Search Results (11,218)

Tirzepatide, a dual glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) receptor agonist, demonstrates robust efficacy in glycemic control and weight reduction. However, substantial interindividual variability in treatment response is observed in clinical practice. In this narrative review, we summarize current evidence on clinical, genetic, and molecular predictors of tirzepatide response and discuss their implications for a precision medicine framework. Data from pivotal clinical trials, post hoc analyses, and relevant preclinical and clinical studies were evaluated to identify determinants of glycemic and weight loss responses, as well as hepatic and renal protective effects. Key clinical predictors include tirzepatide dose, duration of diabetes, β-cell function, baseline glycated hemoglobin, sex, age, race, concomitant therapies, and early treatment response. Genetic factors implicated in treatment variability include variants in GLP-1 receptor, GIP receptor, β-arrestin 1, transcription factor 7-like 2, fat mass and obesity-associated protein, and melanocortin 4 receptor, although tirzepatide-specific validation remains limited. Molecular biomarkers such as branched-chain amino acids, insulin-like growth factor–binding protein-1 and -2, the adiponectin-to-leptin ratio, high-sensitivity C-reactive protein, and interleukin-6 show potential as pharmacodynamic indicators of metabolic response. For organ-specific outcomes, procollagen type III N-terminal peptide and magnetic resonance imaging–proton density fat fraction are supported for assessing hepatoprotective effects, while cystatin C–based estimated glomerular filtration rate and urine albumin-to-creatinine ratio are validated markers of renoprotection. Additional candidates—including tumor necrosis factor receptor 1/2, kidney injury molecule-1, and neutrophil gelatinase-associated lipocalin—are promising but require prospective validation. Overall, predicting response to tirzepatide’s multifaceted therapeutic effects necessitates an integrated, multidimensional approach that incorporates clinical characteristics, genetic variation, and molecular profiling. Ongoing validation and harmonization of these predictors may help establish a precision medicine framework for optimizing tirzepatide therapy. Full article

Diabetes mellitus is a chronic and increasingly prevalent metabolic disorder characterized by persistent hyperglycemia, resulting from defects in insulin secretion, insulin action, or both. Despite the availability of pharmacological agents that effectively manage blood glucose levels, many are associated with adverse effects, limited efficacy over time, and high costs. Consequently, there is growing interest in alternative therapies, especially those derived from traditional medicinal plants, that have long been employed in various cultures for managing diabetes. Recent advances in phytochemistry have identified bioactive plant secondary metabolites with promising antidiabetic properties. This review aims to provide a comprehensive overview of plant-derived compounds that exhibit inhibitory activity against key diabetes-related enzymes, including α-glucosidase, α-amylase, protein tyrosine phosphatase 1B (PTP1B) and dipeptidyl peptidase-4 (DPP-4). These enzymes play critical roles in glucose metabolism and insulin signaling pathways. The review highlights the structural diversity of these natural inhibitors, their mechanisms of action, and their effectiveness in preclinical models. Understanding the molecular interactions and pharmacological profiles of these metabolites may facilitate the development of safer and more effective antidiabetic agents. Full article

Osteoporosis is a systemic skeletal disorder characterized by low bone mass, microarchitectural deterioration, and an increased risk of fracture. Its pathogenesis is closely associated with disturbances in energy metabolism, particularly glucose metabolic reprogramming in bone cells. Under osteoporotic conditions, the balance between osteoblasts and osteoclasts is disrupted, accompanied by impaired oxidative phosphorylation, dysregulated glycolysis, and reduced tricarboxylic acid cycle efficiency, ultimately leading to mitochondrial dysfunction. These metabolic alterations result in an insufficient energy supply and accelerate bone loss. Accordingly, the modulation of key enzymes involved in glucose metabolism has emerged as a promising therapeutic strategy. Strategies include the use of natural compounds, traditional Chinese medicine formulas, and specific inhibitors to modulate glucose metabolism processes and related pathways, thereby restoring cellular energy homeostasis and bone remodeling balance. This review summarizes pharmacological agents regulating glucose metabolism and proposes a hierarchical framework for therapeutic prioritization: first, inhibiting pathological glycolysis in osteoclasts (particularly via LDHA and PKM2). Second, restoring oxidative phosphorylation in osteoblasts (e.g., via COX I–V or ATP synthase). And third, employing multi-target traditional Chinese medicine formulas as complementary strategies. By establishing this cell-type-specific and pathway-specific hierarchy, the review aims to provide a theoretical basis for future research on metabolic interventions in bone diseases. Full article

Background/Objectives: Obesity represents a significant global health challenge. Although alternate-day fasting (ADF) has been shown to effectively improve metabolic parameters, long-term adherence to this regimen remains limited. This study aimed to investigate whether highly polymerized persimmon tannin (DP31) could serve as a practical alternative to ADF for the prevention of high-fat diet (HFD)-induced obesity in mice. Methods: Male C57BL/6J mice (n = 10 per group) were subjected to an HFD for 11 weeks, during which they concurrently received either DP31 or ADF. Body weight, fat mass, serum lipid levels, glucose tolerance, fasting glucose, and insulin levels were assessed. Additionally, hepatic transcriptomics, Western blotting, 16S rRNA sequencing, and short-chain fatty acids (SCFAs) analysis were conducted. Results: DP31 demonstrated comparable efficacy to ADF in reducing body weight gain and improving lipid profiles, while exhibiting superior effects on glucose tolerance and fasting glucose levels (p < 0.05). Both interventions effectively reversed HFD-induced hepatic gene dysregulation, leading to the upregulation of genes involved in processes related to steroid metabolism. In addition, both treatments activated the hepatic AMPK-mTORC1-Lpin1 axis, suppressed lipogenesis, upregulated PGC1α, and increased β-hydroxybutyrate levels, indicating enhanced fatty acid oxidation (p < 0.05). Notably, DP31 outperformed ADF in enriching beneficial gut genera, such as Akkermansia, and boosting SCFAs production, which may elucidate its superior glycemic control. Overall, DP31 exhibits comparable effects to ADF in preventing obesity-related metabolic disorders, while demonstrating superior effects on glucose homeostasis. Full article

This study investigated the individual and combined effects of SFO and LP supplementation on growth performance, carcass traits, meat quality, fatty acid profile, and serum biochemical indices in crossbred (Boer × Saanen) buck goats. Twenty-eight bucks (4 months old; 18.42 ± 2.03 kg) were randomly assigned to four treatments (n = 7): control, SFO (5–10 mL/day), LP (10 mL containing 10⁷ CFU/goat on alternate days), and SFO+LP. Growth performance was not affected; however, the feed conversion ratio (FCR) improved significantly (p < 0.001) in supplemented groups, with improved efficiency observed in SFO+LP, indicating enhanced feed utilization efficiency despite differences in feed intake. Carcass traits were unchanged. Meat quality improved in SFO and SFO+LP groups, as evidenced by lower pH at 45 min postmortem (p = 0.045) and reduced Warner–Bratzler shear force (p = 0.036), indicating enhanced tenderness. The combined SFO+LP treatment significantly increased C18:2 n6t (p = 0.036), total CLA (p = 0.003), and total PUFA (p = 0.001), indicating improved nutritional value of the lipids. Significant treatment × time interactions (p < 0.05) were observed for lipid and enzyme parameters, with values increasing over time in the supplemented groups, while glucose remained unchanged. These results indicate a synergistic interaction between SFO and LP, likely through modulation of rumen biohydrogenation and lipid metabolism, enhancing feed efficiency and meat functional quality without compromising metabolic health. Full article

Obesity development is linked to disturbances in the gut microbiota. Inonotus obliquus polysaccharides (IOPs) have potential therapeutic efficacy in alleviating metabolic disorders. However, the mechanism by which IOP prevents obesity via regulating gut microbiota remains elusive. IOP was extracted and structurally characterized by FT-IR and NMR spectroscopy, confirming typical polysaccharide structures. Structurally, IOP is a 5.4 kDa polysaccharide predominantly composed of glucose, galactose, xylose, mannose, galacturonic acid, glucuronic acid, as well as rhamnose, arabinose, and methyl-galactose. Administration of IOP to high-fat diet (HFD)-fed mice effectively curtailed weight gain and improved serum lipid parameters. Furthermore, it mitigated lipid deposition within hepatic and adipose tissues, while successfully countering HFD-triggered liver damage. Notably, IOP induced significant changes in microbial diversity and composition by selectively increasing the abundance of Streptococcaceae while suppressing Faecalibaculum rodentium at the family and species levels. These findings highlight that IOP is a promising functional food ingredient that regulates gut microbiota for obesity prevention. Full article

Selenium (Se) is an important micronutrient that is required in very small amounts and plays a significant role in enhancing plant growth, stress resistance, and fruit quality. In this study, we investigated the effects of different sodium selenite concentrations (CK, 0 mg/L; Se1, 0.50 mg/L; Se2, 1.00 mg/L, Se3, 2.00; and Se4, 3.00 mg/L) on the growth, nutrient absorption, antioxidant capacity, and leaf metabolome of blueberry (Vaccinium corymbosum L. ‘Brigitta’) in hydroponic culture. Our results showed that moderate Se concentration (1.00 mg/L, Se2) had noticeable enhancements in key traits like taller plants, thicker stems, a greater number of leaves, and stem fresh weight, with increases of 60.23%, 61.90%, 36.05%, and 87.97%, respectively, compared to the CK. In addition, the appropriate application of Se fertilizer (1.0 mg/L, Se2) can enhance the absorption of macronutrients by plants, with the total contents of nitrogen (N), phosphorus (P), and potassium (K) increasing by 48.11%, 15.85%, and 14.25%, respectively, compared to CK. In comparison to CK, the content and accumulation of total Se rose dramatically under the Se4 treatment, showing increases of 2300% and 2514%. The contents of chlorophyll and antioxidant enzyme activities were maximized at Se2, while excessive Se (Se4) led to oxidative damage, as indicated by elevated MDA, H₂O₂, and O₂⁻ levels. Moreover, metabolomic analysis revealed that moderate Se concentration (Se2) significantly altered metabolic pathways related to aminoacyl-tRNA biosynthesis, arachidonic acid metabolism, and ABC transporters, with downregulation of key metabolites in sugar and organic acid metabolism (e.g., α-D-glucose-6-phosphate, L-lactic acid, maleic acid). In contrast, high Se concentration (Se4) disrupted these pathways and promoted volatile compound accumulation. These findings demonstrate that moderate Se application enhances blueberry growth and quality by regulating nutrient uptake, antioxidant defense, and primary metabolism, whereas excessive Se induces metabolic imbalance and oxidative stress. Overall, moderate Se fertilizer (1.00 mg/L) can significantly enhance the growth and quality of blueberries, while excessive selenium may have adverse effects. Full article

Intensive aquaculture of rice field eel (Monopterus albus) is constrained by oxidative stress induced by high-density culture resulting in growth inhibition, while prophylactic antibiotics pose escalating risks of drug resistance and food safety hazards. This study addresses the critical need for developing efficient, environmentally friendly functional feed additives as sustainable growth promoters in intensive aquaculture. To investigate the dietary berberine (BBR) effect on promoting growth performance, hepatic antioxidant capacity and metabolism in M. albus, four experimental groups were established: control (CON, 0 mg/kg) and berberine-supplemented groups (BBR25, 25 mg/kg; BBR50, 50 mg/kg; BBR100, 100 mg/kg). Growth performance, serum biochemical parameters, hepatic antioxidant capacity, and liver metabolomics (LC-MS) were evaluated after the 8-week feeding trial. BBR50 and BBR100 had significantly increased final weight, weight gain rate (WG), and survival rate (SR), while reducing feed conversion ratio (FCR) (p < 0.05). Serum glucose (Glc), total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) were decreased (p < 0.05), while high-density lipoprotein cholesterol (HDL-C) and phosphofructokinase (PFK) activity were increased (p < 0.05). Alanine aminotransferase (ALT), aspartate aminotransferase (AST) and alkaline phosphatase (ALP) were significantly reduced (p < 0.05). Superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were upregulated (p < 0.05), whereas malondialdehyde (MDA) was downregulated (p < 0.05). Metabolomics identified 98 differential metabolites, with significant enrichment of metabolites associated with arachidonic acid metabolism, histidine metabolism, arginine/proline metabolism, tryptophan metabolism, and pathways related to mTOR signaling. Overall, dietary supplementation with 50 mg/kg BBR emerged as a practically favorable dose among the tested concentrations for promoting growth performance and feed utilization efficiency, whereas 100 mg/kg BBR was associated with lipid and amino acid metabolic alterations suggestive of metabolic reprogramming and antioxidant-related shifts, without conferring additional growth benefits. Full article

Obesity contributes to an increase in the prevalence of metabolic dysfunction-associated fatty liver disease (MAFLD) and is diagnosed when hepatic steatosis is accompanied by at least one of the following factors: obesity or overweight, diabetes mellitus, or signs of metabolic abnormalities. MAFLD is a term that encompasses a wide range of liver disorders, ranging from simple steatosis to metabolic steatohepatitis, which can progress to cirrhosis and eventually, hepatocellular carcinoma (HCC). Lipotoxicity generated by a high-fat diet causes liver inflammation, therefore, blocking inflammatory pathways is considered a promising strategy to prevent MAFLD progression. Inflammatory responses and oxidative stress are linked to endoplasmic reticulum stress, thereby activating the unfolded protein response (UPR) pathway. Although drugs such as resmetirom and semaglutide have recently been approved for the treatment of MAFLD, there is still a need to identify complementary therapies with different mechanisms of action. In this context, the present study evaluated the hepatoprotective effect of ellagic acid through the modulation of mRNAs of proteins in the UPR-Perk pathway in a murine model fed a high-calorie diet. This study revealed that the high-calorie diet activated the UPR pathway in response to stress, increasing the expression of the Grp78, Eif2ak3, Eif2α, Ddit3, Atf4, and Nfe2l2 genes in the liver and epididymal adipose tissue. Ellagic acid modulated the pathway genes and reduced levels of glucose, total cholesterol, HDL and VLDL, triglycerides, insulin, and glycated hemoglobin, and could therefore be considered a hepatoprotective agent. Full article

Cardio-renal metabolic (CRM) syndrome, characterized by insulin resistance and dyslipidemia, disrupts renal insulin signaling, enhances oxidative stress, and activates inflammasome pathways, ultimately promoting renal fibrosis and kidney dysfunction. Aberrant renal gluconeogenesis has emerged as a critical contributor to tubular injury under cardiometabolic stress; however, its mechanistic linkage to inflammatory and fibrotic remodeling remains incompletely defined. In this study, ApoE^−/− mice subjected to streptozotocin administration and a high-fat diet developed pronounced cardiometabolic dysfunction, accompanied by elevated blood urea nitrogen, creatinine, uric acid, and glycated hemoglobin levels, as well as severe renal histopathological alterations. N-Acetylcysteine (NAC) supplementation significantly improved metabolic abnormalities and attenuated tubular dilation, glomerular hypertrophy, and mesangial expansion. Mechanistically, NAC suppressed renal gluconeogenesis by downregulating glucose-6-phosphatase and phosphoenolpyruvate carboxykinase expression and mitigated epithelial–mesenchymal transition by restoring E-cadherin and reducing vimentin expression, thereby limiting fibrotic remodeling. Consistent with in vivo findings, NAC reduced reactive oxygen species production, restored PI3K/Akt-dependent insulin signaling, and inhibited inflammasome activation in NRK-52E renal tubular cells exposed to high glucose and oleic acid, resulting in attenuation of inflammatory signaling and gluconeogenic activity. Collectively, these results demonstrate that NAC mitigates cardiometabolic stress-induced renal injury by modulating inflammasome activation and gluconeogenic reprogramming, highlighting its potential as a mechanistic modulator of renal fibrosis under CRM conditions. Full article

Nitzschia sp., a diatom isolated from Paposo (Antofagasta, northern Chile), was evaluated as a biological solution for removing kaolinite-type clay minerals from recycled process water in large-scale copper mining. Optimization of culture conditions to maximize extracellular polymeric substance (EPS) production revealed that supplementing with 0.1 gL⁻¹ of glucose yielded the highest EPS levels on day 17, reaching 1285 ± 58.9 mgL⁻¹ (control equal to 237.8 ± 34 mgL⁻¹ on day 17). However, maximum dry weight biomass productivity was achieved in the presence of sodium carbonate at a concentration of 1 gL⁻¹ (319 ± 12.5 mgL⁻¹d⁻¹), significantly exceeding the productivity of the control group (242.7 ± 5.4 mgL⁻¹d⁻¹). Notably, low glucose supplementation enhanced EPS synthesis. Application of control-derived EPS of 1 gL⁻¹ rapidly decreased kaolinite initial turbidity from ~2024 FNU to ~354 ± 0.74 FNU within one minute. Even more glucose-derived EPS (1 gL⁻¹) further reduced turbidity to ~22.2 ± 0.1 FNU at 5 min, achieving a flocculation efficiency of ~98.9% after 15 min. Genomic analysis and KEGG annotation identified abundant genes for EPS and carbohydrate metabolism, including numerous glycosyltransferases, glycoside hydrolases, and multiple copies of UDP-glucose 4-epimerase, consistent with strong polysaccharide-biosynthesis capacity. Physicochemical characterization (particle sizing, HPLC, SEM, zeta-potential and FT-IR) showed EPS comprised mainly of rhamnose, fucose, arabinose, xylose and glucose, featuring functional groups (–OH, C=O/COO–, O-acetyl, uronic/guluronic signatures) that interact with kaolinite to promote aggregation. These findings demonstrate that Nitzschia-derived EPS, especially from glucose-supplemented cultures, represent promising sustainable bioflocculants for treating kaolinite-contaminated recycled water in mining operations. Full article

Background/Objectives: Dietary adherence to the Dietary Approaches to Stop Hypertension (DASH) pattern is associated with lower blood pressure; however, most prior studies have relied on office-based measurements and non-specific dietary assessment tools. This study examined the association between DASH diet quality, assessed by the validated DASH-Q questionnaire, and 24-h ambulatory blood pressure in treatment-naive adults referred for diagnostic ambulatory blood pressure monitoring (ABPM). Materials and Methods: This cross-sectional study enrolled 227 consecutive treatment-naive adults referred for diagnostic 24-h ABPM at a cardiology outpatient clinic. DASH diet quality was assessed using the validated Turkish version of the DASH-Q questionnaire and categorized as low (<36), moderate (36–49), or high (≥50). Hypertension was defined by ABPM-based thresholds. Multivariable linear regression was performed to identify independent predictors of 24-h mean systolic and diastolic blood pressure, and binary logistic regression was used to evaluate independent predictors of ABPM-defined hypertension, with both models adjusted for age, sex, BMI, smoking, physical activity, and self-reported discretionary salt-adding behavior. Results: DASH-Q total score was the sole statistically significant independent predictor of both 24-h mean systolic blood pressure (B = −1.068, 95% CI: −1.270 to −0.866; β = −0.589; p < 0.001) and diastolic blood pressure (B = −0.560, 95% CI: −0.706 to −0.414; β = −0.470; p < 0.001) in the adjusted models. Each one-unit higher DASH-Q score was also associated with 14.6% lower odds of ABPM-defined hypertension (OR = 0.854, 95% CI: 0.820–0.890; p < 0.001). Higher DASH-Q scores were further associated with a more favorable metabolic profile, including lower LDL cholesterol, triglycerides, glucose, and C-reactive protein levels. Conclusions: DASH diet quality was independently and inversely associated with 24-h ambulatory blood pressure and the odds of ABPM-defined hypertension in this treatment-naive population. Given the cross-sectional design and the possibility of reverse causality, these results should be interpreted as hypothesis-generating and require confirmation in prospective studies. Full article

Type 2 diabetes mellitus is a relevant cardio–renal–metabolic disorder in which chronic low-grade inflammation and oxidative stress have a crucial function in linking insulin resistance, endothelial dysfunction, β-cell impairment, and progressive organ injury. In this context, nutrition has emerged as a key modifiable determinant of metabolic homeostasis, capable of influencing inflammatory signalling, redox balance, mitochondrial function, and gut microbiota–host interactions. The objective of this review is to critically summarise the mechanistic connections among inflammation, oxidative stress, and diabetes progression, and to investigate how dietary factors and patterns, as well as nutrition-responsive biomarkers, influence these pathways and their cardiorenal consequences. We discuss the effects of macronutrient quality, dietary fibre, fatty acids, polyphenols, and specific micronutrients, including vitamin C, vitamin E, selenium, zinc, and magnesium, as well as the role of Mediterranean, DASH, and plant-based diets in improving glycaemic control, endothelial function, and cardio-renal risk profiles. We also summarise established and emerging biomarkers of inflammation and oxidative stress that may improve risk stratification and the evaluation of nutrition-based interventions. Overall, current evidence supports a shift from a purely glucose-centred approach toward an integrated model in which dietary modulation of inflammatory and oxidative pathways helps reduce cardiovascular and renal risk. However, heterogeneity of interventions, variability in biomarker assessment, and interindividual differences in dietary response represent major limitations. Future research should focus on biomarker-informed, precision-oriented nutritional approaches integrated within contemporary cardio–renal–metabolic care. Full article

Background: To investigate the effect of angiotensin-(1-7) [Ang-(1-7)] on serum metabolomics in obese type 2 diabetic (T2DM) mice. Methods: Four-week-old male C57BL/6 mice were fed a high-fat diet and intraperitoneally injected with streptozotocin (35 mg/kg) to establish an obese T2DM model. Mice were randomized into control, T2DM and T2DM+Ang-(1-7) groups (n = 6). Body weight and blood glucose were recorded weekly. At 10 weeks, blood glucose, serum inflammatory factors, lipid profiles, and pancreatic β-cell insulin secretion were detected; serum metabolite alterations were analyzed via untargeted metabolomics. Results: 1. Ang-(1-7) intervention decreased blood glucose (p < 0.05) and CRP levels (p < 0.01), and alleviated dyslipidemia (p < 0.05 or p < 0.01), as well as β-cell morphology and insulin expression in obese T2DM mice. 2. Non-targeted metabolomics analysis suggested that Ang-(1-7) may alleviate abnormal amino acid metabolic pathways by regulating levels of metabolites such as L-valine, L-proline, L-histidine, and glutamic acid. This intervention also tended to reduce multiple lipid metabolites, including Omega-3 Arachidonic Acid Ethyl Ester, phosphatidylcholine, and glycerophosphocholine, thereby participating in the modulation of lipid metabolism balance. KEGG enrichment analysis further indicated that Ang-(1-7) was involved in the regulation of protein digestion and the absorption pathway, as well as the HIF-1 signaling pathway related to oxidative stress, bile acid metabolism pathway, and other signaling pathways, and improving the insulin secretion pathway, pyrimidine metabolism, and TCA cycle energy metabolism pathway. Conclusions: Ang-(1-7) may partially improve metabolic disturbances in obese T2DM mice, which is potentially associated with the modulation of multiple metabolic processes, including amino acid metabolism, lipid metabolism, insulin secretion, and TCA cycle energy metabolism. Full article

Type 2 diabetes mellitus (T2DM) is a major global health challenge that has intensified interest in multi-target nutraceuticals with potential adjunctive benefits. Ganoderma lucidum (Lingzhi/Reishi) is a medicinal mushroom traditionally used in East Asia and is increasingly investigated for its role in glycemic regulation and metabolic disturbances. This review critically synthesizes current evidence on its hypoglycemic effects, focusing on bioactive compounds, molecular mechanisms, and translational limitations. Unlike broader reviews on Ganoderma bioactivity and health-related benefits, this review specifically evaluates the alignment between taxonomic authentication, chemical standardization, preclinical mechanisms, and human clinical evidence in the context of glycemic regulation. This narrative review was based on a targeted literature search conducted in PubMed/MEDLINE, Web of Science, and Scopus for studies published up to October 2025, supplemented by Google Scholar. The included studies comprised in vitro experiments, in vivo animal models, and human clinical trials evaluating glycemic and metabolic outcomes of Ganoderma preparations. In vitro and animal studies indicate that polysaccharides, including β-(1→3)/(1→6)-glucans and proteoglycans such as FYGL, may improve insulin sensitivity via AMPK (AMP-activated protein kinase) and PI3K/Akt pathways, promote GLUT4 (glucose transporter type 4) translocation, suppress hepatic gluconeogenesis, protect pancreatic β-cells, and modulate gut microbiota. In enzyme assays and preclinical models, lanostane-type triterpenoids act primarily by inhibiting α-glucosidase and α-amylase, thereby potentially reducing postprandial glucose excursions. Despite consistent preclinical evidence, clinical findings remain heterogeneous, with the largest randomized controlled trial reporting no significant glycemic benefit. Overall, Ganoderma lucidum shows strong mechanistic plausibility but insufficient clinical evidence for antidiabetic efficacy. Future research should prioritize species authentication, chemical standardization, and adequately powered clinical trials. Full article