall diabetes management. Therefore, this review explores the potential of nanocarriers to enhance drug delivery systems for diabetes mellitus treatment, addressing the limitations of conventional therapies that often suffer from poor bioavailability and frequent dosing requirements. Studies have demonstrated that bridging these bioactive compounds significantly enhance the therapeutic efficacy in the management of diabetes. Challenges remain in translating these technologies from laboratory settings to clinical applications; however, the potential benefits for improving glycemic control and overall quality of life for diabetic patients are substantial. Future research should focus on optimizing these nano-biomedicine strategies to realize their full therapeutic potential in diabetes management.

To investigate the association between metabolic dysfunction-associated steatotic pancreas disease (MASPD) and insulin resistance (IR).

This cross-sectional study involved 157 participants diagnosed with MASPD based on ultrasonography criteria. Baseline demographic data were collected, including age, gender, and body mass index. Serum levels of fasting glucose, insulin, lipid profile (including total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol), glycated hemoglobin and insulin were measured using standardized laboratory techniques. Abdominal ultrasonography was performed on all participants using convex transducer (frequency range, 3,5 MHz) by experienced radiologist blinded to the clinical data. The association between MASPD and IR was assessed using logistic regression analysis, adjusting for potential confounders. Statistical significance was set at a P-value <0.05.

The logistic regression analysis was performed to verify whether MASPD was a risk factor for IR. After adjusting for gender and age, the results demonstrate a significant correlation between MASPD and markers of IR. TyG index: OR (95%IC) 5.72 (1.90-16.00), P 0.021, and HOMA -IR: OR (95%IC) 6.20 (2.1-22.00) P 0.037.

This study presents a description of MASPD and its association with IR indices. Our findings demonstrate a significant correlation between MASPD and markers of IR. These results suggest that MASPD may contribute to the development of insulin resistance and further highlight the importance of pancreatic health in metabolic disorders.