Diabetes & vascular disease research最新文献

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.

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.

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.

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.

BackgroundEarly-onset type 2 diabetes (T2DM), diagnosed before age 40, progresses rapidly and has a higher risk of complications compared to late-onset T2DM. Its global prevalence is rising, but the underlying risk factors are insufficiently understood.ObjectiveThis systematic review and meta-analysis aimed to evaluate risk factors associated with early-onset T2DM to support clinical decision-making and inform preventive strategies.Methods37 studies (cohort, case-control, cross-sectional) were identified from PubMed, Web of Science, and Embase up to October 31, 2024. Data were analyzed using STATA 17.0, and pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. Subgroup analyses were performed by region, study type, and sample size.ResultsCompared with normoglycemic individuals, early-onset T2DM was strongly associated with family history of diabetes (OR = 4.54, 95%CI: 2.31-8.90), high BMI (OR = 2.87, 95%CI: 2.22-3.80), maternal gestational diabetes (OR = 3.01, 95%CI: 2.44-3.72), and elevated fasting glucose (OR = 8.73, 95%CI: 4.91-16.92). Subgroup and sensitivity analyses confirmed the robustness of these findings despite persistent heterogeneity. In comparisons with late-onset T2DM, family history (OR = 2.90), male sex (OR = 1.57), and BMI (OR = 1.12 per unit) remained significant risk factors.ConclusionEarly-onset T2DM is shaped by familial, metabolic, and lifestyle determinants. Incorporating these factors into early screening and intervention programs, particularly lifestyle modification in young high-risk populations, is essential to reduce disease burden and delay progression.

Diabetic neuropathy is a troublesome complication of diabetes mellitus. It affects about 50% of patients with diabetes and may mask symptoms of ischemic conditions. Sudden blockade in blood flow to the limb known as acute limb ischemia (ALI) is a life-threatening disease associated with peripheral artery disease (PAD). Diabetes mellitus predisposes both to ALI and PAD, while also delaying recognition due to diabetic peripheral neuropathy.We report a case of a patient with poorly controlled type 2 diabetes and atrial fibrillation who presented a rare occurrence of painless acute upper limb ischemia. Despite two embolectomies with positive revascularization, ischemia progressed, leading to amputation.In the article we discuss management of the patient and the case's similarity to diabetic foot disease. Our case report highlights the importance of vigilance against diabetes-related complications, which may manifest unusual symptoms and thus mask other dangerous ailments.

ObjectiveWe aimed to explored the association between atherogenic index of plasma (AIP), body mass index (BMI) and stroke risk among people with abnormal glucose metabolism.MethodsThis study included participants with abnormal glucose metabolism from the China Health and Retirement Longitudinal Study (CHARLS). AIP was computed using the formula log (Triglyceride/High-density lipoprotein cholesterol). Participants were categorized into high and low levels based on median values for both AIP and BMI. Logistic regression models were employed to investigate the associations between AIP, BMI, and stroke.ResultsIn the longitudinal analysis, 195 out of 3,682 individuals (5.3%) experienced stroke. Joint effects of AIP and BMI on stroke risk indicated that odds ratios for stroke were 1.41 (0.86-2.31) for high AIP & low BMI group, 1.81 (1.14-2.89) for low AIP & high BMI group, and 2.15 (1.42-3.27) for high AIP & high BMI group when compared to low AIP & low BMI group. A significant interaction was observed between AIP and BMI regarding stroke risk. However, this association appeared diminished within cross-sectional evaluations.ConclusionElevated levels of both AIP and BMI are significantly correlated with an increased risk of stroke among individuals exhibiting abnormal glucose metabolism during longitudinal analysis.

Visceral adiposity is a pivotal pathogenic driver of type 2 diabetes mellitus (T2DM) and its vascular complications. We performed two-sample Mendelian randomization (MR) analyses to examine the causal relationships between visceral adipose tissue (VAT) accumulation and diabetes complications. Single nucleotide polymorphisms (SNPs) specific to VAT accumulation were identified through large-scale genome-wide association studies (GWAS) at genome-wide significance (P < 5 × 10^-8), using the inverse variance weighted (IVW) approach for primary analyses. The MR-IVW random-effects model revealed significant associations between genetically predicted VAT accumulation and increased risks for T2DM complications: multi-organ (OR = 2.58, 95% CI, 2.21-3.03), neurological (OR = 3.58, 95% CI, 2.34-5.47), retinopathy (OR = 2.90, 95% CI, 2.21-3.81), nephropathy (OR = 3.14, 95% CI, 2.23-4.45), and peripheral vascular (OR = 3.32, 95% CI, 2.31-4.76). Consistency across complementary MR methods supported the causal inference. This study provides genetic evidence that VAT accumulation is causally associated with increased risk of multiple T2DM complications, including neurological, ocular, kidney, and peripheral vascular outcomes. Future research should prioritize mechanistic studies to elucidate VAT-driven inflammatory and lipotoxic pathways in diabetic complications.

BackgroundThe SUSTAIN-6 trial showed the cardiovascular disease (CVD) benefits of semaglutide among patients with type 2 diabetes mellitus (T2DM). We estimated the US population eligibility and preventable CVD events from semaglutide.MethodsUS adults with T2DM were selected from the National Health and Nutrition Examination Survey 2011-2020 based on SUSTAIN-6 eligibility criteria. We estimated composite and secondary CVD events from SUSTAIN-6 treated and placebo published event rates multiplied by the weighted US eligible population, the difference being the number of preventable events which was then divided by 2.1 years to provide annualized estimates.ResultsAmong 4755 (projected to 33.6 million [M]) adults with T2DM, 1132 (6.9 million) fit SUSTAIN-6 criteria. Compared to SUSTAIN-6, our sample more likely had female and black patients, shorter diabetes duration, and was less likely with prior CVD. We estimated 75,681 primary outcome CVD events, 128,329 expanded composite CVD events, 72,390 combined nonfatal MI, nonfatal stroke, and all-cause deaths, 36,195 non-fatal stroke events, 85,552 revascularizations, and 75,681 cases of nephropathy could be prevented annually if eligible T2DM subjects were on semaglutide.ConclusionSemaglutide may prevent over 75,000 CVD events annually if provided to eligible T2DM US adults. Efforts to improve use of these therapies are needed.