The estimated glucose disposal rate (eGDR), a marker of insulin resistance, is linked to cardiovascular disease (CVD) risk. However, longitudinal eGDR patterns and their association with CVD remain unclear in Chinese populations. To identify 5-year eGDR trajectories and assess their association with incident CVD in a Chinese cohort. We analyzed health check-up data from West China Hospital (2010–2022). eGDR trajectories were modeled over 5 years using group-based trajectory modeling. Participants free of CVD at baseline were followed for 5–8 years. Cox regression assessed the relationship between eGDR trajectories and CVD risk, adjusting for covariates; subgroup analyses tested consistency. Among 5,039 participants (mean age 44.65 years; 59.18

Stress fiber-generated traction forces critically regulate mesenchymal stem cell (MSC) behavior, yet how mechanical cues are integrated across transcriptional programs remains unclear. Here, we attenuated actomyosin contractility in human MSCs and performed parallel Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq), YAP-targeted Cleavage Under Targets and Tagmentation sequencing (CUT&Tag) and RNA-seq profiling. We show that reduced stress fiber traction force selectively reorganizes chromatin accessibility into coherent functional modules, resulting in diverse transcriptional programs. The mechanosensitive co-activator YAP functions as a parallel force-responsive regulatory layer coordinating with chromatin accessibility changes. Integration of chromatin accessibility, YAP occupancy, and transcriptomic profiles reveals pathway-specific regulatory responses, identifying focal adhesion and PI3K-Akt signaling as central mechanosensitive pathways coordinated across layers. Together, these findings establish a modular framework for force-dependent gene regulation, demonstrating how mechanical signals are integrated across epigenomic and transcriptional networks to shape MSC transcriptional programs.

Cardiac fibrosis remains an unresolved clinical issue in patients with heart diseases. CircRNAs have emerged as potential targets for treatment of heart diseases. Exploring the functional circRNAs in fibroblast activation is one of the ways to develop innovative drugs for the treatment of cardiac fibrosis. This study aimed to screen for fibroblast-related circRNAs in cardiac fibrosis and elucidate their roles and underlying mechanisms. By screening for fibrosis-responsible circular RNAs (circRNAs), we identified a highly conserved circRNA, circular RNA Sterile alpha motif domain containing 4 (circSamd4), that drives cardiac fibrosis. circSamd4 is prominently expressed in cardiac fibroblasts (CFs) and is upregulated in the fibrotic hearts of humans and mice. Fibroblast-specific silencing of circSamd4 reduced cardiac fibroblast activation and alleviates cardiac fibrosis. Conversely, overexpression of circSamd4 in fibroblasts exacerbates cardiac fibrosis and rescues cardiac function. Bioinformatics and functional analyses revealed that circSamd4 regulates the plasminogen activation. Plasminogen activator inhibitor-1 (PAI-1, encoded by Serpine1) is a key effector of plasminogen activation and redox homeostasis and contributes to fibrotic diseases. Here, PAI-1 serves as a leading functional downstream factor of circSamd4 because PAI-1 is highly expressed in cardiac fibroblasts and contributes to circSamd4 functions in regulating fibroblast activation and cardiac fibrosis. Mechanistically, circSamd4 functions as a sponge for miR-1894-3p to trigger Serpine1 expression and subsequent fibroblast activation, and cardiac fibrosis. Therefore, we identified a fibroblast-specific circSamd4-miR-1894-3p-Serpine1 axis driving fibroblast activation and cardiac fibrosis. Adeno-associated virus (AAV)-mediated knockdown of circSamd4 or Serpine1 alleviated cardiac fibrosis and cardiac dysfunction. These findings suggest that circSamd4 and Serpine1 are promising therapeutic targets for inhibiting cardiac fibrosis.

Bone aging compromises skeletal integrity and increases vulnerability to osteoporosis and other age-related disorders, underscoring the need for new therapeutic strategies. Although pharmacological and genetic approaches have been widely explored, how cellular mechanical remodeling contributes to bone aging remains unclear. Here, we find that senescent bone marrow stem cells show markedly reduced intracellular force and impaired mechanical behavior. Moderate mechanical stimulation in cell culture and in mice restores cellular force, increases chromatin accessibility at the FOXO1 locus, activates its expression, and reverses cellular senescence and bone aging. These mechanical interventions also improve physical performance in aged female mice and show a tendency to reduce systemic inflammation, whereas excessive force induces chromatin overextension and DNA damage, indicating the necessity of precise force control. In this work, we show that optimized mechanical stimulation provides a simple and effective strategy to counteract age-related bone deterioration and systemic inflammation, offering potential for clinical translation.

Cells actively sense and transduce microenvironmental mechanical inputs into chemical signals via cytoskeletal rearrangements. During these mechanosensation and mechanotransduction processes, the role of the actin cytoskeleton is well-understood, whereas the role of the tubulin cytoskeleton remains largely elusive. Here, we report the dynamic changes in microtubules in response to microenvironmental stiffness during chondrocyte mitosis. Mechanical stiffness was found to be coupled with microtubule generation, directing microtubule dynamics in mitotic chondrocytes. Refilin B was found to be a key regulator of microtubule assembly in chondrocytes in response to mechanical stiffness. It was found to play its role in microtubule formation via the p-Smad3 signaling pathway. Additionally, integrin-linked kinase (ILK), triggered by mechanical stiffness, was found to play an indispensable role in the process of microtubule dynamics mediated by refilin B. Our data emphasizes stiffness-mediated dynamic changes in the microtubules of chondrocytes in a quiescent state (G0) and at anaphase, which improves our understanding of the mechanical regulation of microtubule assembly during the chondrocyte cell cycle and provides insights into microenvironment mechanics during tissue maintenance, wound healing, and disease occurrence.

Human mesenchymal stem cells (hMSCs) undergo progressive functional decline during long-term ex vivo expansion, which limits their therapeutic potential. However, the contribution of intercellular adhesion to this process remains unclear. By comparing hMSCs at different passage stages, we found that replicative senescence is accompanied by impaired collective motility homeostasis in near-confluent monolayers, diminished traction forces and altered monolayer stress distribution, concomitant with upregulated N-cadherin expression. Notably, N-cadherin knockdown or pharmacological blockade of its homophilic binding using ADH-1 restored migratory dynamics, enhanced traction generation and alleviated senescence-associated phenotypes. These findings identify N-cadherin as a crucial regulator of replicative senescence and highlight intercellular adhesion as a potential target for delaying senescence during ex vivo stem cell expansion.

Cardiovascular aging is a major contributor to the development of cardiovascular diseases (CVDs), yet the mechanisms linking metabolic imbalance to age-related cardiovascular dysfunction remain unclear. Protein palmitoylation, a reversible lipid post-translational modification, regulates protein localization, stability, and signaling, but its role in cardiovascular aging has not been systematically defined. Importantly, protein palmitoylation appears to act as a double-edged sword: whereas its physiological regulation is indispensable for cardiovascular homeostasis, aberrant palmitoylation under metabolic stress may drive aging and disease progression. In this review, we summarize current evidence indicating that dysregulated palmitoylation contributes to key features of cardiovascular aging, including mitochondrial dysfunction, impaired autophagy, oxidative stress, and cellular senescence. We further integrate findings across cardiomyocytes, endothelial cells, fibroblasts, and immune cells to highlight the role of palmitoylation in coordinating cellular dysfunction and intercellular communication during cardiovascular aging and disease. We propose a "palmitoylation-driven metabolic vicious cycle" that links metabolic disorders to enhanced palmitoylation and progressive cardiovascular injury. In addition, we discuss emerging detection approaches and therapeutic strategies targeting palmitoylation. Overall, this review provides a mechanistic framework linking palmitoylation to cardiovascular aging and disease and identifies potential targets for intervention in aging-related CVDs.

Rationale: The tertiary structure of normal podocytes prevents protein from leaking into the urine. However, observing the complexity of podocytes is challenging because of the scale differences in their three-dimensional structure and the close proximity between neighboring cells in space. In this study, we explored podocyte-secreted angiopoietin-like 4 (ANGPTL4) as a potential morphological marker via super-resolution microscopy (SRM). Methods and Results: Specimens from patients with minimal change disease (MCD), focal segmental glomerulosclerosis (FSGS), and membranous nephropathy (MN), along with normal controls, were analyzed via immunofluorescence and immunohistochemistry to determine the expression and localization of ANGPTL4, confirming its extensive presence in podocytes across both healthy and diseased conditions. Immunoelectron microscopy revealed that ANGPTL4 is distributed throughout the podocyte cell body, primary processes, and foot processes. Compared with conventional podocyte markers such as nephrin and synaptopodin, ANGPTL4 excels in depicting the three-dimensional structure of podocytes via SRM imaging. We then refined a protocol using tyramide signal amplification staining and confocal microscopy to uniformly enhance podocyte fluorescence, facilitating the clinical assessment of biopsies. In patients diagnosed with MCD and FSGS, measurements of slit diaphragm density, primary process width, and foot process width were taken after further co-staining with nephrin to identify patterns of podocyte morphological alterations. Distinctive patterns of foot process effacement were identified in MCD and FSGS patients, with FSGS patients showing more pronounced podocyte injury. Conclusions: ANGPTL4 serves as a reliable morphological marker for podocyte analysis, offering enhanced visualization of their three-dimensional structure and facilitating the identification of distinct pathological changes in nephrotic syndrome patients.

Rheumatoid arthritis (RA) is a complex and highly disabling chronic autoimmune disease. As the disease progresses, patients often develop complications such as joint destruction and cardiovascular diseases, posing significant threats to human health. Celastrol, a major bioactive compound extracted from the traditional Chinese herb Tripterygium wilfordii Hook. f., exhibits potent immunomodulatory and anti-inflammatory properties. However, the specific mechanisms underlying its protective effects against bone destruction in RA remain poorly understood. To elucidate its potential therapeutic mechanisms, this study retrieved three gene expression datasets—GSE55235, GSE93777, and GSE200815—from the Gene Expression Omnibus (GEO) database. The primary molecular targets of celastrol were obtained from the HERB and TCMSP platforms. Functional mechanisms associated with these targets were explored using gene set variation analysis (GSVA) and weighted gene co-expression network analysis (WGCNA). Furthermore, molecular docking, immune infiltration analysis, and single-cell RNA sequencing analysis were employed to investigate the role of key target genes. In this study, thirteen potential target genes of celastrol in RA have been identified, including ADAMTS5, AGTR1, ALOX5, CTSB, MMP3, MMP9, MYC, TNF, ITGA4, ITGB7, MMP1, MMP13, and PPARG. Among these, ALOX5 was found to significantly promote MMP3 protein expression, based on which a regulatory model with high predictive power was constructed. GSVA analysis revealed that the TNF-NFκB pathway was significantly activated in RA and exhibited a strong positive correlation with ALOX5 expression. Further experimental analysis demonstrated that knockdown of ALOX5 and its shared transcription factor with MMP2 resulted in a significant downregulation of both genes and inhibition of TNF-NFκB pathway activity. Single-cell transcriptomic analysis showed that ALOX5 was predominantly expressed in macrophages, and the AddModuleScore of celastrol-targeted genes in this cell type was significantly higher than in other cell types, suggesting that macrophages may serve as key effector cells in celastrol-mediated treatment of RA. Celastrol might attenuate RA bone destruction by inhibiting the expression of the ALOX5 gene in macrophages, thereby suppressing the activation of the NF-κB pathway and subsequently reducing the production of matrix metalloproteinases.

Chronic kidney fibrosis poses a significant global health challenge with effective therapeutic strategies remaining elusive. While cell-extracellular matrix (ECM) interactions are known to drive fibrosis progression, the specific role of focal adhesions (FAs) in kidney fibrosis is not fully understood. In this study, we investigated the role of FAs in kidney tubular epithelial cell fibrosis by employing precise nanogold patterning to modulate integrin distribution. We demonstrate that increasing ligand spacing disrupts integrin clustering, thereby inhibiting FA formation and attenuating fibrosis. Importantly, enhanced FA activity is associated with kidney fibrosis in both human disease specimens and murine models. Mechanistically, FAs regulate fibrosis through mechanotransduction pathways, and our in vivo experiments show that suppressing mechanotransduction significantly mitigates kidney fibrosis in mice. These findings highlight the potential of targeting FAs as a therapeutic strategy, offering new insights into clinical intervention in kidney fibrosis.

Objective:This study investigates the association between myeloperoxidase (MPO) levels and anxiety risk in Chinese adults and explores potential effect modifiers, with implications for neuroinflammatory biomarker-guided anxiety prevention strategies. Methods:Using cross-sectional data from 30,418 adults undergoing routine health examinations (July 2020-June 2021), anxiety severity was assessed via the Self-Rating Anxiety Scale (SAS; score ≥ 50 as clinically relevant). Plasma MPO was quantified by ELISA. Multivariate logistic regression, restricted cubic splines (RCS), threshold effect analysis, and subgroup interactions were conducted to evaluate nonlinear associations. Results:A U-shaped relationship between MPO and anxiety risk was identified. In fully adjusted models, participants in the lowest (Q1: ≤29.77 ng/mL, OR = 1.15, 95% CI: 1.03-1.28, p = 0.01) and highest quintiles (Q5: ≥47.3 ng/mL, OR = 1.17, 95% CI: 1.05-1.31, p = 0.004) exhibited significantly elevated anxiety risks compared to the reference quintile (Q2: 29.8-34.7 ng/mL). RCS analysis confirmed a nonlinear association (p for nonlinearity < 0.01), with an inflection point at 30 ng/mL: below this threshold, each 1 ng/mL MPO increase reduced anxiety risk (OR = 0.982, CI: 0.970-0.994), while levels above it heightened risk (OR = 1.004, CI: 1.001-1.008). Diabetes mellitus significantly modified this relationship (p-interaction = 0.028), with diabetic individuals showing amplified risks at higher plasma MPO (Q5 OR = 1.84 vs. non-diabetic Q5 OR = 1.15). Conclusion:Plasma MPO demonstrates a U-shaped association with anxiety risk independent of cardiometabolic confounders. Diabetic individuals exhibit heightened susceptibility to MPO-related anxiety, suggesting synergistic neuroinflammatory pathways. Monitoring MPO may aid in risk stratification and personalized interventions, particularly in populations with diabetes.

Recent multiomics advancements have improved our understanding of immune dysregulation in dilated cardiomyopathy (DCM). However, specific immune cell subsets and their regulatory genes are still ambiguous. This study aimed to explore immune cell imbalances and regulatory genes in DCM, discover diagnostic biomarkers, and identify potential therapeutic targets. Immune cell infiltration in DCM patients was quantified via deconvolution algorithms and single-cell RNA sequencing. Flow cytometry validation in 40 DCM patients and 40 healthy controls confirmed a notable increase in CD4+ effector memory T cells (CD4+ TEM cells) in DCM patients. Differential expression analysis of the GSE101585 dataset revealed 1783 genes. Weighted gene coexpression network analysis (WGCNA) identified a core immune-regulatory gene set, and protein-protein interaction (PPI) analysis highlighted 36 hub genes. Machine learning cross-validation identified four diagnostic biomarkers (LRRTM4, PTPN22, FAM175B, and PROM2) whose transcriptional changes had been validated by qPCR. Among these genes, PTPN22 was strongly correlated with CD4+ TEM cell abundance. Additionally, DSigDB analysis predicted 87 potential therapeutic drugs, with PTPN22 being the target of the most drugs. This study reveals a CD4+ T cell subset-centered immunoregulatory network in DCM, identifying novel diagnostic biomarkers and druggable targets to guide precision immunomodulatory strategies for DCM management.

Cardiovascular disease (CVD) is one of the leading causes of mortality in humans, with a high prevalence. Moreover, this disease poses a serious threat to the economy. At present, treatment strategies are inadequate in both the prevention and cure of CVD. Thus, further investigations are required for the development of novel therapeutic options. Notably, gene- and cell-based therapies exhibit potential in the treatment of CVD. In the present article, gene- and cell-based therapies were reviewed in the context of CVD. The present review may provide a novel theoretical basis for improving the efficacy of CVD treatment, and demonstrate the potential of gene- and cell-based therapy in clinical practice. In addition, market analysis was carried out in the present study.

Objectives: This study investigates the nonlinear association between myeloperoxidase (MPO) levels and Helicobacter pylori (H. pylori) infection risk in Chinese adults, evaluating potential modifiers and clinical implications for infection prevention. Methods: An analysis was conducted on cross-sectional data from 15,180 adults who underwent routine health examinations between January and December 2021. H. pylori infection was diagnosed using the 14C-urea breath test with a threshold of disintegrations per minute (DPM) ≥ 100. ELISA was used to measure plasma MPO levels. Nonlinear associations were assessed through logistic regression, restricted cubic splines, threshold effect analysis, and subgroup interactions. Results: The study identified a U-shaped correlation between MPO levels and the risk of H. pylori infection. Compared to the middle tertile (T2: 20.6–31 ng/mL), participants in the lowest (T1: ≤20.6 ng/mL; OR = 1.36, 95% CI: 1.24–1.49) and highest tertiles (T3: ≥31 ng/mL; OR = 1.12, 1.02–1.22) exhibited elevated infection risk after full adjustment (p < 0.001). DPM levels were notably elevated in T1 (β = 37.1, 26.66–47.57) and T3 (β = 19.27, 8.81–29.72) relative to T2 (p < 0.0001). RCS-based threshold analysis identified a nonlinear inflection at 24.0 ng/mL of MPO, where each additional 1 ng/mL of MPO below this threshold was associated with a reduced infection risk (OR = 0.959, 95% CI: 0.947–0.971), whereas levels above increased the risk (OR = 1.004, 95% CI: 1.002–1.007). This pattern aligned with H. pylori breath test values, which mirrored the U-shaped trend across MPO tertiles. Subgroup analyses revealed uniform associations between MPO and H. pylori infection risk/DPM across various factors such as age, sex, BMI, and metabolic comorbidities, with all interaction p-values exceeding 0.05. Conclusions: MPO levels exhibit a robust U-shaped association with H. pylori infection risk, independent of anthropometric and metabolic confounders. Monitoring MPO may aid in identifying individuals at bidirectional infection risk, suggesting novel insights into the inflammation–infection interplay. The study’s cross-sectional design limits the ability to establish causal relationships, necessitating further longitudinal research to validate these findings and elucidate their clinical implications.

Background:Myeloperoxidase (MPO) is a key enzyme involved in immune responses and oxidative stress, yet its roles in gastric physiology and gastric cancer remain incompletely understood. This study comprises two independent analyses: (1) to investigate the association between MPO and gastric mucosal injury markers (pepsinogen I, II, and PGR) in a large healthy population, and (2) to evaluate the prognostic significance and immune-regulatory mechanisms of MPO in gastric adenocarcinoma (GA). Methods:We analyzed data from 16,943 individuals in a healthy population-based cohort and 375 GA patients from The Cancer Genome Atlas (TCGA). In the healthy cohort, multivariate linear regression was used to evaluate associations between MPO and pepsinogen levels. In the GA cohort, survival analyses (OS, DSS, PFI) were conducted using Kaplan-Meier and Cox regression models. Gene expression analysis, functional enrichment (GO, KEGG, GSEA), and immune infiltration analysis (ssGSEA) were performed to explore MPO-related mechanisms in GA. Results:In the healthy cohort, MPO was inversely associated with PGR (β = -0.009, P < 0.0001) and PGI (β = -0.057, P < 0.0001). Subgroup and threshold effect analyses revealed non-linear associations and stronger effects among hypertensive individuals, smokers, and alcohol consumers. In the TCGA cohort, high MPO expression was an independent predictor of poor OS (HR = 2.781, P = 0.002) and DSS (HR = 3.667, P < 0.001). Functional analyses showed that MPO was associated with immune-related pathways and increased infiltration of macrophages (R = 0.379, P < 0.001) and dendritic cells (R = 0.377, P < 0.001). Conclusion:This study highlights the distinct roles of MPO in gastric mucosal injury and gastric cancer. In healthy individuals, MPO is associated with markers of gastric mucosal damage, while in GA patients, MPO serves as a prognostic biomarker linked to immune dysregulation. These findings suggest that MPO may be a potential target for monitoring or intervention in gastric mucosal injury and gastric cancer.

ABSTRACT Cell mechanics is a fundamental regulator of numerous cellular processes, orchestrating critical biological activities spanning from embryogenesis to senescence. Cells continuously sense and respond to mechanical cues through specialized interactions between membrane‐bound adhesion proteins, such as integrins, and adhesive ligands within the extracellular matrix (ECM). This bidirectional interaction forms the basis of mechanotransduction—a complex, dynamic process that ultimately leads to alterations in nuclear mechanics and governs essential cellular functions, including migration, tissue morphogenesis, and so on. In this review, we provide an overview of these dynamic cell–ECM interactions and delve into the intricate molecular mechanisms underlying mechanotransduction. We further introduce advanced research methodologies and emerging clinical tools used to investigate cellular mechanical phenotype, mechanotransduction, and diseases progression. In addition, we analyzed the roles of mechanical biomarkers in the development and progression of cancer, fibrosis, and aging. We highlighted the necessity of drug development targeting mechanotransduction, providing examples of drugs that have already entered clinical trials and preclinical tools. By integrating current findings and outlining emerging perspectives, this review aims to provide critical insights and inspire future efforts in understanding, manipulating, and clinically exploiting mechanotransduction‐targeted markers to regulate the progression of diseases such as cancer, fibrosis, and aging.

Cardiovascular diseases (CVDs), including hypertension, atherosclerosis, myocardial ischemia, and myocardial infarction, constitute the primary cause of mortality worldwide. Transcription factors play critical roles in the development of CVDs and contribute to the pathophysiology of these diseases by coordinating the transcription of many genes involved in inflammation, oxidative stress, angiogenesis, and glycolytic metabolism. One important regulator of hemostasis in both healthy and pathological settings has been identified as a purinergic signalling pathway. Research has demonstrated that several signalling networks implicated in the pathophysiology of CVDs are formed by transcription factors that are regulated by purinergic substances. Here, we briefly summarize the roles and mechanisms of the transcription factors regulated by purinergic pathways in various types of CVD. This information will be essential for discovering novel approaches for CVD treatment and prevention.

Heart failure with preserved ejection fraction (HFpEF) accounts for 50 % of heart failure (HF) cases, making it the most common type of HF, and its prevalence continues to increase in the aging society. HFpEF is a systemic syndrome resulting from many risk factors, such as aging, metabolic syndrome, and hypertension, and its clinical features are highly heterogeneous in different populations. HFpEF syndrome involves the dysfunction of multiple organs, including the heart, lung, muscle, and vascular system. The heart shows dysfunction of various cells, including cardiomyocytes, endothelial cells, fibroblasts, adipocytes, and immune cells. The complex etiology and pathobiology limit experimental research on HFpEF in animal models, delaying a comprehensive understanding of the mechanisms and making treatment difficult. Recently, many scientists and cardiologists have attempted to improve the clinical outcomes of HFpEF. Recent advances in clinically related animal models and systemic pathology studies have improved our understanding of HFpEF, and clinical trials involving sodium-glucose cotransporter 2 inhibitors have significantly enhanced our confidence in treating HFpEF. This review provides an updated comprehensive discussion of the etiology and pathobiology, molecular and cellular mechanisms, preclinical animal models, and therapeutic trials in animals and patients to enhance our understanding of HFpEF and improve clinical outcomes.

Abstract Background Diabetic peripheral neuropathy (DPN) is the most prevalent complication of diabetes, and has been demonstrated to be independently associated with cardiovascular events and mortality. This aim of this study was to investigate the subclinical left ventricular (LV) myocardial dysfunction in type 2 diabetes mellitus (T2DM) patients with and without DPN. Methods One hundred and thirty T2DM patients without DPN, 61 patients with DPN and 65 age and sex-matched controls who underwent cardiovascular magnetic resonance (CMR) imaging were included, all subjects had no symptoms of heart failure and LV ejection fraction ≥ 50%. LV myocardial non-infarct late gadolinium enhancement (LGE) was determined. LV global strains, including radial, circumferential and longitudinal peak strain (PS) and peak systolic and diastolic strain rates (PSSR and PDSR, respectively), were evaluated using CMR feature tracking and compared among the three groups. Multivariable linear regression analyses were performed to determine the independent factors of reduced LV global myocardial strains in T2DM patients. Results The prevalence of non-infarct LGE was higher in patients with DPN than those without DPN (37.7% vs. 19.2%, p = 0.008). The LV radial and longitudinal PS (radial: 36.60 ± 7.24% vs. 33.57 ± 7.30% vs. 30.72 ± 8.68%; longitudinal: − 15.03 ± 2.52% vs. − 13.39 ± 2.48% vs. − 11.89 ± 3.02%), as well as longitudinal PDSR [0.89 (0.76, 1.05) 1/s vs. 0.80 (0.71, 0.93) 1/s vs. 0.77 (0.63, 0.87) 1/s] were decreased significantly from controls through T2DM patients without DPN to patients with DPN (all p < 0.001). LV radial and circumferential PDSR, as well as circumferential PS were reduced in both patient groups (all p < 0.05), but were not different between the two groups (all p > 0.05). Radial and longitudinal PSSR were decreased in patients with DPN (p = 0.006 and 0.003, respectively) but preserved in those without DPN (all p > 0.05). Multivariable linear regression analyses adjusting for confounders demonstrated that DPN was independently associated with LV radial and longitudinal PS (β = − 3.025 and 1.187, p = 0.014 and 0.003, respectively) and PDSR (β = 0.283 and − 0.086, p = 0.016 and 0.001, respectively), as well as radial PSSR (β = − 0.266, p = 0.007). Conclusions There was more severe subclinical LV dysfunction in T2DM patients complicated with DPN than those without DPN, suggesting further prospective study with more active intervention in this cohort of patients.