Type 2 diabetes and hypertension frequently coexist and substantially elevate the risk of cardiovascular complications due to interconnected metabolic and vascular mechanisms. The combined presence of these conditions accelerates atherosclerosis, endothelial dysfunction, and inflammatory processes, leading to an increased incidence of adverse cardiovascular events. Existing literature primarily emphasizes individual therapeutic interventions, while limited evidence explores the combined impact of pharmacological treatments and system-level strategies in real-world clinical settings. This study evaluates evidence on therapeutic approaches and integrated care models in relation to cardiovascular outcomes among affected populations. A systematic review with narrative synthesis was conducted without meta-analysis, incorporating 10 studies identified through structured database searches, screened according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria, and evaluated using the Newcastle-Ottawa Scale where appropriate. Across the included studies, evidence clustered around three main themes: pharmacological cardioprotection, cardiometabolic risk-factor stability, and integrated care delivery. The findings indicate that sodium-glucose cotransporter 2 (SGLT2) inhibitors and glucagon-like peptide 1 (GLP-1) receptor agonists were associated with more favorable cardiovascular profiles compared to conventional glucose-lowering therapies. Stable glycemic control and reduced hemoglobin A1c (HbA1c) variability were consistently associated with improved cardiovascular outcomes. Hypertension-related findings showed that SGLT2 inhibitors were associated with a lower risk of incident hypertension compared with dipeptidyl peptidase-4 (DPP-4) inhibitors, while multifactorial risk-factor control involving blood pressure, glycemia, lipid parameters, and smoking reduction was associated with fewer cardiovascular events. At the care-delivery level, integrated care frameworks, including HEARTS-aligned approaches, may support healthcare delivery through standardized protocols, multidisciplinary coordination, and continuous monitoring; however, protocol-level HEARTS evidence should be interpreted as implementation-planning evidence rather than proof of improved cardiovascular outcomes. These observations reinforce the importance of adopting a comprehensive, patient-centered approach that integrates both therapeutic advancements and structured healthcare systems for optimal disease management.

[This corrects the article DOI: 10.3389/fimmu.2026.1809126.].

This study aimed to screen and validate such biomarkers to clarify the role of vascular endothelial injury (VEI) in the pathogenesis of gestational diabetes mellitus (GDM) and provide clues for future diagnostic and mechanistic studies.

VEI scores were calculated using a published VEI-related gene set. VEI-correlated gene modules were classified by weighted gene co-expression network analysis (WGCNA), with module genes subjected to GO/KEGG enrichment analysis and intersected with differentially expressed genes (DEGs) from the GSE70493 dataset. Core genes were filtered using three machine learning algorithms, including random forest, LASSO regression, and SVM-RFE, followed by analyses of diagnostic performance, hallmark pathway correlations, and immune infiltration associations.

DEGs were enriched in endoplasmic reticulum protein localization, oxidative stress, and mitochondrial pathways and overlapped with the yellow gene module. Machine learning identified COX7B, GLRX5, and OR52H1 as the candidate biomarkers for GDM. These genes showed favorable diagnostic performance and distinct correlations with hallmark pathways and immune infiltration features, suggesting their potential involvement in VEI-related molecular changes in GDM.

This study identified VEI-related hub genes in GDM but is limited by its reliance on a single dataset, a small validation sample, and the lack of experimental validation, warranting further confirmation.

COX7B, GLRX5, and OR52H1 were identified as VEI-associated diagnostic biomarkers in GDM. These findings support the involvement of VEI-related molecular alterations in GDM but should be regarded as hypothesis-generating, requiring further validation in larger clinical cohorts and experimental models.

Background/Objectives: Diabetic peripheral neuropathy (DPN) is a common and debilitating complication of diabetes mellitus characterized by progressive nerve degeneration and chronic neuropathic pain. Current therapies, including pregabalin, primarily provide symptomatic pain relief and have limited effects on preventing structural nerve damage. Therefore, the development of disease-modifying therapies remains an important unmet clinical need. This study investigated the neuroprotective effects of choline alfoscerate (CA) and its ability to attenuate mechanical hypersensitivity in a streptozotocin (STZ)-induced rat model of DPN. Methods: Diabetes was induced in rats using STZ, and administration protocols were optimized to establish sustained hyperglycemia while minimizing mortality. CA treatment was initiated immediately after STZ administration and continued throughout the study period. Mechanical sensitivity was assessed using the von Frey test. Histopathological examination of sciatic nerves was performed to evaluate structural alterations, and serum biochemical and lipid parameters were analyzed to assess systemic metabolic changes. Results: STZ-treated diabetic rats developed persistent hyperglycemia, mechanical allodynia, elevated serum triglyceride levels, and marked structural deterioration of sciatic nerve fascicles. CA treatment significantly increased paw withdrawal thresholds despite sustained hyperglycemia, indicating attenuation of mechanical hypersensitivity independent of glycemic control. Histopathological evaluation demonstrated reduced nerve fiber degeneration, attenuation of edema-like changes, and preservation of sciatic nerve architecture in CA-treated animals. In addition, CA significantly reduced serum triglyceride levels compared with diabetic controls. Conclusions: CA attenuated mechanical hypersensitivity and exerted neuroprotective effects in STZ-induced diabetic rats. These benefits occurred independently of glucose lowering and were accompanied by improvements in nerve morphology and lipid metabolism. The findings suggest that CA may represent a promising therapeutic candidate for preserving peripheral nerve integrity and attenuating neuropathic progression in diabetic peripheral neuropathy.

Background/Objectives: Diabetes mellitus type 2 (T2DM) is often associated with hypertension, necessitating treatment with combinations of medications that address both glycemic control and blood pressure. Whether commonly co-prescribed antihypertensives modify the glycemic efficacy of a sulfonylurea remains insufficiently characterized in controlled preclinical models. Methods: One hundred adult male Wistar rats were allocated to ten parallel groups (n = 10): healthy and diabetic untreated controls; glimepiride, bisoprolol or amlodipine monotherapy (in healthy and diabetic animals); and the diabetic combinations glimepiride+bisoprolol and glimepiride+amlodipine. T2DM was induced with a high-fat diet plus low-dose streptozotocin (35 mg/kg, i.p.) and confirmed by fasting blood glucose ≥ 200 mg/dL. Glycated hemoglobin (HbA1c) was measured weekly for 11 weeks. Non-parametric inference (Kruskal-Wallis, Dunn's with Bonferroni correction, Mann-Whitney U, Wilcoxon signed-rank) was complemented by Random Forest regression and PCA/K-means clustering. Results: Week-11 HbA1c differed markedly across groups (Kruskal-Wallis H = 94.3, p < 0.001). Glimepiride + bisoprolol achieved near-normal control (4.37% ± 0.15), statistically indistinguishable from healthy groups (p ≥ 0.33), and was the only diabetic regimen with a declining trajectory (-0.66 percentage points; Wilcoxon p = 0.004). Adding either antihypertensive to glimepiride did not worsen glycemic control. Amlodipine monotherapy did not attenuate hyperglycemia (8.47% ± 0.20), approaching that of untreated diabetic controls (9.31% ± 0.18), consistent with the absence of intrinsic glucose-lowering activity. All agents showed pronounced disease-state dependence (healthy-diabetic divergence 2.33-3.13 points). Random Forest prediction was accurate (R² = 0.985), and unsupervised clustering separated effective from ineffective regimens, corroborating the statistical findings. Conclusions: In this model, bisoprolol co-administration enhanced and amlodipine co-administration preserved glimepiride-mediated glycemic control. Glimepiride+bisoprolol emerged as the most effective regimen, supporting cardioselective β-blockade as a metabolically favorable antihypertensive partner for sulfonylurea therapy and warranting clinical confirmation. More broadly, these results provide a preclinical, evidence-based rationale for selecting metabolically favorable antihypertensives in patients with coexisting T2DM and hypertension, with the potential to improve glycemic outcomes and reduce the risk of adverse drug-disease interactions during combination therapy.

Considered by some to be the largest metabolic organ of the body, the functional integrity of skeletal muscle is highly dependent on its exceptional plasticity, which is primarily governed by mitochondrial quality control. The signaling axis composed of AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) serves as a critical hub that senses cellular energy status, coordinates mitochondrial biogenesis, regulates muscle fiber type switching, and maintains protein homeostasis. This review systematically delineates the structural functions and synergistic regulatory network of the AMPK/SIRT1/PGC-1α signaling axis. It further elucidates the regulatory roles of this pathway under physiological conditions-such as exercise adaptation and muscle fiber-type transformation-and its dysregulated mechanisms in the pathogenesis of various skeletal muscle disorders, including sarcopenia, disuse atrophy, cachexia, neurogenic atrophy, muscular dystrophy, and type 2 diabetes mellitus-related myopathy. Building on this foundation, this review critically analyzes current multifaceted therapeutic strategies targeting this pathway, encompassing exercise and physical therapy, nutritional and natural products, and small molecule drugs, as well as gene and cell-based therapies. Finally, this review delves into the challenges facing clinical translation in this field, such as the complexity of the signaling network, individual variability, and bioavailability issues. It also proposes future research directions focused on developing precision intervention tools, establishing effective biomarker systems, and exploring combination intervention strategies. Collectively, the AMPK/SIRT1/PGC-1α signaling axis is central to maintaining skeletal muscle metabolic homeostasis, and targeting this pathway provides a robust theoretical foundation and broad application prospects for the prevention and treatment of skeletal muscle-related diseases.

Glycemic variability is a stand-alone risk factor for diabetic complications. Background/Objectives: We investigated whether combining quercetin-rich Allium cepa L. (white onion) juice with the sodium-glucose cotransporter-2 (SGLT2) inhibitor dapagliflozin could reduce glycemic variability beyond that achieved with monotherapy in experimental diabetes. Methods: Wistar rats were made diabetic with streptozotocin (35 mg/kg) and maintained for 60 days in the following groups: vehicle, dapagliflozin (0.1 mg/day), fresh onion juice (5 mL twice daily), and dapagliflozin + fresh onion juice (5 mL twice daily). Diabetic Wistar rats (n = 10/group) were gavaged with vehicle, dapagliflozin (0.1 mg/day), fresh onion juice (5 mL twice daily), or both. The juice was expected to contain phytochemicals (quercetin derivatives and organosulfur compounds) based on published reports on similar A. cepa cultivars. A validated immunoassay was used to measure glycated hemoglobin (HbA1c) every 10 days. All treatments reduced HbA1c to the same level (~7.1-7.2%) as compared to diabetic controls (9.0 ± 0.3%) (p < 0.001), though only the combination treatment reduced glycemic variability (HbA1C coefficient of variation 3.9 ± 0.6% vs. 7.8 ± 1.2% with dapagliflozin and 11.2 ± 1.8% with onion) (p < 0.001). Results: Across the 10-day sampling schedule, the combination kept HbA1c within a narrow 6.8-7.2% band, whereas the monotherapies fluctuated more widely; because intraday and postprandial glucose were not captured, effects on short-term excursions could not be directly assessed. There were no cases of severe hypoglycemia and only infrequent and non-repeated cases of mild hypoglycemia. Conclusions: In this exploratory, hypothesis-generating study, the additive interaction between onion phytochemicals and dapagliflozin was associated with lower glycemic variability via mechanisms proposed in the literature; quercetin-rich A. cepa juice may therefore warrant further investigation as an adjunct in diabetes management, pending batch-specific phytochemical characterization and confirmatory studies.

Background: Previous studies have explored the association between ambient ozone (O₃) exposure and gestational diabetes mellitus (GDM). However, little is known about the association of O₃ with different GDM clinical classifications-diet-controlled GDM (GDMA1) and insulin-treated GDM (GDMA2), and whether temperature modifies the associations. Methods: We conducted a retrospective cohort study including 11,491 pregnant women between 2017 and 2023 in Tianjin, China. O₃ exposure levels for each participant were assessed using the Tracking Air Pollution in China dataset. Logistic regression models were employed to analyze the associations of trimester-specific O₃ exposure with GDMA1 and GDMA2. Distributed lag nonlinear model (DLNM) was used to identify potential critical gestational weeks of O₃ exposure. Ambient temperature was categorized using the 10th and 90th percentiles to evaluate the effect modification of extreme temperatures on these associations. Results: No statistically significant association was observed in the fully adjusted trimester-specific models. In the weekly-specific DLNM analyses, we observed 5-12 weeks before pregnancy and 26-28 gestational weeks as sensitive windows where O₃ exposure was weakly associated with elevated GDMA1 risk, and 11-25 gestational weeks for GDMA2. Each 10 μg/m³ increase in O₃ during pregnancy was associated with small increases in the odds of GDMA1 (28 weeks: OR = 1.019, 95% CI: 1.002, 1.035) and GDMA2 (25 weeks: OR = 1.018, 95% CI: 1.002, 1.035). High temperatures appeared to strengthen the observed association between preconception O₃ exposure and GDMA1. Additionally, O₃ exposure during pregnancy may increase the risk of GDMA1 among women aged <35 years, preconception obesity, gestational hypertension, and family history of diabetes. Conclusions: This study suggests possible weak weekly-specific associations between O₃ exposure and GDM classifications and indicates that ambient high temperature may modify the O₃-GDM association. These findings should be interpreted cautiously and require confirmation in future studies.

Infective endocarditis (IE) is a severe pathology with recent changes in its epidemiological profile, characterised by older patients with more comorbidities. The objective of this study is to describe the clinical and microbiological characteristics, as well as potential factors associated with mortality, of patients with IE in a tertiary academic centre. Material and Methods: Descriptive, retrospective, and observational study of patients over 18 years of age with a confirmed diagnosis of IE, conducted between 2021 and 2023 at the Dr Hernán Henríquez Aravena Hospital in Temuco, Chile. Biodemographic variables, risk factors, microbiology, echocardiographic findings, and complications were analysed using descriptive statistics and logistic regression models. Results: 119 patients were included (average age 60 years; 65.5% male; 28.5% rural). The most frequent risk factors were arterial hypertension (55%) and diabetes mellitus (29%). 18% were on haemodialysis (HD). Microbiological isolation was achieved in 78.1% of cases, with Streptococcus gallolyticus the most frequent isolate (16.8%), followed by Staphylococcus aureus (15.1%) and coagulase-negative Staphylococcus (15.1%). Complications were present in 69% of cases, mainly emboli (43%) and septic shock (23%)-59.6% required surgery. Global mortality was 44.5%, with a decreasing annual trend (from 58% in 2021 to 33% in 2023). Comorbidities and complications independently associated with mortality were chronic renal failure on HD (OR 5.76; p = 0.001), heart failure (OR 3.13; p = 0.025), and septic shock (OR 3.31; p = 0.016). Conclusions: IE in this centre presents an aggressive profile and a high burden of comorbidities. The prevalence of S. gallolyticus is a notable regional observation not reported in similar populations. Mortality remains high, with an improving trend.