Cardiovascular diabetology. Endocrinology reports最新文献

{"title":"Association of hemoglobin glycation index with the severity and mortality of cardiovascular-kidney-metabolic syndrome: a population-based cohort study.","authors":"Leiluo Geng, Xue Diao, Hong-Jie Yu, Aimin Xu","doi":"10.1186/s40842-025-00262-4","DOIUrl":"10.1186/s40842-025-00262-4","url":null,"abstract":"<p><strong>Background: </strong>Cardiovascular-kidney-metabolic (CKM) syndrome is a recently proposed multisystem disorder with high prevalence and progressive stages from 0 to 4, characterized by uncertain risk factors. Hemoglobin glycation index (HGI), a simple marker reflecting individual variation in glycated hemoglobin, has been linked to diabetic and cardiovascular outcomes. However, its association with CKM syndrome severity and mortality remains unknown.</p><p><strong>Methods: </strong>This study utilized data from the National Health and Nutrition Examination Survey (1999-2018) and included 14,680 adult participants. Weighted logistic regression was conducted to assess the association of HGI and CKM syndrome stage. Kaplan-Meier survival curves and weighted Cox proportional hazards models were adopted to explore the relationship between HGI and mortality by CKM syndrome stages, followed with analyses of restricted cubic spline and threshold effect.</p><p><strong>Results: </strong>A positive correlation between HGI and CKM syndrome stage was observed after multivariate adjustment (OR 1.24, 95% CI 1.10-1.39). Over a median follow-up period of 7.5 years, a total of 1,111 all-cause deaths and 349 cardiovascular deaths were documented. U-shaped associations between HGI and all-cause mortality were observed, with inflection points at -0.280 (CKM syndrome stage 0-3) and - 0.077 (CKM syndrome stage 4). A one-unit increase in HGI was linked to a 33-39% reduction in all-cause mortality risk below the inflection point, and a 33-42% increase above it. In contrast, HGI showed a linear association with cardiovascular mortality in participants with CKM syndrome stage 4 (HR 1.34, 95% CI 1.08-1.65), however, no significant association was observed in CKM syndrome stage 0-3.</p><p><strong>Conclusions: </strong>A higher HGI was associated with increased severity of CKM syndrome. There was a U-shaped relationship between HGI and all-cause mortality while a linear association between HGI and cardiovascular mortality was observed depending on the CKM syndrome stage. HGI may serve as a valuable biomarker for assessing the risk of CKM syndrome and its related mortality.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"46"},"PeriodicalIF":0.0,"publicationDate":"2025-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12717684/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145795414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Aging, biofilms, and diabetic foot ulcers: disrupting chronic infections with super-oxidized solutions and addressing age-related vulnerabilities.","authors":"Nor Afifah Supardy, Rejith R S Kumar","doi":"10.1186/s40842-025-00261-5","DOIUrl":"10.1186/s40842-025-00261-5","url":null,"abstract":"<p><p>Diabetic Foot Ulcers (DFUs) are a serious complication of diabetes, often leading to chronic infections, prolonged hospitalization, and, in severe cases, amputations. A major challenge in DFU treatment is the presence of polymicrobial biofilms, complex bacterial communities encased in a protective extracellular matrix, which enhances their survival, evade immune responses, and contributes to antimicrobial resistance (AMR). Conventional treatments, such as systemic antibiotics, antiseptics, and mechanical debridement, often fail to fully eliminate biofilms, highlighting the need for more effective therapeutic strategies. Considering the existing ineffective anti-biofilm treatments, super-oxidized solution (SOS) has emerged as a promising non-antibiotic alternative for DFU infections. As a reactive oxygen species (ROS)-based therapy, SOS effectively disrupts biofilm integrity, enhances bacterial eradication, and promotes wound healing by reducing inflammation and supporting tissue regeneration. Additionally, its mechanism of action could significantly minimize the risk of AMR, making it a valuable adjunct to conventional therapies. The purpose of this review is to explore the mechanisms of biofilm formation in DFUs, evaluate the limitations of current treatment approaches, and highlight the therapeutic potential of SOS. Integrating SOS into DFU treatment protocols could improve infection control, reduce chronic wound burden, and enhance patient outcomes. By advancing non-antibiotic solutions like SOS, DFU management can shift toward more effective and sustainable wound care strategies, ultimately reducing the need for surgical interventions and improving the quality of life for diabetic patients.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"45"},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784379","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of tofogliflozin on cardiac sympathetic nerve activity in type 2 diabetes mellitus patients with heart failure (TARGET-HF): rationale and design of the single-arm intervention trial.","authors":"Takahiro Okumura, Yasuko K Bando, Satoshi Isobe, Naotoshi Fujita, Fusako Sera, Yuki Ikeda, Ayumu Yajima, Toshiyuki Nagai, Hiroaki Hiraiwa, Ryota Morimoto, Toshihisa Anzai, Koichi Node, Junya Ako, Yasushi Sakata, Toyoaki Murohara","doi":"10.1186/s40842-025-00260-6","DOIUrl":"10.1186/s40842-025-00260-6","url":null,"abstract":"<p><p>BACKGROUND: Cardiac sympathetic nervous dysfunction is linked to poor prognosis in heart failure with reduced ejection fraction (HFrEF), and patients with HFrEF complicated by type 2 diabetes mellitus (T2DM) represent a particularly high risk. Sodium-glucose cotransporter-2 (SGLT2) inhibitors reduce heart failure (HF) hospitalizations in patients with T2DM, but the mechanisms underlying these benefits are not fully understood; modulation of cardiac sympathetic activity has been proposed as one contributor. The TARGET-HF trial will investigate whether tofogliflozin improves cardiac sympathetic nerve activity, assessed by I-123 metaiodobenzylguanidine (MIBG) scintigraphy, along with other cardiovascular parameters in patients with HFrEF and T2DM. METHODS: This single-arm prospective interventional study will enroll 50 patients with HFrEF (left ventricular ejection fraction < 40%), T2DM (hemoglobin A1c level, 6.5–10.0%), and estimated glomerular filtration rate ≥ 30mL/min/1.73 m². Participants will receive oral tofogliflozin (20 mg/day) for 24 weeks. The primary endpoint is the change in the heart-to-mediastinum ratio on delayed I-123 MIBG scintigraphy from baseline to 24 weeks. Secondary endpoints include changes in the early heart-to-mediastinum ratio, washout rate, echocardiographic parameters, and various biomarkers related to HF, inflammation, and metabolism. DISCUSSION: The TARGET-HF trial is the first interventional study to comprehensively evaluate the effects of tofogliflozin on cardiac sympathetic nerve activity using I-123 MIBG scintigraphy in patients with HFrEF and T2DM. By integrating nuclear imaging, echocardiography, and metabolic and biochemical biomarkers, this study aims to clarify the mechanisms underlying the cardioprotective effects of SGLT2 inhibitors. Improved understanding of these mechanisms may refine patient selection and guide targeted therapeutic strategies in HF management. TRIAL REGISTRATION: Japan Registry of Clinical Trials; approval number: jRCTs041210022 (February 6, 2021). </p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"47"},"PeriodicalIF":0.0,"publicationDate":"2025-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12715907/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145784375","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Altered RBC aggregability in diabetes: a threshold for pathophysiological structure-function RBC changes.","authors":"Ifechukwude Ebenuwa, Pierre-Christian Violet, Stephanie Teng, Thom Greene, Nicholas Munyan, Razi Berman, Irene Rozga, Mary Walter, Kenneth J Wilkins, Nermi Parrow, Mark Levine","doi":"10.1186/s40842-025-00256-2","DOIUrl":"10.1186/s40842-025-00256-2","url":null,"abstract":"<p><p>OBJECTIVE: Vascular complications have been associated with pathophysiological RBC changes including reduced RBC deformability (RBCD): the ability of RBCs to change their shape in the microvasculature and increased red blood cell aggregability (RBCA): the tendency of RBCs to form aggregates (rouleaux). However, understanding of aberrant RBCA in diabetes and its relationship with RBCD is limited. We investigated clinical and RBC structural and functional changes associated with RBCA in comparison with RBCD. METHODS: We conducted an outpatient cross-sectional study of participants with diabetes (n = 81) and nondiabetic controls (n = 78) at the National Institutes of Health. Clinical history was obtained using standardized forms, fasting blood and urine samples were collected for clinical laboratory measurements and ektacytometry studies of RBC physiological parameters: RBCA, RBCD and osmotic fragility. Functional RBC changes were assessed using hemoglobin-oxygen dissociation (p50). Major outcomes assessed differences in RBCA Aggregation Index (AI), with increased RBCA defined as higher AI. Exploratory outcomes assessed differences in subgroups with type 1 (T1D) and type 2 (T2D) diabetes, and associations with clinical, inflammatory, endocrine and RBC physiological parameters. Outcomes were assessed using both nonparametric and multivariable regression methods. RESULTS: Compared with controls, AI was significantly higher in the diabetes cohort (75±8 vs 71 ± 11, p = 0.007), T2D (77±7 vs 71 ± 11, p < 0.001), but not T1D (69±7 vs 71 ± 11, p = 0.242). While RBCD values were similar in T1D and T2D (p = 0.31), mean AI value was significantly higher in T2D vs T1D (p = 0.02). In contrast to RBCD, AI was associated with T2D (p < 0.001), BMI (p < 0.001), insulin resistance (HOMA-IR, p = 0.033), leptin (p < 0.001), C-peptide levels (p = 0.009), but not vascular complications (p = 0.156). While RBCA and RBCD were associated with CRP (p < 0.001 and p = 0.005 respectively), neither was associated with fibrinogen (p = 0.768 and p = 0.118 respectively). In contrast to RBCD, AI was associated with increased osmotic fragility (p < 0.001) and a threshold of altered hemoglobin-oxygen dissociation (p50) estimated at AI of 75 in both groups using piecewise linear statistical modeling. Thus, AI was positively correlated with p50 at AI < 75 (p = 0.033) and negatively correlated at AI ≥ 75 (p = 0.007). CONCLUSIONS: Findings show that in contrast to RBCD, RBCA is characterized by a RBC functional threshold beyond which oxygen release is reduced, and RBC structure-function relationship likely modulated by insulin resistance and pro-inflammatory endocrine factors. The distinct but complementary and synergistic changes in RBCD and RBCA provide a framework for strategies aimed at mitigation of vascular risk in diabetes. </p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"44"},"PeriodicalIF":0.0,"publicationDate":"2025-12-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12713270/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145777257","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Serum PCSK9 is not independently associated with dyslipidaemia in type 2 diabetes: a paired cross-sectional study.","authors":"Peace Ngozi Okoro, Kolawole Wasiu Wahab, John Kola Olarinoye, Biliaminu Sikiru Abayomi","doi":"10.1186/s40842-025-00253-5","DOIUrl":"10.1186/s40842-025-00253-5","url":null,"abstract":"<p><strong>Background: </strong>Dyslipidaemia is common in type 2 diabetes mellitus (T2DM) and contributes substantially to cardiovascular risk. Circulating proprotein convertase subtilisin/kexin type 9 (PCSK9) regulates LDL receptor turnover, yet its relationship to the lipid phenotype in T2DM remains uncertain.</p><p><strong>Objective: </strong>To compare lipid fractions and PCSK9 concentrations between matched individuals with and without T2DM and to determine whether PCSK9 is independently associated with dyslipidaemia.</p><p><strong>Methods: </strong>A total of 100 age- and sex-matched pairs were enrolled. After excluding pairs with incomplete or compromised lipid or PCSK9 measurements, 92 pairs were retained for the primary analysis. Missingness was primarily due to inadequate sample volume and hemolyzed specimens. Fasting total cholesterol (TC), HDL-C, LDL-C, and triglycerides (TG) were measured in mmol/L, and serum PCSK9 was quantified in native assay units. Primary analyses used within-pair differences (paired t and Wilcoxon tests) and linear mixed-effects models (outcome ~ group + (1|pair_id)). Logistic regression evaluated associations of PCSK9 and diabetes status with dyslipidaemia, defined as LDL-C ≥ 3.37 mmol/L, HDL-C < 1.03 mmol/L, or TG ≥ 1.70 mmol/L. Multiple testing was controlled by the Benjamini-Hochberg false-discovery rate and Bonferroni correction.</p><p><strong>Results: </strong>Compared with controls, participants with T2DM had significantly higher lipid fractions but similar PCSK9 concentrations. Mean paired differences (T2DM - Control [95% CI]) were: TC + 0.91 mmol/L (0.46 to 1.37), HDL-C + 1.11 mmol/L (0.90 to 1.32), LDL-C + 2.12 mmol/L (1.78 to 2.46), and TG + 0.59 mmol/L (0.50 to 0.68) (all p < 0.001); PCSK9 - 0.58 (-1.57 to 0.41, p = 0.25). In mixed-effects models, group effects remained significant for all lipid fractions but not for PCSK9. In logistic regression, PCSK9 was not associated with dyslipidaemia (OR 0.99, 95% CI 0.91-1.08, p = 0.81; AUC 0.51).</p><p><strong>Conclusions: </strong>Among matched adults with and without T2DM, serum PCSK9 showed no independent association with dyslipidaemia despite significant elevations in TC, LDL-C, HDL-C, and TG in the diabetic group. Interpretation is limited by the lack of HbA1c and lipid-modifying medication data and by single-time sampling. These findings suggest that PCSK9 alone may have limited utility for classifying dyslipidaemia in T2DM without adjustment for metabolic and therapeutic covariates.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"43"},"PeriodicalIF":0.0,"publicationDate":"2025-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12709774/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145770567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of medication therapy management intervention on medication adherence among adult patients comorbid with diabetes mellitus and hypertension at outpatient clinics in Southwest Ethiopia: a cluster randomized controlled trial.","authors":"Tadesse Sheleme, Firomsa Bekele, Wayessa Olika, Birbirsa Sefera","doi":"10.1186/s40842-025-00254-4","DOIUrl":"10.1186/s40842-025-00254-4","url":null,"abstract":"<p><p>BACKGROUND: Patients with diabetes and hypertension require long-term medication, which may increase the chance of non-adherence to medications. Medication therapy management has been shown to positively impact medication adherence. This study aimed to assess the impact of medication therapy management on medication adherence among patients comorbid with diabetes mellitus and hypertension. METHODS: A cluster randomized controlled trial was conducted at outpatient clinics from January 03 to July 18, 2022. The hospital was randomly assigned to either the intervention or control group. The patients attending hospitals assigned to the interventional group received medication therapy management services in addition to usual care. A systematic random sampling technique was used to select the study participants from each hospital. Medication adherence was assessed using the Adherence in Chronic Diseases Scale. SPSS version 24.0 was used for data analysis. The independent sample t-test and chi-square test were used to compare the variables. RESULT: Of 402 eligible patients, 201 were randomly assigned to the medication therapy management intervention group and 201 patients were randomized to the control group. No significant differences were observed in the baseline characteristics of the patients. The adherence rate in the intervention group increased by 50%, whereas it remained fairly constant in the control group, and the difference was statistically significant (p < 0.001). CONCLUSION: The current study showed that medication therapy management intervention improved the patients’ medication adherence. Hospitals should strengthen and integrate clinical pharmacy services into their healthcare system. TRIAL REGISTRATION: ClinicalTrials.Gov NCT06112925. </p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"41"},"PeriodicalIF":0.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12706876/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Malignant hypertension and pseudohyperaldosteronism associated with rifampicin therapy.","authors":"Alexandre Szedleski, Cédric Ilbert, Véronique Goncette, Laurent Vroonen, Justine Huart","doi":"10.1186/s40842-025-00257-1","DOIUrl":"10.1186/s40842-025-00257-1","url":null,"abstract":"<p><p>We report the case of a 64-year-old woman who developed malignant and treatment-resistant arterial hypertension (HT) following the introduction of rifampicin for spondylodiscitis. Her previously stable blood pressure (BP) deteriorated rapidly despite extensive antihypertensive therapy. The utilisation of pharmaceutical agents that demonstrated minimal or no interaction with rifampicin has yielded only partial control over HT. Furthermore, biological settings provided evidence of pseudohyperaldosteronism. A comprehensive workup ruled out other secondary causes of HT. BP normalized progressively after rifampicin withdrawal, without additional therapeutic intervention. This temporal combination supports a causative role of rifampicin, potentially through mechanisms beyond drug interactions. We discuss hypotheses including corticosterone-driven pseudohyperaldosteronism resulting from cytochrome P450 induction, and pregnane X receptor agonism as contributors to HT. This case highlights the importance of recognizing rifampicin as a potential inducer of severe HT, even in patients receiving adjusted antihypertensive regimens, and suggests a pathophysiological mechanism that may extend beyond pharmacokinetic interferences.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"42"},"PeriodicalIF":0.0,"publicationDate":"2025-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12706878/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145764945","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SGLT2 inhibitors in cardiac amyloidosis: mechanistic insights and clinical perspectives-a narrative review.","authors":"Bülent Özlek, Veysel Ozan Tanik","doi":"10.1186/s40842-025-00252-6","DOIUrl":"10.1186/s40842-025-00252-6","url":null,"abstract":"<p><strong>Background: </strong>Cardiac amyloidosis (CA) is an infiltrative cardiomyopathy characterized by progressive extracellular amyloid deposition, leading to restrictive heart failure (HF) and high morbidity. Disease-modifying therapies remain limited, particularly in patients with advanced HF. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, originally developed for diabetes management, have shown consistent cardiovascular and renal benefits in large randomized trials of non-amyloid HF populations. Their potential mechanistic and clinical relevance in CA has recently gained attention, yet evidence remains largely observational.</p><p><strong>Main text: </strong>This narrative review, based on literature identified through PubMed, Embase, and Cochrane Library searches up to October 2025, summarizes emerging mechanistic and clinical insights on the potential role of SGLT2 inhibitors in CA. Preclinical and translational data suggest that SGLT2 inhibition may favorably influence key pathophysiologic pathways, including hemodynamic, metabolic, inflammatory, fibrotic, renal, and endothelial mechanisms. Observational and registry studies have reported associations with improved survival, symptoms, stable renal function, and favorable biomarker trajectories, although these findings derive from retrospective analyses with inherent limitations. No randomized controlled trials (RCTs) have specifically evaluated SGLT2 inhibitors in CA, and the risk of immortal time bias and residual confounding limits causal interpretation.</p><p><strong>Conclusion: </strong>SGLT2 inhibitors may offer a promising adjunctive approach in CA by targeting multiple disease mechanisms and improving overall cardiorenal balance. However, current evidence is based solely on non-randomized data, with low-to-moderate certainty for clinical outcomes such as mortality, HF hospitalization, and biomarker change. Across available studies, therapy was generally well tolerated, with low discontinuation rates and infrequent genitourinary or hypotensive events, consistent with safety profiles observed in broader HF populations. Dedicated amyloidosis-specific RCTs are required to establish efficacy and safety before routine implementation in clinical practice.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"40"},"PeriodicalIF":0.0,"publicationDate":"2025-12-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12703937/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145759305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chronic hyperglycemia and cardiovascular dysfunction: an in-depth exploration of metabolic and cellular pathways in type 2 diabetes mellitus.","authors":"Araiz Hussain","doi":"10.1186/s40842-025-00247-3","DOIUrl":"10.1186/s40842-025-00247-3","url":null,"abstract":"<p><p>Chronic hyperglycemia is the defining feature of type 2 diabetes mellitus (T2DM) and a central driver of its long-term complications, including microvascular and macrovascular diseases. Among these, cardiovascular disease (CVD) remains the leading cause of morbidity and mortality in individuals with T2DM. Persistent glucose elevation activates multiple interrelated biochemical pathways, including the polyol pathway, formation of advanced glycation end-products, protein kinase C activation, oxidative stress via several cellular mechanisms, as well as the hexosamine biosynthetic pathway. These processes collectively promote excessive oxidative damage, endothelial dysfunction, inflammation, and adverse cardiac remodeling, ultimately accelerating cardiovascular damage. Research has further revealed that hyperglycemia imprints long-lasting molecular changes through metabolic memory, largely mediated by epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs, and sustaining vascular dysfunction even after glycemic control. Building on both classical and emerging evidence, this review synthesizes advances in understanding hyperglycemia-induced vascular damage and highlights promising therapeutic targets within these pathways. Strategies under investigation include inhibitors of enzymatic reactive oxygen species sources, modulators of mitochondrial dynamics and function, regulators of protein kinase C, blockers of glycation pathways, and epidrugs targeting epigenetic modifications. By integrating these mechanistic insights with therapeutic innovation, the field is shifting from a narrow focus on glucose lowering to a broader approach aimed at preventing and potentially reversing the vascular complications of diabetes. This perspective emphasizes the urgent need for pathway-specific therapeutic strategies to effectively address the cardiovascular burden of T2DM.</p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"39"},"PeriodicalIF":0.0,"publicationDate":"2025-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12699840/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145746605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Real-world prescriptions of GLP-1RAs and SGLT2is in type 2 diabetes prioritise BMI and age over cardiorenal risk: a machine learning-based large cohort analysis.","authors":"Dario Tuccinardi, Rita Zilich, Paola Ponzani, Nicoletta Musacchio, Valeria Manicardi, Alberto Rocca, Roberto Pontremoli, Paola Fioretto, Andrea Muscarà, Graziano Di Cianni, Riccardo Candido, Salvatore A De Cosmo, Giuseppina Russo","doi":"10.1186/s40842-025-00251-7","DOIUrl":"10.1186/s40842-025-00251-7","url":null,"abstract":"<p><p>BACKGROUND: Understanding how SGLT2 inhibitors (SGLT2is) and GLP-1 receptor agonists (GLP-1RAs) are prescribed in relation to cardiorenal risk is crucial for assessing adherence to guidelines and optimize outcomes in type 2 diabetes (T2D). This study aimed to determine whether prescription patterns across different cardiorenal phenotypic subgroups reflect clinical risk or are affected by demographic factors. Explainable artificial intelligence (XAI) was used to identify the key factors influencing therapeutic decisions. METHODS: We analyzed 139,202 adults with T2D from the Italian AMD Annals registry (2023), stratified into four cardiorenal phenotypic subgroups based on ADA criteria: low risk, chronic kidney disease (CKD) without cardiovascular disease (CVD), atherosclerotic CVD without heart failure, and heart failure. Predictive models were developed using a Logic Learning Machine (XAI algorithm), with variable importance ranked by normalized relevance scores. Business intelligence tools and statistical analysis were used for validation. RESULTS: SGLT2i prescriptions were strongly associated with cardiorenal markers, including reduced eGFR (31–59 mL/min), intermediate HbA1c (5.5–8.1%), and lower BMI, with model accuracies ranging from 63.7% to 83.1%. Women were consistently less likely to receive SGLT2is across subgroups. GLP-1RA prescriptions were predominantly driven by higher BMI (> 30 kg/m²), younger age, and glycemic extremes (< 5.5% or > 8.1%), with lower model performance (31.6%–54.1%). Individuals with lower BMI were less frequently prescribed GLP-1RAs, even in the presence of renal or cardiovascular risk. CONCLUSIONS: While SGLT2i prescribing generally aligned with cardiorenal risk, sex-based disparities persist. GLP-1RA use was less consistently linked to clinical indications and more heavily influenced by BMI. These findings highlight missed opportunities to deliver proven cardiorenal protective therapies to high-risk individuals, emphasising the need for more equitable, phenotype-driven prescribing strategies in T2D. </p>","PeriodicalId":521069,"journal":{"name":"Cardiovascular diabetology. Endocrinology reports","volume":"11 1","pages":"38"},"PeriodicalIF":0.0,"publicationDate":"2025-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12690812/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145717248","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}