Previous studies suggested that fecal short-chain fatty acids (SCFAs) and branched short-chain fatty acids (BCFAs) are associated with glucose regulation. However, the potential relationship between circulating SCFAs and BCFAs with incident diabetes risk in both men and women remains unidentified in prospective cohort studies. In this study, we examined a panel of nine serum SCFAs and BCFAs in 3414 subjects with incident diabetes, and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort study. In fully adjusted conditional logistic regression models, total SCFAs, total BCFAs, and isovaleric acid were significantly associated with incident type 2 diabetes mellitus (T2DM) (P < 0.05). Interestingly, gender-specific analysis showed that per standard deviation (SD) increment of SCFAs were positively associated with incident T2DM among women, with the odds ratio (95% confidence interval) of 1.16 (1.05–1.29) for total SCFAs and 1.18 (1.07–1.31) for propionate, respectively (P < 0.05, false discovery rate (FDR) < 0.05). No significant associations were observed in men. A significant interaction was detected between men and women for propionate (Pinteraction < 0.001, FDR < 0.01). After further adjustment of insulin measurements, the associations of serum propionate with diabetes remained significant (P < 0.05, FDR < 0.05). Meanwhile, the associations of total BCFAs and isovaleric acid with diabetes were partially mediated by triglycerides, insulin resistance, and β-cell function in mediation analysis. These findings, for the first time in a large prospective cohort, provide evidence for an association between circulating SCFAs and BCFAs with T2DM risk, and support the potential role of circulating propionate with gender disparities in the early pathogenesis of diabetes.

Understanding sex disparities in modifiable risk factors across the lifespan is essential for crafting individualized intervention strategies. We aim to investigate age-related sex disparity in cardiometabolic phenotypes in a large nationwide Chinese cohort. A total of 254,670 adults aged 40 years or older were selected from a population-based cohort in China. Substantial sex disparities in the prevalence of metabolic diseases were observed across different age strata, particularly for dyslipidemia and its components. Generalized additive models were employed to characterize phenotype features, elucidating how gender differences evolve with advancing age. Half of the 16 phenotypes consistently exhibited no sex differences, while four (high-density lipoprotein [HDL] cholesterol, apolipoprotein A1, diastolic blood pressure, and fasting insulin) displayed significant sex differences across all age groups. Triglycerides, apolipoprotein B, non-HDL cholesterol, and total cholesterol demonstrated significant age-dependent sex disparities. Notably, premenopausal females exhibited significant age-related differences in lipid levels around the age of 40-50 years, contrasting with the relatively stable associations observed in males and postmenopausal females. Menopause played an important but not sole role in age-related sex differences in blood lipids. Sleep duration also had an age- and sex-dependent impact on lipids. Lipidomic analysis and K-means clustering further revealed that 58.6% of the 263 measured lipids varied with sex and age, with sphingomyelins, cholesteryl esters, and triacylglycerols being the most profoundly influenced lipid species by the combined effects of age, sex, and their interaction. These findings underscore the importance of age consideration when addressing gender disparities in metabolic diseases and advocate for personalized, age-specific prevention and management.

BackgroundThe triglyceride glucose (TyG) index has been associated with an increased risk in breast cancer. However, this association remains unclear among the Chinese population. This study aimed to investigate whether the TyG index is associated with the risk of prevalent breast cancer in Chinese women.MethodsThis cross-sectional study included 142,184 women from the REACTION (Risk Evaluation of Cancers in Chinese Diabetic Individuals: A Longitudinal) Study, which recruited adults aged 40 years or older from 25 centers across mainland China between 2011 and 2012. The TyG index was calculated according to the formula: Ln (fasting triglycerides [mg/dL] × fasting glucose [mg/dL]/2). Multivariable-adjusted logistic regression models were used to evaluate odds ratios (ORs) and 95% confidence intervals (CIs) regarding the associations between the TyG index and breast cancer.ResultsMultivariable-adjusted logistic regression analysis showed that compared with the lowest quartile of the TyG index, the highest quartile of the TyG index was significantly associated with an increased risk of prevalent breast cancer, with an OR (95% CI) of 1.61 (1.19–2.17). In the stratified analysis, the association of each 1 SD increase in the TyG index with risk of prevalent breast cancer was more dominant in individuals with menarche at age 13–17, those who were postmenopausal, those with a history of breastfeeding, and those who had two to four children, with the ORs (95% CIs) of 1.35 (1.09–1.68), 1.27 (1.05–1.54), 1.26 (1.05–1.52), and 1.32 (1.08–1.62), respectively. Moreover, among those without discernible insulin resistance (homeostatic model assessment-insulin resistance [HOMA-IR] ≥2.5), hyperglycemia and dyslipidemia, each 1 SD increase in the TyG index was associated with a 1.36-fold increase in breast cancer risk, with an OR (95% CI) of 2.36 (1.44–3.87).ConclusionThe TyG index is significantly associated with the prevalent breast cancer risk among middle-aged and elderly Chinese women.

Nationwide estimates of the impact of common modifiable risk factors on mortality remain crucial. We aim to assess the influence of social determinants, lifestyle, and metabolic factors on mortality in 174,004 adults aged ≥40 years from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. We reveal that 17 modifiable factors are independently associated with mortality, accounting for 64.8% of all-cause mortality, 77.4% of cardiovascular mortality, and 44.8% of cancer mortality. Low education emerges as the leading factor for both all-cause and cancer mortality, while hypertension is predominant for cardiovascular mortality. Moreover, low gross domestic product per capita and high ambient particulate matter with a diameter of <2.5 μm (PM2.5) air pollution account for 7.8% and 4.3% for all-cause mortality, respectively, using a different method. Gender-specific analyses reveal distinct patterns, with women's mortality primarily associated with social determinants and men exhibiting stronger associations with lifestyle factors. Targeted health interventions are essential to mitigate mortality risks effectively in China.

Background:Sex differences in blood pressure (BP) levels and hypertension are important and the role of socioeconomic status (SES) in sex differences in hypertension remains unclear. Objective:This study aimed to evaluate the impact of SES on sex differences of hypertension in a nationally representative survey study. Methods:A total of 98,658 participants aged ≥18 years who have lived in their current residence for ≥6 months were recruited from 162 study sites across mainland China. Sex was self-reported. Individual-level SES included the highest level of education and annual household income. Area-level SES included economic development status, urban/rural residency, and north/south location. Outcomes included levels of systolic and diastolic BP, and hypertension. Linear and Cox regression models were used to examine the associations between sex (women vs men) and BP characteristics stratified by individual or combined SES indicators. Results:Systolic and diastolic BP levels and the prevalence of hypertension were higher in men than in women. This sex difference was found across categories of SES with widened sex disparities in participants having more favorable SES. Significant multiplicative interaction effects of SES on the association of sex with BP characteristics were found. Women with improving SES were associated with lower BP and hypertension prevalence compared to men. For combined SES, a 9% (prevalence ratio 0.91, 95% CI 0.83-0.98) and a 30% lower probability (prevalence ratio 0.70, 95% CI 0.63-0.78) of having hypertension were found in women with an overall intermediate SES and high SES, respectively, compared to those with low SES, while no significant reduction was found in men. Conclusions:There are significant sex differences in BP characteristics and SES has a potent impact on the disparities. Sex-specific public health policies to alleviate socioeconomic inequalities, especially in women are important for the prevention of hypertension.

BACKGROUND:Long-chain free fatty acids (FFAs) are associated with risk of incident diabetes. However, a comprehensive assessment of the associations in normoglycemic populations is lacking. OBJECTIVES:Our study aimed to comprehensively investigate the prospective associations and patterns of FFA profiles with diabetes risk among normoglycemic Chinese adults. METHODS:This is a prospective nested case-control study from the China Cardiometabolic Disease and Cancer Cohort (4C) study. We quantitatively measured 53 serum FFAs using a targeted metabolomics approach in 1707 incident diabetes subjects and 1707 propensity score-matched normoglycemic controls. Conditional logistic regression models were employed to estimate odds ratios (ORs) for associations. Least Absolute Shrinkage and Selection Operator (LASSO) penalty regression and quantile g-computation (qg-comp) analyses were implemented to estimate the association between multi-FFA exposures and incident diabetes. RESULTS:The majority of odd-chain FFAs exhibited an inverse association with incident diabetes, wherein the ORs per SD increment of all 7 saturated fatty acids (SFAs), monounsaturated fatty acid (MUFA) 15:1, and polyunsaturated fatty acid (PUFA) 25:2 were ranging from 0.79 to 0.88 (95% CIs ranging between 0.71 and 0.97). Even-chain FFAs comprised 99.3% of total FFAs and displayed heterogeneity with incident diabetes. SFAs with 18-26 carbon atoms are inversely linked to incident diabetes, with ORs ranging from 0.81 to 0.86 (95% CIs ranging between 0.73 and 0.94). MUFAs 26:1 (OR: 0.85; 95% CI: 0.76, 0.94), PUFAs 20:4 (OR: 0.84; 95% CI: 0.75, 0.94), and 24:2 (OR: 0.87; 95% CI: 0.78, 0.97) demonstrated significant associations. In multi-FFA exposure model, 24 FFAs were significantly associated with incident diabetes, most of which were consistent with univariate results. The mixture OR was 0.78 (95% CI: 0.61, 0.99; P = 0.04159). Differential correlation network analysis revealed pre-existing perturbations in intraclass and interclass FFA coregulation before diabetes onset. CONCLUSIONS:These findings underscore the variations in diabetes risk associated with FFAs across chain length and unsaturation degree, highlighting the importance of recognizing FFA subtypes in the pathogenesis of diabetes.

AIMS:To assess the excess risk of cardiovascular disease (CVD) associated with different criteria for metabolic health, and the interplay of body size, insulin sensitivity and metabolic health with CVD risk. MATERIALS AND METHODS:We conducted a prospective study involving 115 638 participants from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. Metabolic health was defined using three different definitions: (1) insulin sensitivity defined by homeostatic model assessment of insulin resistance index; (2) absence of metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III criteria; and (3) simultaneous absence of metabolic abnormalities (diabetes, hypertension, dyslipidaemia). The primary endpoint was a composite of incident CVD events comprising the first occurrence of myocardial infarction, stroke, heart failure, or cardiovascular death. RESULTS:During a mean 3.61-year follow-up period, obese individuals with insulin sensitivity (multivariable-adjusted hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.37-2.08), or without metabolic syndrome (HR 1.46, 95% CI 1.13-1.89) still exhibited increased CVD risks, when compared to their normal-weight counterparts. Otherwise, those with obesity but simultaneous absence of metabolic abnormalities demonstrated similar CVD risk compared to normal-weight individuals (HR 0.91, 95% CI 0.53-1.59). CVD risk increased with the number of abnormalities across body mass index categories, regardless of insulin sensitivity. CONCLUSIONS:This study emphasizes the need for refined definitions of metabolic health and advocates for meticulous screening for metabolic abnormalities to reduce cardiovascular risks, even in individuals with normal weight and insulin sensitivity.

Malnutrition in early life increases the risk of osteoporosis, but the association of early-life undernutrition combined with adulthood obesity patterns with low-energy fracture remains unknown. This study included 5323 community-dwelling subjects aged ⩾40 years from China. Early-life famine exposure was identified based on the participants’ birth dates. General obesity was assessed using the body mass index (BMI), and abdominal obesity was evaluated with the waist-to-hip ratio (WHR). Low-energy fracture was defined as fracture occurring after the age of ⩾40 typically caused by falls from standing height or lower. Compared to the nonexposed group, the group with fetal, childhood, and adolescence famine exposure was associated with an increased risk of fracture in women with odds ratios (ORs) and 95

AIMS:Studies have linked gut microbiome and heart failure (HF). However, their causal relationships and potential mediating factors have not been well defined. To investigate the causal relationships between the gut microbiome and HF and the mediating effect of potential blood lipids by using genetics. METHODS AND RESULTS:We performed a bidirectional and mediation Mendelian randomization (MR) study using summary statistics from the genome-wide association studies of gut microbial taxa (Dutch Microbiome Project, n = 7738), blood lipids (UK Biobank, n = 115 078), and a meta-analysis of HF (115 150 cases and 1550 331 controls). We applied the inverse-variance weighted estimation method as the primary method, with several other estimators as complementary methods. The multivariable MR approach based on Bayesian model averaging (MR-BMA) was used to prioritize the most likely causal lipids. Six microbial taxa are suggestively associated with HF causally. The most significant taxon was the species Bacteroides dorei [odds ratio = 1.059, 95% confidence interval (CI) = 1.022-1.097, P-value = 0.0017]. The MR-BMA analysis showed that apolipoprotein B (ApoB) was the most likely causal lipid for HF (the marginal inclusion probability = 0.717, P-value = 0.005). The mediation MR analysis showed that ApoB mediated the causal effects of species B. dorei on HF (proportion mediated = 10.1%, 95% CI = 0.2-21.6%, P-value = 0.031). CONCLUSION:The study suggested a causal relationship between specific gut microbial taxa and HF and that ApoB might mediate this relationship as the primary lipid determinant of HF.

Objectives Recent studies found that secreted protein acidic and rich in cysteine-like protein 1 (Sparcl1) could inhibit lipid droplets accumulation by peroxisome proliferator-activated receptor-gamma (PPARγ) signal pathway. However, the associations of serum Sparcl1 level with lipids profiles and other metabolic phenotypes remain unknown in human population study. Methods We determined serum Sparcl1 using sandwich enzyme-linked immunosorbent assays among 1750 adults aged 40 years and older from a community in Shanghai, China. Generalized linear regression models were used to evaluate the association between Sparcl1 and metabolic measures. Multivariable-adjusted logistic regression analyses were performed to evaluate the relationship of serum Sparcl1 with prevalent dyslipidemia. Results With the increment of serum Sparcl1, participants tended to have lower level of triglycerides, and higher level of high-density lipoprotein cholesterol (all P for trend < 0.01). No significant associations between serum Sparcl1 and glucose, blood pressure, or body size were observed. The generalized linear regression models suggested that per standard deviation (SD) increment of serum Sparcl1 was significantly inversely associated with triglycerides (β= -0.06, P=0.02). The prevalence of dyslipidemia decreased across the sparcl1 quartiles (P for trend <0.01). After controlling the potential confounders, participants in the highest quartile of sparcl1 concentration had the lowest prevalence of dyslipidemia (odds ratio [OR], 0.69; 95% confidence interval [CI], 0.52-0.91), compared with the lowest quartile. Per SD increment of Sparcl1 was associated with 20% (OR, 0.80; 95%CI, 0.69-0.94) lower prevalence of hypertriglyceridemia and 12% (OR, 0.88; 95%CI, 0.79-0.97) lower prevalence of dyslipidemia. The association between serum Sparcl1 and dyslipidemia were generally consistent across subgroups (all P for interaction > 0.05). Conclusion Serum Sparcl1 was significantly associated with decreased risk of prevalent dyslipidemia in Chinese population. Further studies are warranted to confirm this association.

Background The atherosclerotic cardiovascular disease (ASCVD) risk predicted by traditional risk factors is used to guide preventive treatment. We aimed to investigate whether preferable levels of non-traditional emerging risk factors (i.e., negative risk markers) could downgrade the predicted ASCVD risk beyond traditional risk factors. Methods A total of 7,568 Chinese adults aged ≥ 40 years were followed up during 2010–2015. Negative risk markers including non-traditional lipids, urinary albumin-to-creatinine ratio, electrocardiogram (ECG), and measurements of atherosclerosis were evaluated using diagnostic likelihood ratio (DLR) and continuous net reclassification index (NRI) for their ability to downshift predicted CVD risk in the overall study population and in participants with intermediate (traditional risk factor predicted ASCVD risk 7.5% to 19.9%) or high risk (≥20%). Results During a median follow-up of 4.5 years, 416 participants developed CVD events including non-fatal myocardial infarction, non-fatal stroke, and cardiovascular death. Among negative risk markers examined, lipoprotein(a) ≤ 10th percentile (5 mg/dL), normal ECG, and carotid intima-media thickness (CIMT) ≤ 25th percentile (0.5 mm) provided moderate CVD risk reclassification and downward changes in pre- to post-test risk on top of the traditional CVD risk factors, especially in high-risk participants. The DLRs were 0.41, 0.75, and 0.41, and the NRIs were 18, 22, and 14% for lipoprotein(a), ECG, and CIMT, respectively in high-risk participants. Conclusions Lipoprotein(a) ≤ 5 mg/dL, normal ECG, and CIMT ≤ 0.5 mm might be used as negative non-traditional risk markers to correctly downgrade predicted ASCVD risk in Chinese adults.

Background Age has substantial influence on metabolic diseases patterns. Ethnic disparities of metabolic characteristics between Chinese and other populations also exist. Large-scale investigations of age-specific prevalence, subtypes and modifiable risk factors of metabolic disorders are essential to promote individualized strategies for the control and prevention of metabolic diseases in multi-ethnic populations. The study aims to address the age-specific prevalence, subtype characteristics and risk factor profiles of metabolic diseases among different races/ethnicities. Methods We analyzed data from the China Noncommunicable Disease Surveillance 2010 and the National Health and Nutrition Evaluation Survey (NHANES). We examined the prevalence and subtypes of hypertension, diabetes and hyperlipidemia across age groups in four ethnic populations. We also investigated the odds ratios (ORs) of metabolic diseases associated with 11 classical risk factors in the young and the elder Mainland Chinese. Results The sex and BMI standardized prevalence of hypertension in Chinese aged 18–40 years was 18.5% and was the highest among the four populations. The main pathophysiologic subtype of diabetes was characterized by insulin resistance, instead of β-cell dysfunction in Mainland Chinese, and this pattern was more evident in obese subjects. The major subtype of hyperlipidemia in Mainland Chinese was hypertriglyceridemia, while Non-Hispanic Whites and Blacks were more prone to high low-density lipoprotein cholesterol. For risk of hypertension, diabetes and hyperlipidemia, young Chinese adults were more prone to general and central obesity than older ones. The other factors showed similar effects on the young and the old. Conclusions The age-specific prevalence, subtypes and risk factors of metabolic diseases were substantially different in Chinese and other ethnic/racial populations.

总结新型冠状病毒(新冠)奥密克戎变异株感染疫情下,上海交通大学医学院附属瑞金医院分部院区科研单位的疫情防控运行方案,核心内容是保障留守人员的健康安全,同时保障重大科研项目及临床支持工作的正常开展,包括分部院区的环境、人员及职能特征、疫情防控工作重点,以及核酸采样送检、临床样本处置流程、研究岗位返岗安排、员工人文关怀等内容.积极探索能切实保障留守分部院区科研及后勤人员在安全的工作和生活环境中、及时完成重要的防疫防控管理措施并不间断地完成主要科研和临床保障任务.

BACKGROUND:The updated definition of hypertension by the American College of Cardiology (ACC) and the American Heart Association (AHA) is an important paradigm shift and has lead to extensive discussion. We aimed to examine the association between the updated blood pressure (BP) categories and the risk of cardiovascular diseases (CVDs) with potential modifications from other cardiovascular health metrics (CVHMs). METHODS:This prospective study included 91,204 participants ≥40 years recruited from 20 community sites across mainland China. Participants were followed up during 2010-2016 for CVD events including nonfatal myocardial infarction, stroke, heart failure, and cardiovascular death. BP categories were defined according to the 2017 ACC/AHA guideline and CVHMs included smoking, physical activity, diet, body-mass index, total cholesterol, and fasting glucose. FINDINGS:Overall, 1,985 major CVD events occurred during a mean follow-up of 3.7 years. Having more ideal CVHMs significantly reduced the risk of CVD events in both stage 1 and stage 2 hypertension. Compared with participants without hypertension, participants having ≥4 ideal CVHMs were no longer associated with an increased CVD risk in stage 1 hypertension (HR=1·04; 95% CI=0·83-1·31), but less so in stage 2 hypertension (HR=1·90, 95% CI=1·70-2·13). Such pattern of association was more evident in participants aged <60 years (P for interaction <0·05). INTERPRETATION:Stage 1 hypertension defined by the ACC/AHA identifies individuals at increased CVD risk, which can be attenuated by achieving more preferable cardiovascular health, especially in adults aged <60 years.

Although previous studies suggest that amino acids (AAs) and microbiota-related metabolites (MRMs) are associated with type 2 diabetes mellitus (T2DM), the results remain unclear among normoglycemic populations. We test 28 serum AAs and 22 MRMs in 3,414 subjects with incident diabetes and matched normoglycemic controls from the China Cardiometabolic Disease and Cancer Cohort (4C) Study. In fully adjusted logistic regression models, per SD increment of branched-chain AAs, aromatic AAs, asparagine, alanine, glutamic acid, homoserine, 2-aminoadipic acid, histidine, methionine, and proline are positively associated with incident T2DM. In the MRM panel, serum carnitines, N-acetyltryptophan, and uric acid are positively associated with incident T2DM. Causal mediation analyses indicate 34 significant causal mediation linkages, with 88.2% through obesity and lipids. Variances explained in the serum metabolites are modestly limited in the comprehensive catalog of risk factor-metabolite-diabetes associations. These findings reveal that systematic AAs and MRMs change profile before T2DM onset and support a potential role of metabolic alterations in the pathogenesis of diabetes.

Background Early Vascular Aging and Supernormal Vascular Aging are two extreme phenotypes of vascular aging, and people in the two categories demonstrate distinct clinical characteristics and cardiovascular prognosis. However, the clinical implication of vascular aging categories in the Asian or Chinese population has not been investigated. We aimed to investigate the association between vascular aging categories and cardiovascular events in a Chinese cohort. Methods We explored the association of vascular aging categories with incident cardiovascular disease in a community cohort in Shanghai, China, which included 10,375 participants following up for 4.5 years. Vascular age was predicted by a multivariable linear regression model including classical risk factors and brachial-ankle pulse wave velocity. Early and Supernormal vascular aging groups were defined by 10% and 90% percentiles of Δ-age, which was calculated as chronological minus vascular age. Results We found that cardiovascular risk significantly increased in Early [hazard ratio (HR), 1.597 (95% CI, 1.043–2.445)] and decreased in Supernormal [HR, 0.729 (95% CI, 0.539–0.986)] vascular aging individuals, comparing with normal vascular aging subjects. The associations were independent of the Framingham risk score. Early vascular aging individuals also showed an elevated risk of total mortality [HR, 2.614 (95% CI, 1.302–5.249)]. Further, the associations of vascular aging categories with cardiovascular risk were much stronger in females than in males. Vascular aging categories with different cutoff levels expressed as percentiles (10th, 20th, and 25th) of Δ-age showed similar associations with cardiovascular risk. Conclusions In conclusion, the vascular aging categories could identify people with different levels of cardiovascular risk in the Chinese population, particularly in women.

BACKGROUND:Young-onset diabetes has been increasingly prevalent in China and most of the young patients with diabetes remain undiagnosed. Recently, the American Diabetes Association (ADA) updated their screening criteria and turned down the age threshold of diabetes screening from 45 years to 35 years, which highlighted the importance of identifying young individuals with diabetes. Herein, we aimed to evaluate the clinical relevance of updated ADA screening recommendations in Chinese adults and the metabolic features and risk factor profiles of these newly diagnosed individuals.STUDY DESIGN AND METHODS:Using a complex, multistage, probability sampling design, we analyzed data from a nationally representative sample of 98,658 Chinese adults in 2010. Participants without previously diagnosed diabetes were included into the present study. We calculated the proportion of individuals with diabetes eligible for screening and the number needed to screen (NNS) to identify one patient with diabetes by age groups.RESULTS:Setting an earlier age threshold of diabetes screening can identify additional 6.3 million patients with diabetes and 72.3 million individuals with prediabetes, and the proportion of identified individuals increased more in rural, underdeveloped, and central areas. The NNS in Chinese adults dropped significantly from 28 in 30-34 age group to 15 in 35-45 years of age and remained low afterwards. The undiagnosed patients with diabetes who met the new screening age threshold of ADA recommendation were characterized by younger age, lower blood pressure and blood lipids, but higher proportion of overweight and higher level of insulin resistance, and tended to have an unhealthy diet habit, including low intake of fruits and vegetables and high intake of sugar-sweetened beverages, compared to those aged over 45 years.CONCLUSIONS:The new age threshold of 35 years for diabetes screening would reduce the proportion of undiagnosed diabetes with high cost-effectiveness, given the NNS for a positive test result was much lower in 35-45 age group comparing to the lower age group in Chinese adults.

Abstract Background Prediabetes is an important risk factor of cardiovascular disease (CVD) and is associated with subclinical atherosclerosis. However, the evidence of prediabetes as a cardiovascular risk factor is mainly derived from middle-aged adults. Recently, multiple studies supported that prediabetes in older adults would not lead to higher risk of CVD or mortality. We aimed to investigate the age-specific difference in the association between prediabetes and subclinical atherosclerosis in a Chinese prospective cohort study. Methods We included 4739 individuals aged ≥ 40 years and without diagnosed diabetes or CVD history, and divided them into middle-aged adults (age < 60) and older adults (age ≥ 60). Fasting plasma glucose (FPG), 2-h post-load plasma glucose (2 h-PPG) and glycated hemoglobin (HbA1c) were measured at baseline to identify prediabetes status. At follow-up visits, subclinical atherosclerosis status was assessed by branchial-ankle pulse wave velocity (baPWV) and carotid intima-media thickness (CIMT). Logistic regression analysis, restricted cubic splines and cross-lagged path analysis were used in statistical analysis. Results 1634 participants aged over 60 years, and 64.3% of them had prediabetes. 3105 participants aged 40–59 years, and 49.3% of them had prediabetes. We found that prediabetes was associated with increased risk of subclinical atherosclerosis in middle-aged adults, but the association attenuated substantially in older adults. Impaired glucose tolerance (IGT), compared to normal glucose tolerance, was associated with 39% lower risk of increased baPWV only in older adults. In accordance, the association between 2 h-PPG and risk of increased baPWV was “U-shaped” in older adults, while risk of elevated baPWV increased linearly with 2 h-PPG in middle-aged adults. In the cross-lagged analysis, increase in FPG and 2 h-PPG tended not to precede increase in baPWV in older adults, but appeared to increase simultaneously with baPWV in middle-aged ones. Conclusion Our results indicated that prediabetes might be less related to subclinical atherosclerosis in older adults than in middle-aged adults and suggested that age was important to consider in the care of adults with prediabetes.

Objectives We aimed to investigate the association of circulating retinol-binding protein-4 (RBP4) levels with long-term cardiometabolic risk profiles and whether sex disparity mattered. Methods We included 784 non-diabetic participants aged 40 years and above from a well-defined community-based cohort at baseline in 2005 and they were invited to attend the on-site follow-up examination for two consecutive times with 3-year intervals in 2008 and 2011, respectively. Serum RBP4 was measured at baseline, and the anthropometry and biochemical measurements were performed at each visit. Generalized estimating equation models were used to assess the association of serum RBP4 levels with the dynamic changes in adiposity and glucolipid profile. Results Based on all the baseline and the 3- and 6-year follow-up data, baseline serum RBP4 levels (each 1-unit of log 10 RBP4) were significantly associated with waist circumference [β=3.12, 95% confidence interval (CI) (0.77, 5.47), P=0.01], fasting, and 2-h post-loading glucose [β=0.26 (0.05, 0.47), P=0.02, and 1.70 (1.29, 2.12), P< 0.0001], serum triglycerides [β=0.75, 95% CI (0.54, 0.96), P< 0.0001], total cholesterol [β=0.47, 95% CI [0.23 0.70], P<0.0001), and marginally with body mass index (β=0.97, 95% CI (0.02, 1.93), P=0.046], in total participants, after adjusting potential confounders. The association of RBP4 with 2-h post-loading glucose was stronger in women than that in men [β=1.99, 95% CI (1.49, 2.50) vs. 0.61 (-0.14, 1.36), P for interaction=0.001]. The analysis of change in Z-score of cardiometabolic profiles corresponding to each 1-unit increment in log 10 RBP4 showed consistent results. Conclusions Higher RBP4 levels are associated with longitudinal increase in adiposity and deteriorated glucolipid profile defined by repeated measurements. The associations differ in sex regarding to the 2-h post-loading glucose.