Cardiovasc Diabetol [JOURNAL]
Sun
200 papers
Targeted proteomics of extreme vascular phenotypes in type 1 diabetes: the ESCAPER study.
Ekström O, Kennbäck C, Lyssenko V … +5 more , Löndahl M, Christensson A, Nilsson PM, Gottsäter A, ESCAPER Study Group
Cardiovasc Diabetol · 2026 Jun · PMID 42323624 · Full text
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia...
Cardiovascular disease (CVD) is the leading cause of morbidity and mortality in Type 1 Diabetes (T1D), but a subset of individuals remains free from macrovascular or renal complications despite decades of hyperglycaemia and a significant risk factor burden. We used a targeted proteomic approach (Olink Cardiovascular panel III, targeting 92 proteins) to characterize the proteomic profile of cardiovascular resilience in T1D by comparing 92 patients with long-standing T1D (age 59.8 [53.2, 69.1], duration 40.0 [35.0, 45.2] years) free from macrovascular complications or nephropathy against a reference group of 57 T1D patients with accelerated vascular pathology (age 42.0 [32.0, 56.0], duration 22.0 [18.0, 27.0] years), proliferative retinopathy and/or nephropathy in relation to diabetes duration, termed Rapid Progressors (RP). Twenty proteins differed significantly between RP and Escapers (False Discovery Rate [FDR] < 0.05) after adjustment for age, sex, HbA1c, and eGFR: Caspase-3 was significantly higher in RP (Adjusted difference: + 2.12 Normalized Protein eXpression [NPX], p < 0.001). Proteins associated with platelet activation and leukocyte adhesion with increased levels in RP included Junctional Adhesion Molecule A (+ 1.40 NPX), Glycoprotein VI (GP6: + 1.29 NPX), and P-Selectin (+ 0.82 NPX) (all p < 0.001). PECAM-1 (+ 0.55 NPX) and TNFRSF14 (+ 0.43 NPX), were also elevated. RP also showed higher levels of metabolic and tissue-remodelling proteins; Transferrin Receptor (+ 0.53 NPX) and Fatty Acid Binding Protein 4 (+ 0.52 NPX), as well as higher Bleomycin Hydrolase, Trefoil Factor 3, GDF-15, U-PAR, and Cystatin B. Conversely, von Willebrand Factor (vWF) levels (- 1.35 NPX, p < 0.001) and Paraoxonase 3 (PON3) was lower in RP (- 0.34 NPX, p = 0.003). In conclusion, escaping complications in long-term T1D appears to be associated with active molecular mechanisms. Progression is marked by apoptosis (Caspase-3), fibrosis (CHI3L1) and platelet activation (GP6), whereas resilience is associated with a distinct signature involving higher vWF and PON3. These findings highlight a profound biological divergence between extreme T1D phenotypes and provide a foundation for further research into vascular resilience.
Longitudinal variability of lipoprotein(a) in youth-onset type 1 diabetes: implications for cardiovascular risk stratification.
Iafrate-Luterbacher F, Jimenez-Sanchez C, Anastasiadou ML … +5 more , Prados J, Renström F, Brändle M, Bilz S, Schwitzgebel VM
Cardiovasc Diabetol · 2026 Jun · PMID 42321764 · Full text
BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor, traditionally considered stable across the lifespan, supporting a single lifetime measurement strategy. However,...
BACKGROUND: Lipoprotein(a) [Lp(a)] is a genetically determined and independent cardiovascular risk factor, traditionally considered stable across the lifespan, supporting a single lifetime measurement strategy. However, its longitudinal behaviour during childhood and adolescence remains poorly characterised, particularly in individuals with type 1 diabetes who face a markedly increased lifetime risk of coronary artery disease. We therefore aimed to characterise intra- and inter-individual trajectories of Lp(a) in a paediatric type 1 diabetes cohort and to assess the implications of Lp(a) variability for cardiovascular risk classification. METHODS: We conducted a retrospective single-centre cohort study of children and adolescents with type 1 diabetes attending Geneva University Hospitals between 2012 and 2023. Annual fasting Lp(a) concentrations were analysed longitudinally. Variability was assessed in participants with ≥ 2 measurements. Clinically relevant thresholds were used to evaluate cardiovascular risk reclassification. Paired Wilcoxon tests, Pearson and Kendall correlations, and Holm-adjusted p-values (P < 0.05) were applied. Analyses were conducted in R. RESULTS: A total of 286 participants contributed 1403 Lp(a) measurements, with observation periods varying across individuals (median 6.2 years, IQR 2.9-9.6) and between 1 and 13 measurements per participant. At baseline, 26% had elevated Lp(a) (≥ 300 mg/l). Among participants with serial measurements, 32% showed intraindividual fluctuations exceeding 50% of their individual maximum value. Reclassification across the 300 mg/l cardiovascular risk threshold occurred in 11.9% of participants. Lp(a) concentrations peaked between ages 10 and 13 years and declined thereafter. Modest seasonal variation was observed, with higher concentrations in autumn and winter (P < 0.05). CONCLUSIONS: In youth with type 1 diabetes, Lp(a) is not as stable as previously assumed, exhibiting clinically relevant variability over time. These findings challenge the current paradigm of a single lifetime Lp(a) measurement and suggest that repeated assessment, particularly during adolescence, may improve early cardiovascular risk stratification.
Predictive significance of triglyceride-glucose index in forecasting adverse cardiovascular events among Type 2 diabetes mellitus patients with co-existing metabolic dysfunction-associated steatotic liver disease (MASLD): evidence from two cohort studies.
Xu J, Zhao J, Dai Z … +2 more , Li YC, Li C
Cardiovasc Diabetol · 2026 Jun · PMID 42316208 · Full text
BACKGROUND: Triglyceride-glucose (TyG) is a vital marker for assessing cardiovascular risk and insulin resistance (IR) in individuals with Type 2 diabetes mellitus (T2DM) or metabolic dysfunction-associated steatotic liv...
BACKGROUND: Triglyceride-glucose (TyG) is a vital marker for assessing cardiovascular risk and insulin resistance (IR) in individuals with Type 2 diabetes mellitus (T2DM) or metabolic dysfunction-associated steatotic liver disease (MASLD). Nevertheless, the prognostic significance of TyG, especially in patients manifesting both conditions, is insufficiently characterized. In this study, the association between TyG and the occurrence of major adverse cardiovascular events (MACEs) in patients concurrently diagnosed with T2DM and MASLD was examined. METHODS: In this retrospective cohort study, 1021 patients diagnosed with both T2DM and MASLD at Wenzhou Hospital from 2019 to 2022 were encompassed. To explore the non-linear association between TyG and outcomes, such as all-cause mortality (ACM) or MACEs, a cox proportional hazards model was employed. Additionally, subgroups were analyzed to assess the consistency across different demographic and clinical subgroups. Furthermore, mediation analyses were conducted to investigate the potential mediating effects of body roundness index (BRI) and estimated glomerular filtration rate (eGFR). Parallel supportive analysis was performed on a cohort of 1343 individuals from NHANES 1999-2018. RESULTS: Over a median follow-up of 53.4 months, 62 instances of ACM and 101 MACEs were documented. Cox proportional hazards regression analysis revealed that an elevated TyG was significantly associated with an increased risk of mortality (HR = 1.85, 95% CI: 1.25, 2.73) and MACEs (HR = 1.71, 95% CI: 1.26, 2.33). Subgroup analysis revealed that the association between TyG and the risk of MACE is more prominent among individuals below 60. Mediation analysis revealed that eGFR mediated 8.8% of the total effect of TyG on ACM and 10.6% of the effect on MACEs. BRI accounted for 6.2% of the total effect of TyG on ACM. Incorporating TyG into conventional risk models significantly enhanced the predictive accuracy. CONCLUSION: This study established a strong association between TyG and both ACM and MACEs in patients with T2DM and MASLD in the Wenzhou cohort, with TyG-ACM association independently validated in the NHANES cohort.
Hemoglobin glycation index may contextualize the association between time-varying stress hyperglycemia ratio and mortality in critically ill patients with heart failure: a multicenter retrospective cohort study.
Chen Y, Cai Y, Sha Y … +1 more , Li Q
Cardiovasc Diabetol · 2026 Jun · PMID 42310724 · Full text
BACKGROUND: Stress hyperglycemia is associated with adverse outcomes in critically ill patients, yet the optimal metric and the influence of chronic glycemic background remain unclear. The stress hyperglycemia ratio (SHR...
BACKGROUND: Stress hyperglycemia is associated with adverse outcomes in critically ill patients, yet the optimal metric and the influence of chronic glycemic background remain unclear. The stress hyperglycemia ratio (SHR) adjusts acute glucose for chronic glycemic status, but whether the prognostic association of time-varying SHR differs across hemoglobin glycation index (HGI)-defined glycation phenotypes in critically ill heart failure patients remains unclear. OBJECTIVES: To evaluate the association between time-varying SHR and mortality across HGI tertiles in critically ill heart failure patients. METHODS: This multicenter retrospective cohort study included 2,488 adult heart failure patients from MIMIC-III-CareVue (n = 307), MIMIC-IV v3.1 (n = 1,654), and NWICU v0.1.0 (n = 527). HGI was calculated as the residual from regressing HbA1c on admission glucose within each database, and patients were stratified into tertiles. SHR was modeled as a time-varying exposure using extended Cox proportional hazards models with progressive covariate adjustment. Dose-response relationships were examined using restricted cubic splines, and incremental predictive value was assessed via time-dependent ROC analysis. RESULTS: In fully adjusted models (hazard ratios per 0.1-unit increase in SHR), time-varying SHR was significantly associated with 28-day mortality in MIMIC-III (HR 1.13, 95% CI 1.06-1.21) and MIMIC-IV (HR 1.10, 95% CI 1.07-1.13; both P < 0.001), and with in-hospital mortality across all three cohorts (all P ≤ 0.002). Twenty-eight-day mortality was not available in NWICU. HGI-stratified analyses revealed a numerical gradient in MIMIC-IV (T1: HR 1.13, 95% CI 1.08-1.17; T3: HR 1.06, 95% CI 1.01-1.12), though SHR × HGI interactions were not significant in individual databases. Restricted cubic spline analyses demonstrated J-shaped dose-response curves in larger analyses, with significant nonlinearity in MIMIC-IV and the pooled in-hospital mortality cohort. Adding mean SHR to clinical models modestly improved discrimination (ΔAUC = 0.029-0.032, P ≤ 0.019). Subgroup analyses identified significant effect heterogeneity by age, sex, and Charlson index (all P-interaction < 0.05). Eight sensitivity analyses corroborated the robustness of primary findings. CONCLUSIONS: Time-varying SHR was independently associated with mortality in critically ill patients with heart failure, with a numerical tendency toward stronger associations among patients with low HGI phenotype. These hypothesis-generating findings suggest that dynamic SHR assessment combined with HGI-informed interpretation may potentially aid individualized glycemic risk assessment in this population.
Exercise modalities and dosages on glycated haemoglobin and exerkines in type 2 diabetes: a systematic review with pairwise, network, and dose-response meta-analyses.
Liang LB, Zhao ZH, Li WX … +4 more , Wang S, Shen QS, Wu CQ, Li KP
Cardiovasc Diabetol · 2026 Jun · PMID 42310699 · Full text
BACKGROUND: Exercise is a cornerstone of type 2 diabetes mellitus (T2DM) management; however, the comparative efficacy of specific modalities, optimal dosages, and associated exerkine responses remains incompletely defin...
BACKGROUND: Exercise is a cornerstone of type 2 diabetes mellitus (T2DM) management; however, the comparative efficacy of specific modalities, optimal dosages, and associated exerkine responses remains incompletely defined. This study aimed to synthesise evidence on the effects of different exercise types and doses on glycated haemoglobin (HbA1c) levels and to explore modality-specific patterns of exerkine regulation in adults with T2DM. METHODS: A systematic review and Bayesian evidence synthesis of randomised controlled trials was conducted up to October 2025. Pairwise, network, and model-based dose-response meta-analyses were employed to evaluate the effects of eight exercise modalities on HbA1c levels. Exploratory analyses were performed to evaluate changes in circulating adiponectin, brain-derived neurotrophic factor (BDNF), interleukin-6, leptin, resistin, and tumour necrosis factor-α levels. RESULTS: A total of 127 trials involving 8,744 participants were included. Network meta-analysis ranked combined mind-body resistance training (tai chi + elastic bands) and high-intensity interval training (HIIT) as the most effective modalities for reducing the level of HbA1c (surface under the cumulative ranking curve: 85.9% and 78.6%, respectively). An L-shaped nonlinear dose-response relationship was observed, with the majority of the clinical benefit being achieved at 600 MET-min/week (mean difference: -0.57%; 95% credible interval: -0.72, -0.42) and a plateau beyond approximately 1,000 MET-min/week. Exploratory exerkine analyses suggested modality-specific signatures; specifically, HIIT was associated with greater increases in adiponectin levels, whereas resistance-based interventions trended towards greater reductions in interleukin-6 and tumour necrosis factor-α levels. In pairwise comparisons versus the control, no significant overall changes were detected for adiponectin, BDNF, interleukin-6, or resistin. CONCLUSION: In adults with T2DM, exercise efficacy varies by modality and follows a dose-plateau pattern. The achievement of 600 MET-min/week produces a meaningful reduction in HbA1c levels, with diminishing returns being observed beyond approximately 1,000 MET-min/week. MBRT and HIIT are the most promising modalities, although the evidence concerning MBRT remains preliminary in nature. Modality-specific exerkine patterns were observed; specifically, HIIT ranked highest for adiponectin, whereas RT ranked highest for IL-6 and TNF-α. These findings inform evidence-based, personalised exercise prescription in T2DM patients.
Cardioprotective glucose-lowering drugs, statins, and secondary major adverse cardiovascular events: a nationwide cohort study of individuals with type 2 diabetes and cardiovascular disease.
Ternhamar T, Johansen MØ, Nordestgaard BG … +1 more , Afzal S
Cardiovasc Diabetol · 2026 Jun · PMID 42304446 · Full text
BACKGROUND: In type 2 diabetes, cardioprotective glucose-lowering drugs, including sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, and statins reduce the risk of secondary major a...
BACKGROUND: In type 2 diabetes, cardioprotective glucose-lowering drugs, including sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, and statins reduce the risk of secondary major adverse cardiovascular events. No trials examined the combination of these drugs as withholding statins in high-risk individuals would be unethical. We tested the hypothesis that cardioprotective glucose-lowering drug and statin combined is associated with lower risk of secondary major adverse cardiovascular events than either drug alone. METHODS: Individuals with type 2 diabetes and established cardiovascular disease from December 2012 through 2021 were identified via national Danish health registers. They were analyzed in an active comparator cohort including 15,404 individuals followed from treatment intensification with cardioprotective glucose-lowering drug or dipeptidyl peptidase-4 inhibitor and additionally in a time-varying cohort including 76,853 individuals with yearly updated treatment and covariate status. The treatment groups were: (i) no cardioprotective drug (no use of cardioprotective glucose-lowering drug or statin), (ii) cardioprotective glucose-lowering drug, (iii) statin, and (iv) cardioprotective glucose-lowering drug and statin. The primary outcome was a new major adverse cardiovascular event (myocardial infarction, stroke, or cardiovascular death). RESULTS: During mean 2.7 and 4.7 years of follow-up, 1,843 and 23,051 had major adverse cardiovascular events in the active comparator and time-varying cohorts. In the active comparator cohort, when compared to nonusers of cardioprotective glucose-lowering drug or statin, multivariable adjusted hazard ratios of major adverse cardiovascular events were 0.82 (95% confidence interval: 0.67 to 1.02) for cardioprotective glucose-lowering drug, 0.85 (0.74 to 0.97) for statin, and 0.71 (0.60 to 0.84) for cardioprotective glucose-lowering drug and statin combined. Corresponding hazard ratios in the time-varying cohort were 0.77 (0.69 to 0.86), 0.73 (0.70 to 0.75), and 0.57 (0.54 to 0.60), respectively. When restricting the active comparator cohort to individuals entering observation between 2019 and 2021 with reduced statistical power, the corresponding hazard ratios were 0.86 (0.57 to 1.31), 0.89 (0.60 to 1.30), and 0.79 (0.54 to 1.14), respectively. In both cohorts p for interaction between cardioprotective glucose-lowering drug and statin was > 0.05. CONCLUSIONS AND RELEVANCE: In individuals with type 2 diabetes and established cardiovascular disease, treatment with a cardioprotective glucose-lowering drug and statin in combination was associated with lower risk of secondary major adverse cardiovascular events than using either drug alone. This is important given the persistently suboptimal uptake of both drug classes in real-world practice. Some biases can never be completely excluded in real-world pharmacotherapy use studies such as this one, including confounding by indication, time-related or immortal time biases, and shifting standards of care, rendering causal interpretation unattainable; however, our results seemed consistent across numerous sensitivity analyses and designs.
Integration of triglyceride-glucose index and biological aging to predict cardiovascular disease risk in cardiovascular-kidney-metabolic syndrome stages 0-3: a multiple prospective cohort study.
Shen R, Dong P, Fang S … +9 more , Jia Z, Abudukeremu A, Li J, Huang K, Zuo X, Ma Y, Liu Y, Huang K, Chen Y
Cardiovasc Diabetol · 2026 Jun · PMID 42304381 · Full text
BACKGROUND: The triglyceride-glucose (TyG) index serves as a surrogate marker of insulin resistance and reflects underlying metabolic dysfunction, while biological aging (KDM-BA) independently contributes to cardiovascul...
BACKGROUND: The triglyceride-glucose (TyG) index serves as a surrogate marker of insulin resistance and reflects underlying metabolic dysfunction, while biological aging (KDM-BA) independently contributes to cardiovascular vulnerability. However, no study has attempted to integrate metabolic dysfunction and biological aging to improve cardiovascular disease (CVD) risk prediction in individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3. METHODS: Multiple prospective cohorts were used, including 286,864 participants from the UK Biobank (UKB), 7237 from the China Health and Retirement Longitudinal Study (CHARLS), and 517 from Sun Yat-sen Memorial Hospital, Sun Yat-sen University, which were further included for external validation of the primary outcome. TyG-KDM-BA was calculated by multiplying the TyG index by KDM-BA. Cox proportional hazards models were used to evaluate the association. Time-dependent receiver operating characteristic (ROC) curves, as well as analyses of incremental predictive value, sensitivity analyses, and external validation were conducted to evaluate predictive performance. RESULTS: During a median follow-up of 15.27 years in UKB, 57,896 incident CVD events occurred (cumulative incidence: 20.18%). During a median follow-up of 7.84 years in CHARLS cohort, 1,610 incident CVD events were observed (cumulative incidence: 22.25%). CVD risk increased progressively across TyG-KDM-BA quartiles in both cohorts. In the fully adjusted model, each 1-SD increase in TyG-KDM-BA was associated with higher CVD risk in both cohorts (UKB: HR = 1.65, 95% CI 1.64-1.67; CHARLS: HR = 1.25, 95% CI 1.18-1.32). Participants in the highest quartile had significantly higher CVD risk than those in the lowest (UKB: HR = 3.97, 95% CI 3.86-4.09; CHARLS: HR = 1.92, 95% CI 1.63-2.25). TyG-KDM-BA was positively associated with CHD and stroke risk in both cohorts. Compared with conventional TyG-derived indices, TyG-KDM-BA achieved higher discrimination for CVD risk prediction, with an area under the curve of 0.657-0.659 over 5-15 years in UKB and moderate, consistent performance in CHARLS. Incremental analyses demonstrated that TyG-KDM-BA provided additional predictive value beyond conventional models and its individual components. External validation analyses supported the robustness of results. CONCLUSION: TyG-KDM-BA integrates metabolic and aging dimensions, demonstrating superior predictive ability for CVD risk among individuals with CKM stages 0-3 compared to traditional TyG-derived indicators, and may serve as a more effective tool for the early screening and intervention.
Chamber-specific cardiac proteome remodeling in a Göttingen minipig model of obesity and diabetes.
Gallero S, Voldstedlund CT, Krog S … +3 more , Ludvigsen TP, Olsen LH, Jensen TE
Cardiovasc Diabetol · 2026 Jun · PMID 42304349 · Full text
BACKGROUND: Obesity and Type 2 Diabetes are major contributors to cardiac hypertrophy and dysfunction, yet the molecular mechanisms driving early myocardial alterations remain incompletely understood. Evidence from roden...
BACKGROUND: Obesity and Type 2 Diabetes are major contributors to cardiac hypertrophy and dysfunction, yet the molecular mechanisms driving early myocardial alterations remain incompletely understood. Evidence from rodent models and end-stage human disease suggests that cytoskeletal remodeling and oxidative stress may contribute to early increases in cardiomyocyte stiffness and hypertrophy. Whether these processes are involved at earlier disease stages in translationally relevant large-animal models remains unclear. METHODS: Heart tissue from male Göttingen minipigs subjected to a 13-month intervention with a standard control diet, high-fat-fructose-cholesterol diet, or high-fat-fructose-cholesterol with streptozotocin-induced diabetes was analyzed. Untargeted proteomics was performed on left atrium and left ventricle tissue, followed by pathway enrichment analyses to identify diet- and chamber-specific proteomic alterations. RESULTS: Global proteomic analyses revealed that anatomical region represented the dominant source of variance, with ~ 200-300 proteins significantly regulated across dietary interventions. Pathway enrichment analyses highlighted alterations in protein and macronutrient metabolism, mitochondrial function, and extracellular matrix organization. Correlation and Hallmark analyses further linked ventricular remodeling to glucose-associated and mitochondrial pathways, while atrial remodeling was more closely associated with metabolic and nutrient-sensing pathways. Among 75 microtubule and 53 redox-related proteins examined, 16 and 14, respectively, were significantly altered in a chamber- and intervention-dependent manner. CONCLUSION: Early cardiac hypertrophy associated with obesity and/or diabetes is accompanied by extensive proteomic remodeling, characterized by distinct atrial and ventricular profiles. However, the relatively modest changes in microtubule and redox-related proteins suggest that these are unlikely to be primary drivers of early myocardial remodeling.
Head-to-head comparison of fasting-insulin-based versus non-insulin-based insulin resistance surrogates for predicting all-cause and cardiovascular mortality in hypertensive adults across the glycemic continuum: a prospective cohort study.
Abdu FA, Mohammed AQ, Zhang W … +6 more , Alifu J, Liu L, Yin G, Liao Y, Zhu G, Che W
Cardiovasc Diabetol · 2026 Jun · PMID 42298603 · Full text
BACKGROUND: Insulin resistance (IR) is mechanistically linked to hypertension, yet no study has directly compared fasting-insulin-based and non-insulin-based IR surrogates for predicting mortality across the glycemic spe...
BACKGROUND: Insulin resistance (IR) is mechanistically linked to hypertension, yet no study has directly compared fasting-insulin-based and non-insulin-based IR surrogates for predicting mortality across the glycemic spectrum in hypertensive adults. We evaluated ten IR indices, three insulin-based [homeostasis model assessment of insulin resistance (HOMA-IR), McAuley index, and quantitative insulin sensitivity check index (QUICKI)] and seven non-insulin-based [triglyceride-glucose index (TyG), stress hyperglycemia ratio (SHR), cardiometabolic index (CMI), atherogenic index of plasma (AIP), estimated glucose disposal rate (eGDR), metabolic score for insulin resistance (METS-IR), and lipid accumulation product (LAP)], for all-cause mortality (ACM) and cardiovascular mortality (CVM) by glycemic status. METHODS: This prospective cohort study included 7,548 hypertensive adults from NHANES 1999-2018, classified as normoglycemia (n = 1,869), prediabetes (n = 3,389), and diabetes (n = 2,290). Mortality data were collected through December 31, 2019. Associations were analyzed using Cox models with three levels of adjustment. Dose-response relationships were modeled with restricted cubic splines. RESULTS: Over a mean follow-up of 8.7 ± 5.3 years, 1,752 ACM events (23.2%) and 499 CVM events (6.6%) occurred. In fully adjusted models, HOMA-IR independently predicted ACM (per-unit HR 1.017; Q4 HR 1.165) and CVM (per-unit HR 1.012). eGDR showed the strongest overall associations: ACM: per-unit HR 0.807; Q4 HR 0.559; CVM: per-unit HR 0.774; Q4 HR 0.538. TyG predicted ACM (per-unit HR 1.158; Q4 HR 1.233) and CVM per-unit (HR 1.160). In glycemic-stratified analyses, HOMA-IR was the only index with per-unit ACM significance across all three strata (normoglycemia: HR 1.085; prediabetes: HR 1.039; diabetes: HR 1.012). eGDR showed per-unit and Q4 ACM significance in prediabetes and diabetes, and demonstrated significant quartile-level protection for CVM in both prediabetes (Q4 HR 0.465) and diabetes (Q4 HR 0.463), whereas per-unit associations with CVM were observed only in diabetes. TyG was significantly associated with ACM in diabetes (per-unit HR 1.147; Q4 HR 1.337) and with CVM in diabetes (Q4 HR 1.595). CONCLUSIONS: In hypertensive adults, HOMA-IR was the only fasting-insulin-based index independently associated with ACM across all three glycemic strata. eGDR demonstrated the most consistent non-insulin-based associations with ACM and CVM, particularly in prediabetes and diabetes. TyG provided additional prognostic value for ACM and CVM, particularly in patients with diabetes. These findings support selecting IR indices based on glycemic phenotype and data availability.
Prognostic Value of Coronary CT Angiography Among Patients With and Without Diabetes: The Mass General Brigham CCTA registry.
Shiyovich A, Huck DM, Cardoso R … +19 more , Berman AN, Besser SA, Biery DW, Petranovic M, Weber BN, Hainer J, Blair CV, Meyersohn NM, Singh A, Baliyan V, Lu MT, Steigner M, Aghayev A, Nasir K, Cannon CP, Hedgire S, Di Carli M, Ghoshhajra B, Blankstein R
Cardiovasc Diabetol · 2026 Jun · PMID 42298570 · Full text
BACKGROUND: This study aimed to assess the relationship between coronary CT angiography detected coronary artery disease (CAD) and long-term cardiovascular outcomes among individuals with and without diabetes mellitus (D...
BACKGROUND: This study aimed to assess the relationship between coronary CT angiography detected coronary artery disease (CAD) and long-term cardiovascular outcomes among individuals with and without diabetes mellitus (DM). METHODS: A retrospective cohort study of patients undergoing CCTA at two medical centers between 2006 and 2024. Patients with prior CAD, advanced kidney disease, or malignancy were excluded. DM was defined by diagnostic codes or elevated hemoglobin A1c. CCTA findings were categorized as no CAD, nonobstructive CAD (1-49% stenosis), or obstructive CAD (≥ 50% stenosis). The primary outcome was a composite of cardiovascular death (CVD) or myocardial infarction (MI). RESULTS: Among 22,377 patients (median age 56 [IQR 47-65]; 45% women), 3,245 (14.5%) had diabetes. Individuals with diabetes were older and had more cardiovascular risk factors. Obstructive CAD was more frequent in patients with diabetes (33% vs. 19%), whereas no CAD was less common (23% vs. 42%). Over a median follow-up of 6 years (IQR 3.9-9.5), the primary outcome occurred more than twice as often among those with diabetes (7.8% vs. 3.1%; P < 0.001). Event rates increased with CAD severity and remained higher among individuals with diabetes across all categories. After adjustment, obstructive CAD remained significantly associated with the primary outcome in both groups (DM: HR 2.9 [95% CI 1.8-4.6], P < 0.001; non-DM: HR 2.7 [95% CI 2.1-3.4]), p < 0.001). CONCLUSIONS: Among patients undergoing CCTA, CAD was more frequent and severe in those with diabetes, and the risk of CVD or MI increased with CAD severity, approximately doubling in each category when diabetes was present.
Associations of the atherogenic index of plasma and its modified indices with the incidence and progression of cardiometabolic multimorbidity in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3: a prospective cohort study.
Xue F, Han Q, Li Y … +4 more , Cheng C, Xie L, Yang J, Wan J
Cardiovasc Diabetol · 2026 Jun · PMID 42289689 · Full text
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 reflect a heterogeneous continuum of metabolic, kidney, and cardiovascular abnormalities that are closely associated with the development of cardiomet...
BACKGROUND: Cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 reflect a heterogeneous continuum of metabolic, kidney, and cardiovascular abnormalities that are closely associated with the development of cardiometabolic diseases (CMDs). Although the atherogenic index of plasma (AIP) and obesity-related composite indices have been associated with individual CMDs, their associations with cardiometabolic multimorbidity (CMM) among individuals with CKM syndrome remain unclear. This study primarily investigated whether AIP-related indices were associated with the incidence and progression of CMM in individuals with CKM syndrome stages 0-3. METHODS: This prospective cohort study included 346,868 UK Biobank participants without baseline type 2 diabetes (T2DM), coronary heart disease (CHD), or stroke. CMM was defined as the coexistence of at least two of these conditions. Cox proportional hazards models were used to estimate associations with incident CMM, while multistate models were applied to characterize disease progression. As secondary analyses, the added predictive value of each index was assessed using discrimination and reclassification metrics. Exploratory biomarker analyses examined whether inflammatory, liver, and renal biomarkers statistically accounted for part of the associations. RESULTS: During a median follow-up of 15.9 years, 8573 participants developed CMM. All eight AIP-related indices were positively associated with incident CMM, with hazard ratios per 1-SD increment ranging from 1.12 to 1.37 (all P < 0.001). Multistate analyses suggested stage-specific associations during CMM progression, with stronger associations observed for the transition from baseline to T2DM and from single CMD to CMM involving CHD (all P < 0.001). In secondary prediction analyses, adding each index to conventional risk factors improved discrimination and reclassification, with the AIP-body roundness index (AIP-BRI) showing the greatest overall incremental predictive value. Exploratory biomarker analyses indicated that inflammatory, liver, and renal biomarkers jointly accounted for 32.5-46.4% of the associations, although these findings should not be interpreted as evidence of causal mediation. CONCLUSION: Among individuals with CKM syndrome stages 0-3, AIP-related indices were positively associated with the incidence and progression of CMM, supporting their potential utility for CMM risk stratification within the CKM framework. These indices, particularly AIP-BRI, may provide additional predictive information. Exploratory biomarker findings might provide preliminary clues for future mechanistic research.
Association of fat-to-muscle mass ratio with incident coronary artery disease and the potential role of metabolic signatures.
Hu K, Song Y, Lin Z … +3 more , Liu Z, Wang H, Dou K
Cardiovasc Diabetol · 2026 Jun · PMID 42288890 · Full text
BACKGROUND: The fat-to-muscle mass ratio (FMR) reflects the balance between metabolic burden and capacity. However, the associations of total and regional FMR with incident coronary artery disease (CAD) and their underly...
BACKGROUND: The fat-to-muscle mass ratio (FMR) reflects the balance between metabolic burden and capacity. However, the associations of total and regional FMR with incident coronary artery disease (CAD) and their underlying metabolic mechanisms remain unclear. METHODS: We included 398,435 UK Biobank participants free of baseline cardiovascular disease, diabetes, or lipid-lowering therapy. Total and regional (trunk, arm, leg) FMR were quantified via bioelectrical impedance analysis. Participants were stratified by sex and classified based on FMR thresholds derived from restricted cubic splines and BMI categories. Primary outcome was incident CAD, defined as myocardial infarction, coronary revascularization, or CAD mortality. Metabolic signatures were constructed using elastic net regression on 251 NMR metabolites. RESULTS: During a median follow-up of 12.61 years, 10,740 incident CAD cases were documented. Higher total and regional FMR were significantly associated with increased CAD risk in both sexes. Leg FMR exhibited the strongest independent association; after mutual adjustment for BMI, it remained a significant predictor in both women (HR: 3.672, 95% CI 1.958-6.887) and men (HR: 2.682, 95% CI 1.682-4.275), whereas associations for other FMR types were attenuated. Mediation analysis suggested that metabolic signatures partially accounted for the association between FMR and CAD, explaining over 70% of the statistical effect. Furthermore, adding leg FMR to standard risk factors significantly improved risk reclassification (NRI: 0.142 for women, 0.081 for men; both p value < 0.001). CONCLUSIONS: Elevated FMR, particularly leg FMR, is strongly associated with higher CAD risk independent of BMI. These findings suggest that altered body composition may reflect underlying metabolic dysregulations, and assessing leg FMR could provide additive value for risk reclassification, particularly in women.
Perivascular adipokine signaling in abdominal aortic aneurysm: cardiometabolic drivers of vascular remodeling and translational opportunities.
Zhang X, He H, He H … +7 more , Zhang Y, Zhang Y, Zhou Y, Huang X, Huang J, Ye P, Xia J
Cardiovasc Diabetol · 2026 Jun · PMID 42288888 · Full text
Abdominal aortic aneurysm (AAA) represents a significant vascular pathology characterized by high mortality rates and a paucity of effective pharmacological interventions. Recent research underscores the role of perivasc...
Abdominal aortic aneurysm (AAA) represents a significant vascular pathology characterized by high mortality rates and a paucity of effective pharmacological interventions. Recent research underscores the role of perivascular adipose tissue derived adipokines in establishing a direct connection between obesity and the pathogenesis of AAA. These adipokines exert influence on aneurysmal remodeling by modulating the functions of vascular cells, particularly in relation to inflammation and extracellular matrix degradation. They can be categorized into two broad classes: deleterious (pro-aneurysmal) and protective (anti-aneurysmal). Deleterious adipokines exacerbate AAA through the promotion of inflammation, the weakening of the vascular wall, and the stimulation of aberrant vascular growth. In contrast, protective adipokines contribute to the attenuation of AAA progression via antioxidative, anti-inflammatory, and vascular homeostatic mechanisms. Recent evidence indicates that restoring adipokine balance may serve as a promising therapeutic approach for AAA. Although the majority of studies are still in the preclinical stage, the repurposing of metabolic drugs such as GLP-1 receptor agonists, metformin, and PPAR agonists has shown potential in rebalancing adipokine profiles, reducing inflammation, and promoting vascular repair. Additionally, novel agents targeting adipokine receptors, including adiponectin agonists, chemerin antagonists, and FABP4 inhibitors, have demonstrated preliminary efficacy in modulating adipokine signaling and mitigating vascular inflammation. This review synthesizes the mechanistic roles of adipokines in AAA, with a focus on therapeutic opportunities targeting adipokine driven pathways, and outlines a framework for future translational and clinical research aimed at adipokine-based management of AAA.
Gestational diabetes as an inter-generational cardiometabolic risk factor: spotlight on emerging exerkines.
Senesi P, Luzi L, Sonaglioni A … +3 more , Alberti F, Cipponeri E, Ferrulli A
Cardiovasc Diabetol · 2026 Jun · PMID 42288872 · Full text
Gestational diabetes mellitus (GDM) is an increasingly prevalent global health condition, driven by rising maternal age and the obesogenic environment, currently affecting approximately 14% of pregnancies worldwide. GDM...
Gestational diabetes mellitus (GDM) is an increasingly prevalent global health condition, driven by rising maternal age and the obesogenic environment, currently affecting approximately 14% of pregnancies worldwide. GDM is associated with adverse perinatal outcomes as well as a substantial increase in long-term cardiometabolic risk. Women with a history of GDM exhibit a markedly elevated risk of developing type 2 diabetes (T2D) within the first decade postpartum, together with an approximately twofold higher risk of major cardiovascular events. Importantly, offspring of mothers with GDM are also predisposed to obesity and T2D later in life, underscoring the role of GDM as a major intergenerational determinant of cardiometabolic disease. Physical activity is recommended as an effective non-pharmacological strategy for the prevention and management of GDM; however, the molecular mechanisms underlying its benefits remain only partially understood. Exerkines, bioactive molecules modulated by exercise, have emerged as important regulators of systemic metabolic and cardiovascular adaptations. In addition to the well-characterised exerkines such as leptin, adiponectin, and irisin, emerging evidence supports the relevance of additional mediators, including chemerin, members of the FGF19 subfamily, and adipsin, as contributors to the pathophysiology of GDM and cardiovascular risk. This narrative review summarises the current evidence on these emerging exerkines, focusing on their biological mechanisms and clinical relevance in GDM. A deeper understanding of the exerkine network may provide novel insights into the interplay between exercise, metabolic regulation, and pregnancy, ultimately supporting improved GDM management and long-term cardiometabolic risk stratification across generations.
The effect of empagliflozin on inflammation in patients with overweight or obesity and risk of heart failure: a substudy from the Empire Prevent Metabolic trial.
Andersen CF, Larsen JH, Omar M … +12 more , Nouhravesh N, Kistorp C, Tuxen C, Knop FK, Forman JL, Davidovski FS, Køber L, Sabaratnam R, Højlund K, Schou M, Møller JE, Jensen J
Cardiovasc Diabetol · 2026 Jun · PMID 42286641 · Full text
BACKGROUND: Obesity increases the risk of heart failure (HF), potentially through low-grade inflammatory processes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been suggested to attenuate inflammation, althou...
BACKGROUND: Obesity increases the risk of heart failure (HF), potentially through low-grade inflammatory processes. Sodium-glucose co-transporter 2 (SGLT2) inhibitors have been suggested to attenuate inflammation, although data in patients without diabetes and HF are lacking. Moreover, it is unknown whether SGLT2 inhibitors affect adipose tissue dysfunction. We aimed to investigate the effect of the SGLT2 inhibitor empagliflozin on systemic inflammation, uric acid, and adipose tissue dysfunction in high-risk patients with overweight or obesity. METHODS: Pre-defined secondary analysis of the Empire Prevent Metabolic trial. Outpatients with body mass index (BMI) > 28 kg/m and risk factors for HF, excluding diabetes, were randomised to 180 days treatment with empagliflozin 10 mg or placebo. Patients completed blood sampling and subcutaneous abdominal adipose tissue biopsies at baseline and follow-up. Pre-defined endpoints were the baseline-adjusted estimated treatment differences (ETD) or ratios (ETR) for interleukin-6 (IL-6), high-sensitive C-reactive protein (hsCRP), and uric acid. Furthermore, we explored gene expression changes in selected markers of adipose tissue dysfunction, including inflammation. RESULTS: We randomised 92 patients (empagliflozin: 44, placebo: 48). Median age was 68 years, median BMI was 31.6 kg/m, while 21 (23%) and 54 (59%) patients presented with IL-6 > 7 pg/ml and hsCRP of at least 3 mg/l, respectively. Empagliflozin did not affect IL-6 (ETR: 1.03, 95% CI 0.82-1.30, p = 0.78) or hsCRP (ETR: 1.15, 95% CI 0.87-1.51, p = 0.33) compared to placebo. Meanwhile, uric acid decreased (ETD: - 0.06 mmol/l, 95% CI - 0.08 to - 0.04, p < 0.0001), whereas no changes in adipose tissue gene expression were observed. CONCLUSIONS: In this study, empagliflozin did not demonstrate anti-inflammatory effects but yielded possibly meaningful uricosuric effects in non-diabetic patients with overweight or obesity. Moreover, adipose tissue dysfunction remained unaltered. Trial registration clinicaltrials.gov NCT05042973.
Growth differentiation factor-15 and the incidence, bidirectional progression, and risk prediction of atherosclerotic cardiovascular disease and metabolic dysfunction-associated steatotic liver disease in individuals with cardiovascular-kidney-metabolic syndrome stages 0-3.
Chen X, Tang H, Xu Z … +17 more , Chen X, Tian C, Luo N, Huang J, Lin H, Zhang X, Yang Q, Liang K, Chen P, Qiu X, Jiang L, Lin W, Chen W, Zhang Y, Tan X, Lai J, Chen Y
Cardiovasc Diabetol · 2026 Jun · PMID 42286618 · Full text
BACKGROUND: Growth differentiation factor 15 (GDF-15) is a circulating biomarker reflecting oxidative stress, inflammation, and cellular aging. However, its role in disease risk assessment amongst individuals with cardio...
BACKGROUND: Growth differentiation factor 15 (GDF-15) is a circulating biomarker reflecting oxidative stress, inflammation, and cellular aging. However, its role in disease risk assessment amongst individuals with cardiovascular-kidney-metabolic (CKM) syndrome stages 0-3 remains unclear. METHODS: This study included 29,697 UK Biobank participants with CKM stages 0-3 defined in accordance with the American Heart Association criteria. Associations of GDF-15 with metabolic, inflammatory and liver fibrosis markers and CKM stage were examined using linear or multinomial logistic regression models. Fine-Gray competing risk regression models were used to evaluate associations with incident atherosclerotic cardiovascular disease (ASCVD), metabolic dysfunction-associated steatotic liver disease (MASLD) and their comorbidity (coexistence of both conditions). Bidirectional disease transitions were assessed using a multi-state Markov model. The relative importance of GDF-15 was evaluated using SHapley Additive exPlanations (SHAP) and likelihood ratio (LR) statistics. Improvements in risk prediction models were assessed using time-dependent area under the receiver operating characteristic curve, Brier score, integrated discrimination improvement and continuous net reclassification improvement. RESULTS: Amongst 29,697 participants (mean age of 56.16 years; 57.32% female), 2,786 developed ASCVD and 456 developed MASLD during follow-up. Higher GDF-15 levels were associated with poorer CKM health and showed the strongest associations with renal function markers, followed by insulin resistance indices. Each 1-unit increase in GDF-15 (normalised protein expression, log2 scale) was associated with increased risks of ASCVD (HR = 1.25, 95%CI 1.15-1.36, P = 1.35 × 10), MASLD (HR = 1.62, 95%CI 1.41-1.86, P = 2.06 × 10) and their comorbidity (HR = 1.62, 95%CI 1.32-2.18, P = 4.36 × 10) after multivariable adjustment for age, sex, smoking status, body mass index, diabetes mellitus, glycated haemoglobin, systolic blood pressure, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, C-reactive protein, creatinine, estimated glomerular filtration rate, urinary albumin-to-creatinine ratio, cystatin C, Townsend deprivation index, physical activity, and CKM stage. These associations remained consistent across subgroup analyses. Multi-state analyses indicated that GDF-15 predicted bidirectional progression between ASCVD and MASLD, with 10-year cumulative incidences of ASCVD and MASLD reaching 15.75% and 2.03%, respectively, among individuals in the top 10% of GDF-15 levels, and further increasing to 20.05% and 2.32% in those in the top 5%. SHAP and LR analyses showed that GDF-15 had high relative importance in predicting ASCVD and MASLD. Incorporating GDF-15 into established risk scores (PREVENT, SCORE2, FLI, FIB-4 and ARPI) showed modest improvements in risk discrimination, reclassification, and prediction error, particularly for ASCVD. In several settings, GDF-15 outperformed established biomarkers, including insulin resistance, systemic inflammation, apolipoprotein A/B, lipoprotein(a), cardiac troponin I, and N-terminal prohormone of brain natriuretic peptide. CONCLUSIONS: GDF-15 may serve as a promising biomarker for cardiovascular-kidney-liver-metabolic syndrome risk stratification and management.
Apolipoprotein B100 predicts cardiovascular and limb events in type 2 diabetes patients with chronic limb-threatening ischemia.
Biscetti F, Rando MM, Nicolazzi MA … +8 more , Angelini F, Iezzi R, Eraso LH, Dimuzio PJ, Pitocco D, Massetti M, Gasbarrini A, Flex A
Cardiovasc Diabetol · 2026 Jun · PMID 42286602 · Full text
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) undergoing lower extremity revascularization (LER) face high risks of major adverse cardiovascular events (MACE) and...
BACKGROUND: Patients with type 2 diabetes mellitus (T2DM) and chronic limb-threatening ischemia (CLTI) undergoing lower extremity revascularization (LER) face high risks of major adverse cardiovascular events (MACE) and major adverse limb events (MALE), despite guideline-directed lipid-lowering therapy. Apolipoprotein B100 (ApoB100), reflecting total atherogenic particle number, may identify residual risk beyond LDL-cholesterol (LDL-C). Therefore, we investigated whether baseline ApoB100 levels independently predict MACE and MALE beyond conventional risk factors in this high-risk population. METHODS: In this prospective cohort study, 167 T2DM patients with CLTI undergoing LER were followed for 12 months with visits at 1, 3, 6, and 12 months post-procedure. We measured baseline ApoB100 and assessed its ability to predict MACE, MALE, and composite endpoints, adjusting for clinical covariates. RESULTS: Composite events occurred in 49.1% of patients, MACE in 24%, and MALE in 35.3%. ApoB100 levels were significantly higher in event groups (composite: 62.1 vs 38.0 mg/dL, p < 0.01; MACE: 66.1 vs 44.4 mg/dL, p < 0.01; MALE: 61.0 vs 42.4 mg/dL, p < 0.01). Multivariable analyses confirmed ApoB100 as an independent predictor (composite OR 1.14 per mg/dL, 95% CI 1.08-1.20, p < 0.01; MACE OR 1.10, p < 0.01; MALE OR 1.05, p < 0.01). ROC analysis demonstrated excellent predictive accuracy for ApoB100 (AUC 0.86, 95% CI 0.80-0.91), with optimal ROC-derived cut-off of 56.6 mg/dL. Adding baseline ApoB100 to conventional risk factors significantly improved model discrimination (AUC gains 0.08-0.15, all p < 0.01), while Kaplan-Meier curves by cut-off effectively stratified early events (log-rank p < 0.001). CONCLUSIONS: Elevated baseline ApoB100 independently predicted MACE, MALE, and composite events post-LER in T2DM-CLTI patients, substantially improving clinical risk models. Integrating ApoB100 into post-LER management algorithms could refine individualized therapeutic strategies, especially in patients with residual atherogenic risk despite optimal LDL-C control.
Integrating inflammation, insulin resistance, and visceral adiposity: the C-reactive protein-triglyceride-glucose-Chinese visceral adiposity (CTI-CVAI) index is associated with cardiovascular disease risk across CKM stages 0-3 in a nationwide prospective cohort.
Wang Q, Li J, Qiao H … +4 more , Zhang Y, Xu Y, Zhang S, Zhuang G
Cardiovasc Diabetol · 2026 Jun · PMID 42286579 · Full text
BACKGROUND: Early-stage (0-3) cardiovascular-kidney-metabolic (CKM) syndrome populations require urgent cardiovascular disease (CVD) prevention. Chronic inflammation, insulin resistance, and visceral adiposity are three...
BACKGROUND: Early-stage (0-3) cardiovascular-kidney-metabolic (CKM) syndrome populations require urgent cardiovascular disease (CVD) prevention. Chronic inflammation, insulin resistance, and visceral adiposity are three core interactive CVD pathogenic pathways, while current biomarkers fail to integrate all three. This study aimed to explore the association of the novel three-dimensional composite index CTI-CVAI with incident CVD and its predictive value in Chinese adults with CKM stages 0-3. METHODS: This nationwide prospective cohort study used data from the China Health and Retirement Longitudinal Study (CHARLS, 2011-2020), including 6728 participants aged ≥ 45 years with CKM stages 0-3. CTI-CVAI was calculated by combining the C-reactive protein-triglyceride-glucose index (CTI) and Chinese visceral adiposity index (CVAI). Cox regression, restricted cubic spline, survival analysis, ROC curves, and reclassification analysis were used to evaluate its value. Subgroup and multiple sensitivity analyses, including competing-risks models, were conducted to assess the robustness of the results. RESULTS: During a median follow-up of 9 years, the overall CVD incidence was 23.83%. CTI-CVAI elevation showed a linear, dose-dependent correlation with increased CVD risk (P < 0.001). After full confounder adjustment, per 1-SD CTI-CVAI increment increased CVD risk by 32% (HR = 1.32, 95% CI 1.26-1.39, P < 0.001), and the highest quartile exhibited 2.07-fold higher risk than the lowest (HR = 2.07, 95% CI 1.77-2.42, P < 0.001). Restricted cubic spline analysis revealed a linear association between CTI-CVAI and incident CVD (P for non-linearity > 0.05). CTI-CVAI demonstrated improved risk reclassification (NRI = 0.0566, P < 0.001) compared with single biomarkers. The association was stable across most subgroups. All sensitivity analyses yielded reliable, robust results. CONCLUSIONS: CTI-CVAI is independently and linearly associated with incident CVD risk in Chinese adults with CKM stage 0-3. As a low-cost, accessible biomarker integrating three key pathological pathways, it optimizes early CVD risk stratification and reclassification, providing a promising tool for targeted CVD prevention in CKM high-risk populations.
Associations of metabolic score for insulin resistance and new-onset stroke in middle-aged and older adults: a national cohort study.
Zhang X, Wei R, Hu H … +2 more , Wang X, Li Q
Cardiovasc Diabetol · 2026 Jun · PMID 42277815 · Full text
BACKGROUND: Metabolic score for insulin resistance (METS-IR) is acknowledged as a reliable indicator of insulin resistance and cardiometabolic risk. This study aims to explore the relationship between cumulative METS-IR...
BACKGROUND: Metabolic score for insulin resistance (METS-IR) is acknowledged as a reliable indicator of insulin resistance and cardiometabolic risk. This study aims to explore the relationship between cumulative METS-IR (cumMETS-IR) and METS-IR change patterns with new-onset stroke. METHODS: 4344 participants from the China Health and Retirement Longitudinal Study (CHARLS) with follow-up until 2020 were utilized in this study. cumMETS-IR was calculated as the area under the curve of METS-IR values from 2011 to 2015. K-means clustering analysis was employed to discern distinct METS-IR change patterns over this interval. Associations of cumMETS-IR and METS-IR change patterns with incident stroke were examined using Cox proportional hazards models and restricted cubic splines (RCS). Mediation analysis assessed whether diastolic blood pressure (DBP) accounted for the association between cumMETS-IR and incident stroke. RESULTS: There were 385 (8.86%) new stroke events over 5-years median follow-up. RCS analysis showed that cumMETS-IR was positively correlated with incident stroke (P-overall = 0.013, P-nonlinear = 0.252). Compared with the lowest quartile, the highest quartile was associated with a higher incidence of stroke (adjusted hazard ratio [HR] 1.72, 95% confidence interval [CI] 1.22-2.42, P = 0.002). Four distinct METS-IR change patterns were identified using k-means clustering: low-stable (30.5%), low-to-moderate stable (35.9%), moderate-to-high stable (24.7%), and high-decreasing (8.9%). Participants following the high-decreasing pattern was associated with the highest incidence of stroke compared to those in the low-stable patterns (adjusted HR 1.61, 95% CI 1.08-2.42, P = 0.021). The core findings remained robust across a series of sensitivity analyses. Mediation analysis revealed that DBP partially explained this association, with a mediation proportion of 9.6%. CONCLUSION: Both cumMETS-IR and METS-IR change were associated with increased incidence of stroke in middle-aged and older Chinese adults. Monitoring changes in METS-IR over time may help characterize metabolic status more comprehensively and offer supportive information for stroke-related health assessment.
Predicting subclinical atherosclerosis in adults with type 1 diabetes using cardiovascular risk models: a cross‑sectional study from Italy.
Molinari C, Galotta A, Mushtaq S … +12 more , Frigerio B, Vavassori C, Rondinelli M, Cosentino N, Romandini A, Chiesa M, Vinci MC, Colombo GI, Baldassarre D, Pontone G, Bonomi A, Genovese S
Cardiovasc Diabetol · 2026 Jun · PMID 42277803 · Full text
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among individuals with type 1 diabetes (T1D); nevertheless, cardiovascular risk stratification remains an unmet need in T1D. Cardio...
BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among individuals with type 1 diabetes (T1D); nevertheless, cardiovascular risk stratification remains an unmet need in T1D. Cardiovascular risk tools were developed to predict 10‑year clinical events. Whether they identify subclinical atherosclerosis - a potential gatekeeper for intensified prevention - remains uncertain. METHODS: We conducted a cross-sectional analysis of consecutive T1D adults without a history of CVD enrolled at a secondary centre in Italy. All participants underwent coronary computed tomography angiography (CCTA) and carotid ultrasound. The primary outcome was a composite imaging endpoint, defined as any coronary plaque on CCTA and/or maximum carotid intima-media thickness (cIMT) ≥ 1.5 mm. We compared the performance of T1D-specific CV risk models (2019 European Society of Cardiology [ESC] Guidelines, Steno Type 1 Risk Engine [ST1RE], and Scottish-Swedish CVD risk prediction tool) in predicting the presence of subclinical atherosclerosis. Discrimination was assessed using the Area Under the receiver operating characteristic Curve (AUC), and differences between AUCs were evaluated using the DeLong test; calibration was visualised with calibration plots and summarised by Brier score. Sensitivity analyses evaluated CCTA‑only and carotid‑only endpoints. RESULTS: One hundred and one patients (52.5% males) were included in the study, with a mean age of 45 ± 13 years and a median diabetes duration of 21 years (Q1-Q3 13; 32). The composite imaging endpoint occurred in 66/101 (65.4%); 55 patients (54.5%) had coronary plaques, and 41 patients (40.6%) presented cIMT above threshold. Both ST1RE and the Scottish-Swedish risk scores showed strong discrimination for the combined imaging endpoint (AUC 0.899 and 0.907, respectively). Apparent calibration to the imaging endpoint was acceptable, with Brier scores of 0.126 for ST1RE and 0.128 for the Scottish-Swedish model. CONCLUSIONS: In an Italian cohort of asymptomatic T1D adults, T1D-specific risk scores demonstrated a strong discrimination ability for imaging-defined subclinical atherosclerosis. They might help triage asymptomatic individuals who could benefit from targeted cardiovascular imaging in specific settings. Since these tools predict events rather than imaging findings, recalibration and prospective validation against imaging endpoints are needed before using predicted probabilities as absolute risks informing clinical decision‑making. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT06290544. Registered on 4 March 2024.
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