Search Results (5,476)

Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have rapidly evolved from glucose-lowering agents to central players in cardiovascular risk reduction. Evidence from landmark randomized controlled trials has established their capacity to reduce major adverse cardiovascular events, promote anti-inflammatory signaling, attenuate ischemia–reperfusion injury, and improve myocardial metabolic efficiency. As the prevalence of obesity, type 2 diabetes mellitus, and heart failure in the cardiac surgical population grows, GLP-1 RAs are increasingly encountered in the perioperative setting. Yet the cardiac surgery literature has yet to synthesize their emergent role coherently. This is a narrative review; no systematic review or meta-analysis was performed. This narrative review integrates mechanistic, clinical, and translational evidence to reframe GLP-1 RAs as potential perioperative cardioprotective agents in patients undergoing cardiac surgery. We examine receptor-level biology, evidence from the GLOBE randomized trial, observational data linking GLP-1 RA use to reduced postoperative atrial fibrillation after coronary artery bypass grafting, the rationale for the forthcoming REVERSE-TAVR trial, and evolving perioperative management guidelines. Key evidence gaps are identified, including the absence of prospective data in open cardiac surgery, aortic surgery, and high-acuity populations. We propose a research agenda and conceptual framework to guide future investigation into GLP-1 RAs as a new dimension of perioperative cardioprotection. The current evidence is hypothesis-generating; a definitive perioperative cardioprotective benefit has not yet been demonstrated in cardiac surgery populations, and these agents are presented here as potential rather than proven cardioprotective tools. Full article

Type 2 diabetes mellitus (T2DM) involves progressive muscle wasting, metabolic dysregulation in peripheral tissues, chronic hyperglycemia, and insulin resistance. Momordica charantia is an antidiabetic agent often limited by bitterness. To improve palatability and efficacy, we developed EMS by combining M. charantia and Stevia rebaudiana (9:1). EMS’s antidiabetic effects were tested in streptozotocin (STZ)-induced and genetic db/db mouse models of diabetes. Mice received oral EMS at doses (40, 80, and 120 mg/kg) for six weeks, assessing glucose tolerance, insulin sensitivity, lipid profile, and hepatic markers. Additionally, muscle protein synthesis and degradation mechanisms were analyzed in gastrocnemius tissues. EMS significantly reduced fasting blood glucose and improved insulin sensitivity in both models. EMS decreased liver lipid accumulation and serum ALT and AST levels, indicating hepatic protection. EMS alleviated muscle atrophy by increasing muscle fiber area and was associated with increased expression or activity of AMPK/Sirt1/PGC-1α and IRS-1/PI3K/AKT insulin pathways. It also suppressed FOXO3a-mediated expression of Atrogin-1 and MuRF1, suggesting reduced activation of protein-degradation pathways. Moreover, EMS modulated the gut microbiota, increasing the abundance of beneficial species such as Barnesiella intestinihominis. These findings suggest EMS is a promising multitarget functional ingredient for metabolic complications and musculoskeletal decline in T2DM. Full article

This review examined study characteristics and common practices in continuous glucose monitoring (CGM)-based exercise studies. Following PRISMA guidelines, a systematic search in the PubMed database was conducted. Data were extracted from 93 publications. A minority of studies (12.9%) focused on CGM system validation. Acute exercise studies were more common (87.1%) than chronic exercise studies (12.9%). Randomized crossover designs predominated (71.0%). Participant populations varied and included 46.2% non-diabetic individuals (7.5% athletes), 36.6% individuals with type 1 diabetes mellitus, and 17.2% individuals with type 2. The upper arm was the most common sensor placement site (41.9%), although nearly one-third of studies did not report placement details. Devices were primarily from Abbott (40.9%), Medtronic (36.6%), and Dexcom (26.9%). Sample sizes were typically small, with 40.9% of studies including 10–14 participants. Reporting practices frequently deviated from the International Consensus Statement on CGM Metrics for Clinical Trials. Many studies used modified or non-standard metrics, whereas “mean sensor glucose” was reported in compliance with consensus recommendations in 58.1% of studies. Regarding data completeness, “data gaps” was the most frequently reported consensus-compliant metric (43.0%). In validation studies, accuracy metrics predominated, with “absolute relative difference” representing the most common outcome (87.5%). Overall, substantial heterogeneity limits comparability across studies, highlighting the need for standardized CGM reporting. Full article

Background/Objectives: Diabetic neuropathy is a prevalent complication of type 2 diabetes mellitus (T2DM), but the contribution of dietary factors to neuropathy severity remains insufficiently characterized. This study investigated associations between dietary patterns, nutrient intake, and neuropathy severity in 300 adults with T2DM from Northeastern Romania. Methods: Dietary intake was assessed using a validated food frequency questionnaire, and five dietary patterns were derived using principal component analysis. Neuropathy severity was analyzed as an ordinal outcome using logistic regression models adjusted for age, sex, HbA1c, diabetes duration, and treatment. Results: Higher adherence to Western/fast-food and alcohol and animal fat dietary patterns was associated with greater neuropathy severity in unadjusted analyses, whereas a healthy/prudent pattern showed inverse associations; however, these relationships were attenuated after multivariable adjustment. In contrast, higher intakes of protein (OR = 0.98, 95% CI: 0.97–0.99), magnesium (OR = 0.99, 95% CI: 0.98–1.00), zinc (OR = 0.80, 95% CI: 0.69–0.94), vitamin B3 (OR = 0.94, 95% CI: 0.89–0.99), and vitamin B12 (OR = 0.76, 95% CI: 0.62–0.93) remained independently associated with lower neuropathy severity after adjustment. Conclusions: These findings suggest that specific nutrient intakes may be more strongly associated with diabetic neuropathy severity than overall dietary patterns, highlighting potential nutritional targets for neuropathy risk reduction and clinical management in patients with T2DM. Full article

Atrial fibrillation (AF) is the most prevalent sustained arrhythmia and is increasingly driven by cardiometabolic disease, including type 2 diabetes mellitus (T2DM), obesity, and insulin resistance. These conditions promote atrial electrical instability and a permissive substrate through mitochondrial dysfunction, oxidative stress, inflammation, calcium-handling abnormalities, and profibrotic signaling, culminating in atrial fibrosis and conduction heterogeneity. Metformin, the foundational glucose-lowering therapy for T2DM, exerts pleiotropic actions that intersect with these upstream pathways. Beyond glycemic control, metformin induces mild mitochondrial complex I modulation with reduction of reverse electron transfer-derived reactive oxygen species, activates adenosine monophosphate (AMP) activated protein kinase, and attenuates nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB)-mediated cytokine signaling; experimental data further suggest favorable effects on adiponectin–sarcoendoplasmic reticulum calcium adenosine triphosphatase (SERCA) 2a-dependent calcium cycling, connexin expression, small-conductance Ca²⁺-activated K+ channel remodeling, lipid handling, and transforming growth factor-β (TGF)-β-associated fibrotic remodeling. Observational cohort studies have reported associations between metformin exposure and a modest reduction in incident AF, particularly with longer treatment duration and in higher-risk metabolic phenotypes; device-based surveillance cohorts support a preventive association for new-onset AF rather than reduction of established AF burden. Data after catheter ablation suggest improved freedom from recurrence in metformin-treated patients, whereas evidence in postoperative AF is largely neutral, likely reflecting distinct acute mechanisms. Collectively, metformin may be best conceptualized as a potential substrate-modifying, upstream therapy candidate; however, confounding, exposure misclassification, and heterogeneity in comparators limit causal inference, underscoring the need for prospective randomized trials with AF endpoints. In practice, integration with comprehensive risk-factor modification (blood pressure, weight, sleep apnea, and glycemic optimization) remains essential when considering AF prevention strategies. Full article

Background: Type 2 diabetes mellitus (T2DM) is associated with subclinical myocardial dysfunction, which may occur despite preserved left ventricular ejection fraction. Left ventricular global longitudinal strain (LV GLS) is a sensitive marker of early systolic impairment and may detect subtle changes in myocardial function before conventional echocardiographic parameters become abnormal. The effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on LV GLS in adults with T2DM remains incompletely defined. Objective: To synthesize the available evidence on the effects of SGLT2i therapy on LV GLS or LV strain in adults with T2DM. Methods: Original full-text human studies evaluating SGLT2i therapy in adults with T2DM and reporting LV GLS or LV strain were included. LV GLS was assessed primarily by speckle-tracking echocardiography, while one study used cardiac magnetic resonance feature-tracking. Reviews, conference abstracts, protocols, animal-only studies, and studies without LV strain assessment were excluded. Risk of bias was assessed using RoB 2 for randomized studies and ROBINS-I for non-randomized studies. Results: Twenty-six studies involving more than 2300 participants were included. The studies evaluated dapagliflozin, empagliflozin, ertugliflozin, canagliflozin, or mixed SGLT2i regimens across heterogeneous clinical populations, including patients with preserved ejection fraction, pre-heart failure, diabetes-related cardiomyopathy, chronic heart failure, coronary artery disease, hypertension, non-alcoholic fatty liver disease, and cardio-oncology risk. Most observational and before–after studies reported favorable changes in LV GLS after SGLT2i therapy, whereas randomized and controlled studies showed more variable findings. Several studies also reported improvements in LV remodeling, diastolic function, left atrial function, myocardial work indices, NT-proBNP, cardiometabolic parameters, or epicardial adipose tissue thickness. However, the certainty of evidence was limited by methodological heterogeneity, differences in comparator groups, variable follow-up duration, non-standardized imaging protocols, and risk of bias, particularly in non-randomized and single-arm studies. Conclusions: SGLT2i therapy may be associated with favorable changes in LV GLS in adults with T2DM, suggesting a potential beneficial effect on subclinical left ventricular systolic function. However, current evidence does not definitively establish a consistent treatment effect across all populations. Larger randomized controlled trials with standardized strain imaging protocols, predefined LV GLS endpoints, and clinically relevant follow-up are needed to determine whether SGLT2i-related improvements in LV GLS reflect true myocardial benefit and translate into improved cardiovascular outcomes. Full article

Medium-chain triglycerides (MCTs) are functional lipids with unique physicochemical properties and metabolic advantages. Recently, their regulatory roles in various chronic diseases have attracted considerable attention. This review systematically summarizes recent research progress and the proposed mechanisms of MCTs and their metabolites in metabolic diseases, neurological disorders, gut health, and muscle function. In the metabolic field, MCTs offer potential nutritional strategies for managing obesity, type 2 diabetes mellitus (T2DM), and various metabolic liver diseases. These effects are primarily mediated by improving insulin sensitivity, regulating lipid metabolism, and modulating energy expenditure. In neurological diseases, MCTs demonstrate potential for preventing and treating Alzheimer’s disease (AD), Parkinson’s disease (PD), and epilepsy through multiple pathways, including ketogenic energy supply, anti-inflammatory and antioxidant effects, and mitochondrial protection. Regarding gut health, MCTs and their derivatives may benefit digestive health by modulating gut microbiota and enhancing barrier function. For muscle health, MCTs help optimize energy metabolism and protein homeostasis, showing promise for countering sarcopenia and improving exercise performance. In conclusion, the prospects for MCTs are broad. Future research should focus on promoting their scientific application in precision nutrition and disease therapy, and more rigorous clinical trials are needed to confirm their efficacy and safety. Full article

The treatment of type 2 diabetes (T2DM) faces numerous challenges. Oral insulin (Ins) and other short-acting compounds still encounter significant obstacles in the hostile gastrointestinal environment, including low bioavailability and rapid metabolic clearance. Platycodin D (PD) is a natural compound with demonstrated hypoglycemic and lipid-lowering effects. In this study, PD was encapsulated using alginate to prepare orally administrable, pH-responsive, gut-targeted gel microspheres (PD@MPs), and their efficacy in improving T2DM prognosis was investigated. In vitro release studies demonstrated that PD@MPs avoided degradation by gastric acid and were released in the intestine. Cell experiments indicated that PD possessed significant antioxidant and anti-apoptotic properties. Masson, immunohistochemistry, and immunofluorescence staining revealed that PD@MPs alleviated inflammation in key metabolic organs and maintained normal pancreatic tissue function and morphology. Western blot analysis assessed the expression of proteins related to hepatic glycogen synthesis, including IRS-1, GLUT2, GSK-3β, and AKT. The research results indicate that the assembly strategy using sodium alginate (SA) as the coating layer has enabled the oral administration of PD and has demonstrated its potential in the treatment of diabetes. Full article

Glutathione (GSH), the most abundant intracellular antioxidant, plays a central role in maintaining redox homeostasis, regulating immune responses, and protecting cellular integrity. In chronic diseases such as type 2 diabetes mellitus (T2DM), GSH deficiency is a consistent hallmark, contributing to oxidative stress, mitochondrial dysfunction, inflammation, and progressive organ damage. This review critically examines the efficacy and safety of GSH supplementation and precursor strategies, synthesizing evidence across mechanistic studies, clinical trials, and translational research. In T2DM, GSH augmentation has been linked to improved insulin sensitivity, reduced oxidative damage, and better microvascular outcomes, although findings remain preliminary and heterogeneous. Safety profiles across populations are highly favorable, with gastrointestinal discomfort being the most reported adverse effect and serious toxicities rare. Importantly, both acute and chronic studies reinforce the compatibility of GSH and its precursors with standard antiretroviral and antidiabetic therapies. Despite this encouraging data, significant research gaps remain. Standardization of biomarkers, dose–response mapping, and long-term outcomes are urgently needed to move from proof-of-concept to clinical trials. Future directions include integrating mechanistic endpoints such as mitochondrial function and multi-omic profiling, exploring targeted delivery systems, and embedding implementation science to ensure real-world feasibility and equity. Collectively, the emerging evidence supports GSH-centered strategies as promising adjuncts for oxidative stress-driven chronic disease. Rigorous, well-designed trials are now required to define their definitive role in clinical care. Full article

Background: Psoriasis is a chronic inflammatory disease frequently associated with obesity and type 2 diabetes mellitus (T2DM). Glucagon-like peptide-1 receptor agonists (GLP-1RAs), widely used for T2DM and obesity, have demonstrated anti-inflammatory and immunomodulatory properties that may be relevant in psoriasis. However, individual GLP-1RAs differ substantially in their pharmacological characteristics and clinical effects. Our objective was to systematically review the available evidence on the effects of individual GLP-1RAs in patients with psoriasis. Methods: A systematic review was conducted according to PRISMA 2020 guidelines. PubMed and Scopus were searched up to April 2026 for studies evaluating GLP-1RAs in psoriasis. Case reports, case series, observational studies, and randomized controlled trials were included. Preclinical, clinical and safety outcomes were extracted and narratively synthesized. Results: Twenty-six studies met the inclusion criteria. Most involved patients with concomitant obesity and/or T2DM. Overall, semaglutide, liraglutide, exenatide, and tirzepatide were associated with improvements in psoriasis severity, often accompanied by reductions in body weight, glycated haemoglobin, inflammatory markers, and cardiometabolic risk factors. Semaglutide and liraglutide showed the most consistent evidence of benefit. Experimental and clinical data also suggested direct immunomodulatory effects on pathways involved in psoriasis pathogenesis. However, paradoxical psoriasiform eruptions and psoriasis exacerbations were reported with some agents. The evidence base was limited by the predominance of case reports and small observational studies, substantial heterogeneity, and the limited availability of randomized controlled trials. Conclusions: Current evidence suggests that GLP-1RAs may improve both psoriatic disease activity and cardiometabolic outcomes, particularly in patients with obesity or T2DM. Nevertheless, potential differences among individual agents warrant further investigation in larger controlled studies. Full article

Background: Syzygium cumini and other Myrtaceae plants are widely used as traditional remedies for dysglycemia, yet clinical evidence remains fragmented and heterogeneous. This study aimed to evaluate the efficacy and safety of S. cumini and related Myrtaceae interventions in individuals with dysglycemia. Methods: A systematic review and meta-analysis of randomized controlled trials was conducted in accordance with PRISMA 2020 and registered in PROSPERO (CRD420261332539). PubMed, Scopus, Embase, MEDLINE, and Web of Science were searched from inception to 3 September 2025. Eligible trials enrolled participants with type 2 diabetes mellitus (T2DM) or prediabetes and evaluated Myrtaceae interventions versus controls. Random-effects meta-analyses were performed to estimate mean differences (MDs) with 95% confidence intervals (CIs). Results: Thirteen trials comprising 802 participants were included. Myrtaceae interventions were associated with a statistically significant but modest reduction in fasting plasma glucose (MD −14.40 mg/dL, 95% CI −23.12 to −5.67; I² = 98.57%). However, effects on postprandial glucose (MD −12.99 mg/dL, 95% CI −27.74 to 1.76; I² = 97.93%) and HbA1c (MD −0.46%, 95% CI −0.98 to 0.06; I² = 99.20%) were not statistically significant. Overall effects on lipid outcomes and laboratory safety markers were also not significant. Subgroup analyses suggested possible variation by participant type, plant part, formulation composition, comparator type, and treatment duration, but these findings were exploratory and accompanied by substantial heterogeneity. Conclusions: Myrtaceae interventions may provide a modest short-term reduction in fasting glycemia among adults with T2DM or prediabetes. However, the clinical significance and generalizability of this finding remain uncertain due to high heterogeneity, short follow-up, absence of low-risk trials, and low to very low certainty of evidence. Current evidence does not support consistent benefits for PPG, HbA1c, lipid outcomes, or long-term safety. These interventions should be considered promising but unproven adjuncts rather than alternatives to standard dysglycemia management. Full article

Background: Type 2 diabetes mellitus (T2DM) is associated with impaired skeletal muscle mass and function; however, respiratory muscle involvement has not been fully investigated, particularly in Japanese patients. This study aimed to evaluate respiratory muscle strength and identify its associated factors in Japanese patients with T2DM. Methods: This cross-sectional study included 55 patients with T2DM without respiratory disease. Maximal inspiratory pressure (PImax) and maximal expiratory pressure (PEmax) were measured and expressed as percentages of the predicted values (PImax %pred and PEmax %pred). Clinical variables, including age, sex, body mass index (BMI), diabetic polyneuropathy (DPN), skeletal muscle index (SMI), handgrip strength, and 6-min walk distance (6MWD), were assessed. Correlation and multiple regression analyses were performed to identify factors associated with PImax %pred. Results: PImax %pred was significantly lower than the predicted value (69.5% [95% CI: 63.1–75.9], p < 0.001), whereas PEmax %pred did not differ significantly from the predicted value (95.6% [95% CI: 86.8–104.3]). PImax %pred was significantly associated with age, BMI, SMI, handgrip strength, and 6MWD. In multiple regression analysis, age, sex, BMI, and handgrip strength were independently associated with PImax %pred, whereas DPN was not. These findings remained unchanged after adjusting for smoking habits. Conclusions: Inspiratory muscle strength was selectively reduced in Japanese patients with T2DM and was independently associated with general physical characteristics and overall muscle strength. Inspiratory muscle weakness may reflect generalized skeletal muscle dysfunction rather than solely a neuropathic impairment. This assessment of respiratory muscle strength may provide additional insights into the physical function of patients with T2DM. Full article

Metabolic syndrome (MeS) is a major risk factor for cardiovascular disease and is characterized by chronic low-grade inflammation, immune dysregulation, and metabolic abnormalities. However, the molecular mechanisms linking MeS to diabetic coronary artery disease (DMCAD) remain incompletely understood. Publicly available peripheral blood mononuclear cell (PBMC) transcriptomic datasets of MeS and DMCAD were analyzed using an integrative bioinformatics approach. Differentially expressed genes (DEGs) were identified using the limma package, followed by functional enrichment, protein–protein interaction (PPI) network construction, weighted gene co-expression network analysis (WGCNA), gene set enrichment analysis (GSEA), and miRNA regulatory network analysis. Candidate genes were further evaluated using an independent type 2 diabetes mellitus (T2DM) dataset for external transcriptomic validation. Integrated analyses identified immune-inflammatory and immuno-metabolic pathways as central features of both MeS and DMCAD. Enrichment analyses highlighted cytokine signaling, leukocyte activation, chemotaxis, complement activation, oxidative stress, and vascular inflammatory responses. Network analyses identified CD86, CD33, CCR1, C5AR1, FPR1, CXCL16, and LILRA5 as key hub genes associated with immune regulation and cardiometabolic dysfunction. External transcriptomic validation supported the relevance of CD33, CD86, and LILRA5. miRNA network analysis identified members of the miR-17/92 family and miR-146a-5p as potential upstream regulators. TAM 2.0 enrichment analysis further linked these miRNAs to metabolic syndrome, diabetes mellitus, atherosclerosis, coronary heart disease, immune response, inflammation, and angiogenesis. Our findings suggest that coordinated immune-inflammatory and metabolic signaling networks contribute to the progression from MeS to DMCAD. The identified hub genes and miRNAs may serve as potential biomarkers and therapeutic targets for inflammation-driven cardiometabolic disease. Full article

Background: The onset of type 2 diabetes mellitus (T2DM) is often preceded by prediabetes, a reversible state of insulin resistance and impaired glucose regulation driven by the chronic consumption of a high-calorie diet and sedentary lifestyle. Prediabetes is characterised by impaired glucose tolerance and elevated glycated haemoglobin (HbA1c). Although metformin improves insulin sensitivity, adherence limitations to lifestyle interventions highlight the need for alternative drugs that can be effective even without dietary intervention. In our laboratory, we synthesised a novel ruthenium complex that exhibits elevated biological activity. Accordingly, this study investigated the metabolic effects of a novel ruthenium (II)–uracil Schiff base complex in HFHC diet-induced prediabetic rats, with and without dietary intervention. Methods: Forty-eight male Sprague-Dawley rats (150–180 g) were divided into two groups, the standard diet (n = 12) and HFHC diet groups (n = 36), for prediabetic induction. Prediabetic animals were randomly assigned to respective treatment groups. The ruthenium complex was administered to prediabetic rats once a day, every third day, for 12 weeks, while monitoring changes in blood glucose, caloric intake, and body weight. Results: Diet-induced prediabetes resulted in increased fasting blood glucose and elevated HbA1c. The administration of the ruthenium (II)–uracil Schiff base complex reduced fasting blood glucose, improved insulin levels and ghrelin, enhanced GLUT4 expression, and significantly increased skeletal muscle glycogen, especially when combined with dietary intervention. Conclusions: The findings showed that the ruthenium complex exerts a pronounced effect on ameliorating glucose homeostasis, enhancing skeletal muscle glucose uptake, and improving overall metabolic function. Full article

Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major global health challenge due to its high prevalence and association with chronic complications, highlighting the need for reliable predictive tools to support clinical decision-making. Methods: This study proposes a two-stage hierarchical prediction system based on a Random Forest (RF) classifier. In Stage 1, the model performs multiclass classification into healthy (H), T2DM without complications (D), and T2DM with complications (C). In Stage 2, patients classified as C are further stratified into microvascular or macrovascular complications. The dataset included 31 biochemical, molecular, inflammatory, and oxidative stress variables from Mexican and Spanish cohorts. Feature selection was performed using Pearson correlation, and feature relevance was further assessed using RF importance measures. Model training used stratified cross-validation, with additional evaluation on a hold-out set to approximate real-world performance. Results: The optimized RF achieved an accuracy of 92% and a macro F1-score of 0.92, outperforming baseline models, with an AUC-ROC of 0.89 for complication prediction. Key predictive features included IL-18, miR-126, duration of T2DM, HbA1c, and IL-10. Conclusions: The novelty of this study lies in integrating heterogeneous biomarkers within a hierarchical predictive framework, rather than in the machine learning algorithm itself. This multimodal approach, combined with interpretable machine learning techniques, is designed to deliver clinically meaningful insights for patient stratification and personalized management in T2DM. Full article