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.

ObjectiveThis study aims to evaluate the associations of complete blood cell count-derived inflammatory markers—including monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Systemic Immune-Inflammation Index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI)—with acute gouty arthritis in males.MethodsA cross-sectional study was conducted in 380 males from the Department of Endocrinology and Department of Physical Examination, Central Hospital of Dalian University of Technology, between January 2022 and January 2024. Multivariable logistic regression models were used to investigate the independent associations between six inflammatory markers and acute gouty arthritis. Restricted cubic splines (RCS) were employed to model the dose–response relationships of inflammatory markers with acute gouty arthritis. Subgroup analyses were performed to identify susceptible populations. The diagnostic capabilities of the inflammatory markers were evaluated and compared using receiver operating characteristic (ROC) curves.ResultsA total of 380 male participants were included, with a mean age of 54 years. Among them, 108 participants had AGA, giving a prevalence of 28.4%. Significant associations with AGA were observed for monocyte-to-lymphocyte ratio (MLR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), Systemic Immune-Inflammation Index (SII), systemic inflammatory response index (SIRI), and aggregate index of systemic inflammation (AISI). Further analysis using RCS revealed nonlinear dose–response relationships between SII and AGA (p-nonlinear = 0.001), as well as between AISI and AGA (p-nonlinear <0.001). Subgroup analysis showed that inflammatory markers (NLR, PLR, SII, SIRI, and AISI) were more effective in assessing AGA onset among men with fatty liver. ROC analysis indicated that when compared with other inflammatory markers (MLR, NLR, PLR, and SIRI), SII and AISI demonstrated superior diagnostic accuracy and discriminatory power in assessing the risk of AGA in men.ConclusionIn men, AGA is closely associated with inflammatory markers. In addition, compared with other inflammatory markers (MLR, NLR, PLR, and SIRI), SII and AISI may serve as more accurate indicators for the diagnosis of AGA.

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.

AIMS:Prediabetes affects 35% of Chinese adults and is associated with increased risks of cardiovascular disease and mortality. However, findings are inconsistent on the effects of lifestyle and pharmacological interventions in the prediabetes population achieving remission. This analysis aimed to compare the effects of metformin plus lifestyle intervention versus lifestyle intervention alone for prediabetes remission. MATERIALS AND METHODS:This was a secondary analysis of the China Diabetes Prevention Program (CDPP), a multicentre unblinded randomised controlled trial of 1678 participants aged 18-70 years with impaired glucose regulation from 43 hospitals across China (NCT03441750). Participants were randomly assigned (1:1) using block randomisation stratified by glucose status (impaired fasting glucose or impaired glucose tolerance), presence of hypertension and use of anti-hypertensive medication. They received either metformin plus lifestyle intervention or lifestyle intervention alone for 2 years. The primary outcome was prediabetes remission rate. RESULTS:During a median follow-up of 2.03 years, remission was achieved in 262/831 (31.5%) (138/396 men; 124/435 women) participants in the metformin plus lifestyle group versus 213/847 (25.1%) (106/397 men; 107/450 women) in the lifestyle alone group, with similar effects across subgroups. After adjusting for baseline characteristics, addition of metformin increased the rate of remission (HR 1.39, 95% CI 1.16-1.67, p < 0.001). Higher baseline HbA1c was associated with lower remission rates (HR 0.23, 95% CI 0.18-0.29, p < 0.001). CONCLUSIONS:Adding metformin to a lifestyle intervention significantly improved prediabetes remission rates over lifestyle intervention alone in Chinese adults with impaired glucose regulation. This may be an effective approach for prediabetes management.

ContextNocturnal hypoglycemia (NH) is a common adverse event in elderly patients with type 2 diabetes (T2D). This study aims to develop a clinically applicable model for predicting the risk of NH in elderly patients with T2D.MethodsThis retrospective cohort study, conducted from May 2018 to June 2024, analyzed 1,128 elderly T2D patients undergoing continuous glucose monitoring, with an independent validation involving 100 outpatients. Clinical characteristics were collected, and feature engineering was performed to select a manageable set of clinically accessible features. An ensemble model was developed using multiple base models and a stacking approach. The best-performing model was deployed as an online risk calculator.ResultsOf the development set, 288 (25.5%) experienced NH, while 40 (40%) of the independent validation cohort experienced NH. The final ensemble model, “RF-ET-KNN”, combined random forest, Extra Trees, and K-nearest neighbor as base learners, with Extra Trees serving as the meta-learner. It incorporated eleven clinical features and achieved an AUROC of 0.926 and sensitivity of 0.853 on the test set, and an AUROC of 0.947 and sensitivity of 0.929 on the internal validation set. SHAP analysis identified that daytime lowest blood glucose (BG), fasting blood glucose (FBG), and daytime hypoglycemia events were closely related to NH. A user-friendly calculator is available at http://122.51.219.102:8000/.ConclusionThe “RF-ET-KNN” model, integrating eleven clinically accessible features, effectively predicts NH in elderly T2D patients. Daytime lowest BG, FBG, and daytime hypoglycemia events were significant risk factors.

BACKGROUND:Pre-diabetes is a transitional metabolic stage between health and diabetes, serving as a critical warning signal for disease progression. Early intervention targeting risk factors in prediabetic individuals prevents the progression to type 2 diabetes. AIM:To investigate the predictive value of the triglyceride-glucose (TyG) index and its derived indicators for new-onset diabetes in patients with pre-diabetes. METHODS:A prospective community-based cohort study was carried out based on subjects aged over 40 years with pre-diabetes in Dalian, Liaoning Province, China. A total of 1352 subjects with complete follow-up data attended the follow-up survey. Multivariable Cox regression models were performed to assess the association of the TyG index and its derived indicators with risk of diabetes in patients with pre-diabetes. The diagnostic values of the TyG index and derived indicators in predicting new-onset diabetes were analyzed, and suitable cutting points were determined using the receiver operating characteristic (ROC) curve. RESULTS:During a 3-year follow-up period, 153 cases with incident diabetes were identified, with a cumulative incidence of diabetes of 11.3%; 12.6% (43/341) in males and 10.9% (110/1011) in females (χ 2 = 0.760, P = 0.375). After adjusting for confounding factors including age, gender, body mass index (BMI) and insulin levels, the risk of diabetes with higher TyG and derived indexes [TyG-BMI and TyG-waist circumference index (TyG-WC)] increased significantly. The TyG index [hazard ratio (HR) = 1.389, 95% confidence interval (CI): 1.011-1.908, P = 0.043], TyG-BMI (HR = 1.010, 95%CI: 1.005-1.015, P = 0.000) and TyG-WC (HR = 1.003, 95%CI: 1.001-1.005, P = 0.001) were all strongly positively correlated with the risk of future diabetes. The ROC curve analysis showed that the area under the curve (AUCs) of the TyG, TyG-BMI and TyG-WC for predicting new diabetes were 0.578 (95%CI: 0.533-0.624), 0.622 (95%CI: 0.574-0.670) and 0.609 (95%CI: 0.562-0.657), respectively. The difference in AUC between TyG-BMI and TyG was significant (P = 0.047), while the differences between TyG-BMI and TyG-WC (P = 0.464) and between TyG-WC and TyG (P = 0.175) were not. The TyG-BMI had a larger AUC than the TyG and TyG-WC, and its difference from TyG was significant. The best cut-off points for predicting new diabetes were TyG > 8.6, TyG-BMI > 247 and TyG-WC > 860. Although the AUC values were modest, these indices may serve as preliminary screening tools in resource-limited settings. CONCLUSION:The TyG index and its derived indicators were risk factors for the pre-diabetes to diabetes outcome, and may be regarded as predictors of the outcome. The risk of conversion of pre-diabetes to diabetes increased with increases in the TyG index and its derived indicators. The TyG-BMI was better than TyG and TyG-WC in predicting the 3-year outcome for diabetes. Although these indices could aid in the initial risk stratification in primary care, their modest accuracy warrants cautious interpretation.

IntroductionGiven the established relationship between lipid metabolism and dysglycemia, this longitudinal study aimed to investigate the association between the triglyceride-high density lipoprotein cholesterol-glucose body index (TyHGB) and the risk of developing prediabetes or diabetes among middle-aged and elderly postmenopausal women.MethodsData were collected from the REACTION study in Dalian, China. The study included postmenopausal women with normal baseline glucose tolerance who were followed up over a three-year period. We used multivariable logistic regression to evaluate the relationship of TyHGB with incident prediabetes and diabetes. Restricted cubic splines (RCS) were employed to examine dose-response relationships. The predictive performance of TyHGB and traditional indices for prediabetes and diabetes was evaluated and compared using receiver operating characteristic (ROC) curve analysis.ResultsAmong the 2,138 postmenopausal women with normal glucose levels at baseline, 598 developed prediabetes and 124 developed diabetes during the follow-up period. Multivariable logistic regression revealed a significant positive association between TyHGB and the risk of both prediabetes and diabetes. Restricted cubic spline analysis confirmed a nonlinear dose-response relationship, with prediabetes risk increasing steeply below an inflection point of 8.52 before plateauing, whereas diabetes risk remained stable below 6.47 and increased sharply thereafter. Subgroup analyses demonstrated that this association remained consistent across strata defined by age, hypertension, hyperlipidemia, and coronary heart disease (CHD). Additional ROC curve analyses suggested that TyHGB may provide effective predictive value for diabetes in postmenopausal women.ConclusionIn a middle-aged and elderly postmenopausal population, the TyHGB index is a significant independent risk factor for prediabetes and diabetes.

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.

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic, multisystem autoimmune disease characterized by marked clinical heterogeneity and substantial morbidity. Although rash, arthritis, and renal involvement are common manifestations, atypical presentations may delay diagnosis. In rare cases, growth retardation and delayed puberty may precede typical systemic features, posing a diagnostic challenge. We report the case of a 12-year-old Chinese girl who presented to the endocrinology clinic with progressive growth retardation and delayed pubertal development. Comprehensive growth assessment demonstrated discordance among height velocity, weight gain, and pubertal progression. Further evaluation revealed proteinuria, hypoalbuminemia, generalized lymphadenopathy, and immunological abnormalities, leading to a diagnosis of cSLE. Following immunosuppressive therapy, systemic manifestations improved and laboratory indices gradually normalized; however, longitudinal follow-up showed that impairment in growth and pubertal progression persisted despite disease control. This case highlights that cSLE, although a rare cause of growth retardation and delayed puberty, should be considered in adolescents with unexplained short stature or pubertal delay, particularly when accompanied by proteinuria or immunological abnormalities. Early recognition and multidisciplinary management are essential to improve long-term growth and overall clinical outcomes.

Background:Hashimoto's thyroiditis (HT) is the leading cause of autoimmune hypothyroidism, and dietary factors have been implicated in its pathogenesis through immune and metabolic pathways. We aimed to identify dietary and metabolic factors associated with HT risk in a large community cohort and to evaluate whether tuber-associated metabolites causally influence HT susceptibility using Mendelian randomization (MR). Methods:Cross-sectional analysis of 7,878 community-dwelling adults (≥40 years) from the REACTION cohort, Dalian, China. HT was defined by thyroid autoantibody seropositivity (anti-TPO ≥5.61 IU/mL or anti-Tg ≥4.11 IU/mL). Forty-nine variables spanning dietary intake, lifestyle behaviours, anthropometrics, and metabolic parameters were screened by univariable and multivariable logistic regression. For MR, eight tuber-associated metabolites identified via the FoodB database were analysed as instrumental variable exposures against a published HT genome-wide association study (GWAS; N = 395,640; 15,654 cases) using inverse-variance weighted (IVW) as the primary method, with MR-Egger and weighted median as sensitivity analyses, and MR-PRESSO to assess and correct for horizontal pleiotropy. Results:HT prevalence was 29.3% (2,305/7,878). Female sex (OR 1.97, 95% CI 1.68 to 2.33), elevated total cholesterol (OR 1.13, 95% CI 1.02 to 1.26), and lower fasting glucose (OR 0.95, 95% CI 0.91 to 1.00) were independent metabolic predictors. Adequate tuber intake (50-100 g/day; OR 0.75, 95% CI 0.64 to 0.88; P = 0.001) and adequate vegetable intake (OR 0.87, 95% CI 0.79 to 0.96; P= 0.006) were independently protective, with tuber protection most pronounced in women (OR 0.76, 95% CI 0.63 to 0.90; P = 0.002). A dose-response analysis revealed a U-shaped pattern: adequate intake was protective (OR 0.77) while excessive intake (>100 g/day) was associated with increased risk (OR 1.50; P for trend = 0.45, non-significant linear trend). Four sensitivity analyses consistently confirmed the primary findings. In univariable MR, folic acid supplementation propensity was the only metabolite with adequate genetic instrumentation (mean F-statistic = 46.75; 736 harmonised SNPs). Genetically predicted folic acid supplement use causally increased HT risk across all three MR methods (IVW: β = 0.105, SE = 0.001; P < 0.001; Weighted Median: β = 0.112; P < 0.001), with outlier-robust analysis confirming a consistent estimate after removal of 74 influential SNPs (β = 0.109; effect change 4.1%). Conclusions:Adequate tuber intake is an independent, novel protective dietary factor for HT, with a U-shaped dose-response pattern confirmed across four sensitivity analyses. Mendelian randomization identifies folic acid supplementation as a causal risk factor for HT, a finding with direct public health relevance given widespread supplement use in women of reproductive age. These findings support moderate tuber and vegetable consumption as a low-cost HT prevention strategy, and warrant caution regarding high-dose folic acid supplementation in HT-susceptible individuals.

The relationship between maternal thyroid function and intellectual development of offspring is controversial. Iodine may be an important confounding factor. This study investigated whether maternal iodine status could affect the efficacy of levothyroxine (LT4) treatment during early pregnancy on the intellectual growth of progeny.This prospective study divided participants into two groups; the normal iodine group included 53 mother–child pairs and the low iodine group included 60 mother–child pairs (urinary iodine concentration (UIC) ≥ 150 µg/L and UIC < 150 µg/L). Each iodine status group was further subdivided according to specific maternal thyroid disorders. The two groups were categorized as follows: Control(N), hypothyroxinemia (IH) + LT4, subclinical hypothyroidism (SCH) + LT4, positive thyroid peroxidase antibodies (TPOAbs) + LT4. Finally, the study included eight groups. The Bayley Scales of Infant Development-II were employed to evaluate the neurodevelopment of children (age: 12 -30 months). The main results were age-adjusted scores from the Mental Development Index (MDI) and Psychomotor Development Index (PDI).We found that: 1) Under the similar conditions of thyroid function and treatment, iodine deficiency during early pregnancy reduced the MDI value of the offspring (P < 0.001), while, the PDI value was not affected (P = 0.276). Linear regression demonstrated a substantial positive correlation between maternal UIC and MDI of offspring (B = 0.09 [CI 0.06–0.13]; P = 0.01). In the case of iodine deficiency during pregnancy, LT4 treatment on SCH and IH could not improve offspring MDI scores (P < 0.001, P = 0.037, respectively) in contrast to the normal group. However, under normal iodine status during pregnancy, LT4 treatment on SCH and IH could improve offspring MDI scores (P = 0.525, P = 0.650, respectively) compared with the normal group. Concurrently, the PDI of the aforementioned categories did not differ significantly (P > 0.05). 3) In comparison to the normal group, LT4 treatment on TPOAbs during pregnancy could not improve the MDI of the offspring, regardless of whether the iodine nutritional status was normal or not (P < 0.001, P = 0.047, respectively). These findings suggest that concurrent assessment and optimization of both thyroid function and iodine status during early pregnancy may be essential for maximizing offspring intellectual development.

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.

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.

IntroductionFamilial hypocalciuric hypercalcemia (FHH) is an autosomal dominant disorder caused by an inactivating mutation in the CASR gene, while Gitelman syndrome (GS) is an autosomal recessive renal tubular disorder resulting from a pathogenic mutation in the SLC12A3 gene. Both genetic disorders are relatively rare. This report presents a patient with both FHH and GS, exhibiting unique clinical and genetic complexities.Case summaryWe report a case of a 69-year-old Asian female patient who had previously presented to the hospital on multiple occasions with complaints of joint stiffness, fatigue, dizziness, or other symptoms. The patient was readmitted to the hospital at the age of 66, presenting with the following clinical findings: hypocalciuria, hypercalcemia, normal or mildly elevated parathyroid hormone (PTH) levels, hypokalemia, hypomagnesemia, hypophosphatemia, normal blood pressure, chondrocalcinosis (CC), and diabetes mellitus. Our careful analysis suggested that the patient might have the co-occurrence of GS and FHH. Genetic testing revealed a novel heterozygous CASR p.Tyr161* mutation and a homozygous SLC12A3 p.Thr60Met mutation, which ultimately confirmed the diagnosis of familial hypocalciuric hypercalcemia type 1 (FHH1) combined with GS.ConclusionFor the first time, we report a case of FHH combined with GS. The novel CASR mutation in this patient expands the variant spectrum of FHH, provides new genetic evidence for its pathogenesis, and underscores the importance of genetic counseling for consanguineous families. This case also suggests a potential association between FHH and CC, the mechanism of which warrants further investigation. In addition, this report highlights possible potential interactions between FHH and GS. Clinically, hypokalemia and hypomagnesemia associated with GS are more detrimental than hypercalcemia linked to FHH and should be prioritized in management. Finally, genetic testing and molecular diagnostics are crucial for pediatric and adolescent populations with FHH and/or GS, and further studies are needed to clarify the genotypic and phenotypic relationships between FHH and GS comorbidities.