Cardiovascular-kidney-metabolic (CKM) syndrome links adiposity, insulin resistance, kidney dysfunction, and vascular disease. Whether a composite combining the triglyceride-glucose index (TyG), visceral adiposity, and LDL-C burden is associated with incident stroke beyond simpler component indices remains uncertain. We conducted a prospective landmark analysis of the China Health and Retirement Longitudinal Study. Baseline TyG-VLR used 2011 biomarkers, and cumulative TyG-VLR summarized 2011 and 2015 measurements. Participants free of stroke at the 2015 landmark were followed through 2020. Cox models used a covariate set that excluded the modifiable biochemical and adiposity components embedded in TyG-VLR while retaining age as an essential stroke confounder. Fine–Gray models accounted for death as a competing event. TyG, CVAI, VLR, and TyG-VLR were compared in mutually exclusive models using Harrell’s C statistic. Restricted cubic splines, medication analyses, 20-dataset multiple imputation, and selection-weighted and outcome-definition sensitivity analyses were performed. Among 5,226 participants, 452 incident strokes were reported over a median follow-up of 5.0 years. The principal fully adjusted model included 3,347 participants and 253 events. Each 1-SD increment in baseline TyG-VLR was associated with incident stroke (HR 1.15, 95
Body Roundness Index (BRI) has emerged as a superior anthropometric measure for assessing visceral adiposity compared with traditional body mass index. However, the longitudinal relationship between BRI trajectory patterns and type 2 diabetes development remains underexplored, particularly in Chinese populations. We analyzed 4,965 participants aged ≥ 45 years from the China Health and Retirement Longitudinal Study. BRI trajectories were characterized using group-based trajectory modeling across 2011–2016. Incident diabetes was identified through self-reported physician diagnosis during 2017–2020 follow-up. Cox proportional hazards regression examined associations between BRI trajectory patterns and diabetes risk. Receiver operating characteristic (ROC) curve analysis, continuous Net Reclassification Improvement (NRI), and Integrated Discrimination Index (IDI) were used to evaluate the incremental predictive value of BRI trajectories. Three distinct BRI trajectory patterns emerged: low-stable (43.8
The rising prevalence of cardiometabolic risk factors in China poses a significant public health challenge. This study aimed to evaluate the prevalence and clustering of hypertension, diabetes, dyslipidemia, and overweight/obesity, and their associations with major adverse cardiovascular events (MACE) and all-cause mortality. We analyzed 98,373 adults (mean age 54.2 years; 60.7
Insulin resistance is closely involved in the development of diabetes, dyslipidemia, adiposity-related metabolic dysfunction, and cardiovascular disease. The single-point insulin sensitivity estimator (SPISE), derived from triglycerides, HDL-C, and body mass index, may provide a simple marker of insulin sensitivity-related metabolic status. We examined the association between SPISE and incident cardiometabolic multimorbidity (CMM) among middle-aged and older Chinese adults. This prospective cohort study included 7,628 participants aged 45 years or older from the China Health and Retirement Longitudinal Study who were free of CMM at baseline. Baseline SPISE was calculated from triglycerides, HDL-C, and body mass index. Incident CMM was defined as the occurrence of at least two cardiometabolic conditions, including diabetes, heart disease, and stroke. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95
In patients with hypertriglyceridemia-induced acute pancreatitis (HTG-AP) and coexisting diabetes mellitus (DM), effective post-discharge care depends on simultaneous glycaemic and lipid management, alongside diet, medication, exercise, monitoring, and recurrence prevention. Yet, existing studies have largely addressed acute management and near-term endpoints, with little attention to how these patients interpret risk or maintain self-management in daily life. We adopted the Health Action Process Approach (HAPA) for its motivational-volitional phase distinction, which provides a structured lens to investigate how behavioural intentions are translated into action plans, enacted, and sustained in this high-risk group. A Husserlian descriptive phenomenological study was conducted, with the Health Action Process Approach used as a sensitising framework during the interpretive stage. Twenty patients with HTG-AP and coexisting DM were purposively recruited from two hospitals in eastern China between November 2025 and January 2026. We collected data through face-to-face semi-structured interviews, which were audio-recorded and transcribed verbatim. Data collection and preliminary analysis were carried out simultaneously. Saturation was judged to have been reached after the 20th formal interview, when no new codes, categories or themes were identified and the existing themes showed no further substantive development. The transcripts were organised using NVivo 15.0 and subjected to Colaizzi’s seven-step analytical framework. Twenty participants (aged 22–59 years; 15 men) comprised three groups: DM first diagnosed during the index hospitalisation with first-episode HTG-AP (n = 6), pre-existing DM with first-episode HTG-AP (n = 3), and pre-existing DM with recurrent HTG-AP (n = 11). Three themes and 14 subthemes were identified: divergent risk perceptions; barriers and facilitators in translating intention into action; and long-term confidence amid persistent challenges. First-episode participants described acute threat and limited practical experience, whereas recurrent participants reported heterogeneous risk perceptions, accumulated knowledge and reduced self-efficacy. Long-term maintenance was constrained by contextual and psychological barriers. Self-management support may be more useful when tailored to disease trajectory and risk-perception pattern. Nurses can link risk communication to individualised action and coping plans, address emotional responses to recurrence, involve family members and coordinate multidisciplinary transitional follow-up.
Insulin resistance promotes both arterial stiffening and carotid atherosclerosis, but the comparative value of TyG-related indices for these phenotypes is unclear. Using a cohort with childhood anthropometry measured in 1987, we compared two vascular phenotypes, functional arterial stiffness (AS) and structural carotid intima–media thickening (cIMT), in relation to a common metabolic exposure, tested independence from early-life adiposity, and examined how the choice of exposure design (baseline, cumulative, or change) shaped these associations. Within the Hanzhong Adolescent Hypertension Cohort (established 1987), we analysed 1,294 (incident AS) and 1,408 (incident cIMT) adults free of the respective outcome in 2017 and re-examined in 2023. Eight indices (TyG, TyG-BMI, TyG-WC, TyG-WHtR, TyG-WWI, TyG-BRI, TyG-CVAI, METS-IR) were modelled as baseline, cumulative, and 6-year change exposures. Incident AS was defined as brachial–ankle pulse wave velocity ≥ 1,400 cm/s, and incident cIMT thickening as mean cIMT ≥ 0.9 mm. Logistic regression, restricted cubic splines, and discrimination/reclassification metrics were applied, with additional adjustment for childhood (1987) BMI Z-score. Over 6 years, 296 (22.9
Normal body mass index (BMI) may lower clinical suspicion of hepatic steatosis. We quantified the burden and metabolic phenotype of ultrasound-detected steatosis among normal-weight Chinese adults without diagnosed diabetes or conventional hypertension. This single-center cross-sectional study used 2024 health-examination data. Of 149,003 adults screened, 93,562 met all criteria: fasting glucose < 6.1 mmol/L, no diagnosed diabetes or hypertension, blood pressure < 140/90 mmHg, abdominal ultrasonography, and complete measurements. Primary analyses used Chinese normal weight (BMI 18.5–<24 kg/m²). Participants were cross-classified by normal weight vs. BMI ≥ 24 kg/m² and steatosis. Associations were evaluated with logistic regression, quartiles, and restricted cubic splines, adjusting for age, sex, smoking, current alcohol use, BMI, and systolic and diastolic blood pressure. Sensitivity analyses used alternative BMI, glucose, and blood-pressure thresholds and excluded alcohol users or hepatitis-seropositive participants. Hepatic steatosis was detected in 33,042 participants (35.3
Diabetic kidney disease (DKD) is a major manifestation of cardiovascular-kidney-metabolic (CKM) syndrome and remains a leading cause of chronic kidney disease, kidney failure, heart failure, atherosclerotic cardiovascular disease, and premature mortality. Over the past decade, sodium-glucose cotransporter-2 inhibitors (SGLT2is), glucagon-like peptide-1 receptor agonists (GLP-1RAs), and the non-steroidal mineralocorticoid receptor antagonist (ns-MRAs), currently represented clinically by finerenone, have transformed the therapeutic landscape of DKD and related CKM phenotypes. Their benefits extend beyond glucose lowering and have been reproduced, to varying degrees, across populations with DKD, heart failure, obesity, and high cardiovascular risk. Although these drug classes act on distinct proximal targets, they appear to converge on several shared downstream mechanisms, including restoration of hemodynamic homeostasis, attenuation of inflammation and oxidative stress, preservation of mitochondrial and cellular metabolic integrity, and suppression of maladaptive fibrosis. At the same time, each class retains mechanistic strengths that may explain their partially distinct clinical profiles, with SGLT2is showing prominent benefits in heart failure and kidney disease progression, GLP-1RAs exerting stronger effects on weight reduction and atherosclerotic cardiovascular risk, and ns-MRAs such as finerenone targeting mineralocorticoid receptor-driven inflammatory and fibrotic injury. In this review, we synthesize current mechanistic and randomized clinical evidence supporting the convergent and complementary cardiorenal-metabolic effects of these three therapeutic pillars. We further discuss the biological rationale for dual- and triple-pathway combination strategies, the emerging role of phenotype-guided treatment selection, persistent residual risk, and unresolved questions regarding sequencing, safety, and implementation. A mechanistically integrated framework may help move DKD care within the broader CKM spectrum from conventional risk-factor management toward precision cardiorenal-metabolic medicine.
The PREVENT equations have been recommended by recent AHA guidelines for estimating 10-year ASCVD risk to inform lipid-lowering strategies in primary prevention. Among individuals with low-to-borderline 10-year ASCVD risk according to the PREVENT equations, treatment decisions should be further refined by considering risk-enhancing factors. Although insulin resistance (IR) is closely associated with ASCVD, it remains unclear whether IR-related indices capture residual risk in this low-to-borderline risk population and whether commonly used indices differ in their associations with incident ASCVD or incremental predictive performance. This prospective cohort study included 2,664 participants from CHARLS with low-to-borderline risk. Six IR-related indices were assessed, including the TyG, its derived measures, and estimated glucose disposal rate (eGDR). The primary outcome was incident ASCVD. Associations with incident ASCVD were examined using Cox proportional hazards models. Kaplan–Meier analyses and restricted cubic spline (RCS) models were used to evaluate cumulative incidence patterns and dose-response relationships. Standalone discrimination was assessed using receiver operating characteristic curves (ROC), and incremental performance beyond the base PREVENT model was evaluated using changes in AUC, calibration, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Calibration was assessed using bootstrap-corrected calibration curves with 500 resamples. Over the observation period, 324 participants developed ASCVD. In Model 3, TyG-BMI, TyG-WHtR, and TyG-CVAI were positively related to ASCVD occurrence, whereas eGDR was linked to lower risk. In ROC analyses, TyG-CVAI, eGDR, TyG-BMI, and TyG-WHtR yielded higher AUCs than TyG and CTI. TyG-CVAI had the highest AUC (0.578, 95
The accumulation of Advanced Glycation End Products (AGEs), resulting from the Maillard Reaction formed via exogenous intake from food and a hyperglycemic internal environment in the body, can cause or exacerbate various complications of Diabetes Mellitus. This article discusses the chemistry of AGEs formation and their pathobiochemistry, with a particular focus on the cardiovascular system, musculoskeletal system, and peripheral nervous system, which significantly affect population health. AGEs not only alter the normal physiological state of the system in a high-glucose environment through cross-linking with tissues and cells and related metabolites, but also induce the release of inflammatory factors and reactive oxygen species through multiple pathways, including NF-κB and NADPH pathways, by binding to receptors, and regulate the p38 and JNK pathways, affecting the imbalance of osteoclasts and osteoblasts. This review, drawing upon clinical studies, explores both conventional and novel detection methods for AGEs, along with their associated limitations, and suggests their potential as biomarkers and therapeutic targets for associated diseases. The review also discusses emerging therapeutic strategies aimed at reducing AGE accumulation and inhibiting AGE–RAGE interactions. These methods include natural products such as resveratrol and chrysin, as well as related inhibitors that exert their effects through competitive inhibition and by altering their active states. Unlike previous studies that primarily focus on a single system, diabetes typically causes complications in multiple organ systems. By elucidating both the shared and system-specific mechanisms of AGE action, and summarizing intervention strategies and the application of novel inhibitors, this review aims to provide new insights into the clinical treatment and prevention of diabetic complications.
Metabolic syndrome (MetS) - a cluster of conditions including hypertension, dyslipidemia, insulin resistance, and central obesity - affects 20–30
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by hyperglycemia, insulin resistance, and impaired insulin secretion. The high global prevalence of T2DM contributes significantly to worldwide morbidity and mortality. Irisin, an exercise-induced myokine, has been shown to modulate energy metabolism by regulating insulin action. However, the precise regulatory network of irisin, particularly concerning its interaction with the metabolism-inflammation axis and alternative splicing (AS) modulation, requires comprehensive evaluation and description. This study aimed to investigate the therapeutic effects of irisin on glucose and lipid metabolism and to elucidate its molecular regulatory mechanisms in T2DM utilizing a multi-omics approach. To investigate the interactions between irisin and T2DM, a high-fat diet (HFD) was used along with multiple, low-dose injections of streptozotocin (STZ) to create T2DM model in C57BL/6J mice. After five weeks, the mice were treated with irisin every other day. Fasting blood glucose (FBG) and fasting insulin (FINS) were measured using ELISA, and the homeostatic model assessment of insulin resistance (HOMA-IR) was calculated to evaluate insulin sensitivity. Lipid metabolism was assessed by determining total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). RNA sequencing (RNA-seq) of skeletal muscle was performed to identify differentially expressed genes (DEGs) and regulated alternative splicing events (RASEs), followed by functional enrichment analysis. Then RT-qPCR was used for validation of the key DEGs found. Irisin treatment significantly ameliorated insulin resistance and dyslipidemia in T2DM mice (P < 0.05). RNA-seq analysis identified 1169 DEGs between the model and control groups (727 upregulated, 442 downregulated), and 414 DEGs post-irisin treatment (202 upregulated, 212 downregulated), alongside 511 significant RASEs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that these DEGs and alternative splicing events (ASEs) were predominantly associated with metabolic and inflammatory pathways. Key DEGs, including Bdh1, Pdpr, Dglucy, Lrtm1, Ccl6, Cd163, Fcgr3, and Adamts5, were successfully validated via RT-qPCR. Irisin mitigates skeletal muscle insulin resistance in T2DM mice, potentially through coordinated regulation of the metabolism-inflammation axis and remodeling mRNA splicing patterns, indicating its potential as a therapeutic strategy for T2DM.
Moderate caloric restriction facilitates sustained weight control and reduces the incidence of type 2 diabetes, while meal timing and prolonged fasting may augment these advantages. Additionally, advancements in diabetes technology are improving glycemic control, by targeting Glycemic Variability (GV). However, dietary intervention studies on GV remain limited. We aimed to evaluate the changes in GV following a Continuous Calorie-restricted (CCR) Diet (reducing daily energy intake by 500 kcal/day) versus Time Restricted Intermittent Fasting (TRIF) (Calorie-matched as CCR but with restricted feeding window and only two meals) among individuals with type 2 diabetes. An interventional clinical trial with a cross-over design (CTRI/2022/07/044356) was done with 51 participants between 25 and 55 years of age, with type 2 diabetes of ≤ 5 years, taking only Metformin or drug-naive, and HbA1c between 6.5 and 8
The hemoglobin glycation index (HGI), which quantifies individual variation in the relationship between hemoglobin A1c and glucose levels, has been associated with adverse outcomes across various clinical populations. However, the prognostic significance of HGI in critically ill patients with atrial fibrillation remains unknown. We investigated the association between HGI and all-cause mortality in this population. We conducted a retrospective cohort study using the MIMIC-III and MIMIC-IV databases. Adult patients (≥ 18 years) with atrial fibrillation during ICU admission were included. HGI was calculated as the difference between observed and predicted hemoglobin A1c values (predicted HbA1c = 0.013 × glucose + 4.804). Primary outcomes were in-hospital and 30-day mortality. Patients were stratified into HGI quartiles. Statistical analyses included Kaplan-Meier survival analysis, restricted cubic splines, and multivariable logistic and Cox regression models. Subgroup and sensitivity analyses were performed. Among 9,924 critically ill patients with atrial fibrillation (median age 72.3 years, 63.1
Diabetic kidney disease (DKD) is a common microvascular complication of diabetes. The clinical potential of miR-519d-3p in DKD and its function in podocyte injury were investigated, providing novel insight into the clinical management of DKD. A total of 117 DKD patients were included in the present study, with 93 diabetes patients as controls, and serum miR-519d-3p levels were compared between the two groups. The clinical value of miR-519d-3p was evaluated from the perspectives of diagnosis, severity assessment, and prognosis prediction. In vitro, a podocyte injury model was established by high-glucose stimulation. The effect of miR-519d-3p on cell viability, inflammation, oxidative stress, and fibrosis activation was evaluated. The involvement of STAT3 in the function of miR-519d-3p was assessed. miR-519d-3p was downregulated in DKD patients, which discriminated DKD patients from diabetes patients without DKD. Lower serum miR-519d-3p levels were observed in advanced DKD patients, and significant correlations were observed between miR-519d-3p and renal function of DKD patients. miR-519d-3p was revealed to be associated with the occurrence of ESRD in DKD patients, which was also identified as an independent risk factor. High glucose conditions induced podocyte injury and downregulation of miR-519d-3p, and overexpressing miR-519d-3p significantly attenuated high-glucose-induced injury. STAT3 was enriched as a direct target of miR-519d-3p related with DKD onset and progression. Its overexpression could reverse the protective effect of miR-519d-3p. Reducing serum miR-519d-3p can be considered a promising diagnostic and prognostic biomarker for DKD. Overexpressing the miR-519d-3p/STAT3 axis would be a promising therapeutic strategy for DKD.
Patients with type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD) face compounded cardiorenal risk. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have demonstrated cardiovascular and renal benefits in randomized trials, yet real-world evidence in populations with established CKD stages 2 through 4 remains limited. We aimed to compare cardiorenal outcomes between new users of GLP-1 RAs and dipeptidyl peptidase-4 inhibitors (DPP-4i) in this high-risk population. Using the TriNetX Global Collaborative Network, we conducted a new-user, active-comparator cohort study emulating a target trial. Adults with T2DM and CKD stages 2–4 who initiated GLP-1 RA or DPP-4i between January 2017 and December 2021 were identified. After 1:1 propensity score matching on 40 covariates, 28,824 patients per group were retained. Three co-primary outcomes—MAKE, MACE, and all-cause mortality—were assessed at 1, 2, and 3 years from the same matched cohort. Secondary outcomes included a safety composite and hypoglycemia. Conjunctivitis served as a negative control outcome. Restricted mean survival time was calculated as a supplementary analysis. At 3 years, GLP-1 RA initiation was associated with significantly lower risks of MAKE (hazard ratio [HR] 0.837; 95
Existing evidence suggests the importance of oxidative stress in the etiology of metabolic syndrome (MetS), which is a growing global health problem. However, the impact of serum antioxidant vitamins (C and E) levels on the clinical outcomes of the MetS population is unknown. This cohort study included 2102 adults diagnosed with MetS, who participated in the National Health and Nutrition Examination Survey from 2003 to 2006. Serum levels of vitamin C, α-tocopherol, and γ-tocopherol were measured. Hazard ratios (HRs) and 95
Early-onset gestational diabetes mellitus (eGDM) is a distinct phenotype with insulin resistance and adverse metabolic profiles, but its association with secondary maternal and neonatal complications remains unclear. We aimed to evaluate this association compared with late-onset GDM (LGDM). PubMed, EMBASE, Cochrane Central, Web of Science, and CINAHL were searched up to April 20, 2026. Observational studies and secondary analyses of randomised controlled trials comparing eGDM with LGDM were included. Outcomes comprised hypertensive disorders, postpartum haemorrhage, stillbirth, congenital malformations, small for gestational age (SGA), macrosomia, respiratory distress syndrome (RDS), shoulder dystocia, and neonatal hypoglycaemia. Random-effects meta-analysis was performed. Thirty-two studies (113,889 pregnancies) were included. eGDM was associated with higher odds of hypertensive disorders (OR 1.36, 95
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia worldwide, with a rising global prevalence. Post-ablation AF recurrence remains frequent, particularly among patients with obesity and metabolic syndrome. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have demonstrated favorable cardiometabolic and cardiovascular effects, but their association with AF recurrence after ablation remains uncertain. PubMed, Scopus, Embase, and Web of Science were searched through June 18, 2026. Cohort studies evaluating GLP-1RA therapy in adults with atrial fibrillation undergoing catheter ablation were included. The primary outcome was post-ablation atrial fibrillation recurrence (or recurrent atrial tachyarrhythmia, as defined by the individual studies). Adjusted hazard ratios (HRs) with 95
