BackgroundThe incidence of arteriosclerosis is steadily increasing, and arteriosclerosis is closely associated with cardiovascular diseases. The objective of this research was to create and verify a tool for forecasting arteriosclerosis in middle-aged and elderly individuals within the community.MethodsA cohort study was conducted in multiple communities, and 4107 participants over 40 years of age were enrolled. The participants were randomly divided into a derivation cohort (n = 2875) and a validation cohort (n = 1232) at a ratio of 7:3. LASSO analysis and multivariate logistic regression were employed to analyze factors influencing arteriosclerosis and to establish a prediction model, which was visualized as a nomogram and then evaluated. The primary outcome is incident arteriosclerosis, defined as baPWV ≥ 1400 cm/s.ResultsOver an average follow-up period of 3.25 ± 1.14 years, 1688 subjects (41.0%) were diagnosed with arteriosclerosis. Independent risk factors for arteriosclerosis included age, BMI, hypertension, triglyceride levels, glycosylated hemoglobin, sex, and fasting blood glucose. The area under the receiver operating characteristic curve for the derivation and validation cohorts was 0.811 (95% CI: 0.795–0.827) and 0.816 (95% CI: 0.796–0.830), respectively. The Hosmer-Lemeshow test showed good model accuracy (P = 0.123, P = 0.428). Calibration curves illustrated high consistency between predicted and observed results. Decision curve analysis demonstrated favorable net benefits of the model.ConclusionThe predictive model established in this study holds promise for identifying arteriosclerosis in middle-aged and elderly individuals. Understanding the related risk factors and individualized prediction may assist physicians in early detection and intervention, ultimately improving patient prognosis.

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

BACKGROUND:Neutrophil extracellular traps (NETs) have been implicated in various autoimmune diseases; however, their role in Hashimoto's thyroiditis (HT) remains poorly understood. This study aimed to characterize NETs formation, explore its association with thyroid dysfunction and adaptive immunity, and evaluate the therapeutic potential of vitamin D (VD) in experimental autoimmune thyroiditis (EAT). METHODS:EAT was induced in BALB/c mice via thyroglobulin immunization combined with excess iodine intake. The VD group received additional intraperitoneal calcitriol supplementation. Thyroid histopathology, MHC-II expression, thyroid antibodies (TGAb and TPOAb), plasma DNase-I and 1,25(OH)₂D₃ levels, NETs formation, and splenic T cell subsets (Th17, Treg, Th1, Th2) and cytokines were assessed. Parallel experiments were conducted using neutrophils isolated from HT patients. RESULTS:Neutrophils from both EAT mice and HT patients exhibited enhanced NETosis compared to controls. EAT mice showed lower levels of DNase-I, 1,25(OH)₂D₃, Treg, and Th1 cells, along with higher Th17 and Th2 cells, elevated Th17/Treg ratio, and heightened thyroid MHC-II expression. NETs levels positively correlated with Th17, Th2, and MHC-II expression, and negatively with Treg, Th1, 1,25(OH)₂D₃, and DNase-I. VD supplementation mitigated thyroiditis and TPOAb levels, suppressed NETs formation, and reduced the Th17/Treg ratio and IL-17 levels. CONCLUSIONS:NETs contribute to Th17 bias and MHC-II over-expression in HT, suggesting a role in shaping the adaptive immune response. Vitamin D restrains NETosis and restores T-cell homeostasis, highlighting its potential as an adjunctive therapy for HT.

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

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

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

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

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

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

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

BackgroundAcute thyrotoxic myopathy (ATM) is a relatively rare and severe complication of hyperthyroidism, mainly reported in individual cases and lacking standardized treatment protocols.ObjectiveThis study evaluated the efficacy of glucocorticoids (GCs), adenosine triphosphate (ATP), and antithyroid drugs (ATDs) in treating ATM to guide clinical management.MethodsWe retrospectively analyzed 42 ATM patients treated with GCs, ATP, and ATDs. The Acute Thyrotoxic Myopathy Symptom Score (ATMSS) was applied to evaluate efficacy at baseline (T0), day 7 (T7), and day 28 (T28) of treatment. Binary logistic regression was used to identify predictors of therapeutic efficacy, examining the impact of pre-treatment biochemical indicators and ATMSS on symptom relief (R) at T7 and complete remission (CR) at T28.ResultATMSS demonstrated significant improvement at both T7 and T28 (P < 0.001). R and CR rates differed among symptoms, with nasal reflux, dysphagia, and dyspnea showing markedly higher rates than dysarthria, gag reflex, and muscle weakness (T7: χ² = 30.89, T28: χ² = 36.71, both P < 0.001). Binary logistic regression analysis indicated that higher baseline dysarthria scores were associated with lower R rates at T7 (OR = 0.216, 95% CI = 0.056–0.836, P = 0.027), while more severe muscle weakness at T7 predicted lower CR at T28 (OR = 0.564, 95% CI = 0.323–0.984, P = 0.044).ConclusionThe combination of GCs, ATP, and ATDs effectively alleviated the ATMSS in the short (7day) and medium (28day) term. However, recovery rates differ among symptoms. Specifically, dysarthria at baseline and muscle weakness at T7 showed significant predictive value for treatment outcomes.

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

Acute thyrotoxic myopathy (ATM) is a rare yet severe complication of thyrotoxicosis that affects the central nervous system and is associated with a high mortality rate if not diagnosed and treated promptly. Currently, the diagnosis of ATM primarily relies on clinical manifestations, and there is a lack of specific serological markers to support the diagnostic process. This study aimed to investigate the differences in serum CD40 levels between patients with acute thyrotoxic myopathy (ATM), those with Graves’ disease, and healthy controls, and to evaluate its potential as a diagnostic biomarker for differentiating ATM. Additionally, the study examined the correlation between serum CD40 levels and various parameters, including the ATM symptom score (ATMSS), FT3, FT4, TSH, TGAb, TRAb, and TPOAb. This retrospective cross-sectional study included 17 patients with ATM, 17 patients with Graves’ disease, and 17 healthy controls, all recruited from the First Affiliated Hospital of Guangxi Medical University between January 2022 and August 2024. Clinical evaluations, serum thyroid hormone and related antibody testing, and CD40 level measurements were conducted. The predictive value of CD40, FT3, FT4, TSH, TGAb, TRAb, and ATMSS for ATM was assessed using receiver operating characteristic (ROC) curve analysis. Spearman correlation analysis was performed to explore the relationship between CD40 levels and ATMSS, FT3, FT4, TSH, TGAb, TRAb, and TPOAb. Serum levels of CD40[259.17(227.50,378.03)vs.190.71(174.08,198.96)vs. 166.98(142.94,175.90)], FT3[28.34(17.13,37.65) vs. 8.82(6.36,21.00) vs. 5.02(3.93,5.45)], and FT4 [67.58(37.53,77.23)vs.27.03(15.96,47.05)vs.16.82(13.59,17.90)]in ATM patients were significantly higher than those in Graves’ disease patients and the control group, with statistically significant differences (P < 0.01). ROC analysis demonstrated that CD40 has high predictive value for distinguishing between GD and ATM, with an area under the curve (AUC) of 0.99, and both sensitivity and specificity of 94.1%. Correlation analysis revealed a positive correlation between CD40 and the ATM symptom score (ATMSS) (r = 0.72, P < 0.01). Positive correlations were also observed between CD40 and FT3 (r = 0.53, P < 0.01) and FT4 (r = 0.56, P < 0.01). TSH showed a negative correlation trend with CD40 (r = -0.21, P = 0.23), but this difference was not statistically significant. No significant correlations were found between CD40 and TGAb (r = 0.10, P = 0.59), TRAb (r = 0.26, P = 0.13), or TPOAb (r = 0.06, P = 0.72). Elevated serum CD40 levels are associated with the severity of ATM symptoms and may serve as a potential biomarker for ATM. The role of CD40 as an adjunct in the early diagnosis of ATM holds clinical significance, offering new insights into the differential diagnosis and treatment of ATM.

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

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

BackgroundDefinition and staging rationale of cardiovascular-kidney-metabolic syndrome were developed. The utility of cardiovascular-kidney-metabolic construct in risk stratification and target strategies of health and behavior modifications needs to be addressed. The study aims to investigate the individual and combined associations of cardiovascular-kidney-metabolic stage and cardiovascular health (CVH) by Life's Essential 8 (LE 8) with incident cardiovascular events (CVD), and determine the distribution and contribution of domain-specific CVH across cardiovascular-kidney-metabolic stages.MethodsThe study included 100,727 individuals in the China Cardiovascular Disease and Cancer Cohort with complete data on cardiovascular-kidney-metabolic factors and LE 8 metrics, with a median follow-up of 10.1 years. Cardiovascular-kidney-metabolic stages and CVH metrics (nicotine exposure, diet, physical activity, sleep, body mass index, blood lipids, blood pressure, blood glucose) were defined according to Presidential Advisory from the American Heart Association. Incident CVD events including cardiovascular death, myocardial infarction, and stroke were validated. The Fine-Gray hazard model was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs) of CKM stages or CVH status associated with CVD.ResultsCompared with cardiovascular-kidney-metabolic stage 0, the adjusted competing HRs and 95% CIs of CVD events were 1.20 (0.95-1.51), 2.45 (1.97-3.04), 4.43 (3.53-5.58), and 5.95 (4.75-7.45) from stage 1 to stage 4, respectively. Optimal CVH status and each optimal CVH metric presented a significantly decreased risk of CVD events. Variation was observed in the association between cardiovascular-kidney-metabolic stage and CVD events with different CVH status or numbers of optimal CVH metrics. Compared with those in stage 0, Participants in stage 1 or 2 with optimal CVH no longer had elevated risks for incident CVD events. Suboptimal health factor contributed larger population attributable fractions to CVD events in cardiovascular-kidney-metabolic stage 0-2 (51.2%) than in stage 3-4 (25.2%), whereas suboptimal health behavior exhibited larger contribution in advanced stages (13.1% in stage 0-2 and 18.2% in stage 3-4).ConclusionsThe study indicated that cardiovascular-kidney-metabolic stage was associated with cardiovascular events, and optimal cardiovascular health could attenuate this risk. Health factor contributed predominantly at the early-stage, whereas health behavior exhibited consistent and slightly increased contribution along the spectrum. These findings support the utility of cardiovascular-kidney-metabolic construct and highlight the importance of target health improvement based on LE 8 framework.

This research critically assesses the global prevalence and trends of Type 2 diabetes (T2D) among women of reproductive age (15-39 years) spanning the period from 1990 to 2021. We conducted an analysis of the age-standardized incidence rates (ASIR), Disability-Adjusted Life Years (DALYs), and Estimated Annual Percentage Change (EAPC) using data from the Global Burden of Diseases (GBD) Study 2021. The global ASIR and DALYs per 100,000 among reproductive-aged women increased from 101.01 to 205.17 and from 113.25 to 198.41, respectively. The EAPC for ASIR was 2.32 [95% Confidence Interval (CI): 2.25 to 2.39], and that for DALYs was 1.76 (95% CI: 1.69 to 1.83), both indicating an upward trend. The increase in T2D prevalence was more prominent in the 25-29 age group and younger women. According to Socio-demographic Index (SDI) category, the highest ASIR and age-standardized DALY rate were observed in low-middle SDI regions (ASIR 104.44; age-standardized DALY rate 136.78). The most significant increases in ASIR were recorded in High-income North America (EAPC=3.64, 95% CI 3.46 to 3.82) and Cameroon (EAPC=4.30, 95% CI 4.14 to 4.46). In terms of age-standardized DALY rates, the steepest rises were seen in East Asia (EAPC=2.71, 95% CI 2.34 to 3.08) and Turkmenistan (EAPC=4.21, 95% CI 3.89 to 4.52). This study shows a remarkable increase in global T2D burden in women of reproductive age between 1990 and 2021. Interventions should be targeted towards women aged 25-29 years and lifestyle risk factors in low-middle SDI, specifically in countries in North Africa and the Middle East, East Asia, Oceania.

OBJECTIVE:This study aims to investigate the potential of denticleless E3 ubiquitin protein ligase homolog (DTL) as a biomarker for adrenocortical carcinoma (ACC) detection through bioinformatics analysis and experimental validation. METHODS:Differentially expressed genes (DEGs) between ACC and adrenocortical adenoma (ACA) were identified through bioinformatics analysis. A protein-protein interaction (PPI) network was constructed using Cytoscape software, and core genes were screened with the CytoHubba MCODE plug-in. Survival analysis was performed using the University of ALabama at Birmingham CANcer (UALCAN) data analysis portal. Immunohistochemistry was employed to assess DTL expression in adjacent normal tissues, ACA, and ACC. RESULTS:Two gene expression series (GSEs) retrieved from the Gene Expression Omnibus (GEO) database yielded 115 DEGs. Using the PPI network, three core genes were identified, among which (DTL) and TPX2 were highly expressed in ACC. Notably, (DTL) had the highest core gene score. Elevated DTL expression in individuals with ACC was significantly associated with a poor prognosis (P < 0.0001). Immunohistochemistry analysis revealed a significantly higher positive expression rate and a strong positive expression rate of DTL in ACC compared to ACA (χ2 = 11.708, P < 0.01). The positive expression rate of DTL in both ACC and ACA was significantly higher than in the adjacent normal adrenal cortex (P < 0.01). The expression of DTL followed a gradient, being highest in ACC, followed by ACA, and lowest in the normal adrenal cortex adjacent to the tumor. Additionally, (DTL) protein expression was significantly correlated with tumor size and infiltration metastasis (P < 0.05). Individuals with high (DTL) expression had significantly shorter survival times than those with low DTL expression (P < 0.05). CONCLUSION:(DTL) exhibits potential as a novel biomarker for distinguishing between benign and malignant adrenocortical tumors and may serve as a prognostic indicator for ACC.

Objectives: Acute thyrotoxic myopathy (ATM) is characterized by bulbar paralysis and limb myasthenia on the basis of hyperthyroidism, which can cause respiratory failure, coma and death. However, the diagnosis of ATM is challenging. The purpose of this study was to develop a symptom rating scale named Acute Thyrotoxic Myopathy Symptom Score (ATMSS) to assist in the early diagnosis of ATM in clinical practice. Methods: (1) The ATM reference cohort was constructed by searching for patients diagnosed with ATM or thyrotoxic bulbar palsy in the PubMed, Embase and Web of Science databases (ATM cohort); (2) the ATMSS was formulated based on the ATM cohort after multidisciplinary discussion; and (3) 38 patients with ATM and 40 patients with Graves’ disease (GD) were enrolled in the study; (4) receiver operating characteristic (ROC) curve analysis was applied to appraisal diagnostic value of the ATMSS for differentiating patients with ATM from patients with GD; (5) we also evaluated the correlation between ATMSS and age of onset, sex, thyroid function and thyroid‐related antibody. Results: The ATMSS showed better diagnostic value at an optimal cut‐off value of 4.5 [area under the curve (AUC) = 0.978; 95% confidence interval (CI) = 0.949–1; p < 0.0001; sensitivity = 94.7%; specificity = 95%]. The ATMSS was positively correlated with free triiodothyronine (FT 3 ) [Spearman correlation coefficient ( r s ) = 0.409, p < 0.001], free thyroxine (FT 4 ) ( r s = 0.486, p < 0.001) and thyrotrophin receptor antibody (TRAb) ( r s = 0.332, p = 0.003), but negative correlation with the age of onset ( r s = −0.349, p = 0.002). Conclusions: We developed a symptom rating scale named the ATMSS, which is effective in diagnosing ATM from GD, and ATMSS is positively correlated with thyroid function and TRAb, but negative correlation with the age of onset. ATMSS can be used as an additional tool for diagnosing ATM.

Prediabetes, an intermediate stage of developing diabetes, exhibits considerable phenotypic heterogeneity. Here, we apply the Discriminative Dimensionality Reduction Tree (DDRTree) algorithm to explore prediabetes heterogeneity in 55,777 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) study. Based on 12 clinically available variables, we identify four distinct phenotypes and observe differential risks of type 2 diabetes mellitus (T2DM), chronic kidney disease (CKD), and cardiovascular disease (CVD). Phenotype 4, characterized by hyperglycemia, insulin resistance, obesity, elevated triglycerides, and liver enzymes, has the highest T2DM risk, while phenotype 3, predominantly driven by obesity, insulin resistance, hyperglycemia, and dyslipidemia, has the highest CKD risk. Phenotypes 3 and 4 show higher CVD risk, with distinct distributions of CVD subtypes. These findings are validated in the external cohort SN_2009-2021, and a user-friendly online tool is provided for individual risk prediction. Overall, our study elucidates the intricate dynamics of prediabetes progression, aiding in personalized management for prediabetes care.