Prospective evidence linking greenness and cardiovascular disease (CVD) in rapidly urbanizing developing countries remains limited. Here, among 159,590 adults aged ≥40 years from the nationwide China Cardiometabolic Disease and Cancer Cohort with a median follow-up of 10.1 years, we examine the association between residential greenness, measured by satellite-derived normalized difference vegetation index (NDVI) within 500 m of residence, and incident CVD, and evaluate its joint effects with cardiovascular health as defined by Life’s Essential 8. Individuals in the highest quartiles of contemporaneous, one-year, and cumulative NDVI consistently show lower CVD risk compared with those in the lowest quartiles, although associations vary across subpopulations. Notably, individuals with high cardiovascular health scores living in low-NDVI areas exhibit similar CVD risk to those residing in high-NDVI areas. These findings highlight the complementary importance of both green infrastructure and healthy lifestyles in reducing CVD risk in rapidly urbanizing regions of China.

BACKGROUND:Heart failure (HF) is a severe complication of type 2 diabetes (T2D), yet the association between plasma proteins and HF in individuals with T2D remains underexplored. OBJECTIVES:This study aimed to investigate the association between plasma proteomic profiles and HF, and further evaluate whether proteomic data could enhance HF prediction beyond clinical variables, polygenic risk, and N-terminal prohormone of brain natriuretic peptide (NT-proBNP). METHODS:This cohort study included 2198 participants with T2D from the United Kingdom Biobank. Cox proportional hazards models were employed to examine associations between 2920 plasma proteins and incident HF. Clinical and protein predictors were selected using the least absolute shrinkage and selection operator method based on 10-fold cross-validation. The predictive performance of models was evaluated using Harrell's C-index, calibration slope, net reclassification improvement, integrated discrimination improvement, decision curve analysis, and calibration plots. RESULTS:During a median follow-up of 13.1 y, 298 individuals developed incident HF. A total of 455 proteins (447 positively and 8 inversely) were associated with HF, primarily involved in cell adhesion, extracellular space, signaling receptor activity, and cytokine-cytokine receptor interaction pathways. The top protein associated with increased risk of HF was whey acidic protein (WAP) 4-disulfide core domain protein 2, with a per-SD increment hazard ratio (HR) of 1.90 [95% confidence interval (CI): 1.65, 2.19)]. Conversely, the top protein inversely associated with HF risk was apolipoprotein C-I, with a per-SD increment HR of 0.75 (95% CI: 0.66, 0.85). Seventeen proteins were subsequently selected as proteomic predictors, and the resulting 17-protein risk score improved HF prediction beyond clinical variables, polygenic risk, and NT-proBNP, yielding a maximum C-index of 0.833 with an increment of 0.091. CONCLUSIONS:This study identified proteomic biomarkers for HF, highlighted potential pathways that inform biological mechanisms, and demonstrated that proteomic data enhanced HF risk prediction in individuals with T2D.

Adipose tissue senescence is increasingly recognized as a key driver of systemic aging and age-related functional decline, yet the endocrine regulators that actively promote this process remain poorly defined. Angiopoietin-like protein 8 (ANGPTL8) is a metabolic factor implicated in lipid metabolism and inflammation and has been associated with multiple aging-related disorders. However, its direct role in adipose tissue senescence and organismal aging remains unclear. Here, we identify ANGPTL8 as a previously unrecognized regulator of adipose tissue aging through integrative analyzes of human cohorts, animal models, transcriptomics, and cellular studies. In a large human cohort, circulating ANGPTL8 levels were strongly associated with biological aging and mortality risk and significantly improved machine learning-based models for age and survival prediction. Consistent with these findings, genetic deletion of Angptl8 in mice extended lifespan, attenuated aging-associated functional decline, and reduced senescence markers in adipose tissue. Transcriptomic analyzes revealed age-dependent upregulation of ANGPTL8 in adipocytes accompanied by activation of pro-senescent transcriptional programs. Mechanistically, ANGPTL8 directly interacted with AKT2 and activated the AKT-mTOR-S6K signaling pathway, thereby promoting cell-autonomous adipocyte senescence. Genetic or pharmacological inhibition of this pathway abolished the pro-senescent effects of ANGPTL8. Collectively, our findings identify ANGPTL8 as an endocrine regulator linking metabolic dysfunction to adipose tissue senescence and systemic aging, highlighting the ANGPTL8-AKT2-mTOR axis as a potential therapeutic target for delaying age-associated functional decline.

There is an urgent need to implement population-based actions to prevent diabetes mellitus (DM) in China. However, the current knowledge is limited on a prospective association of seafood intake with DM risk in Chinese adults. We aimed to determine the association between seafood consumption and the incident DM in a nationwide cohort of Chinese populations. A prospective cohort study of 104,816 participants, free of DM, aged ≥ 40 years across various geographical regions in China was conducted at baseline (China Cardiometabolic Disease and Cancer study). Habitual consumptions of seafood were assessed using a semi-quantitative food frequency questionnaire, and DM was diagnosed according to the WHO 1999 criteria. Primary outcomes were the incident DM, presented as hazard rations (HRs) with 95

BACKGROUND:The genetic architecture of circulating amino acids (AAs) and microbiota-related metabolites (MRMs) in relation to cardiometabolic disease remains poorly characterized in East Asian populations, limiting ancestry-specific insights. METHODS:In a prospective cohort of 2953 Chinese individuals, we performed a large-scale genome-wide association study (GWAS) of 28 serum AAs and 22 MRMs. We conducted a cross-ancestry comparison of variant-metabolite associations. Using colocalization and Mendelian randomization (MR), we further investigated causal roles of 50 AAs and MRMs in 25 cardiometabolic diseases from the BioBank Japan. Furthermore, we explored differences in the genetic regulation of these metabolites between incident T2DM cases and healthy controls. RESULTS:We identified 33 metabolite-variant associations, 22 of which were previously unreported, and revealed several loci specific to East Asian ancestry. Integrative colocalization and MR analyses established 49 causal relationships between metabolite levels and cardiometabolic diseases, most notably implicating genetically predicted N-acetyltryptophan to increased risk of type 2 diabetes. Moreover, we observed distinct patterns of genetic regulation between T2DM cases and controls, highlighting substantial heterogeneity of effects and dynamic gene-disease interplay. CONCLUSIONS:These findings offer crucial insights into the ancestry-specific genetic determinants of metabolic traits, and shed new light on their causal roles in the etiology of cardiometabolic diseases in East Asian populations.

Optimization of HbA1c, blood pressure and cholesterol, referred to as the “ABCs”, is central to the management of diabetes. However, the age-specific associations of these factors with mortality in patients with diabetes remains unclear. In this prospective cohort study, 43,732 Chinese adults aged ≥ 40 years with diabetes were included from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Participants were stratified by age (< 55, 55-<65, 65-<75, ≥ 75 years). Cox proportional hazards regression and Fine-Gray competing risk models were employed to estimate the associations of HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) with all-cause, cardiovascular, and non-cardiovascular mortality across age groups. Relative importance and population attributable fractions (PAFs) were computed for each metabolic factor. During a median follow-up of 10.1 years, 3,975 deaths were documented. Age significantly modified the associations of HbA1c, SBP, and LDL-C with all mortality outcomes (all P for interaction < 0.05). Among participants aged < 75 years, HbA1c showed graded positive associations with all-cause, cardiovascular, and non-cardiovascular mortality. The SBP thresholds associated with increased mortality risk were 140 mmHg in those aged < 65 years and 160 mmHg in those aged 65–<75 years. Among those aged ≥ 75 years, however, the patterns of these associations differed markedly. Elevated mortality risk was observed only at HbA1c ≥ 9

Optimal control of hemoglobin A1c (HbA1c), blood pressure, and cholesterol (ABC risk factors) is essential for reducing cardiovascular disease (CVD) risk in individuals with diabetes. However, age-specific contributions of these factors remain inadequately characterized. Using data from the China Cardiometabolic Disease and Cancer Cohort study, we assessed the associations between ABC risk factors and incident CVD among Chinese adults with diabetes, stratified by age groups of < 55, 55 to < 65, 65 to < 75, and ≥ 75 years. Cox proportional hazards models and population-attributable fractions (PAFs) were used to quantify the associations between ABC risk factors and incident CVD. During a median follow-up of 10.1 years, 4707 incident cases of CVD were documented. Higher levels of baseline HbA1c, systolic blood pressure (SBP), and low-density lipoprotein cholesterol (LDL-C) were significantly associated with increased CVD risk. Age modified these associations (P interaction < 0.05), with progressively attenuated hazard ratios (HRs) observed in older age groups. Compared with HbA1c < 7.0%, HbA1c ≥ 9.0% showed stronger CVD associations in adults aged < 55 years (HR = 2.42; 95% confidence interval [CI]: 1.98-2.97) than in those aged ≥ 75 years (HR = 1.50; 95% CI: 1.12-2.02), and SBP ≥ 140 mmHg and LDL-C ≥  4.1 mmol/L were significant only in younger groups. The leading contributor to PAFs for CVD was SBP (28.3%), followed by HbA1c (12.0%) and LDL-C (9.2%), with diminishing impacts across older groups. These results underscore the importance of age-specific management of ABC risk factors in diabetes care, with the benefit of stricter risk factor management in younger adults and the need for a more flexible approach in older populations.

Hypoglycemia is a major barrier to safe diabetes management. Although deep learning has been widely applied to blood glucose (BG) prediction, most studies provide limited hypoglycemia forewarning and are trained on small type 1 diabetes cohorts with restricted generalizability. We developed MT-HypoNet, a multitask neural network for real-time BG prediction and hypoglycemia forewarning from continuous glucose monitoring data. To improve detection near the hypoglycemia boundary, we introduce a statistically guided soft-label strategy. MT-HypoNet was validated on a multicenter cohort of 1,662 patients with type 1 and type 2 diabetes and prospectively evaluated in 36 perioperative patients with type 2 diabetes. In internal validation, MT-HypoNet achieved an AUC of 0.946 (95% CI: 0.946-0.947) for hypoglycemia forewarning and an RMSE of 19.84 ± 4.92 mg/dL for BG prediction. It generalized well to external datasets and maintained high prospective performance (AUC 0.966; RMSE 16.62 ± 4.01 mg/dL), supporting proactive management and improved safety.

BACKGROUND:Postoperative cognitive dysfunction (POCD) is a common disorder following surgery. The mechanisms underlying this are still under exploration. We hypothesize that hormonal changes in patients who have undergone pituitary surgery contribute to the pathogenesis of POCD. METHODS:In a 12-month follow-up study, a total of 103 patients with pituitary adenoma who received pituitary surgery were included. Patients were categorized into three groups based on their postoperative hormonal supplement: stable, sufficient, and insufficient to eliminate the effects of surgery and hormone dosage. Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) were employed as evaluation tools to assess the degree of cognitive impairment. RESULTS:The MoCA score in the stable group showed no significant decrease, while in the sufficient and insufficient groups, the score began to decrease from the 6th month compared to the 0 month of each group. Compared to the stable group at the same time point, the MoCA scores in both groups decreased at the 6th month and 12th month. A similar trend was observed in the MMSE score. Cognitive impairment (mild cognitive impairment and dementia) in both the sufficient group and the insufficient group increased significantly by the 3rd month after surgery, but the rate of increase was much slower subsequently in the sufficient group than in the insufficient group. CONCLUSION:Our study confirms that POCD is highly prevalent in patients after pituitary tumor surgery. Postoperative hormone deficiency plays a crucial role in the progression of POCD, especially adrenocorticotropic hormone and the glucocorticoids it affects. It is worth mentioning that a novel aspect of our study is the identification of hormonal rhythm disturbance as a potential contributor to POCD, which provides valuable insights into the mechanisms of POCD in pituitary surgery. We call for more personalized and chronobiological hormone replacement therapy approaches.

ABSTRACT Background Metabolic diseases remain a fast‐growing global health burden. Besides other known factors, socioeconomic status (SES) has been recognized as a key determinant of metabolic health. This study aimed to investigate the association between SES and the prevalence of metabolic diseases in the Chinese population. Methods We analyzed data from a nationwide community‐based cross‐sectional study in China. SES was derived to a composite score (range 0–3) using three indicators (educational attainment, living conditions, and marital status), with higher scores indicating better SES. Chronic diseases were diagnosed through biochemical testing and clinical assessments. Logistic regression models were applied to estimate associations between SES scores and metabolic diseases. Results Among 201 532 participants, the lowest SES group had 87.1% higher odds of metabolic diseases than the highest SES group (odds ratio [OR] = 1.871, 95% confidence interval [CI]: 1.739, 2.016). One‐point decrease in SES score was associated with increased prevalence of hypertension (OR = 1.096, 95% CI: 1.080, 1.113) and obesity (OR = 1.112, 95% CI: 1.091, 1.134). In contrast, lower SES scores were linked to a reduced prevalence of dyslipidemia (OR = 0.931, 95% CI: 0.918, 0.945) and diabetes (OR = 0.974, 95% CI: 0.958, 0.990) after adjusting for covariates. We also observed that lower SES scores showed stronger associations with increased prevalence of obesity and hypertension in women but decreased risks of diabetes, dyslipidemia, and obesity in men. Conclusions Lower SES was associated with a higher prevalence of hypertension and obesity but a lower prevalence of dyslipidemia and diabetes, with significant gender differences.

Background: Evidence supports the effectiveness and safety of open-source automated insulin delivery (AID) in patients with type 1 diabetes. However, evidence regarding the clinical application of open-source AID in perioperative patients with type 2 diabetes remains limited. Methods: This was an open-label, single-center, exploratory pilot randomized controlled trial (RCT) with parallel groups. Patients with diabetes (excluding type 1 diabetes mellitus) scheduled for elective surgery were randomly assigned to the closed-loop group (open-source hybrid closed-loop AID system) or the control group (conventional insulin pump). The primary outcome was the percentage of time in the target glucose range (TIR, 3.9-10.0 mmol/L). Other efficacy and safety outcomes were also compared between the groups. Results: A total of 49 participants were included and randomized to the closed-loop group (n = 25) or the control group (n = 24). Participants underwent abdominal, orthopedic, thoracic surgery, or neurosurgery during hospitalization. Patients in the closed-loop group had significantly higher TIR than patients in the control group (76.4 ± 14.1% vs. 61.2 ± 20.0%, p = 0.005). Compared with the control group, the closed-loop group also exhibited a 15.6 percentage point reduction in time above range (TAR, >10 mmol/L) without increasing time below range (TBR, <3.9 mmol/L). There were no episodes of severe hypoglycemia (<2.2 mmol/L) or diabetic ketoacidosis in either group. Conclusions: This study demonstrates that in patients with diabetes undergoing elective surgery, the open-source hybrid closed-loop AID system provides better glycemic control than conventional insulin pump therapy.

Little has been found regarding the lifetime cumulative effect of reproductive factors on chronic kidney disease (CKD), and how this relationship varies with cardiovascular health (CVH) remains unexplored. This study aimed to assess the relationships of lifetime cumulative estrogen exposure reflected by reproductive factors, and LE8 CVH status with incident CKD among postmenopausal women. The study included 33,700 postmenopausal participants from the China Cardiometabolic Disease and Cancer Cohort (4 C) Study, enrolled between 2011 and 2012 with follow-up assessments conducted between 2014 and 2016 (median follow-up: 3.1 years). Lifetime cumulative estrogen exposure due to reproductive factors was evaluated through reproductive lifespan (RLS), endogenous estrogen exposure (EEE), and total estrogen exposure (TEE). Health behaviors information in Life’s Essential 8 (LE8) was collected by questionnaire and laboratory examination. The risk of CKD was analyzed with Cox proportional hazards models. Shorter lifetime cumulative estrogen exposure was associated with an increased risk of CKD (RLS, HR: 1.42, 95

BACKGROUND:Albuminuria from low-grade to clinically elevated range confers cardiorenal risks. OBJECTIVES:The authors aimed to investigate the differential roles of lifestyle/metabolic factors in the association of fine-categorized and continuously measured urinary albumin-to-creatinine ratio (UACR) levels with cardiorenal outcomes. METHODS:A total of 82,509 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study were included, with a median follow-up of 3.0 years. Outcomes included incident cardiovascular disease (CVD), incident CKD, their composite, along with surrogate markers. Lifestyle factors included tobacco use, alcohol use, diet, physical activity and sleep. Metabolic factors included diabetes, hypertension, abdominal obesity, and elevated low-density lipoprotein cholesterol. Cox proportional hazard models were used to calculate hazard ratios. RESULTS:Compared to the lowest UACR, participants with mildly elevated UACR (≥10 to <30 mg/g) had a 39% higher risk of composite cardiorenal outcomes (multivariable-adjusted HR: 1.39, 95% CI: 1.29-1.50), whereas those with clinically elevated UACR (≥30 mg/g) had over double the risk (HR: 2.29, 95% CI: 2.12-2.47). A nonlinear J-shaped association was observed between continuous UACR and cardiorenal outcomes (Pnonlinearity = 0.0009), with UACR ≥10 mg/g already conferring risks, a pattern also reflected by the deterioration of PREVENT score and estimated glomerular filtration rate. Optimal lifestyle and metabolic status generally attenuated CVD risk related to low-grade albuminuria, while improvement of the latter additionally decreased CVD and cardiorenal risk, even in clinically elevated albuminuria (additive Pinteraction <0.0001). Hypertension showed the largest relative contribution to cardiorenal risk, particularly in UACR <30 mg/g. CONCLUSIONS:Our findings highlighted low-grade albuminuria as a key preventive window for cardiorenal outcomes requiring both aspects of modifiable risk factors, and the cardiovascular benefits of metabolic improvement in established albuminuria.

Hyperuricemia (HUA) is closely linked to glycolipid metabolism disorder. The Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index, an innovative composite glucolipid index, has been suggested as a potential diagnostic indicator for type 2 diabetes mellitus (T2DM). However, the associations between CHG and HUA in T2DM patients remain unknown. The purpose of this study was to elucidate the relationship between CHG and the risk of HUA in individuals with diabetes. A total of 1908 inpatients with T2DM between 2023 and 2024 were cross-sectionally assessed. The correlation between CHG and the risk of HUA was evaluated with multiple logistic and linear regression model, restricted cubic spline (RCS) method, and subgroup analysis. The prevalence of HUA was 23.43

Summary Background Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease associated with significant morbidity and mortality, yet management options remain limited. Although glucagon-like peptide-1 receptor agonists such as semaglutide have shown benefits in metabolic health, their efficacy and safety in patients with MASH require further elucidation. Methods We systematically searched PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov for randomized controlled trials (RCTs) evaluating semaglutide in patients with MASH from inception through August 23, 2025. This meta-analysis was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Results A total of 22 RCTs involving 32,013 patients were included. Semaglutide significantly improved MASH Resolution (RR = 1.98, 95%CI: 1.57 to 2.50) but did not yield significant improvement in Fibrosis Regression (RR = 1.18, 95%CI: 0.74 to 1.88). Semaglutide also reduced Liver Steatosis (WMD = -11.30%, 95%CI: -18.70 to -3.91) and the Enhanced Liver Fibrosis (ELF) score (WMD = -0.49, 95%CI: -0.70 to -0.29). Significant reductions were observed in liver enzymes, including alanine aminotransferase (ALT; WMD = -5.55 U/L, 95%CI: -9.21 to -1.89) and aspartate aminotransferase (AST; WMD = -3.85 U/L, 95%CI: -7.67 to -0.03). Additionally, semaglutide improved weight management, glycemic and lipid parameters, and reduced all-cause mortality (RR = 0.82, 95%CI: 0.74 to 0.91) and cardiovascular risk (RR = 0.83, 95%CI: 0.75 to 0.92). Subgroup analyses revealed the greatest benefits in patients receiving higher doses (≥ 2.0 mg weekly) and longer intervention durations (≥12 months). Conclusion Semaglutide represents a promising pharmacotherapeutic option for MASH, demonstrating significant improvements in histologic resolution, liver injury biomarkers, and metabolic parameters, particularly at higher doses and longer intervention durations, though its effect on fibrosis regression remains limited.

AIMS:To investigate the associations of general and central obesity with premature mortality in a Chinese population. MATERIALS AND METHODS:A total of 162 776 participants from the China Cardiometabolic Disease and Cancer Cohort Study were included in the current analysis. General and central obesity were assessed using body mass index (BMI) and waist-to-hip ratio (WHR), respectively. Premature mortality was defined as all-cause mortality occurring before the age of 75 years, including cardiovascular disease (CVD)-related and non-CVD-related premature mortality. Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:During a median follow-up of 10.1 years, 5477 (3.36%) premature deaths were documented. Compared with normal weight (18.5 to <24 kg/m2), those with general obesity (BMI ≥28 kg/m2) were associated with elevated risk of CVD-related premature mortality (HR: 1.53; 95% CI: 1.30-1.82). Central obesity (WHR ≥0.95 for men or ≥0.90 for women) was associated with increased risks of all-cause (HR: 1.20; 95% CI: 1.11-1.31), CVD-related (HR: 1.51; 95% CI: 1.29-1.77) and non-CVD-related premature mortality (HR: 1.11; 95% CI: 1.01-1.22). These associations persisted after mutual adjustment for BMI and WHR. A significant interaction between BMI and WHR on the risk of premature mortality was observed (p for interaction = 0.028). Individuals with normal weight but central obesity exhibited the highest risk of all-cause premature death (HR: 1.21; 95% CI: 1.06-1.37), whereas the highest risk of CVD-related mortality was observed in those with both general and central obesity (HR: 1.89; 95% CI: 1.50-2.39). CONCLUSIONS:The combination of normal weight and central obesity significantly increases premature mortality risk, emphasizing the importance of integrating WHR into obesity assessments to improve risk stratification and prevention strategies among Chinese adults.

The heterogeneous and complex nature of prediabetes presents a major challenge in identifying individuals predisposed to developing incident diabetes and related complications. We aimed to identify phenotypic subgroups of prediabetes at risk and to explore their distinct associations with cardiometabolic outcomes. This study included 79,000 individuals with prediabetes from the three large-scale prospective cohorts in China. Phenotypic heterogeneity was identified using a soft-clustering algorithm based on the proximity network derived from uniform manifold approximation and projection (UMAP), combined with graph-clustering and Gaussian mixture models. Associations between phenotype probabilities and the incidence of type 2 diabetes (T2D), cardiovascular disease (CVD), and kidney events were assessed to evaluate risk differences across the identified profiles. Six phenotypic profiles were identified, including five with distinct metabolic features (representing 70

Context Emerging studies have revealed associations between dietary medium-chain fatty acids (MCFAs) and glucose homeostasis. However, the relationship between serum MCFAs and the incidence of diabetes, and potential interactions with genetic predisposition, remains unclear in prospective cohort studies.Objective This work aimed to investigate associations and genetic susceptibility between serum MCFAs and diabetes risk.Methods We investigated baseline serum MCFAs (n = 5) in a nested case-control study comprising incident diabetes cases (n = 1707) and matched normoglycemic control individuals (n = 1707) from the China Cardiometabolic Disease and Cancer Cohort Study. Associations between MCFAs and type 2 diabetes mellitus (T2DM) were examined, both overall and stratified by diabetes genetic susceptibility. Genetic risk scores (GRS) were calculated based on 86 T2DM-associated genetic variants.Results In the fully adjusted conditional logistic regression model, serum octanoic acid and nonanoic acid exhibited inverse dose-response relationships with diabetes risk, showing odds ratios (95% CI) of 0.90 (0.82-0.98) and 0.84 (0.74-0.95), respectively. Subgroup analysis demonstrated that inverse associations between MCFAs and incident diabetes were more pronounced among individuals with physical inactivity (Pinteraction = .042, .034, and .037, for octanoic, nonanoic and decanoic acid, respectively). Moreover, inverse associations of octanoic acid with diabetes risk were notably enhanced among individuals with high genetic risk compared to those with low genetic risk. Statistically significant interactions were observed between octanoic acid and GRS on T2DM risk (Pinteraction = .003).Conclusion These findings provide evidence supporting inverse associations between serum MCFAs and T2DM risk, and reveal potential interplay between genetic susceptibility and circulating octanoic acid in modulating diabetes risk.

ObjectiveThis study aimed to investigate the associations of the triglyceride-glucose (TyG) index with kidney function decline, cardiovascular disease (CVD) events, and all-cause mortality across different glucose tolerance statuses.MethodsWe analyzed 8,434 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. The primary outcomes were kidney function decline, CVD events, and all-cause mortality. Associations between the TyG index and outcomes were evaluated using binary logistic regression models.ResultsDuring a 5-year follow-up, 150 participants (1.80%) developed kidney function decline, 357 (4.30%) experienced CVD events, and 335 (4.00%) died from all causes. An elevated TyG index was associated with increased risks of kidney function decline, nonfatal CVD events, and all-cause mortality in the overall population and among participants with diabetes (quartile 4 [Q4] vs. quartile 1 [Q1]: hazard ratio [HR] [95% confidence interval, P-value] = 4.97 [1.41-31.71, P = 0.034], 4.63 [1.25-30.19, P = 0.047], and 4.54 [1.70-15.88, P = 0.007], respectively). These associations were not statistically significant in participants with normal glucose tolerance or prediabetes. Notably, an elevated TyG index was significantly associated with increased risk of fatal CVD events in the overall population and across all glucose tolerance subgroups, with the strongest association observed in participants with prediabetes rather than diabetes.ConclusionsThe TyG index is significantly associated with the risks of kidney function decline, CVD events, and all-cause mortality, and these associations differ by glucose tolerance status.

Type 2 diabetes (T2D) is a heterogeneous condition, but its phenotypic variation and links with mortality are unclear. We apply the discriminative dimensionality reduction with trees (DDRTree) algorithm to seven clinical variables in 10,091 adults with newly diagnosed T2D from a nationally representative Chinese cohort. Distinct mortality patterns are observed across phenotypes. Cardiovascular mortality is highest in the most hypertensive and obese individuals, while diabetic ketoacidosis/coma mortality is largely driven by the combination of hyperglycemia and dyslipidemia. Additionally, chronic obstructive pulmonary disease mortality is higher in those with elevated high-density lipoprotein (HDL) and total cholesterol levels. These patterns are similar in UK Biobank, though cardiovascular mortality is highest in those with dyslipidemia and obesity. Predictive models incorporating these variables show good performance and an online tool is provided for individual risk prediction. Overall, this study visualizes phenotypic variation in T2D and its impact on mortality, underscoring the need for personalized treatment strategies.