Search Results (10,854)

Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM), characterized by cardiac dysfunction, inflammation, and fibrosis. In this study, a T2DM mouse model was established by administering a high-fat diet (60% fat) in combination with streptozotocin injection in male C57BL/6J mice. The mice subsequently underwent an eight-week exercise intervention consisting of swimming training, resistance training, or high-intensity interval training (HIIT). The results showed that all three forms of exercise improved cardiac function and attenuated myocardial hypertrophy in DCM mice. Exercise training further downregulated the expression of pro-inflammatory cytokines, including interleukin-6, tumor necrosis factor-α, nuclear factor κB, and monocyte chemoattractant protein-1, and mitigated myocardial fibrosis by suppressing fibronectin, α-SMA, collagen type I alpha 1 chain, collagen type III alpha 1 chain, and the TGF-β1/Smad signaling pathway. Moreover, exercise inhibited the expression of PANoptosis-related genes and proteins in cardiomyocytes of DCM mice. Notably, HIIT produced the most pronounced improvements across these pathological markers. In addition, all three exercise modalities effectively suppressed the aberrant activation of the cGAS–STING signaling pathway in the myocardium. In conclusion, exercise training exerts beneficial effects against DCM by improving cardiac function and reducing inflammation, PANoptosis, and fibrosis, and HIIT emerged as the most effective strategy. Full article

Type 2 diabetes mellitus (T2DM) is frequently complicated by atherosclerosis (AS), with substantial overlap in their underlying pathophysiological mechanisms, posing serious threats to patient health. Tirzepatide, a novel dual agonist of glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1) receptors, has demonstrated remarkable efficacy in glycemic control, weight reduction, and cardiometabolic improvement, making it a promising candidate for managing T2DM comorbid with AS. However, substantial interindividual variability in treatment response suggests a role for genetic determinants. This review systematically summarises current evidence on pharmacogenomic variants influencing the efficacy and toxicity of tirzepatide, explores the interplay between drug response genes and genetic susceptibilities to T2DM and AS, and highlights the potential of pharmacogenomics in guiding precision subtyping and individualised therapy. Finally, we highlight key challenges and future directions in the clinical translation of tirzepatide pharmacogenomics, aiming to inform personalized, genomics-guided therapy for cardiometabolic disease. Full article

Gestational diabetes mellitus (GDM) is a frequently encountered medical complication during pregnancy that is increasing at a rapid pace globally, posing significant public health concerns. Similarly, there is a rising trend in the number of women who have utilized assisted reproductive technology (ART). Numerous studies have been carried out to investigate the relationship between GDM and ART. This comprehensive systematic review seeks to identify potential biomarkers for the early diagnosis of GDM in pregnancies conceived through ART. We conducted a PubMed search covering the past five years to identify studies that explore biomarkers associated with the development of GDM in pregnancies conceived through ART. The outcome measures included human chorionic gonadotropin (HCG), the body mass index (BMI), the Follicle Stimulating Hormone to Luteinizing Hormone (FSH/LH) ratio, increased hemoglobin A1c levels, fasting insulin concentrations, homeostatic model assessment of insulin resistance (HOMA-IR), triglyceride levels, total cholesterol levels, low-density lipoprotein cholesterol concentrations, low-density lipoprotein/high-density lipoprotein (LDL/HDL), total cholesterol to high-density lipoprotein (TC/HDL), the estradiol/follicle ratio, soluble fms-like tyrosine kinase-1 (sFlt-1), Placental Growth Factor (PLGF), endometrial thickness, and psychological stress. Seventeen studies were included. The identification and development of serum or ultrasound biomarkers for the early detection of GDM in pregnancies conceived through ART pose considerable challenges. These challenges arise from the multifactorial nature of GDM, the methodological variations in ART, and the limited availability of relevant studies. The most promising biomarker identified was the estradiol/follicle ratio. Women with a higher estradiol/follicle ratio exhibited significantly lower rates of GDM. There is a pressing necessity for biomarkers to enable the early detection of GDM in pregnancies conceived through ART. E2 levels, β-hCG, and the E2/F ratio, along with the TC/HDL and LDL/HDL ratios, show potential as reliable biomarkers for identifying GDM. Full article

Gestational complications, such as preeclampsia and gestational diabetes mellitus (GDM), pose significant risks to maternal and fetal health and increase long-term cardiovascular disease risk in offspring. This review aims to synthesize current knowledge on the roles of ferroptosis and neutrophil extracellular trap formation (NETosis)—two regulated cell death pathways—in these pregnancy-related conditions. We performed a comprehensive analysis of preclinical and clinical studies that investigate the involvement of dysregulated iron metabolism, oxidative stress, inflammation, and endothelial dysfunction mediated by ferroptosis and NETosis in gestational pathologies. Evidence indicates that disturbances in maternal iron homeostasis and enhanced formation of lipid peroxides and NETs contribute to placental dysfunction and systemic inflammation, exacerbating disease severity. Therapeutic strategies targeting these pathways are emerging but require further validation. Our review also identifies key gaps in mechanistic understanding, biomarker development, and translational research needs. We conclude that modulation of ferroptosis and NETosis offers promising avenues for improving diagnosis and treatment of pregnancy complications, though carefully designed clinical studies are essential to confirm their clinical utility and safety. Full article

Background/Objectives: We identified the factors related to post-intensive care syndrome in a sample of patients from northern Colombia. Methods: This study employed a quantitative, observational, descriptive, and correlational approach. A sample of 277 adults was obtained through non-probabilistic convenience sampling, and a characterization form comprising sociodemographic and clinical variables was applied. The Healthy Aging Brain Care Monitor (HABC-M) instrument was also used, which is a clinical tool with a high capacity to detect post-intensive care syndrome (PICS) in surviving intensive care unit (ICU) patients. Results: The final sample consisted of 277 adults, 67.5% male, with university degrees, cohabiting in a marital union, working, from urban areas, and of the Catholic religion. Seventy percent of the sample presented both cardiovascular and neurological alterations and was admitted to the ICU, and 66% had a personal history of arterial hypertension (AHT) and type 2 diabetes mellitus (DM2). Patients had a mean ICU stay of 10.7 days, with a standard deviation of 4 days, and displayed a moderate risk of morbidity and mortality according to Acute Physiology and Chronic Health Evaluation II (APACHE II). A total of 38.6% of the sample received mechanical ventilation, with a mean duration of 8.3 days, and 7.5% underwent tracheostomy. As for sedation, 38.6% were administered fentanyl. In total, 83.4% of the sample presented the syndromes under study, with a predominance of the severe category. The global score of the scale was taken as the dependent variable, and statistical significance (p < 0.05) was found with sociodemographic variables, including origin and religion, and with clinical variables such as receiving pharmacological treatment. Conclusions: The sample presented PICS globally and showed how it affects the different dimensions, showing associations with the sociodemographic and clinical variables of interest. Full article

Background: Adhesive small bowel obstruction (ASBO) is a common and challenging surgical condition. In the absence of peritonitis, bowel ischemia, or clear surgical indicators on CT imaging, the initial management is typically non-operative. While clinical and radiological factors influencing non-operative management (NOM) are well described, the role of age and chronic health conditions remains less well defined. The primary aim of this study was to evaluate the incidence of NOM failure in patients with various comorbidities. Methods: This study utilized data from the National Inpatient Sample to analyze cases of ASBO between 2016 and 2019. Collected data included demographics, diagnosis, presence of chronic health conditions (diabetes mellitus, congestive heart failure, chronic kidney disease, chronic pulmonary diseases, peripheral vascular disease), length of hospital stay, and mortality. Patients were divided into two groups: Group A (18–65 years) and Group B (>65 years). We compared demographics comorbidities, NOM failure rates, and mortality between the groups. Univariate analysis was performed to assess age and comorbidities and risk factors for NOM failure in each group, followed by multivariable analysis within each group. Results: A total of 1,611,099 admissions with ASBO were identified in the NIS database; 63.03% were females. The failure rate of NOM in patients without comorbidities was 21%, compared to 26.5% in patients with one or more comorbidities. In Group A, 20% of patients required surgery, compared to 26.2% of patients in Group B (p = 0.001). Conclusions: Being aged over 65 and the presence of chronic health disease, excluding diabetes mellitus, are independent predictors of NOM failure in patients with ASBO. The presence of multiple comorbidities further increases the risk of NOM failure. Full article

Background: The present study aims to evaluate the effectiveness of ESYSTA^® (Emperra GmbH E-Health Technologies, Germany), a CE-certified digital health application made to support insulin-treated diabetes patients to improve their disease management through better self-empowerment. Methods: To evaluate the effectiveness of ESYSTA^®, data from patients who used ESYSTA^® for at least 12 months and participated in an originally prospective one-arm study were evaluated. This study was conducted in cooperation with the German health insurance company AOK Nordost (2012–2015). From a real-world data pool of insured AOK Nordost patients, a control group was matched to mimic a controlled trial that allows the use of ESYSTA^® to be compared with standard care in the context of a disease management program (DMP). Results: The study results show significant and clinically relevant reductions in HbA1c values of at least 0.4% in ESYSTA^® users after 6 months. After 12 months, users achieved, on average, an HbA1c reduction of approximately 0.7%. These reductions are more pronounced compared to the matched control group. Conclusions: The present study shows the effectiveness of the digital health application ESYSTA^®. Using a matched control group further increased the internal and external validity of the study results. Full article

Background: Hydrogen sulfide (H₂S) is an endogenously produced gaseous neurotransmitter. H₂S donors exhibited neuroprotection in oxidative-stress-related disorders in preclinical studies, but odor and short half-lives have limited their clinical use. However, endogenous H₂S stimulators with antioxidant properties have advantages over H₂S donors regarding safety and patient compliance. Empagliflozin (EMPA), a sodium–glucose cotransporter-2 (SGLT2) inhibitor widely used in the treatment of diabetes mellitus (DM), exerted similar neuroprotective and antioxidant effects as H₂S and shares common mechanisms. This study aimed to investigate the role of H₂S in the antioxidant effects of EMPA in the brain. Methods: The effects of EMPA on H₂S production and reactive oxygen species (ROS) formation were assessed ex vivo in mouse brain under normal conditions and pyrogallol-induced oxidative stress. Moreover, rats were divided into the following four groups: nondiabetic, EMPA-treated nondiabetic, streptozotocin (STZ)-induced diabetic, and EMPA-treated, STZ-induced diabetic. Endogenous H₂S and ROS levels in the brain were measured using methylene blue and chemiluminescence assays, respectively. Results: Ex vivo EMPA treatment significantly increased endogenous H₂S formation in both healthy and pyrogallol-induced oxidative stress, as well as reduced ROS formation in mouse brain; these effects were significantly reversed by the H₂S synthesis inhibitor aminooxyacetic acid (AOAA). Oral EMPA administration significantly elevated brain H₂S levels in both nondiabetic and diabetic rats and reduced ROS formation. These effects were inhibited by AOAA. Conclusions: Our study revealed a novel mechanism by which EMPA can reduce oxidative stress in neurodegenerative disorders by triggering H₂S synthesis in the brain. Full article

Diabetes mellitus (DM) poses an increasingly high global health burden nowadays, while in adults, chronic kidney disease (CKD) associated with DM impacts 20–40% of those with the condition. Effective management of CKD in patients with diabetes necessitates a comprehensive, multidisciplinary approach. Numerous factors, including glomerular hyperfiltration, oxidative stress, inflammation, and hypoxia are linked to the advancement of diabetic kidney disease (DKD). Currently, no specific treatment for DKD has been established, prompting extensive exploration of new approaches. Renin-angiotensin-aldosterone system inhibitors and sodium-glucose cotransporter 2 inhibitors have demonstrated renoprotective effects in various human clinical trials. Additionally, glucagon-like peptide 1 receptor agonists and mineralocorticoid receptor antagonists have been reported as effective in managing DKD, while new therapeutic candidates are also under investigation, such as soluble guanylate cyclase activators and aldosterone synthase inhibitors. Recent evidence has shown that treating diabetic nephropathy by reducing albuminuria levels and retarding its progression is a complex skill. The purpose of this review is to support the impressive results that appear in reducing albuminuria and the progression of diabetic nephropathy with early and intensive combination treatment compared to the recently emerged conventional monotherapy, with agents that act on different pathophysiological mechanisms. Full article

Background and Objectives: This study evaluated the correlation between hyperferritinemia and markers of liver steatosis, fibrosis, and risk of liver-related events in patients with type 2 diabetes mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD). Material and Methods: This study included 271 patients that underwent a comprehensive medical evaluation. Hyperferritinemia was defined by values >200 ng/mL (females) and >300 ng/mL (males). Liver fibrosis and steatosis were evaluated by several non-invasive indexes, and Liver Risk Score (LRS) was calculated to determine the risk of liver-related events. Their correlation with serum ferritin was investigated by bivariate and multiple regression analyses. Receiver Operating Characteristic (ROC) analyses were used to assess the accuracy to predict advanced fibrosis and increased LRS. Statistical significance was set at p < 0.05. Results: The median serum ferritin level was 94.4 [128.1] ng/mL. Metabolic hyperferritinemia was present in 12.54% of patients. Patients with hyperferritinemia had higher liver enzymes, HbA1c, HOMA-IR, and increased markers of liver steatosis and fibrosis, with a higher prevalence of advanced fibrosis (OR = 3.744 [1.481, 9.460], p = 0.0081). LRS was highest in patients with hyperferritinemia (7.99 ± 2.01 vs. 7.12 ± 1.32 vs. 6.54 ± 1.06, p < 0.0001). Serum ferritin levels were correlated with LRS (β = 0.190 [0.001; 0.003], p < 0.001), liver fibrosis (Fibrotic NASH Index) (β = 0.198 [0.000; 0.001], p < 0.001), and steatosis, while haptoglobin concentrations were correlated negatively with them. Serum ferritin predicted the moderate risk of liver-related outcomes with an acceptable performance (area under the ROC curve = 0.726 [0.590; 0.862], p = 0.001). Conclusions: Hyperferritinemia is associated with liver fibrosis and steatosis and a higher risk of liver-related events in patients with T2DM and MASLD. Full article

Type II diabetes mellitus (T2DM) is characterized by chronic glycolipid metabolic dysregulation. This study aimed to investigate the effects and mechanisms of Artemisia integrifolia Linn. (LH) as a functional food in a T2DM rat model. The UPLC-Q-TOF-MS/MS technique was used to identify the components of LH. T2DM was induced in rats via a high-fat/high-sugar diet combined with streptozotocin (STZ, 35 mg/kg, i.p.). The rats were subsequently treated with LH (90 mg/kg, 180 mg/kg) for 15 days. A total of 66 compounds were identified in both positive and negative ions. LH treatment resulted in an increase in body weight while reducing FBG levels. It also improved insulin resistance, blood lipid levels, liver pathology, function, and lipid accumulation. Furthermore, 18 metabolites and 5 metabolic pathways were identified in the liver. Mechanistically, LH may improve T2DM through modulation of the S1P and PI3K/AKT signaling pathway. Caffeic acid, coumarin, trifolin, and apigetrin were identified as the likely active components. In conclusion, LH may mitigate glycolipid metabolism disorders in T2DM rats by modulating metabolic profiling, S1P, and the PI3K/AKT signaling pathway, supporting its potential as a functional food. Full article

Objectives: We investigated the relationship between bone metabolic markers or bone mineral density (BMD) and sarcopenia in patients with type 2 diabetes mellitus (T2DM). Methods: In this cross-sectional study involving 119 subjects (76 women and 43 men), bone metabolic markers were evaluated by bone alkaline phosphatase and bone tartrate-resistant acid phosphatase (TRACP-5b). BMD was measured using the dual-energy X-ray absorptiometry method, and sarcopenia was diagnosed using skeletal muscle mass index (SMI), evaluated by body composition measurement and handgrip strength. Results: Significant correlation was observed between handgrip strength or SMI and TRACP-5b in both sexes (correlation coefficients were −0.50 in handgrip strength and −0.41 in SMI in men; −0.25 in handgrip strength and −0.21 in SMI in women). Furthermore, significant correlation was observed between handgrip strength or SMI and BMD of the femoral neck in both sexes (correlation coefficients were 0.33 in handgrip strength and 0.44 in SMI in men; 0.34 in handgrip strength and 0.47 in SMI in women). The concentrations of TRACP-5b with sarcopenia were significantly higher than those without (643.8 ± 261.9 vs. 455.7 ± 165.6 mU/dL), and BMD of femoral neck with sarcopenia was significantly lower than those without (0.54 ± 0.12 vs. 0.66 ± 0.16 g/cm²). TRACP-5b (odds ratio 1.05, 95% confidence interval 1.01–1.10) and femoral neck BMD (odds ratio 0.30, 95% confidence interval 0.14–0.68) were associated with the presence of sarcopenia after adjustment for confounders. Conclusions: TRACP-5b and BMD of the femoral neck were associated with sarcopenia in patients with T2DM. Full article

Background and Objectives: Type 2 diabetes (T2DM) substantially increases cardiovascular risk; beyond the well-recognized left-ventricular involvement in diabetic cardiomyopathy, emerging data indicate subclinical right-ventricular (RV) dysfunction may also be present. This study aimed to evaluate whether speckle-tracking echocardiography identifies subclinical right-ventricular systolic dysfunction in type 2 diabetes, despite normal conventional indices and preserved global systolic function. Materials and Methods: We conducted a cross-sectional, single-center study in accordance with STROBE recommendations, enrolling 77 participants, 36 adults with T2DM, and 41 non-diabetic controls, between December 2024 and July 2025. All participants underwent comprehensive transthoracic echocardiography, including conventional parameters (tricuspid annular plane systolic excursion (TAPSE), tricuspid annular systolic velocity (TV S’), right ventricular fractional area change (RVFAC)) and deformation imaging (right ventricular global longitudinal strain (RV GLS), right ventricular free wall longitudinal strain (RVFWS)) using speckle-tracking echocardiography. Biochemical and clinical data, including glycosylated hemoglobin (HbA1c), were recorded. Correlation and ROC curve analyses were performed to explore associations and predictive value. Results: The mean age was comparable between the two groups (62.08 ± 9.54 years vs. 60.22 ± 13.39 years; p = 0.480). While conventional RV parameters did not differ significantly between groups, diabetic patients had significantly lower RV GLS (−13.86 ± 6.07% vs. −18.59 ± 2.27%, p < 0.001) and RVFWS (−15.64 ± 4.30% vs. −19.03 ± 3.53%, p < 0.001). HbA1c levels correlated positively with RV strain impairment (RVFWS r = 0.41, p < 0.001). Both RV GLS and RVFWS were independent predictors of RV dysfunction in logistic regression analysis. ROC analysis showed good diagnostic performance for RV GLS, AUC = 0.84 with an optimal cut-off −17.2% (sensitivity 86.1% and specificity 80.5%) and RVFWS, AUC = 0.76 with cut-off −17.6% (sensitivity 77.8; specificity 80.5%) in identifying early myocardial involvement. Conclusions: RV systolic dysfunction may occur early in T2DM, even when traditional echocardiographic indices remain within normal limits. Speckle-tracking echocardiography, particularly RV GLS and RVFWS, offers sensitive detection of subclinical myocardial impairment, reinforcing its value in early cardiovascular risk stratification among diabetic patients. Full article

Aim: To investigate the synergistic effects of exercise training and Brassica oleracea var. italica (broccoli sprout) supplementation on Apolipoprotein A-I, B-100, and J levels in men with Type 2 diabetes mellitus (T2DM). Methods: Forty-four males with T2DM were randomly assigned to four groups: Control (CG), Supplement (SG), Training (TG), and Training + Supplement (TSG) groups. Participants in the supplement groups (SG and TSG) received 10 g of broccoli supplement after meals for 12 weeks, while those in the training groups (TG and TSG) participated in a structured exercise program (resistance and aerobic), performed three times per week for 12 weeks, at intensities of 60–70% one-repetition maximum (1RM) for resistance training and 60–70% peak oxygen uptake (VO_2peak) for aerobic training. Results: Circulating levels of apolipoproteins improved after 12 weeks in the TSG, TG, and SG groups. However, the TSG group exhibited the most pronounced improvements across metabolic and lipoprotein markers, reflecting an additive effect of both interventions. Specifically, the TSG group demonstrated absolute reductions in ApoB-100 (−48.30 ± 7.20 mg/dL) and ApoJ (−44.05 ± 5.76 mg/dL), along with an increase in ApoA-I (+44.92 ± 6.05 mg/dL). Main effect analysis revealed that exercise training elicited the most substantial improvements across metabolic and lipoprotein markers, with large effect sizes for glucose (η²p = 0.787), insulin (η²p = 0.640), HOMA-IR (η²p = 0.856), ApoA-I (η²p = 0.685), ApoB-100 (η²p = 0.774), ApoJ (η²p = 0.848), and HDL-C (η²p = 0.535). Supplementation showed moderate effects, particularly on HOMA-IR (η²p = 0.370), ApoA-I (η²p = 0.383), and ApoB-100 (η²p = 0.334), supporting an additive but exercise-dominant benefit. The combined intervention group (TSG) showed the most pronounced improvements across all measured outcomes, with large effect sizes for ApoA-I (η²p = 0.883), glucose (η²p = 0.946), insulin (η²p = 0.881), HOMA-IR (η²p = 0.904), and ApoJ (η²p = 0.852). Conclusions: The effects of combining training and broccoli sprout supplementation on apolipoprotein levels are likely to result from the activation of two separate pathways, one from training and the other from supplementation. This dual-modality intervention could serve as an effective complementary strategy in managing metabolic and cardiovascular risk factors for individuals with T2DM. However, the magnitude of change induced by the combination of exercise training and broccoli supplementation was largely driven by the training component, with supplementation providing complementary but less consistent benefits. Full article

Background/Objectives: We report on the association of clinical, demographic, and peri- and intraoperative factors with patient outcomes in large- and, separately, medium-vessel acute ischemic stroke (AIS) occlusions treated with mechanical thrombectomy or medical thrombolysis. Increasingly, neuroimaging, particularly novel markers of collateral status, has become useful in predicting response to endovascular treatment (EVT) among AIS patients. However, the relationship between these neuroimaging markers, documented predictors of stroke outcomes, and post-EVT functional status in anterior circulation large-vessel occlusions (LVOs) as compared to medium-vessel occlusions (MeVOs) remains unclear. We evaluated whether shared predictors of 90-day post-EVT functional outcomes in LVO compared to MeVO AIS patients within our institution exist. Methods: We retrospectively evaluated AIS patients treated at our institution between 9 January 2017 and 10 January 2023. The following were the inclusion criteria were applied: (i) CTA confirmed anterior circulation large or medium vessel occlusion; (ii) diagnostic CT perfusion was performed; (iii) mechanical thrombectomy was performed. A low modified Rankin score (mRS) indicating good functional outcomes (i.e., functional independence) was defined as less than or equal to 2, in accordance with prior studies. Univariate and multivariate logistic regression analyses were conducted to determine associations between demographic, clinical, and radiologic factors and mRS ≤ 2. Results: A total of 249 LVO (mean age 65.3 ± 16.2, 53.8% female) and 91 MeVO (mean age 68.9 ± 13.3, 46.2% female) patients met the inclusion criteria. Upon multivariate regression adjusted for race, age, hypertension, diabetes mellitus, radiologic features, IV alteplase, admission NIHSS, and reperfusion status, young age (p = 0.004), low admission NIHSS (p = 0.0001), and good reperfusion status (p = 0.007) were associated with good functional outcomes in LVO stroke. By contrast, no factors were significantly associated with good functional outcomes in MeVO stroke. Conclusions: Known factors, including young age, low admission stroke severity, and successful reperfusion predict EVT outcomes in LVO stroke but not necessarily in MeVO stroke. Further studies regarding predictors of MeVO outcomes in nonsurgical cases, including collateral status, may guide optimal medical management for this population. Full article