Diabetes & vascular disease research最新文献

BackgroundHypoglycemia in type 2 diabetes patients is associated with metabolic abnormalities and inflammation that affect vascular beds. The relationship between hypoglycemia and panvascular disease (PVD) is not clear. This study aimed to investigate the association between PVD and hypoglycemia, and to identify potential mediators.MethodThis retrospective cross-sectional study enrolled Patients from two centers in Chongqing China, and the results were further validated using UK Biobank data. Logistic regression was used to test the association of hypoglycemia and PVD. Stratification and interaction analyses to test the effects across study subgroups. Forward (hypoglycemia to PVD) and reverse (PVD to hypoglycemia) relationships were analyzed by structural equation modeling (SEM), which included interleukin-6, neutrophil-to-lymphocyte ratio, uric acid, hemoglobin A1c, and systolic blood pressure.Results22,128 patients diagnosed with T2DM at two large centers and 44442 T2DM participants from the UK Biobank were enrolled. A significant association between hypoglycemia and PVD was found. Subgroup analysis found hypoglycemia was more strongly associated with PVD in patients with inflammatory abnormalities and metabolic dysfunction. SEM suggested a correlation structure between hypoglycemia and PVD which might mutually aggravated each other through inflammation and metabolism pathways.ConclusionThis is the first study that described the correlation structure between hypoglycemia and PVD with a large population. Within this potential mutual association, inflammation and metabolism might be mediators. Our study also highlights the insufficient attention clinicians pay to hypoglycemia and PVD, and further attention is needed in future clinical practice and research.

BackgroundDepression and insulin resistance-measured by the estimated glucose disposal rate (eGDR)-are both linked to cardiovascular disease (CVD), but whether eGDR mediates this relationship remains unclear. We examined the mediating role of eGDR and its joint and interactive effects with depression on incident CVD.MethodsData were derived from the China Health and Retirement Longitudinal Study (2011-2020). Participants without baseline CVD and with complete eGDR and CESD-10 data were included. eGDR was calculated as 21.158 - (0.09 × waist circumference) - (3.407 × hypertension) - (0.551 × HbA1c). Depressive symptoms were defined as CESD-10 ≥ 12. Cox models adjusted for demographic and lifestyle factors assessed CVD risk across four groups defined by eGDR and depression status.ResultsDuring a median 9-years follow-up, 1643 CVD events occurred. Participants with low eGDR and depression had the highest CVD risk (HR = 1.87, 95% CI: 1.40-2.49, p < 0.001). Additive interaction analysis indicated biological synergy (relative excess risk = 1.37; attributable proportion = 0.32). eGDR mediated 9.82% of the depression-CVD association. Interactions were stronger in older adults.ConclusionLow eGDR and depressive symptoms synergistically elevate CVD risk, highlighting the importance of integrating metabolic and psychological assessments in CVD prevention.

BackgroundDiabetes-related foot ulcers (DFUs), often complicated by peripheral arterial disease (PAD), remain a major therapeutic challenge. In patients unsuitable for revascularization, alternative treatments are essential. This study is the first to evaluate bipolar radiofrequency (RF) ablation as part of lumbar sympathetic block (LSB) for enhancing wound healing in DFU patients with critical limb ischemia.MethodsThis retrospective cohort study included 31 DFU patients with severe PAD who were not candidates for revascularization. Group 1 (n = 18) received LSB with bipolar RF plus medical care; Group 2 (n = 13) received medical care alone. Wound healing, amputation rates, pain scores (NRS, DN4), and complications were analyzed.ResultsComplete wound healing was significantly higher in Group 1 (55.5%) than in Group 2 (15.3%) (p = 0.031). Amputation was required in 23.1% of Group 2 patients, while none occurred in Group 1 (p = 0.063). Group 1 showed significant reductions in DN4 (p = 0.0057) and NRS (p = 0.0013) at 6 months. No complications related to LSB were observed.ConclusionsLSB with bipolar RF ablation is a safe, potentially effective option for DFU patients with PAD not eligible for revascularization. It significantly improves wound healing and pain outcomes. Larger prospective studies are needed to confirm these results.

BackgroundAtherosclerosis (AS) and type 2 diabetes mellitus (T2DM) frequently coexist, jointly accelerating cardiovascular complications through shared inflammatory and metabolic pathways. Despite extensive research, the molecular mechanisms linking these chronic diseases remain incompletely defined.PurposeThis study aimed to delineate the shared transcriptional signatures and identify candidate biomarkers contributing to T2DM-associated AS progression using an integrative multi-omics strategy.Research DesignA retrospective bioinformatics investigation integrating differential expression analysis, co-expression network modeling, protein-interaction profiling, immune deconvolution, and machine-learning-based biomarker prioritization was conducted.Study Sample: Publicly available transcriptomic datasets were obtained from the NCBI Gene Expression Omnibus, including AS tissue samples (GSE100927), pancreatic islet samples from individuals with T2DM (GSE25724), and two independent datasets for external validation (GSE30169 and GSE26168).Data Collection and/or AnalysisDifferentially expressed genes (DEGs) were identified for AS (n = 3,368) and T2DM (n = 4,553). DEG intersection and Weighted Gene Co-expression Network Analysis (WGCNA) revealed 443 shared crosstalk genes. Enrichment analyses highlighted immune activation processes (e.g., leukocyte-mediated immunity, lysosomal pathways) and metabolic dysregulation (e.g., mitochondrial-mediated apoptosis, TGF-β signaling). A protein-protein interaction network was constructed, identifying high-degree hub genes such as HLA-DRB1, JAK3, and MFN1. Immune cell profiling using CIBERSORTx compared disease microenvironments, demonstrating increased M1 macrophages and helper T cells in AS, and elevated monocytes and B cells in T2DM (p < 0.05). A fine-tuned TabNet model ranked predictive biomarkers (e.g., BTK, ZAP70, CD4) showing strong diagnostic performance (AUC = 0.85 for AS; 0.79 for T2DM).ResultsThe integrative multi-omics workflow uncovered a robust set of immune-metabolic crosstalk genes shared between AS and T2DM. Hub-gene analysis and immune infiltration patterns demonstrated convergent dysregulation in lysosomal activity, mitochondrial integrity, and adaptive immune signaling. Machine-learning prioritization further identified a subset of biomarkers capable of discriminating disease states with high accuracy, strengthening their translational potential.ConclusionsThis study provides a comprehensive molecular framework linking T2DM and AS, revealing previously unrecognized lysosomal and mitochondrial pathways that may drive their synergistic pathology. The identified biomarkers and immune signatures offer promising avenues for early diagnosis and targeted therapeutic development in patients with comorbid T2DM and atherosclerosis.

BackgroundChronic kidney disease (CKD) comorbid with cardiovascular disease (CVD) results in substantial mortality. The predictive value of the triglyceride-glucose (TyG) index for mortality in this population remains unverified. We aimed to evaluate the association of the TyG index with mortality in individuals with CKD and CVD.MethodsUsing National Health and Nutrition Examination Survey (NHANES) data (1999-2018), we analyzed 1104 adults with CKD and CVD. Multivariable Cox proportional hazards models and restricted cubic splines assessed associations between the TyG index and mortality. Threshold effects were evaluated.ResultsOver a median 10.3-years follow-up, 623 all-cause and 311 cardiovascular deaths occurred. A significant U-shaped association existed between the TyG index and both all-cause (p-nonlinear = 0.002) and cardiovascular mortality (p-nonlinear = 0.014). Above a threshold of 8.91, higher TyG index predicted increased all-cause mortality risk (HR 1.34, 95% CI 1.07-1.67; p = 0.01). Below 8.91, the association was non-significant (HR 0.82, 95% CI 0.62-1.28; p = 0.537). This U-shaped relationship was significant in males (p-nonlinear < 0.05) but not females.ConclusionsThe TyG index demonstrates a U-shaped association with all-cause and cardiovascular mortality in patients with comorbid CKD and CVD. Maintaining TyG index within a specific range may reduce mortality risk, highlighting its potential role in risk stratification and targeted management.

BackgroundFirst-degree relatives (FDRs) of individuals with type 2 diabetes mellitus (T2DM) are at increased cardiometabolic risk due to genetic predisposition, even in the absence of overt disease. To evaluate subclinical myocardial dysfunction using speckle-tracking echocardiography (STE) and to assess serum levels of endothelial dysfunction related biomarkers, Endothelin-1 (ET-1), E-selectin, and Endocan, in normoglycemic FDRs of patients with T2DM, compared with healthy controls.MethodsThis study included 151 normoglycemic participants, comprising 75 individuals in the study group and 76 in the control group. Global longitudinal and circumferential strain values were assessed using STE. Serum levels of ET-1, E-selectin, and Endocan were measured using ELISA.ResultsET-1 levels were significantly higher in the study group (p = 0.047). STE revealed lower strain values in the study group in both SAX Basal/Mid/Apical (p = 0.027) and A4C/A2C/A3C mean views (p = 0.013). E-selectin showed a negative correlation with myocardial strain values, although no significant between-group difference was observed.ConclusionsNormoglycemic FDRs of T2DM patients exhibited subclinical myocardial strain abnormalities and elevated ET-1 levels, suggesting early cardiovascular alterations associated with genetic predisposition. ET-1 and E-selectin may serve as potential biomarkers for preclinical myocardial dysfunction in at-risk individuals.

ObjectiveThis study aimed to compare hemoglobin glycation index (HGI) and glycation gap (GG), markers of the discordance between measured and predicted hemoglobin A1c levels, for predicting all-cause and cardiovascular disease (CVD) mortality in a nationally representative population.MethodsData of 3468 adults were retrieved from the 1999-2004 US National Health and Nutrition Examination Survey. Participants were stratified into four groups based on the median of absolute values of HGI and GG. Associations between HGI, GG and mortality risk were evaluated with Cox proportional hazard model and time-dependent receiver-operating characteristic curves.ResultsOver a median follow-up of 101 months, 733 (12.48%) participants died, of which 210 were from CVD causes. Compared to the HGI-/GG-group, the HGI+/GG+ group had an hazard ratio (95% confidence interval) of 1.36 (1.02-1.82) for all-cause mortality and 1.91 (1.00-3.64) for CVD mortality. Restricted cubic spline curves demonstrated a positively linear relationship between absolute values of HGI, GG and mortality risk. Time-dependent receiver-operating characteristic curves revealed comparable predictive accuracy for HGI and GG, with area under the curve ranged between 0.50 and 0.60 across follow-up periods.ConclusionsCombined HGI and GG assessment may provide guidance on risk stratification and identification of high-risk individuals.