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To detect the levels of plasma High-Mobility Group Box-1(HMGB1) in Chinese subject with obesity and type 2 diabetes mellitus (T2DM), and to investigate the correlations between plasma HMGB1 concentration and parameters of body fat, insulin resistance (IR) metabolism and inflammation. This study recruited 79 normal glucose tolerance (NGT) subjects and 76 newly diagnosed T2DM patients. NGT and T2DM groups were divided into normal weight (NW) and obese (OB)subgroups respectively. Anthropometric parameters such as height, weight, waist circumference, hip circumference and blood pressure were measured. Plasma concentrations of HMGB1, IL-6, fasting plasma glucose (FPG), 2 hours post challenge plasma glucose (2hPG), serum lipid, glycated hemoglobin (HbA1C) and fasting insulin (FINS) were examined. The homeostasis model assessment (HOMA) was performed to assess IR status. Plasma HMGB1 levels were higher in T2DM group than that in NGT group. The concentrations of serum HMGB1 were also higher in subjects with OB than those in subjects with NW both in NGT and T2DM groups. Plasma levels of HMGB1 were positively correlated with waist hip ratio (WHR), blood pressure, FPG, FINS, HOMA-IR, TG, IL-6 and negatively correlated with HOMA-βand high-density lipoprotein-cholesterol (HDL-c) independent of age, gender and BMI. Plasma levels of HMGB1 were significantly correlated with diabetes in fully adjusted models. Plasma HMGB1 levels were increased in Chinese subjects with pure T2DM, which might be caused by IR. Serum HMGB1 participated in the pathological process of obesity and T2DM via its proinflammatory effect.

Metabolic diseases are the most common and rapidly growing health issues worldwide. The massive population-based human genetics is crucial for the precise prevention and intervention of metabolic disorders. The China Metabolic Analytics Project (ChinaMAP) is based on cohort studies across diverse regions and ethnic groups with metabolic phenotypic data in China. Here, we describe the centralized analysis of the deep whole genome sequencing data and the genetic bases of metabolic traits in 10,588 individuals from the ChinaMAP. The frequency spectrum of variants, population structure, pathogenic variants and novel genomic characteristics were analyzed. The individual genetic evaluations of Mendelian diseases, nutrition and drug metabolism, and traits of blood glucose and BMI were integrated. Our study establishes a large-scale and deep resource for the genetics of East Asians and provides opportunities for novel genetic discoveries of metabolic characteristics and disorders.

Both longer habitual day napping and Non-Alcoholic Fatty Liver Disease (NAFLD) are associated with diabetes and inflammation, but the association between day napping and NAFLD remains unexplored. To investigate the association between the duration of habitual day napping and NAFLD in an elderly Chinese population and to gain insight into the role of inflammatory cytokines in this association. We conducted a series of cross-sectional studies of the community population in Chongqing, China, from 2011 to 2012. Among 6998 participants aged 40 to 75 years, 6438 eligible participants were included in the first study and analyzed to observe the association between day napping duration and NAFLD. In a separate study, 80 non-nappers and 90 nappers were selected to identify the role of inflammatory cytokines in this association. Logistic regression models were used to examine the odds ratios (ORs) of day nap duration with NAFLD. Day nappers had a significantly higher prevalence of NAFLD (P<0.001). Longer day napping duration was associated in a dose-dependent manner with NAFLD (P trend <0.001). After adjustment for potential confounders, the ORs were 1.67 (95% CI 1.13-2.46) for those reporting 0.5-1 h and 1.49 (95% CI 1.01-2.19) for those reporting >1 h of day napping compared with individuals who did not take day naps (all P<0.05). Longer-duration day nappers had higher levels of IL-6 and progranulin (PGRN) but lower levels of Secreted frizzled-related protein-5 (SFRP5, all P trend <0.001). After adjusting for IL-6, PGRN, and SFRP5, the association between day napping duration and NAFLD disappeared (all P>0.05). Longer day napping duration is associated with a higher prevalence of NAFLD, and inflammatory cytokines may be an essential link between day napping and NAFLD.

Background Whether smoking modifies the associations of diabetes and risk factor management with subsequent risk of cardiovascular disease (CVD), and whether the smoking related CVD risk differs among people with and without diabetes are unclear. This study aimed to examine the associations and interactions of smoking, diabetes, and risk factor management in relation to incident CVD. Methods This nationwide, population-based, prospective cohort study of 20 communities from various geographic regions recruited adults aged 40 years or older during 2011–2012. The follow-up survey was conducted between 2014 and 2016. This study included 126,181 participants who were free from CVD at baseline. Results Study participants included 19,397 current smokers (15.4%), 6,049 former smokers (4.8%), and 100,735 never smokers (79.8%). Mean (SD) age ranged from 55.8 (8.6) years to 60.7 (9.1) years. Compared with never smokers, heavy smokers exhibited a greater risk of CVD events among participants with diabetes (multivariable-adjusted hazard ratio [HR], 1.45; 95% CI, 1.17–1.78) than among participants without diabetes (HR, 1.20; 95% CI, 1.01–1.42; P for interaction = 0.006). Compared with participants without diabetes, participants with diabetes who were never smokers and had 5 or more controlled risk factors showed no significantly excess CVD risk (HR, 0.93; 95% CI, 0.71–1.22), but the cardiovascular benefits from risk factor management were counteracted among participants with diabetes who were current smokers (HR, 1.28; 95% CI, 0.77–2.14) or former smokers (HR, 1.22; 95% CI, 0.66–2.28). Conclusions Smoking and diabetes interacted with each other in relation to increased risk of CVD events, and the beneficial effect of risk factor management on CVD risk among participants with diabetes was attenuated by current or former smoking.

BackgroundAlthough socioeconomic inequality in mortality has long been a public health focus, the associations of area-level socioeconomic status (SES) and individual-level factors with mortality have not been well investigated, especially in China with rapid industrial development.MethodsIn this nationwide, population-based, prospective cohort study, adults aged over 40 from 29 counties were included in the China Cardiometabolic Disease and Cancer Cohort study. The composite area deprivation index of area-level SES was generated from national census data and categorised into tertiles. Cox proportional hazards models were fitted to calculate HRs and 95% CIs for area-level SES with the risk of mortality, and comprehensive individual socioeconomic, lifestyle, and metabolic factors were examined as potential mediators.ResultsA total of 174 004 participants were included. During a median follow-up of 10.1 years, low area-level SES was associated with 34% increased risk of all-cause mortality (95% CI 1.27 to 1.42), 76% increased risk of cardiovascular disease (CVD) mortality (95% CI 1.59 to 1.94) and 13% increased risk of non-CVD mortality (95% CI 1.05 to 1.21) compared with high area-level SES. The association between area-level SES and all-cause mortality was partly mediated by individual socioeconomic, lifestyle and metabolic factors, contributing 3.8%, 20.7% and 8.9%, respectively. Furthermore, individuals with low area-level SES and low individual SES, unhealthy lifestyles, or poor metabolic status had the highest risk of mortality.ConclusionsSignificant area-level socioeconomic inequalities in mortality exist in China. Comprehensive interventions targeting both area-level circumstances and individual socioeconomic, lifestyle and metabolic factors were key strategies to reduce these inequalities.

Aims/Introduction The purpose of the present study was to observe the relationship between serum α‐klotho (KL) protein level and diabetic retinopathy (DR), and to further examine the effects of KL protein on apoptosis induced by palmitic acid (PA) in human retinal endothelial cells. Materials and Methods A total of 17 healthy people and 60 type 2 diabetes patients were included. According to the results from fundus fluorescein angiography, the diabetes patients were divided into three subgroups: without DR, non‐proliferative DR and proliferative DR. Serum KL level was measured by enzyme‐linked immunosorbent assay. In vitro, human retinal endothelial cells were exposed to PA with or without KL protein. Apoptosis rates were analyzed by flow cytometry analysis. Apoptotic‐related protein expressions were detected by western blotting analysis. Results Serum KL level was lower in diabetes patients than that in healthy participants (P = 0.007), and was gradually decreased among the without DR, non‐proliferative DR and proliferative DR subgroups (P = 0.045). A logistic regression analysis showed that after adjusting for the other confounding factors, serum KL level was independently and negatively related with DR (P = 0.049). Furthermore, the increased apoptosis rates induced by PA were inhibited with the addition of KL protein. Consistently, KL protein reversed the expression levels of the increased pro‐apoptotic protein Bax and the decreased anti‐apoptotic protein Bcl‐2 induced by PA. However, the anti‐apoptotic effect of KL protein was attenuated by LY294002 through the phosphatidylinositol 3 kinase‐serine∕threonine kinase pathway. Conclusions The data suggested that KL protein was probably a potential protective factor against retinopathy in type 2 diabetes patients. α‐Klotho plays important vasculoprotective roles. We analyzed the relationship between serum klotho level and diabetic retinopathy by clinical and cell data. The results suggested that klotho protein was probably a potential protective factor against retinopathy in type 2 diabetes patients.

Aims Nonalcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome and is closely associated with insulin resistance (IR). The ZJU index is based on body mass index (BMI), fasting plasma glucose (FPG), triglycerides (TG) and the serum alanine aminotransferase-to-aspartate transaminase ratio, and is proven to be a novel and effective parameter for screening NAFLD in the Chinese population. We aimed to analyze the relationship between the ZJU index and IR. Methods A cross-sectional study of 3329 Chinese adults was performed. Blood pressure (BP), anthropometric measurements and biochemical parameters were tested. The BMI, ZJU index and homeostasis model assessment of IR (HOMA-IR) were calculated. Results In both genders, BP, waist circumference, BMI, total cholesterol, TG, low-density lipoprotein cholesterol levels, FPG, postprandial glucose levels, fasting insulin and the HOMA-IR gradually increased, while the HDL-C decreased across the quartiles of the ZJU index ( P  < 0.001). The logistic regression analysis showed that the risk of IR was significantly elevated in the highest quartile of the ZJU index. Additionally, the area under the receiver operating characteristic curve of the ZJU index was 0.833 (95 % CI 0.809–0.858) in males and 0.788 (95 % CI 0.758–0.818) in females and was relatively higher than other common variables. Conclusions The ZJU index is a useful indicator for recognizing IR in the Chinese general population.

Growth factor receptor-bound protein 10 (Grb10) is an adaptor protein that can negatively regulate the insulin-like growth factor 1 receptor (IGF-1R). The IGF1-1R pathway is critical for cell growth and apoptosis and has been implicated in kidney diseases; however, it is still unknown whether Grb10 expression is up-regulated and plays a role in diabetic nephropathy. Catalpol, a major active ingredient of a traditional Chinese medicine, Rehmannia, has been reported to possess anti-inflammatory and anti-aging activities and then used to treat diabetes. Herein, we aimed to assess the therapeutic effect of catalpol on a mouse model diabetic nephropathy and the potential role of Grb10 in the pathogenesis of this diabetes-associated complication. Our results showed that catalpol treatment improved diabetes-associated impaired renal functions and ameliorated pathological changes in kidneys of diabetic mice. We also found that Grb10 expression was significantly elevated in kidneys of diabetic mice as compared with that in non-diabetic mice, while treatment with catalpol significantly abrogated the elevated Grb10 expression in diabetic kidneys. On the contrary, IGF-1 mRNA levels and IGF-1R phosphorylation were significantly higher in kidneys of catalpol-treated diabetic mice than those in non-treated diabetic mice. Our results suggest that elevated Grb10 expression may play an important role in the pathogenesis of diabetic nephropathy through suppressing IGF-1/IGF-1R signaling pathway, which might be a potential molecular target of catalpol for the treatment of this diabetic complication.

Background Definition 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. Methods The 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. Results Compared 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). Conclusions The 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. Graphic abstract

Vascular disease is the leading cause of death worldwide. Predicting the burden of vascular disease and identifying modifiable key risk factors are critical for developing effective prevention strategies. This study aimed to project the global and regional burden of peripheral artery disease (PAD) from 2021 to 2050, with a specific focus on the impact of modifiable key risk factors and the potential benefits of their management. Compared to the 2021 Global Burden of Disease Study (GBD 2021), the number of PAD cases worldwide is projected to increase by 220% by 2050, reaching a staggering 360 million (95% uncertainty interval, 270 to 450). Age-standardized mortality is expected to double, while disability-adjusted life years (DALYs) are forecasted to rise from 19.7 to 33.1 per 100,000. Among individuals aged ≥65 years, PAD prevalence is projected to surge to 21.7% in women and 14.8% in men. Moreover, over 50% of PAD cases are expected to occur in low- and middle-income countries (LMICs). Metabolic diseases are anticipated to be the primary drivers of the rising PAD burden, with diabetes playing a key role in increasing PAD prevalence and severity. By effectively managing metabolic risk factors, age-standardized prevalence could be reduced by 36%, mortality by 17%, and DALYs by 10%. As metabolic risks, particularly diabetes, continue to rise alongside population aging, the global PAD burden is expected to increase substantially, especially in LMICs. Importantly, proactive metabolic risk management strategies have the potential to markedly alleviate the burden of vascular disease and reduce the growing geographic health disparities.