Cardiovasc Diabetol [JOURNAL]
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200 papers
Association of various insulin resistance surrogate markers with mortality risk in critically ill patients with ischemic stroke: a retrospective cohort study.
Wu B, Yu W, Lin B … +5 more , Zhang G, Jiang H, Zou D, Xu C, Wu N
Cardiovasc Diabetol · 2026 Apr · PMID 42015108 · Full text
BACKGROUND: Ischemic stroke poses a substantial global health burden and represents one of the leading causes of death and disability. Insulin resistance (IR), a core feature of metabolic dysfunction, is recognized to pl...
BACKGROUND: Ischemic stroke poses a substantial global health burden and represents one of the leading causes of death and disability. Insulin resistance (IR), a core feature of metabolic dysfunction, is recognized to play a critical role in the pathogenesis and progression of ischemic stroke. However, the predictive value of different surrogate markers of IR for mortality in patients with ischemic stroke remains unclear. METHODS: Using the public eICU-CRD database, we screened 1709 critically ill patients with ischemic stroke admitted to the intensive care unit (ICU). Patients were stratified by quartiles according to 8 distinct IR surrogate markers. The primary endpoint was in-hospital mortality. Statistical analyses included Cox regression, Kaplan-Meier curves, and restricted cubic spline (RCS) models. RESULTS: Among the 1709 ICU-admitted patients, 437 deaths occurred, with an in-hospital mortality rate of 25.57%. Multivariable Cox regression analyses demonstrated that all IR surrogate markers were significantly associated with mortality risk in patients with ischemic stroke. TyG-derived indices, TG-HDL, METS-IR, AIP, and CHG were positively correlated with mortality, whereas SPISE showed an inverse association (all P for trend < 0.05). Kaplan-Meier curves confirmed the associations between the 8 IR surrogate markers and in-hospital mortality. RCS analyses revealed nonlinear relationships between SPISE, TG-HDL, METS-IR, TyG-BMI, TyG-RC, CHG and all-cause mortality. CONCLUSION: Multiple IR surrogate markers independently predict in-hospital mortality in critically ill patients with ischemic stroke. Incorporation of these indices into risk stratification may facilitate early identification and targeted intervention for high-risk individuals.
Continuous glucose monitoring trajectories in patients with acute coronary syndrome.
Díaz-Expósito A, García-Ruiz V, Castillo-Barnes D … +15 more , Ortiz A, Larrubia-Valle JI, Molinero A, Puyol-Ruiz F, Barquero-Alegre O, González-Aguado N, Martín-Chaves L, Segovia-Reyes J, Urbano-Carrillo C, Gómez Doblas JJ, Jiménez-Navarro M, García-Alemán J, Rodríguez-Capitán J, Gómez Peralta F, Costa F
Cardiovasc Diabetol · 2026 Apr · PMID 42010565 · Full text
BACKGROUND: Continuous glucose monitoring (CGM) captures dysglycaemia and glycaemic variability after acute coronary syndrome (ACS), but patient-level trajectories from early recovery to mid-term follow-up—particularly i...
BACKGROUND: Continuous glucose monitoring (CGM) captures dysglycaemia and glycaemic variability after acute coronary syndrome (ACS), but patient-level trajectories from early recovery to mid-term follow-up—particularly in people without diabetes—remain insufficiently characterized. METHODS: In this prospective multicenter observational study (ORACLE program), consecutive high-risk ACS patients wore a FreeStyle Libre 3/3 Plus sensor for 14–15 days near discharge and again at ~ 4 months. We quantified CGM time-in-range metrics (70–180 mg/dL and tight range 70–140 mg/dL), time above/below range, and variability/risk indices, including within-day profiles. Clinically relevant changes were categorized using pre-specified thresholds, and predictors of worsening were explored using multivariable models. RESULTS: Among all patients, 213 patients had analyzable baseline CGM recordings meeting quality criteria. In the early post-ACS period, median [IQR] time in range 70–180 mg/dL was 96.57% [86.91–98.92], time in tight range 70–140 mg/dL was 85.00% [62.16–93.24], time above range > 180 mg/dL was 1.12% [0.18–9.82], and time below range < 70 mg/dL was 0.43% [0.00–1.84], with a mean glucose of 114.26 mg/dL [106.26–133.96] and a median glucose management indicator of 6.04% [5.85–6.51]. CGM demonstrated marked inter-individual heterogeneity and a reproducible late-morning (10:00–12:00) vulnerability window with lower range time and higher hyperglycaemic exposure, consistent across diabetes status and similar on weekdays and weekends; adverse CGM profiles were more prominent in patients with diabetes, older individuals, and women. Although CGM parameters improved modestly during the initial monitoring period, glycaemic control showed a slight but consistent deterioration from baseline to ~ 4 months after ACS, including in patients without diabetes. Tight-range time decreased by 4.5% (p = 0.008) and mean glucose increased by 4.67 mg/dL (p = 0.03), accompanied by a parallel worsening of variability and glycaemic risk indices. In contrast, HbA1c remained stable over follow-up. Across CGM endpoints, ~ 20–40% of patients showed a worsening trajectory (20.2% by broad time-in-range thresholds); higher comorbidity burden clustered with deterioration, with hypertension and COPD independently associated with tight-range worsening. CONCLUSIONS: After ACS, CGM reveals substantial inter-individual heterogeneity and a reproducible late-morning vulnerability window. From discharge to mid-term follow-up, deterioration—also affecting patients without diabetes—may be preferentially detected by tight-range and variability/risk metrics that traditional monitoring of blood glucose and static measures such as HbA1c may overlook, supporting CGM-informed phenotyping to refine post-ACS metabolic surveillance.
Diabetes does not attenuate the benefit of physiology-guided complete revascularization in older patients with myocardial infarction.
Sarti A, Verardi FM, Cavazza C … +24 more , Erriquez A, Casella G, Guiducci V, Moreno R, Escaned J, Marchini F, Cocco M, Caglioni S, Farina J, Vadalà G, Capecchi A, Gallo F, Cerrato E, Menozzi A, Gil JLD, Santos IA, Ruozzi M, Barbierato M, Picchi A, Pavasini R, Scarsini R, Tebaldi M, Campo G, Biscaglia S
Cardiovasc Diabetol · 2026 Apr · PMID 41981421 · Full text
BACKGROUND: In patients with myocardial infarction (MI) and multivessel disease, diabetes mellitus is associated with more diffuse coronary atherosclerosis and worse clinical outcomes, often influencing revascularization...
BACKGROUND: In patients with myocardial infarction (MI) and multivessel disease, diabetes mellitus is associated with more diffuse coronary atherosclerosis and worse clinical outcomes, often influencing revascularization decisions. The Functional Assessment in Elderly MI Patients with Multivessel Disease (FIRE) trial demonstrated the superiority of physiology-guided complete revascularization in older patients with MI. Whether this benefit is preserved in patients with diabetes remains uncertain. METHODS: In FIRE, 1445 patients aged ≥ 75 years with MI and multivessel disease were randomized to culprit-only or physiology-guided complete revascularization. In this prespecified analysis, outcomes were assessed according to diabetes status. The primary endpoint was a composite of death, MI, stroke, or revascularization at 3 years. The key secondary endpoint was cardiovascular death or MI. The safety endpoint included contrast-associated acute kidney injury, stroke, or Bleeding Academic Research Consortium type 3–5 bleeding. RESULTS: Among 1445 patients, 463 (32%) had diabetes. After adjustment for baseline characteristics, diabetes was independently associated with a higher risk of the primary endpoint (hazard ratio [HR] 1.26, 95% confidence interval [CI] 1.02–1.56) and heart failure (HR 1.35, 95% CI 1.01–1.83) at 3 years. Physiology-guided complete revascularization reduced the primary outcome in both patients with diabetes (HR 0.70, 95% CI 0.50–0.97) and without diabetes (HR 0.75, 95% CI 0.58–0.97), with no evidence of effect modification by diabetes status (p for interaction = 0.712). Similar consistency was observed for the key secondary and safety endpoints. CONCLUSIONS: In older patients with MI and multivessel disease, physiology-guided complete revascularization reduces ischemic events irrespective of diabetes status, supporting its use in elderly diabetic patients. Trial registration ClinicalTrials.gov Identifier NCT03772743.
The cholesterol, high-density lipoprotein, and glucose index and its derived indices predict diabetic kidney disease development and progression: evidence from two nationwide cohorts and a biopsy-proven clinical cohort.
Cui W, Jiang S, Yu T … +4 more , Yang Z, Zhou J, Liu L, Li W
Cardiovasc Diabetol · 2026 Apr · PMID 41975454 · Full text
BACKGROUND: The Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index is a recently proposed composite metric, but its utility in predicting the development and progression of diabetic kidney disease (DKD) remai...
BACKGROUND: The Cholesterol, High-Density Lipoprotein, and Glucose (CHG) index is a recently proposed composite metric, but its utility in predicting the development and progression of diabetic kidney disease (DKD) remains insufficiently explored. This study aimed to evaluate the predictive value of the CHG index and its anthropometric-adjusted derivatives for DKD development and progression, comparing their performance with traditional surrogate markers of insulin resistance. METHODS: We analyzed 10-year longitudinal data from the China Health and Retirement Longitudinal Study (CHARLS, 2011–2020), including 984 diabetic patients without baseline renal injury. Incident DKD risk was evaluated using Cox proportional hazards models and Kaplan–Meier analysis, while restricted cubic splines (RCS) assessed non-linear dose–response relationships. External validation utilized the cross-sectional National Health and Nutrition Examination Survey (NHANES 1999–2018). Furthermore, disease progression (estimated glomerular filtration rate [eGFR] < 60 mL/min/1.73 m2) was evaluated in an independent clinical cohort of 217 patients with biopsy-proven DKD. Discriminative ability was evaluated via Receiver Operating Characteristic (ROC) analyses. Subgroup and interaction analyses evaluated prognostic consistency across patient profiles. RESULTS: In CHARLS, elevated CHG-BMI independently predicted incident DKD in fully adjusted models (Quartile 3 HR = 2.19, P = 0.020), showing significant integrated discrimination improvement (IDI, P = 0.030) over traditional markers. Subgroup analyses revealed higher risk estimates for CHG-BMI in non-overweight and normolipidemic individuals (P for interaction < 0.05). NHANES analysis replicated these associations, identifying significant J-shaped trajectories for CHG and CHG-BMI. In the biopsy-proven cohort, CHG and CHG-BMI were independently associated with reduced eGFR (P < 0.05), unlike traditional markers. They yielded adjusted AUCs of 0.733 and 0.730 for predicting DKD progression. E-value analysis for unmeasured confounding was 4.81 for CHG-BMI (Q3). Significant interactions emerged between CHG-BMI and Renal Pathology Society (RPS) grades, with significant associations in classes IIa and IIb. CONCLUSION: The CHG index and CHG-BMI independently predict DKD development and progression, outperforming traditional insulin resistance markers. Both indices aid clinical risk stratification, with CHG-BMI specifically identifying elevated risks in early pathological stages and among individuals without overt metabolic comorbidities.
Lipid management in type 2 diabetes and non-HDL-cholesterol: target all atherogenic lipoproteins.
Brandts J, Verket M, Zambon A … +3 more , Marx N, Müller-Wieland D, Federici M
Cardiovasc Diabetol · 2026 Apr · PMID 41968323 · Full text
Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in individuals with diabetes, partly driven by dyslipidemia. While low-density lipoprotein cholesterol (LDL-C) reduction i...
Atherosclerotic cardiovascular disease (ASCVD) remains a leading cause of morbidity and mortality in individuals with diabetes, partly driven by dyslipidemia. While low-density lipoprotein cholesterol (LDL-C) reduction is the primary target of lipid management, many patients with diabetes exhibit mixed dyslipidemia characterised by elevated triglycerides and increased concentrations of atherogenic remnant lipoproteins, which are more comprehensively captured by non-high-density lipoprotein cholesterol (non-HDL-C). Current guidelines from international societies, including the American Diabetes Association (ADA), the American Association of Clinical Endocrinology (AACE), and the European Society of Cardiology (ESC), recommend LDL-C and non-HDL-C targets based on individual cardiovascular risk profiles. Despite clear therapeutic algorithms, lipid target attainment remains suboptimal in routine clinical practice, necessitating more intensive and individualised treatment strategies. Lipid-lowering therapies, including statins, ezetimibe, bempedoic acid and PCSK9 inhibitors, effectively reduce LDL-C and non-HDL-C, significantly lowering cardiovascular risk. Triglyceride-lowering therapies, including omega-3 fatty acids and fibrates, have demonstrated substantial reductions in triglyceride levels, but their impact on cardiovascular outcomes remains uncertain. Given the heterogeneity of dyslipidemia in diabetes, non-HDL-C and apolipoprotein B (apoB) have emerged as superior markers for assessing atherogenic burden. While LDL-C reduction remains central, additional efforts are needed to optimise the management of residual atherogenic lipoprotein particles in diabetes. Future research should focus on refining risk stratification, improving lipid target attainment, and integrating novel lipid-modifying agents to enhance cardiovascular outcomes in this high-risk population.
Cumulative exposure and dynamic trajectories of the C-reactive protein-triglyceride-glucose index (CTI) versus the cholesterol, high-density lipoprotein, and glucose index (CHG) for incident hypertension prediction: a national cohort study.
Dou J, Zhang S, Ding C … +2 more , Li H, Zhang P
Cardiovasc Diabetol · 2026 Apr · PMID 41968314 · Full text
BACKGROUND: The C-reactive protein-triglyceride-glucose index (CTI) and cholesterol-high-density lipoprotein-glucose index (CHG) are emerging composite biomarker indices, but their cumulative exposure and comparative val...
BACKGROUND: The C-reactive protein-triglyceride-glucose index (CTI) and cholesterol-high-density lipoprotein-glucose index (CHG) are emerging composite biomarker indices, but their cumulative exposure and comparative value for predicting incident hypertension remain unclear. METHODS: Leveraging a nationwide longitudinal cohort from the China Health and Retirement Longitudinal Study (CHARLS), the cumulative burden of CTI and CHG was modeled. These cumulative indices were defined as the average of the values measured at Wave 1 and Wave 3, multiplied by the time interval between these two assessments. Then, multivariable Cox proportional hazards models were used to assess associations and restricted cubic splines (RCS) for dose–response relationships. Group-based trajectory modeling (GBTM) was used to identify trajectory patterns. To gauge the predictive performance at 7 and 9 years, we analyzed time-dependent receiver operating characteristic (ROC) curves, alongside the C-index, net reclassification improvement (NRI), and integrated discrimination improvement (IDI), and cuCTI was further compared with triglyceride-glucose (TyG). Finally, the findings were further subjected to subgroup and sensitivity analyses to test their robustness. RESULTS: Over a median follow-up of 9 years, 408 of 2673 participants (15.3%) developed hypertension. Both elevated cuCTI and cuCHG significantly increased hypertension risk. In the fully adjusted model, participants in the highest quartile had a higher risk of hypertension for both cuCTI (HR = 2.16; 95% CI 1.63–2.87) and cuCHG (HR = 1.63; 95% CI 1.24–2.15). Crucially, cuCTI demonstrated superior predictive accuracy in time-dependent ROC analysis (9 years DeLong P = 0.025). In the fully adjusted model, adding cuCTI improved the 7 years C-index from 0.572 to 0.609 (P = 0.014) and the 9 years C-index from 0.582 to 0.618 (P = 0.003), compared with 0.590 and 0.597 for cuCHG (P = 0.110 and 0.094, respectively). Furthermore, cuCTI showed stronger gains in NRI and IDI compared to cuCHG (NRI: 30.31% vs. 12.61% at 7 years and 35.47% versus 15.77% at 9 years; IDI: 0.86% versus 0.47% at 7 years and 1.32% vs. 0.71% at 9 years; all P < 0.05). Further comparison with TyG also suggested superior predictive performance of cuCTI. Subgroup and sensitivity analyses also showed consistent results. CONCLUSION: Both indices were independently associated with incident hypertension, and cuCTI showed better long-term predictive performance than cuCHG. These findings support the value of monitoring cumulative inflammatory-metabolic burden for early hypertension risk stratification.
Association of cumulative exposure and change patterns of triglyceride-glucose index combined with novel obesity indices with glycemic transitions in prediabetes: evidence from the China Health and Retirement Longitudinal Study (CHARLS).
Wang C, Peng Y, Cheng G … +3 more , Duan Q, Wang W, Peng N
Cardiovasc Diabetol · 2026 Apr · PMID 41965747 · Full text
BACKGROUND: Prior research indicates that the triglyceride-glucose (TyG) index and its derivatives are cost-effective and easily accessible tools for assessing glucose metabolism risk. This study aimed to systematically...
BACKGROUND: Prior research indicates that the triglyceride-glucose (TyG) index and its derivatives are cost-effective and easily accessible tools for assessing glucose metabolism risk. This study aimed to systematically evaluate the longitudinal associations between TyG-novel obesity indices [TyG-body roundness index (TyG-BRI), TyG-chinese visceral adiposity index (TyG-CVAI), TyG-weight-adjusted waist index (TyG-WWI), TyG-a body shape index (TyG-ABSI)] and glycemic transitions in individuals with prediabetes. METHODS: This analysis used data from the China Health and Retirement Longitudinal Study, encompassing 2004 participants with prediabetes. Employing longitudinal data from baseline and a 3‑year follow‑up, we systematically quantified the baseline values, cumulative exposure, and change patterns of TyG‑novel obesity indices. Multiple statistical models were applied to assess the associations of these indices with glycemic transitions in prediabetes and to examine the potential mediating effect of inflammatory burden. RESULTS: During follow‑up, 306 participants progressed to diabetes and 452 reverted to normoglycemia. Compared with static baseline measurements, cumulative exposure and change patterns of TyG‑novel obesity indices strengthened their associations with glycemic transitions. Notably, TyG-BRI and TyG-CVAI exhibited the strongest associations at baseline, whereas TyG-WWI showed the most prominent performance in the analyses of both cumulative exposure and change patterns. Compared with individuals exhibiting well-controlled (low baseline with a slight increase over follow-up) or low cumulative exposure, those with poor control (high baseline and minimal change over follow-up) or the highest cumulative exposure to TyG-WWI, TyG-ABSI, TyG-BRI, and TyG-CVAI faced a significantly higher risk of diabetes progression, with TyG-WWI showing the strongest association with diabetic outcomes. Conversely, elevated levels of all four TyG-novel obesity indices were associated with a reduced likelihood of reverting to normoglycemia, with the strongest inverse associations observed for TyG-BRI (both at baseline and cumulative exposure) and TyG‑WWI (cumulative exposure). For the predictive analysis of glycemic status transitions in prediabetes, the continuous net reclassification improvement demonstrated that the TyG-BRI model exhibited the greatest ability to reclassify individuals into more accurate risk categories, followed by TyG-CVAI, TyG-WWI, and TyG-ABSI. Finally, mediation analysis showed that the progression of prediabetes associated with the TyG-novel obesity indices was partially mediated (2%) by long-term inflammatory burden. CONCLUSION: Cumulative exposure and change patterns of TyG-novel obesity indices are significant factors influencing glycemic transitions in individuals with prediabetes.
Diabetes-related differences in body composition and their prognostic value among patients with heart failure and preserved ejection fraction: a cardiac-MRI-based study.
Xiao SY, Li Y, Min CY … +4 more , Fang H, Li JK, Shi K, Yang ZG
Cardiovasc Diabetol · 2026 Apr · PMID 41957641 · Full text
BACKGROUND: Heart failure and diabetes mellitus share common risk factors and can independently regulate the body composition profile of patients. Approximately one-third of patients with heart failure and preserved ejec...
BACKGROUND: Heart failure and diabetes mellitus share common risk factors and can independently regulate the body composition profile of patients. Approximately one-third of patients with heart failure and preserved ejection fraction (HFpEF) have concomitant diabetes mellitus, but the additional impact of diabetes on the body composition of HFpEF patients and its associations with prognosis have not been explored. METHODS: This study included 281 HFpEF patients, among whom 87 had type 2 diabetes (T2DM). On the basis of their cardiac magnetic resonance (MR) images, regional adipose tissue (including subcutaneous, visceral and paracardial adipose tissue) as well as thoracic skeletal muscle were measured and compared between the diabetic and non-diabetic groups. Clinical endpoints were recorded and the predictive performance of body composition parameters and body mass index (BMI) for adverse events was assessed using multivariable Cox regression analysis in the overall HFpEF population and subgroups stratified by diabetes. RESULTS: HFpEF patients with concomitant diabetes were significantly older (65.06 ± 12.92 vs. 57.98 ± 14.44 years, p < 0.001). The LVEDV index and LVSV index were significantly lower in the T2DM group. The paracardial adipose tissue (ParaAT index) was noticeably greater in the T2DM group than in the non-T2DM group (76.21 vs. 65.60 ml/m, p = 0.005). In the overall HFpEF population, the increase in the skeletal muscle index (SMI) corresponded to a linear decrease of prognostic risks. In contrast, the increase in the ParaAT-VAT ratio and ParaAT-muscle ratio corresponded to linearly increasing risks of poor outcomes. BMI demonstrated a non-linear correlation with survival risks (p for nonlinearity: 0.031) and the lowest tertile compared with the middle tertile increased survival risks significantly. Subgroup analysis revealed that the prognostic risks associated with the ParaAT-VAT ratio and ParaAT-muscle ratio were greater in diabetic HFpEF patients (adjusted HR: 1.069 [1.022, 1.117] and 1.948 [1.391, 2.729], respectively) than in nondiabetic patients (adjusted HR: 1.053 [1.006-1.103] and 1.597 [1.018, 2.505], respectively). Protective role from increased SMI persisted among the non-T2DM patients (adjusted HR: 0.968 [0.951, 0.985], p < 0.001) but not among the T2DM patients (adjusted HR: 0.990 [0.968, 1.012], p = 0.380). The lowest tertile group of BMI for non-T2DM patients or instead, the highest tertile group of BMI for T2DM patients led to an unfavorable prognosis. CONCLUSIONS: Concomitant diabetes exacerbated paracardial adipose excess among HFpEF patients and worsened the association between body composition and adverse outcomes.
Hepatic metabolic burden and all-cause mortality across glucose metabolism statuses in a cardiovascular-kidney-metabolic syndrome population: insights from the National Health and Nutrition Examination Survey (NHANES).
Liu T, Dai Q
Cardiovasc Diabetol · 2026 Apr · PMID 41957630 · Full text
BACKGROUND: Hepatic metabolic burden is an integral component of cardiometabolic risk. However, the association of hepatic metabolic burden assessed by the fatty liver index (FLI) with all-cause mortality in cardiovascul...
BACKGROUND: Hepatic metabolic burden is an integral component of cardiometabolic risk. However, the association of hepatic metabolic burden assessed by the fatty liver index (FLI) with all-cause mortality in cardiovascular-kidney-metabolic (CKM) syndrome has not been well described when individuals are stratified by glucose metabolism status. Therefore, this study aimed to evaluate the association between FLI and all-cause mortality across different glucose metabolism states in adults with CKM syndrome. METHODS: Data were derived from the National Health and Nutrition Examination Survey (NHANES) 1999-2018. Adults with CKM syndrome according to the AHA/ADA framework were included and categorized by glucose metabolism status as normoglycemia, prediabetes, or diabetes. Hepatic metabolic burden was assessed using FLI. Weighted multivariable Cox proportional hazards models and restricted cubic spline (RCS) analyses were applied to examine the associations between FLI and all-cause mortality across glucose metabolism status. Additionally, joint analyses with combined FLI (FLI ≥ 60 vs. <60) and glycemic categories and multiple sensitivity analyses were performed. RESULTS: Among 19,107 participants with CKM syndrome (weighted N = 105,007,226), 2482 deaths occurred over a median follow-up of 9.42 years. No robust independent association was observed between FLI and all-cause mortality among individuals with normoglycemia or prediabetes after multivariable adjustment. In contrast, among individuals with diabetes, multivariable Cox regression and RCS analysis indicated that higher FLI was significantly associated with increased mortality risk and demonstrated a J-shaped nonlinear dose-response relationship. Joint analyses further showed that elevated FLI was associated with progressively higher death risk in the presence of impaired glucose metabolism, with the highest risk observed among individuals with diabetes and FLI ≥ 60. Multiple sensitivity analyses confirmed that the main analysis results were robust. CONCLUSIONS: Within the CKM syndrome spectrum, elevated FLI was associated with a higher risk of all-cause mortality among individuals with diabetes, with a J-shaped association, whereas the association between FLI and all-cause mortality was not significant among individuals with normoglycemia or prediabetes. These findings suggest that the relationship between FLI and mortality in CKM populations may vary according to glycemic status and highlight the importance of considering glycemic context when interpreting liver-related metabolic markers.
The prognostic significance of cholesterol, high-density lipoprotein and glucose (CHG) index in evaluating all-cause mortality risk in metabolic dysfunction-associated steatotic liver disease (MASLD) individuals: evidence from two cohort studies.
Wang J, Tu G, Tao Q … +5 more , Li R, Zhai H, Hong S, Shi X, Zhang G
Cardiovasc Diabetol · 2026 Apr · PMID 41943105 · Full text
BACKGROUND: The prognostic assessment of metabolic dysfunction-associated steatotic liver disease (MASLD) is of critical importance. Although previous international studies have suggested an association between the chole...
BACKGROUND: The prognostic assessment of metabolic dysfunction-associated steatotic liver disease (MASLD) is of critical importance. Although previous international studies have suggested an association between the cholesterol, high-density lipoprotein, and glucose (CHG) index and mortality in MASLD patients, its generalizability in the Chinese population remains unclear, and there is a lack of predictive tools directly applicable for individual risk stratification. METHODS: A total of 6936 participants with MASLD were sourced from the China Health and Retirement Longitudinal Study (CHARLS) database from 2011 to 2020. Survival differences were visualized using the Kaplan-Meier method. Multivariate Cox regression was employed to assess the association between the CHG index and mortality risk. Smooth curve fitting analysis was conducted to examine the nonlinear relationship between them. Mediation analysis was performed to explore the mediating roles of C-reactive protein (CRP) and triglyceride glucose-weight-adjusted waist index (TyG-WWI). To evaluate the predictive value of the CHG index, we implemented a set of eight distinct machine learning (ML) models. Subgroup and sensitivity analyses were conducted to verify the robustness of the results. Concurrently, the National Health and Nutrition Examination Survey (NHANES) database (1999–2018) was utilized for external validation. RESULTS: The median follow-up duration was 7.44 years. A total of 615 mortality events were recorded. After adjusting for multiple confounding factors, an elevated CHG index was significantly associated with an increased risk of mortality (highest vs. lowest tertile, HR = 1.49, 95% CI [1.21–1.84], P = 0.0002). Kaplan-Meier curves demonstrated that higher CHG index levels were significantly associated with reduced survival (P < 0.0001). Smooth curve fitting and threshold effect analysis revealed a nonlinear relationship between them. Mediation analysis indicated that CRP and TyG-WWI mediated 13.36% and 45.33% of the effect of CHG index on mortality, respectively (all P < 0.05). Logistic Regression model showed superior discrimination. Decision curve analysis confirmed that the Logistic Regression model provided significant clinical net benefit across a wide range of risk thresholds. The primary analyses were replicated using data from the representative NHANES cohort, revealing a significant positive association between CHG index and mortality. CONCLUSIONS: Elevated CHG index is significantly associated with an increased risk of mortality in the Chinese MASLD population, demonstrating a nonlinear relationship. Furthermore, indicators related to inflammation and insulin resistance (IR) significantly mediate these associations. The CHG index serves as an important tool for predicting long-term adverse outcomes in this population. RESEARCH INSIGHTS: What is currently known about this topic? 1. International studies have suggested that the CHG index is associated with mortality in patients with MASLD. 2. However, its generalizability in Chinese populations remains unclear, and there is a lack of prediction tools that can be directly applied for individual risk stratification. What is the key research question? 1. How does the CHG index influence mortality risk in Chinese MASLD individuals? What is new? 1. This is the first Chinese cohort study to investigate the relationship between CHG index and mortality risk in MASLD individuals. 2. A prediction model was constructed using ML. 3. Mediation analysis revealed the mediating role of inflammatory and IR-related indicators for the first time. How might this study influence clinical practice? 1. This research may promote the integration of the CHG index into routine risk assessment for MASLD patients. By providing a low-cost risk-stratification tool, it could facilitate early intervention. The identified threshold effect may offer evidence-based support for establishing personalized management cut-off values.
Associations between the C-reactive protein-triglyceride glucose index and the incidence and progression trajectory of cardiometabolic multimorbidity: a multi-state model study.
Yuan L, Zhao Z, Peng H … +6 more , Zong W, Zhu J, Qu H, Liang C, Nilsson J, Chen Y
Cardiovasc Diabetol · 2026 Apr · PMID 41937151 · Full text
BACKGROUND: The C-reactive protein-triglyceride-glucose index (CTI) has been proposed as a novel biomarker for insulin resistance and inflammation. However, its role in the progression trajectory of cardiometabolic multi...
BACKGROUND: The C-reactive protein-triglyceride-glucose index (CTI) has been proposed as a novel biomarker for insulin resistance and inflammation. However, its role in the progression trajectory of cardiometabolic multimorbidity (CMM) remains unclear. We aimed to investigate the involvement of the CTI in the CMM progression trajectory. METHODS: This prospective study included 266,049 individuals from the UK Biobank, who were free of cardiometabolic diseases (CMD) at baseline. CMM was defined as the presence of two or more CMDs, including type 2 diabetes (T2D), coronary heart disease (CHD), and stroke. The CTI was calculated using the formula: 0.412 × ln (CPR) + ln (TG×FPG/2). Cox proportional hazards, Kaplan–Meier curves, restricted cubic spline (RCS) and multi-state models were employed to examine associations of CTI with the incidence and progression of CMM. Receiver operating characteristic (ROC) curve, C-index analysis, net reclassification index (NRI) together with integrated discrimination improvement index (IDI) were carried out to examinate the predictive performance of CTI. The robustness of results was further evaluated via stratified and sensitivity analyses. RESULTS: CTI was positively and significantly associated with CMM development. Compared with the low-CTI group, the high-CTI group exhibited an increased risks of T2D (HR: 3.60, 95% CI 3.39–3.83), stroke (HR: 1.11, 95% CI 1.03–1.19), CHD (HR: 1.52, 95% CI 1.46–1.58), first cardiometabolic disease (FCMD, HR: 1.86, 95% CI 1.81–1.92), CMM (HR: 2.50, 95% CI 2.23–2.80), and death (HR: 1.25, 95% CI 1.20–1.29). Among CMM and its component diseases, CTI showed the greater predictive capacity for T2D and CMM risk. Additionally, CTI exhibited incremental predictive value over TyG and CRP for incident CHD, FCMD and CMM with the highest C-index and NRI values. Stratified analyses indicated the consistent association of CTI with all outcomes except for stroke across age, gender and BMI. Specifically, stronger associations were observed in younger, female and lower BMI individuals. In state transition analysis, the high-CTI group showed elevated risks for transitions from baseline to FCMD (HR: 1.86, 95% CI 1.80–1.91), baseline to death (HR: 1.18, 95% CI 1.12–1.23), and FCMD to CMM (HR: 1.39, 95% CI 1.24–1.56). In disease-specific transitions, a higher CTI was linked to increased risks of transitions from baseline to T2D (HR: 3.68, 95% CI 3.45–3.93), baseline to CHD (HR: 1.49, 95% CI 1.43–1.56), baseline to death (HR: 1.18, 95% CI 1.12–1.23), stroke to CMM (HR: 1.43, 95% CI 1.09–1.86), and CHD to CMM (HR: 1.52, 95% CI 1.29–1.79). Similar findings were observed when the CTI was treated as a continuous variable. CONCLUSION: Our data revealed that CTI was positively correlated with the incidence and progression trajectory of CMM. CTI could serve as a simple and scalable tool for risk stratification in CMM, highlighting its potential utility in screening population with cardiometabolic-inflammatory burden.
Assessment of seven insulin resistance surrogate indexes for predicting cardiometabolic multimorbidity among Chinese middle-aged and older adults: a national prospective cohort study.
Lai J, Liu Z, Wang H … +3 more , Kong X, Wei Y, Cao Y
Cardiovasc Diabetol · 2026 Apr · PMID 41937148 · Full text
BACKGROUND: Cardiometabolic multimorbidity (CMM) poses a mounting health challenge worldwide. Seven surrogate indexes of insulin resistance (IR)-the triglyceride-glucose index (TyG), TyG-body mass index (TyG-BMI), TyG-wa...
BACKGROUND: Cardiometabolic multimorbidity (CMM) poses a mounting health challenge worldwide. Seven surrogate indexes of insulin resistance (IR)-the triglyceride-glucose index (TyG), TyG-body mass index (TyG-BMI), TyG-waist circumference (TyG-WC), Chinese visceral adiposity Index (CVAI), Metabolic score for IR (METS-IR), Atherogenic index of plasma (AIP), and estimated glucose disposal rate (eGDR)-are well-established. However, comparative studies evaluating their predictive capacity for CMM incidence in Chinese middle-aged and older adults remain scarce. This study aimed to assess the associations between these seven IR indexes and CMM risk within this population and determine their relative predictive abilities. METHODS: Utilizing the China Health and Retirement Longitudinal Study (CHARLS) 2011-2020 datasets, this prospective cohort investigation assessed Chinese participants aged ≥ 45 years. We applied Kaplan-Meier curve plotting, multivariable Cox proportional hazards models, and restricted cubic splines (RCS) to quantify associations of insulin resistance surrogate indexes with CMM risk. Predictive accuracy was appraised via time-dependent receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). Subgroup evaluations further verified findings robustness. RESULTS: During a median follow-up of 9 years, 1043 (14.49%) of the 7197 participants developed CMM. After adjusting for potential confounders, we observed that each standard deviation (SD) increase in eGDR was associated with a reduced risk of CMM, with an adjusted hazard ratio (HR) of 0.834 [95% confidence interval (CI): 0.781-0.891]. In contrast, each SD increase in TyG, TyG-BMI, TyG-WC, METS-IR, AIP and CVAI were associated with an increased risk of CMM. Restricted cubic spline analyses showed that TyG-BMI, TyG-WC, METS-IR, and eGDR were nonlinear associated with incident new-onset CMM (P-nonlinearity < 0.05). eGDR showed a L-shaped association (P-nonlinearity < 0.05), with CMM risk decreasing until the inflection point at 11.82 (HR = 0.758; 95% CI: 0.702-0.818). Conversely, TyG-WC displayed a U-shaped relationship (inflection point: 572.14). Moreover, the time-dependent AUC analysis revealed that eGDR exhibited superior predictive discrimination (AUC 0.68-0.76) during early follow-up and across all intervals. The optimal cut-off value for eGDR was determined to be 7.64. CONCLUSION: All seven insulin resistance surrogate indexes independently demonstrated elevated CMM risk. In the context of Chinese middle-aged and elderly cohorts, eGDR demonstrated a notable predictive capacity for CMM. ROC-derived cut-offs (eGDR < 7.64) are utilised for identifying high-risk individuals requiring intervention. Spline-derived thresholds (eGDR = 11.82) serve as therapeutic targets for risk reduction.
Sweet relief: exploring mechanisms and therapeutic approaches of sodium-glucose cotransporter-2 inhibitors in cardiovascular-kidney metabolic syndrome.
Hua J, Wang Q, Liu Y … +11 more , Luo S, Shi A, Yan Z, Zhang J, Gu W, Zhu L, Zhang Y, Zhang L, Yu P, Liu X, Wang W
Cardiovasc Diabetol · 2026 Apr · PMID 41937138 · Full text
The escalating global burden of chronic multimorbidity has necessitated a fundamental transition from organ-centric treatment models toward integrated, multisystemic management strategies. Central to this evolution is th...
The escalating global burden of chronic multimorbidity has necessitated a fundamental transition from organ-centric treatment models toward integrated, multisystemic management strategies. Central to this evolution is the recognition of the cardiovascular–kidney–liver-metabolic (CKM) syndrome, a clinical framework arising from the profound and bidirectional pathophysiological crosstalk between metabolic dysfunction, chronic kidney disease, and heart failure. Sodium-glucose cotransporter-2 inhibitors (SGLT-2i) have transitioned from simple glucose-lowering drug to a critical pillar of the area of cardiovascular metabolism, demonstrating profound benefits across the cardiovascular, metabolism and renal systems. These therapeutic effects are driven by a complex interplay of hemodynamic and non-hemodynamic mechanisms, including the restoration of tubuloglomerular feedback, optimization of myocardial energetics, and the attenuation of systemic inflammation and oxidative stress. This pharmacological profile aligns precisely with the multi-stage progression of CKM syndrome, offering a cohesive intervention to interrupt the vicious cycle of systemic risk. In this review, we delineated the mechanistic pathways by which SGLT-2i modulate the CKM axis and evaluate the clinical evidence supporting its important role for integrated CKM management, providing a comprehensive perspective on optimizing long-term outcomes through multisystemic targeting.
The association between liver fat content and plasma metabolite profiles in fasting and postprandial states: an integration of a cohort study and a randomized controlled trial.
Fang Y, de Mutsert R, Gijbels A … +7 more , Deng K, Lamb H, Rosendaal FR, Mook-Kanamori DO, van Dijk KW, Afman LA, Li-Gao R
Cardiovasc Diabetol · 2026 Apr · PMID 41935270 · Full text
BACKGROUND: Postprandial metabolic impairments play a key role in the pathophysiology of cardiometabolic diseases. While liver fat content has been linked to distinct fasting metabolite profiles, its relationship with po...
BACKGROUND: Postprandial metabolic impairments play a key role in the pathophysiology of cardiometabolic diseases. While liver fat content has been linked to distinct fasting metabolite profiles, its relationship with postprandial metabolite profiles remains unexplored. In this study, we aimed to (1) examine to what extent liver fat content is associated with the postprandial metabolomic profile beyond fasting metabolites; and (2) investigate whether diet-induced changes in liver fat content are associated with changes in plasma metabolites identified in objective 1. METHODS: In a subpopulation (n = 1986) of an existing cohort study and a 12-week dietary intervention study (n = 80), liver fat content was measured by proton magnetic resonance spectroscopy and categorized as low (< 2.5%), middle (2.5-5.5%), or high (> 5.5%). In the cohort study, plasma metabolomic profiles were quantified by NMR spectroscopy at fasting (T) and 150 min after a mixed meal (T). We examined associations between liver fat content and plasma metabolites at T, T and postprandial response (ΔT-T) using multivariate linear regression. In the intervention study, plasma metabolomic profiles were quantified at fasting (T) and at multiple postprandial time points (120, 240, and 360 min) following a mixed meal, both before and after the intervention. We further examined associations between liver fat content and plasma metabolites at T, and postprandial response (incremental area under the curves [iAUCs]) and explored associations between diet-induced changes in liver fat content and changes in identified metabolites at fasting and postprandial responses (iAUCs). RESULTS: High liver fat group was characterized by higher fasting and postprandial levels of triglycerides, all VLDL and the small LDL/HDL subclasses, ApoB, fatty acids, glycoprotein acetyls, and BCAAs, and lower medium/larger HDL subclasses, and acetate compared to the low liver fat group. In the high vs. low liver fat group, postprandial responses of cholesterol content of S-LDL, IDL, and S-HDL, glutamine and histidine, omega-3% and DHA % were lower. Diet-induced reductions in liver fat were associated with reductions in 40 fasting plasma metabolites, including VLDL-TG, tyrosine, isoleucine, fatty acid ratios, and most of the VLDL subclasses. CONCLUSIONS: Postprandial metabolomic profiling revealed additional associations between liver fat content and plasma metabolites beyond fasting measures, particularly in lipoprotein cholesterol and fatty acid composition. Diet-induced reductions in liver fat were associated with favorable changes in fasting metabolites, but not postprandial metabolite responses. Future studies with harmonized postprandial assessment are needed to further elucidate the postprandial observations and the underlying mechanisms. TRIAL REGISTRATION: The trials in this study were registered at clinicaltrials.gov as NL21981.058.08/P08.109 and NCT02194504.
Novel amino acid and fatty acid signatures linked to type 2 diabetes risk after gestational diabetes mellitus.
Qiu C, Chen W, Kang N … +8 more , Liao J, Yang Z, Tran V, Jones DP, Gilliland FD, Buchanan TA, Xiang AH, Chen Z
Cardiovasc Diabetol · 2026 Apr · PMID 41933349 · Full text
BACKGROUND: Women with gestational diabetes mellitus (GDM) history carry increased risks of type 2 diabetes compared to women without GDM history. This study aims to identify the dysregulated metabolic pathways and metab...
BACKGROUND: Women with gestational diabetes mellitus (GDM) history carry increased risks of type 2 diabetes compared to women without GDM history. This study aims to identify the dysregulated metabolic pathways and metabolite signatures during pregnancy that predict the risk of developing type 2 diabetes post-GDM. METHODS: 101 Hispanic women with GDM diagnoses were followed from the 3rd trimester of index pregnancy to 12 years post-delivery. Oral and intravenous glucose tolerance tests were performed every 12–15 months until development of type 2 diabetes, lost-to-follow-up or the end of the study. Type 2 diabetes incidence was identified as a fasting glucose concentration ≥ 126 mg/dL or 2-hour glucose ≥ 200 mg/dL. In this study, archived plasma samples from the 3rd trimester of pregnancy were assayed for untargeted metabolomics using mass-spectrometry to explore metabolic signatures of diabetes development. Metabolome-wide association analysis was performed to assess the association of metabolomic features with type 2 diabetes incidence using Cox proportional hazards models adjusted for age at delivery, along with post-delivery body mass index, additional pregnancy, and self-reported daily calorie intake at each follow-up visit as time-varying covariates, followed by Mummichog pathway enrichment analysis. RESULTS: Among the 101 women, 52 developed diabetes in 12 years. Metabolomics analysis suggested that nine amino acid and fatty acid metabolic pathways were associated with the risk of developing type 2 diabetes in GDM women (p-values of pathway enrichment tests < 0.05). Higher plasma levels of agmatine, hydroxyproline/5-aminolevulinate, along with lower plasma levels of threonine/homoserine, 25-hydroxycholesterol, FA12:0 (laurate), FA20:0 (arachidic acid), FA20:3 (homolinoleic acid), FA18:3 n-3 or n-6 (linolenic acid) in 3rd trimester were associated with a 12%–60% higher hazard of developing type 2 diabetes during the up to 12 years’ post-delivery period (all p-values < 0.05). CONCLUSION: Levels of amino acid and fatty acid metabolomic signatures in pregnancy may help identify individuals at an elevated risk of developing type 2 diabetes after GDM-complicated pregnancy, highlighting opportunities for earlier, more targeted prevention that require confirmation in larger, prospective studies.
Joint association of triglyceride-glucose (TyG) and atherogenic index of plasma (AIP) with stroke risk: findings from a nationwide prospective cohort.
Nian C, Huang Y, Ma X … +6 more , Meng X, Guo L, Tian W, Li H, Zhao Y, Sun J
Cardiovasc Diabetol · 2026 Apr · PMID 41933347 · Full text
BACKGROUND: The triglyceride-glucose (TyG) index and the atherogenic index of plasma (AIP) are established surrogate markers for insulin resistance and dyslipidemia, respectively, each independently linked to stroke. How...
BACKGROUND: The triglyceride-glucose (TyG) index and the atherogenic index of plasma (AIP) are established surrogate markers for insulin resistance and dyslipidemia, respectively, each independently linked to stroke. However, their combined predictive value for stroke is underexplored. Consequently, this study aims to evaluate the predictive performance of the combined TyG and AIP indices for incident stroke in a middle-aged and elderly Chinese cohort. METHODS: We included 7652 adults aged ≥ 45 years without baseline stroke from the China Health and Retirement Longitudinal Study (CHARLS). TyG and AIP were calculated and dichotomized by median. The primary outcome was new-onset stroke. Cox proportional hazards models assessed associations, examining interactions on both additive (Relative Excess Risk due to Interaction, RERI) and multiplicative scales. Restricted cubic spline (RCS) analysis was used to examine nonlinear relationships. Predictive performance was assessed using area under the receiver operating characteristic curve (AUC), and model performance differences were evaluated using the DeLong test, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULT: Over 9 years, 744 strokes (9.72%) occurred. High TyG (HR = 1.41, 95% CI 1.21–1.64) and high AIP (HR = 1.44, 1.24-1.67) independently increased risk. The combination showed highest risk (HR = 1.49, 1.27-1.75). AIP had a nonlinear association (inflection ~ 0.22); TyG was linear. The combined AUC (0.633) was not significantly better (DeLong test, P > 0.05), and both NRI and IDI were non-significant. Subgroup analysis revealed stronger effects of combined indicators in aged < 60 years old and those without diabetes or heart disease history. Sensitivity analysis supported robust results. Multiplicative interaction was significant (P = 0.021), while additive interaction was non-significant (RERI = 0.280, 95% CI -0.220-0.779). CONCLUSION: Both the TyG index and AIP are independent risk factors for stroke. The primary value of combining these two indicators lies in identifying individuals at extremely high risk, rather than significantly enhancing overall predictive performance. This combined metric can serve as a comprehensive metabolic risk assessment tool, particularly suitable for primary stroke prevention in individuals under 60 years of age without a history of diabetes or heart disease. Future studies are needed to further validate its risk reclassification capability and intervention value.
Collective exerkines mediate physical activity mitigating new-onset heart failure risk in older adults with prediabetes or diabetes: a community-based longitudinal cohort study.
Liu W, Shang L, Li P … +5 more , Yao Y, Yin H, Zhang H, Liu Z, Guo Y
Cardiovasc Diabetol · 2026 Apr · PMID 41933332 · Full text
BACKGROUND: Evidence regarding how collective exerkines mediate the association between physical activity (PA) and heart failure (HF) risk in older adults with prediabetes and diabetes remains limited. METHODS: This pros...
BACKGROUND: Evidence regarding how collective exerkines mediate the association between physical activity (PA) and heart failure (HF) risk in older adults with prediabetes and diabetes remains limited. METHODS: This prospective cohort study enrolled 5,886 older adults with prediabetes or diabetes from community dwellings in Shandong, China, between 2008 and 2011. PA metabolic equivalent task (MET) scores and plasma concentrations of ten exerkines, such as brain-derived neurotrophic factor (BDNF) and interleukin (IL)−6, were evaluated. The new-onset of HF during follow-up served as the outcome. RESULTS: Over a median follow-up of 11.1 years, 615 participants developed HF, with an incidence rate of 9.59 per 1000 person-years. A U-shaped dose-response association emerged between PA MET scores and HF risk. Compared to light PA, moderate and vigorous PA reduced HF risk by 57.0% (HR: 0.43; 95% CI: 0.33–0.56) and 36.0% (HR: 0.64; 95% CI: 0.49–0.83), respectively. A quartile increase across all examined exerkines was associated with a 32% decreased HF risk (HR: 0.68, 95% CI: 0.63–0.73). Among these exerkines, BDNF was the most significant negative contributor, while IL-6 emerged as the predominant positive contributor to HF risk. Principal component analysis revealed IL-6 and BDNF as the primary contributors to component 1, explaining 42.87% of the data variance. Population attributable risk analysis indicated that low BDNF levels carried the highest attributable risk percentage at 18.6%, followed by elevated IL-6 levels at 12.6%. Recreational-leisure PA MET scores demonstrated a significant positive correlation with BDNF and a significant negative correlation with IL-6. In contrast, correlations between occupational PA MET scores and both BDNF and IL−6 were not statistically significant. The collective exerkines mediated 67.83% and 20.48% of the associations of the PA MET scores and hyperglycemic status with HF risk, respectively (Padjustment <0.001). CONCLUSIONS: Collective exerkine activity plays a crucial mediating role in the relationship between PA and HF risk among older adults managing prediabetes or diabetes. Cultivating optimal physical activity habits is paramount for preventing HF onset in this vulnerable group. This includes moderately increasing recreational-leisure pursuits, strategically reducing occupational and household activities, enhancing protective exerkines like BDNF, and suppressing harmful ones such as IL-6. Trial registration Retrospectively registered number: ChiCTR-EOC-17013598.
Association of C-reactive protein-triglycerides-glucose index-waist to height ratio and cardiometabolic multimorbidity in middle-aged and older adults: a nationwide cohort study.
Du J, Man Z, Bai X … +6 more , Luo D, Guo Q, Wang Y, Yan Y, Su X, Zheng W
Cardiovasc Diabetol · 2026 Apr · PMID 41923235 · Full text
BACKGROUND: Cardiometabolic multimorbidity (CMM) poses a severe global health burden. Effective prediction requires biomarkers capturing its complex pathophysiology, integrating inflammation, insulin resistance (IR), and...
BACKGROUND: Cardiometabolic multimorbidity (CMM) poses a severe global health burden. Effective prediction requires biomarkers capturing its complex pathophysiology, integrating inflammation, insulin resistance (IR), and central obesity. The C-reactive protein-triglycerides-glucose index-waist to height ratio (CTI-WHtR) is a composite index synthesizing these three pathways, but its longitudinal association with CMM risk remains unestablished. METHODS: This prospective analysis utilized data from the China Health and Retirement Longitudinal Study (CHARLS). Cohort 1 (n = 8,875), free of CMM at baseline (2011), was established to assess the association between baseline CTI-WHtR and incident CMM. Cohort 2 (n = 5,807), a sub-cohort of longitudinal analysis, was analyzed to evaluate the impact of cumulative CTI-WHtR (cuCTI-WHtR) exposure (up to 2015) on CMM risk. The primary outcome was new-onset CMM (≥ 2 of diabetes, heart disease, or stroke). Cox proportional hazards models, restricted cubic splines, threshold analysis, and ROC curves were employed. RESULTS: During the follow-up period, 873 and 490 incident CMM cases occurred in Cohort 1 and Cohort 2, respectively. After multiple adjustment, participants in the highest quartile of baseline CTI-WHtR had a 2.85-fold (95% CI 2.26–3.58) higher CMM risk compared to the lowest quartile (P < 0.001). A similar dose–response relationship was observed for cuCTI-WHtR (Q4 HR = 2.76, 95% CI 2.04–3.75). RCS analysis revealed a non-linear association with a significant inflection point. Both baseline and cumulative CTI-WHtR demonstrated superior predictive performance for CMM compared to its individual components (CTI or WHtR). Results remained robust across multiple sensitivity analyses. CONCLUSION: Both baseline and cumulative CTI-WHtR are strong, independent, and non-linear predictors of new-onset CMM. This integrative index, combining inflammation, IR, and central obesity, outperforms its components, offering a practical tool for early identification of high-risk individuals for targeted prevention.
Association of the C-reactive protein-triglyceride glucose index with all-cause and cardiovascular mortality among U.S. adults with metabolic dysfunction-associated steatotic liver disease: a national cohort study.
Assempoor R, Jodeiri F, Javadi M … +10 more , Seighali N, Shenava SAS, Najafi K, Antoun I, Hassanabad AF, Kuno T, Biering-Sørensen T, Hernandez AV, Nelson JR, Hosseini K
Cardiovasc Diabetol · 2026 Apr · PMID 41923130 · Full text
BACKGROUND: Insulin resistance and systemic inflammation are recognized as primary contributors to the development of metabolic dysfunction–associated steatotic liver disease (MASLD). Nevertheless, the relationship betwe...
BACKGROUND: Insulin resistance and systemic inflammation are recognized as primary contributors to the development of metabolic dysfunction–associated steatotic liver disease (MASLD). Nevertheless, the relationship between the C-reactive protein-triglyceride glucose index (CTI), a novel composite marker reflecting both systemic inflammation and insulin resistance, and mortality in MASLD patients has not yet been clearly established. METHODS: Data from 5,029 MASLD patients enrolled in the National Health and Nutrition Examination Survey (1999–2010, 2015–2018) were analyzed. Participants were categorized into CTI quartiles. Associations between CTI, all-cause mortality (ACM), and cardiovascular mortality (CVM) were assessed through multivariate Cox proportional hazards models and restricted cubic spline analyses to evaluate both linear and nonlinear relationships. Mediation and subgroup analyses were conducted to identify factors that mediate or modify the CTI–mortality association. Additional sensitivity analyses were conducted to evaluate the stability and reliability of the findings. RESULTS: Over a median follow-up of 122 months, a total of 1,072 ACMs and 352 CVMs were observed. Participants in the highest CTI quartile had a significantly elevated risk of ACM (HR: 1.86; 95% CI: 1.50–2.31; P < 0.001) and CVM (HR: 2.07; 95% CI: 1.44–2.97; P < 0.001) compared to those in the lowest quartile. Restricted cubic spline analysis revealed a significant nonlinear relationship, with mortality risk rising sharply for CTI values above 8.8. Subgroup analyses revealed significant interactions with age and the fibrosis-4 index, with stronger associations observed in participants younger than 60 years and those with lower fibrosis-4 scores. Exploratory mediation analysis identified several metabolic and inflammatory markers as potential mediators, including neutrophils (mediation proportion: 16%) and glycated hemoglobin (mediation proportion: 33%) for the CTI-ACM link. Adding CTI to a conventional risk model provided the greatest improvement in discriminatory ability for both ACM and CVM compared to CRP or TyG index alone. Sensitivity analyses supported the robustness of the results. CONCLUSION: Elevated CTI values are significantly associated with increased ACM and CVM among MASLD patients. CTI may serve as a unique marker for risk stratification within this group.
Associations of the triglyceride-glucose index and its obesity-related derivatives with cardiac structure, function, and incident atrial fibrillation: a prospective cohort study using cardiac magnetic resonance.
Fan Z, Shi T, Yang C … +18 more , Zheng T, Sieme M, Sasko B, Wintrich J, Khan M, Liu X, Aweimer A, Mügge A, Maffia P, Pellicori P, Akin I, van Heerebeek L, El-Battrawy I, Schotten U, Norata GD, Paneni F, Yang J, Hamdani N
Cardiovasc Diabetol · 2026 Mar · PMID 41917952 · Full text
BACKGROUND: The triglyceride-glucose (TyG) index and its obesity-related derivatives have emerged as surrogate markers of insulin resistance associated with cardiovascular outcomes. However, whether these indicators infl...
BACKGROUND: The triglyceride-glucose (TyG) index and its obesity-related derivatives have emerged as surrogate markers of insulin resistance associated with cardiovascular outcomes. However, whether these indicators influence atrial fibrillation (AF) risk through cardiac structural and functional remodeling remains unclear. METHODS: This is a post-hoc analysis of a prospective cohort study of 32,500 UK Biobank participants free of AF who underwent baseline cardiac magnetic resonance (CMR) imaging. The TyG index and its obesity-related derivatives (TyG-body mass index (BMI), TyG-waist circumference (WC), and TyG-waist-to-height ratio (WHtR)) were calculated at baseline. Multivariable Cox regression models were used to assess associations with incident AF, and mediation analyses quantified the contribution of CMR-derived cardiac parameters to these associations. RESULTS: Over a median follow-up of 13.61 years, 1,288 incident AF cases occurred. The TyG index alone showed no independent association with AF risk. In contrast, all TyG obesity-related derivatives were significantly associated with incident AF, with TyG-WC demonstrating the strongest association (HR = 1.245, 95% CI 1.169-1.325), followed by TyG-BMI (HR = 1.223, 95% CI 1.158-1.293) and TyG-WHtR (HR = 1.190, 95% CI 1.122-1.262). Mediation analyses identified left atrial maximum volume (LAVmax) as the predominant mediator, accounting for 70.63%, 47.83%, and 40.79% of the associations for TyG-BMI, TyG-WHtR, and TyG-WC, respectively. CONCLUSIONS: TyG obesity-related derivatives, particularly TyG-WC, were independently associated with incident AF. Cardiac structural remodeling, especially LA enlargement, appeared to be a key mediating pathway. These findings support the importance of early metabolic intervention to prevent adverse atrial remodeling and reduce AF susceptibility.
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