Background and aims Accumulating evidence has demonstrated the benefits of soy and its extracts on glycemic control and insulin sensitivity. We hypothesized that different soy components might exhibit differentiated blood glucose and insulin sensitivity regulation effects. The goal of this network meta-analysis of randomized clinical trials (RCTs) was to estimate and rank the relative effects of soy and its extracts on glycemic control and insulin sensitivity. Methods We performed a strategic literature search of PubMed, Embase, and the Cochrane Library for relevant RCTs. Random-effects network meta-analyses, ranking analyses based on surface under the cumulative ranking curves (SUCRAs), and sensitivity analyses based on potential sources of heterogeneity were performed. We registered the study protocol at PROSPERO (no. CRD42022345831). Results Sixty-one RCTs enrolling 4,744 participants were included in the quantitative analysis. In random-effects network meta-analyses. Whole soy was ranked as the best diet (SUCRA: 91.0%) regarding fasting glucose-lowering effects, with isolated isoflavones was ranked as second (SUCRA: 79.1%). For fasting insulin regulation, the best soy component choices was whole soy (SUCRA: 95.4%) and isolated isoflavones (SUCRA: 74.7%). For HOMA-IR regulation, the best soy component choices was whole soy (SUCRA: 83.4%) and Soy protein + isoflavones (SUCRA: 83.3%). No soy products showed significant effect on regulating glycated HbA1c. Conclusions These findings highlight that different soy components exhibit distinct effects on regulating blood glucose and insulin sensitivity. In this network meta-analysis, whole soy and isolated isoflavones were identified as potentially superior choices for improving blood glucose control and insulin sensitivity compared with other soy products. Systematic review registration http://www.crd.york.ac.uk/ PROERO, identifier CRD42022345831.

Background Insulin resistance and visceral obesity are key pathologic mechanisms of CVD. However, the combined effect of the triglyceride glucose (TyG) index and body roundness index (BRI) on CVD risk in the diabetic population has not been thoroughly investigated. Methods The cohort study used data from four waves of the China Health and Retirement Longitudinal Study (CHARLS) conducted from 2011 to 2018, involving 1,010 participants with diabetes. Participants were categorized according to the median TyG index and/or BRI. Cox proportional risk regression models were used to examine the individual and joint associations of the two metrics with CVD risk. The study further estimated additive and multiplicative interaction effects. Results During a median follow-up of 7 years, 251 participants developed CVD. The study confirmed a significant joint association between TyG index and BRI and the development of CVD in middle-aged and elderly persons with diabetes. Specifically, after adjusting for confounders, participants with both high TyG index and high BRI had a 123% increased risk of CVD compared with participants with both low TyG index and low BRI, and 85% for high BRI alone. In addition, the study did not find an additive and multiplicative interaction between BRI and TyG index on CVD. Conclusion This study found that high TyG index and high BRI were significantly associated with increased risk of new-onset CVD in a Chinese middle-aged and elderly diabetic population, and the combined assessment of the TyG index and BRI enhanced the prediction of CVD.

Pseudomonas spp. are ubiquitous, metabolically versatile bacteria that exhibit remarkable adaptability to thrive in diverse ecological niches contaminated with aromatics, such as pesticide-polluted agricultural soils, industrial wastewater, and lignin-based waste. This review highlights the unique genetic and metabolic traits of Pseudomonas bharatica CSV86T, a novel soil bacterium capable of degrading a wide range of aromatics, including lignin-derived phenylpropanoid compounds. Unlike other pseudomonads, aromatic metabolism in strain CSV86T is not subjected to carbon catabolite repression by simple carbon sources. Instead, it preferentially utilizes aromatics over glucose/glycerol and co-metabolizes them with organic acids, circumventing a major bottleneck in biodegradation. The strain is plasmid-free and naphthalene metabolism pathway genes are present on conjugatively transferable integrative conjugative element, ICEnahCSV86, offering potential for genetic bio-augmentation. Notably, the strain grows slowly on glucose and metabolizes it exclusively via phosphorylative pathway, as oxidative routes are absent. Beyond aromatic metabolism, it displays multifarious plant growth-promoting and beneficial eco-physiological traits for niche colonization and adaptation, crucial for restoration of contaminated sites. Collectively, these unique traits position strain CSV86T as a niche-adapted alternative to model biodegradation strains, such as P. putida KT2440. Its potential can be further leveraged through metabolic engineering for detection, degradation, and up-cycling of aromatic pollutants.

N6-methyladenosine (m6A), a critical epitranscriptomic modification, regulates RNA metabolism and antiviral defenses. However, how pathogens evade m6A-mediated RNA decay in plants remains poorly understood. Here, we uncover a dynamic m6A modification arms race during infection of sugarcane mosaic virus (SCMV), a prevalent potyvirus that infects maize and causes 20%–80% yield loss. We demonstrate that maize m6A methyltransferase (ZmMTA) specifically deposits m6A at A6556 of the SCMV genomic RNA, enabling recognition by the m6A reader EVOLUTIONARILY CONSERVED C-TERMINAL REGION 23 (ZmECT23). ZmECT23 directly recruits the ZmCCR4-NOT (carbon catabolite repressor 4–negative on TATA) complex to facilitate viral RNA decay. Strikingly, SCMV counters the defense via its nuclear inclusion protein a protease (NIa-Pro), which hijacks maize eukaryotic initiation factor 4A-III (ZmeIF4A3) into viral replication complexes. ZmeIF4A3 sterically blocks ZmMTA-mediated m6A deposition, thereby preventing viral RNA from degradation. Mechanistic conservation is observed in potato virus Y and turnip mosaic virus, two other potyviruses that are modified with m6A. Our study identifies eIF4A3 as a key m6A regulator in plants and reveals a strategy used by potyviruses to subvert m6A-based immunity via exploiting host RNA helicases. These findings provide mechanistic insights into host-pathogen interactions as mediated by m6A and suggest eIF4A3 as a potential target for engineering m6A-based antiviral crops.

Characterizing the interactions between murine cytomegalovirus M72 and the carbon catabolite repression 4-negative on TATA-less (CCR4-NOT) complex.

Enhanced glutathione production in Saccharomyces cerevisiae via transporter activation and catabolic pathway engineering.

2,3-Butanediol (2,3-BDO) is recognized for its industrial competitiveness and is predominantly produced in its enantiomerically pure form via microbial fermentation. The economical production of 2,3-BDO relies on the effective use of complex lignocellulosic materials and the advancement of inhibitor-resistant microbial strains. The robust expression of 2,3-BDO dehydrogenase in bacteria enhances volumetric productivity in inhibitor-rich lignocellulose hydrolysate. For instance, isolation of an inhibitor-resistant Klebsiella pneumoniae from palm oil effluent facilitated the synthesis of 75g L⁻¹ of 2,3-BDO through separate hydrolysis and fermentation process. Conversely, the electrochemical detoxification of sugarcane bagasse hydrolysate increased the production of 2,3-BDO to 114.3g L⁻¹ in Enterobacter aerogenes. Furthermore, deletion of glucose transporter (ptsG) in 2,3-BDO-producing bacteria mitigated carbon catabolite repression (CCR). Adaptive evolution of Paenibacillus polymyxa in non-detoxified wheat straw hydrolysate enhanced 2,3-BDO productivity to 0.72g L⁻¹ h⁻¹. However, the rational engineering of yeast is complex, encompassing the heterologous expressions of xylose metabolism, 2,3-BDO dehydrogenase, and the deletion of the Crabtree effect. Nevertheless, partial disruption of the Crabtree effect in polyploid Saccharomyces cerevisiae resulted in increased production of 2,3-BDO (132g L⁻¹) during the fed-batch fermentation of cassava hydrolysate. This review paper discusses the benefits and drawbacks of 2,3-BDO metabolism in both bacteria and yeast. The paper seeks to clarify the differences in 2,3-BDO production between detoxified and non-detoxified lignocellulosic hydrolysates. Further, the study illustrates the importance of generating 2,3-BDO from untreated lignocellulose via the development of microbial consortia. Economic factors that facilitate the commercialization of 2,3-BDO fermentation have been discussed in detail.

Effect of exogenous glucose and sucrose on quality maintenance of 'Huangguogan' fruit during postharvest storage.

Diabetic wound healing has long been plagued by a series of complex problems caused by the pathological environment of high glucose, such as ischemia, hypoxia, and inflammatory responses. In order to solve this dilemma, we developed a new gel preparation with both green natural characteristics and excellent biological activity, aiming to provide an efficient and safe solution for diabetic wound healing. The gel uses microalgae as the core carrier, and it also plays an important role as an oxygen supply source. Through covalent bonding, the functional component concanavalin A and PEG-modified gold nanoparticles (PEG-AuNPs) were efficiently loaded on the polymer, which ensured the stable existence and controlled release of the components. Subsequently, the composite system was incorporated into the pre-gel fluid of the photocrosslinked methacryloylated gelatin to obtain our designed gel composite. On the one hand, the microalgae present in the material can continuously produce oxygen driven by light, effectively improve the local hypoxic microenvironment of the wound, and provide sufficient oxygen for cell proliferation and tissue repair. On the other hand, concanavalin A can specifically bind to glucose, and then cooperate with AuNPs with glucose oxidase activity to exert an efficient local hypoglycemic effect, thereby alleviating the adverse effects of high glucose on healing from the root. Through systematic experimental verification, this study confirmed the application prospects of this biocomposite material with multiple pro-healing properties in the field of diabetic wound management.

Fluoride is commonly used in dentistry to prevent dental caries, however, excessive exposure may pose risks to soft tissues, particularly the kidneys, which are responsible for approximately 60% of fluoride excretion. Diabetic nephropathy, a major complication of diabetes mellitus, may share pathogenic pathways with fluoride-induced renal toxicity. However, the combined effects of chronic hyperglycemia and fluoride exposure on kidney cells remain poorly understood. This study investigated the effects of fluoride on murine renal tubular epithelial cells (M-1) and on murine kidneys under normal and hyperglycemic conditions. M-1 cells were cultured under high-glucose conditions (22.5 mM) and/or treated with fluoride (1 µM or 5 µM) for 24 to 72 h. Diabetic C57BL/6J mice received drinking water containing fluoride (10 mgF/L or 50 mgF/L) for 21 days. Evaluations included cell viability and morphology in vitro, collagen deposition in renal tissue by birefringence analysis, and expression of the kidney injury marker KIM-1 by immunofluorescence in both models. M-1 cells exposed to fluoride alone showed increased viability at 72 h, while KIM-1 expression was elevated in high-glucose and high-glucose + 1 µM fluoride conditions, suggesting a stress or adaptive response. In diabetic mice, glomerular collagen accumulation, indicative of early fibrosis, was observed but attenuated by fluoride treatment. However, high KIM-1 levels in fluoride-treated diabetic mice, particularly at the higher dose, indicated potential kidney injury. These results highlight a complex, dual role of F in the diabetic kidney, potentially protecting against glomerular fibrosis while exacerbating tubular injury at high doses. Careful monitoring of F exposure is needed, especially in areas with endemic fluorosis and high chronic kidney disease risk.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10735-025-10670-6.

Synergistic and divergent effects of dietary sugars on hepatocyte viability and steatosis.

BackgroundHypoglycaemia stimulates growth hormone (GH) secretion, whereas hyperglycaemia suppresses it. However, the underlying mechanisms are not fully understood, particularly the potential role of gut-derived hormones released in response to oral glucose.AimTo investigate whether GH suppression is modulated by the route of glucose administration.MethodsA two-day intervention study in healthy volunteers. GH, insulin, glucagon-like peptide-1 (GLP-1), and glucose-dependent insulinotropic polypeptide (GIP) responses during a 2-h oral glucose tolerance test (OGTT) were compared with those during a 2-h isoglycaemic intravenous (IV) glucose infusion. GH levels were analyzed using paired t-test of GH concentrations at every blood sample time point. The effect of intervention on all measured hormones were also assessed by paired t-test of Area Under the Curve (AUC).Results12 healthy volunteers (6 females, mean age 47.9 ± 5.4 years) were included. In 9 of the 12 subjects, IV glucose induced an early peak in plasma-GH followed by a decrease. At 20 min after glucose intake GH levels increased by 46% during IV glucose compared to a decrease of 17% during oral glucose. The biggest numerically difference in GH between oral vs IV glucose was seen at 45 min (median [range], 0.30 [0.05–1.13] vs. 0.46 [0.05–9.82] µg/l, p = 0.072). There was no difference between AUC of GH levels (p = 0.381). During IV glucose, two subjects did not reach the threshold for excluding acromegaly. Oral glucose showed significant increases compared to IV glucose for insulin (p < 0.001), GLP-1 (p = 0.002) and GIP (p < 0.001) when using paired t-test of AUC.ConclusionsRoute of glucose exposure might influence the suppressive effect of glucose on GH secretion. This finding suggests that stimulation of other hormone systems may play a contributing role on the regulation of GH. The potential mechanism behind remains elusive but changes in gut-derived hormones might be of importance.

The triglyceride-glucose (TyG) index is an important determinant influencing the incidence of cardiometabolic multimorbidity (CMM). However, it remains unclear whether combining the TyG index with novel obesity indices (CVAI/BRI/ABSI/WWI) can improve the risk stratification of CMM. This study aimed to systematically compare the incremental risk assessment and predictive value of the TyG index, TyG-traditional obesity indices (TyG-WC/TyG-WHtR/TyG-BMI), and TyG-novel obesity indices (TyG-CVAI/TyG-BRI/TyG-ABSI/TyG-WWI) for CMM. Trajectory changes and cumulative exposure of TyG-related parameters were quantified using repeated measurements from the CHARLS cohort (n = 3,885). The study endpoint CMM was defined as a comorbid condition encompassing two or more cardiometabolic diseases, namely diabetes, stroke and heart diseases. A multi-model analytical strategy was employed to evaluate the associations between TyG-related parameters and CMM, as well as the contribution of their components. The net reclassification index and integrated discrimination improvement were employed to evaluate the improvement in predictive performance of these indices. Over a median follow-up period of 8 years, we identified a linear positive association between TyG-related parameters and CMM, with the cumulative effects of glucose and obesity emerging as the key drivers. Compared with the baseline TyG index, the incremental risk assessment value for CMM improved by 10%-17% (baseline) and 12%-20% (cumulative exposure) for TyG-traditional obesity indices, while the improvement for TyG-novel obesity indices ranged from - 1% to 16% and 5%-19%, respectively. In summary, all TyG-traditional obesity indices demonstrated strong associations with CMM, whereas among the TyG-novel obesity indices, only TyG-CVAI showed a similarly strong association. Furthermore, all TyG-related parameters showed significantly increased hazard ratios in their highest-exposure or poor-control status versus the reference (lowest exposure or good control): TyG-index (1.69/2.05), TyG-WC (2.24/2.28), TyG-WHtR (1.92/2.05), TyG-BMI (1.85/2.27), TyG-CVAI (1.89/2.07), TyG-BRI (1.94/2.08), TyG-ABSI (1.70/1.85), and TyG-WWI (1.97/1.95). Predictive analyses showed that, except for TyG index, TyG-ABSI and TyG-WWI, all other TyG-related parameters provided a certain degree of net improvement compared with the baseline risk model. All eight TyG-related parameters can predict the incidence of CMM. Given their relative simplicity, the TyG-traditional obesity indices demonstrate superior incremental risk assessment and predictive value for CMM compared to the TyG-novel obesity indices and the TyG index, positioning them as promising and more practical tools for clinical practice.

BackgroundThe effect of maternal blood lipids and glucose on the relationship between pre-pregnancy body mass index (BMI) and newborn birthweight (NBW) in pregnant women with gestational diabetes mellitus (GDM) remains unclear. This study aimed to examine whether maternal blood lipids and glucose mediate the relationship between pre-pregnancy BMI and NBW in pregnant women with GDM.MethodsA retrospective study was conducted on 1257 women with GDM who gave birth at the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China, between November 2017 and July 2021. Maternal blood lipids were measured at the first prenatal care (6–13 weeks of gestation). Glucoses, including mid-pregnancy fasting plasma glucose (FPG) and post-load glucose, were measured at 24–28 gestational weeks using an oral glucose tolerance test (OGTT). Multivariable linear regression was used to evaluate the significance of assumed paths. According to the results of multivariable linear regression, significant lipids and glucose were included in a multiple mediation analysis as mediators. Sensitivity analysis was performed to verify the robustness of the results.ResultsEarly-pregnancy high-density lipoprotein cholesterol (HDL-C) and mid-pregnancy FPG were associated with pre-pregnancy BMI and NBW. Early-pregnancy HDL-C was associated with mid-pregnancy FPG. The multiple mediation analysis revealed that pre-pregnancy BMI not only had a direct effect on NBW (effect = 23.592, 95% CI [14.366, 32.306]) but also had an indirect effect (effect = 5.602, 95%CI [2.812, 8.648]) on NBW through three paths: the independent mediating role of early-pregnancy HDL-C (effect = 1.649, 95% CI [0.103, 3.472]); the independent mediating role of mid-pregnancy FPG (effect = 3.739, 95% CI [1.653, 6.164]); and the multiple chain-mediating role of early-pregnancy HDL-C and mid-pregnancy FPG (effect = 0.214, 95% CI [0.054, 0.508]). The mediated proportions of the three paths were 5.65%, 12.81%, and 0.73%.ConclusionsMaternal early- pregnancy HDL-C and mid-pregnancy FPG partially mediate the association between pre-pregnancy BMI and NBW in pregnant women with GDM.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12884-025-08264-x.

Type 2 diabetes is highly prevalent, and many adults, especially those not using insulin, struggle to reach HbA1c targets. This review aimed to evaluate the effect of self-monitoring blood glucose (SMBG) and continuous glucose monitoring (CGM) on glycaemic control in adults with type 2 diabetes. We searched MEDLINE, Cochrane Library, Embase, and Scopus from January 2014 to May 2025 for systematic reviews of randomized controlled trials enrolling adults with type 2 diabetes that evaluated SMBG or CGM versus no monitoring or SMBG, respectively. Fifteen systematic reviews comprising 81 unique studies and 23 657 participants were included. Reviews comparing SMBG with no monitoring demonstrated a modest but significant reduction in HbA1c (MD -0.23%, 95% CI -0.29 to -0.18; I2 = 21%). Reviews directly comparing CGM with SMBG showed greater HbA1c reduction with CGM (MD -0.29%, 95% CI -0.34 to -0.24; I2 = 0%). Subgroup analyses for SMBG indicated consistent benefits across follow-up duration, monitoring structure, and study quality, although heterogeneity was high in some comparisons. Subgroup analyses for CGM types found both isCGM/FGM (MD -0.27%, 95% CI -0.43 to -0.11) and rtCGM (MD -0.36%, 95% CI -0.45 to -0.27) superior to SMBG. These findings support glucose monitoring for optimizing glycaemic management and outcomes. Further investment in cost-effectiveness studies is warranted to assess broader implementation in this population.

Temporal changes in blood glucose levels are useful in assessing glucose tolerance. While blood glucose levels are known to be tightly regulated by insulin-dependent and -independent (glucose effectiveness) hypoglycemic effects, their temporal changes and the organs involved have not been sufficiently explored. This study showed how the relative strengths of these effects change over time during the glucose clamp test, using biological experiments and a mathematical model. We found that the glucose effectiveness exhibited a transient effect within 60 min, whereas the insulin-dependent effect showed a sustained effect intensified after 60 min. Additionally, we found that the liver and muscles were responsible for glucose effectiveness and insulin-dependent hypoglycemic effects, respectively. We applied this model to obese mice and found that both hypoglycemic effects decreased as obesity progressed. These results provide insights into hypoglycemic effects and have important implications for the assessment and interpretation of glucose tolerance in mice.

Temporal changes in blood glucose levels are useful in assessing glucose tolerance. While blood glucose levels are known to be tightly regulated by insulin-dependent and -independent (glucose effectiveness) hypoglycemic effects, their temporal changes and the organs involved have not been sufficiently explored. This study showed how the relative strengths of these effects change over time during the glucose clamp test, using biological experiments and a mathematical model. We found that the glucose effectiveness exhibited a transient effect within 60 min, whereas the insulin-dependent effect showed a sustained effect intensified after 60 min. Additionally, we found that the liver and muscles were responsible for glucose effectiveness and insulin-dependent hypoglycemic effects, respectively. We applied this model to obese mice and found that both hypoglycemic effects decreased as obesity progressed. These results provide insights into hypoglycemic effects and have important implications for the assessment and interpretation of glucose tolerance in mice.

Background: Type II Diabetes Mellitus (T2DM) is associated with a prothrombotic state due to altered coagulation and fibrinolysis. Metformin, the first-line treatment for T2DM, may influence coagulation parameters, but this effect is underexplored in the Nepalese population. The purpose of this study was to assess how metformin affected the levels of D-dimer, prothrombin time (PT), and activated partial thromboplastin time (APTT) in patients with type 2 diabetes. Method: Glycemic control and metformin use were used to group 120 T2DM patients and 120 healthy controls in a cross-sectional study. PT, APTT, D-dimer, and platelet count tests were performed on blood samples and the effects of raising glucose concentrations with and without metformin were evaluated using an in vitro model. Result: PT, APTT, and D-dimer levels were significantly higher in T2DM patients (p&lt;0.05), with more noticeable changes in those with poorly controlled diabetes. Patients receiving metformin showed some degree of normalization which indicate that Metformin partially reversed the effects of high glucose on coagulation markers in vitro. Conclusion: Metformin may enhance coagulation profiles, which would support its use in conjunction with glycemic control and lower the risk of thrombosis.

Precise control of gene expression is essential to synthetic biology and metabolic engineering, particularly for microbial production. The widely used IPTG-inducible T7lac promoter (PT7lac) offers strong expression but suffers from metabolic burden, inclusion body formation, and induction heterogeneity. Conversely, the arabinose-inducible araBAD promoter (PBAD) provides tight regulations but yields modest expression levels, is incompatible with glucose media, and requires high inducer concentrations (20-100 mM). We introduce the arabinose-inducible univariant control system (AUCS), a robust, tightly regulated, and low-cost expression platform designed to combine the strengths of PT7lac and PBAD while overcoming their drawbacks. AUCS eliminates carbon catabolite repression and minimizes induction heterogeneity via the constitutive expression of the arabinose transporter AraE. Disruption of the arabinose catabolism enables maximal protein output with only 3 μM l-arabinose, orders of magnitude lower than PT7lac and PBAD systems, achieving a >99% reduction in inducer cost. Leveraging a customized promoter library (PTA1-3), AUCS enables the precise, high-yield expression of single proteins, multienzyme operons, and complex biosynthetic pathways (>10 genes). Benchmarked against PT7lac, AUCS achieved comparable or superior yields of proteins (the egg-white protein ovalbumin), enzymes (terpene synthases, carotenoid cleavage dioxygenases), and secondary metabolites (linalool, nerolidol, and sclareol) while maintaining outstanding reproducibility and stability over 36 generations. AUCS represents a powerful advancement for precision fermentation, enabling sustainable and cost-effective production of high-value biomolecules and substantially reducing the environmental footprint of chemical manufacturing.

Clinical evidence of admission glucose effects in large ischemic stroke remains limited, with unclear optimal approaches for identifying patients who would benefit from glucose management, particularly regarding how hyperglycemia effects vary across treatment modalities and clinical characteristics. This prospective multicenter registry included 725 patients with large ischemic stroke (ASPECTS ≤5) and available admission glucose data from 745 patients across 38 centers. The primary outcome was the modified Rankin Scale score at 90days (range 0-6; higher scores indicate greater disability). Secondary outcomes included moderate neurological outcomes (mRS 0-3), favorable neurological outcomes (mRS 0-2), while the primary safety outcome was 90-day mortality. When admission glucose was analyzed as a continuous variable, higher glucose levels were observed to shift the modified Rankin Scale score distribution towards a less favorable outcome (adjusted OR(aOR), 0.83; 95% CI, 0.78 to 0.89; P<0.001), with an increase in 90-day mortality (aOR, 1.20; 95% CI, 1.11 to 1.29; P<0.001). These findings were supported by secondary outcomes. Significant interactions were observed between glucose and treatment modality (P=0.003), collateral circulation status (P=0.013), stroke etiology (P<0.001), and atrial fibrillation (P=0.018). The adverse effects of hyperglycemia were most pronounced in patients receiving endovascular treatment (EVT), those with atrial fibrillation, poor collateral circulation, and stroke etiology. Critical glucose thresholds were identified at 10.15mmol/L for moderate neurological outcomes and 7.83mmol/L for mortality in high-susceptibility subgroups. Admission glucose exhibits differential impacts based on individual patient characteristics, revealing distinct glycemic susceptibility profiles. These findings demonstrate treatment-dependent glucose effects, with amplified adverse associations in EVT patients and those with high-susceptibility clinical features. Recognition of differential glycemic susceptibility provides mechanistic rationale for personalized glucose management strategies and supports precision medicine approaches in acute stroke.