Heterogeneity in Phenotype and Early Metabolic Response to Lifestyle Interventions in Type 2 Diabetes in China Using a Tree-Like Representation.

Unlabelled: Deciphering the heterogeneity of type 2 diabetes in prognosis and treatment effect is essential. We used a novel dimensionality reduction approach to describe the type 2 diabetes phenotype continuum and visualize the difference in lifestyle intervention efficacy in Chinese patients. Based on 17,816 participants with newly diagnosed type 2 diabetes (aged ≥40 years) from a nationwide cohort, 12 key phenotypes were residualized for age and sex to construct a two-dimensional tree structure.

Heterogeneity of diabetes and disease progression with a tree-like representation: findings from the China Cardiometabolic Disease and Cancer Cohort (4C) study.

Aims/hypothesis: Diabetes heterogeneity has been modelled as a continuum in European populations, but its phenotypes and long-term comorbidity risks remain unclear in Chinese individuals. This study aimed to identify distinct phenotypes and evaluate their links to future cardiometabolic risks in a large Chinese cohort.

Methods: The discriminative dimensionality reduction with trees (DDRTree) algorithm was used to develop a tree structure based on nine clinical variables.

Revisiting obesity thresholds for cardiovascular disease and mortality risk in Chinese adults: Age- and gender-specific insights.

Current obesity classifications may not adequately reflect age- and gender-specific risks in diverse populations. In a prospective cohort study of 166,285 Chinese adults aged ≥40 years without prior cardiovascular disease (CVD) or cancer, we evaluate optimal thresholds of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) for predicting incident CVD and all-cause mortality. We observe monotonically increasing dose-response associations of BMI, WC, and WHR with CVD risk but U-shaped relationships with all-cause mortality.

Identification of gut microbiota causally associated with aging and longevity and mediation roles of the cerebrospinal fluid proteins: proteomic genetic evidence from Mendelian randomization.

Gut microbiota (GM) is implicated in aging biology, yet its dual regulatory role in the distinct yet interconnected processes of lifespan extension and aging remains poorly understood. This study employed genetic approaches to identify GM taxa exerting causal effects on longevity and aging and assess the mediation role of cerebrospinal fluid (CSF) proteins. We leveraged summary statistics of the GM taxa (207 taxa, 7738 participants from the Dutch Microbiome Project), the CSF proteins (7008 aptamers, 3506 participants), and the longevity and aging phenotypes (UK Biobank, Longevity Genomics, and Edinburgh DataShare) from the largest genome-wide association studies so far.

Trajectories of muscle strength and physical performance preceding dementia in older US and European populations.

Background: The association between muscle function and dementia risk remains elusive, as studies suggest that impaired muscle function may act as both a risk factor for and a consequence of dementia, hindering causal inference.

Objectives: We aimed to clarify the temporal relationship between muscle function and incident dementia by investigating non-linear trajectories of muscle function in the years preceding dementia onset in older US and European populations.

Design: Case-control study.

Elucidating the heterogeneity of prediabetes through subphenotyping with a two-dimensional tree structure.

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).

Effects of different levels of physical activity on the health-related quality of life among rural junior high school students in China: the moderating role of parental co-participation in physical activities.

Background: Health benefits are associated with physical activity (PA) and PA levels. This study aims to explore the impact of PA levels (low, moderate, high) on health-related quality of life (HRQoL) among rural junior high school students in China, as well as the moderating role of parental co-participation in physical activities.

Methods: A stratified cluster sampling method was used to select 1,440 junior high school students from rural areas in southwest China.

Associations of area-level socioeconomic status and individual factors with mortality in China: a nationwide prospective cohort study.

Background: Although 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.

Methods: In 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.

The physicochemical characteristics, volatile profiles and sensory attributes of the ciders made with juices or corresponding pomaces from different apple cultivars.

This study examined the differences in physico-chemical, volatile and sensory characteristics between the ciders made with the juices from four apple cultivars (Golden delicious, Fuji, Ralls genet, and Xiushui) and the ciders prepared with corresponding pomaces. These cider characteristics varied with apple cultivar and fermentation raw material, with fermentation raw material imparting more influence. Compared with ciders made with apple juices, the counterparts of apple pomaces showed higher contents of total sugar (2.

Comparison of Different Intermittent Fasting Patterns or Different Extents of Calorie Restriction for Weight Loss and Metabolic Improvement in Adults: A Systematic Review and Network Meta-Analysis of Randomized Controlled Trials.

Context: Continuous energy restriction (CER) and intermittent fasting (IF) are both prevalent diet regimens recommended for weight loss and metabolic improvement.

Objective: The objective of this study was to evaluate the efficacy of CER and IF on weight loss and metabolic improvement in adults with overweight, obesity, or metabolic abnormalities.

Data Sources: PubMed, Embase, and the Cochrane Library (CENTRAL) were searched for randomized controlled trials of 3 degrees of CER diet regimens and 4 categories of IF diet regimens, from inception of the databases to December 2022.

Life's Essential 8 cardiovascular health, cardiovascular-kidney-metabolic syndrome stages, and incident cardiovascular events: a nationwide 10-year prospective cohort study in China.

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.

New Evidence, Creative Insights, and Strategic Solutions: Advancing the Understanding and Practice of Diabetes Osteoporosis.

Background: Diabetes osteoporosis is a debilitating condition that significantly impacts human health. However, it is often underdiagnosed and not addressed in a timely or appropriate manner.

Methods: Recent studies were reviewed to explore the roles of energy metabolism, sarcopeina, low-grade inflammation and gut microbiota in the development of diabetes osteoporosis.

Chain effect of lifecourse reproductive characteristics and body fat and muscle on cardiovascular disease in women: a Mendelian randomization study.

Background: Delineating the causal chain effects of reproductive traits and fat- and muscle-related traits on cardiovascular disease (CVD) is essential for optimizing precision prevention and control of cardiovascular health in women.

Methods: In this study, we applied the two-sample Mendelian randomization (MR) analyses and two-step MR framework to investigate the causal chain effects and the mediating effect pathways among reproductive factors and fat- and muscle-related traits on CVD outcomes in women, applying the genome-wide association study summary statistics of 16 women's reproductive traits across puberty and pre-pregnancy, pregnancy and postpartum, and menopausal transition stages, 16 women's fat- and muscle-related traits, and five CVD outcomes of coronary artery disease (CAD), myocardial infarction (MI), heart failure, atrial fibrillation, and ischemic stroke (IS) from over one million individuals of European descent.

Results: The MR analyses revealed the associations of genetically predicted nine reproductive traits (i.

Identifying PDAP1 as a Biological Target on Human Longevity: Integration of Mendelian Randomization, Cohort, and Cell Experiments Validation Study.

Identifying factors affecting lifespan, including genes or proteins, enables effective interventions. We prioritized potential drug targets and provided insights into biological pathways for healthy longevity by integrating Mendelian randomization, cohort, and experimental studies. We identified causal effects of tissue-specific genetic transcripts and serum protein levels on three longevity outcomes: the parental lifespan, the top 1% and 10% extreme longevity, utilizing Mendelian randomization and multi-traits colocalization, combining the latest genetics data of gene expression (eQTLGen and GTEx) and proteomics (4746 proteins from five studies).

Intensive systolic blood pressure control in patients with or without worsening renal function.

Aims: Intensive systolic blood pressure (BP) control is associated with a lower risk of cardiovascular disease (CVD) but an increased risk of worsening renal function (WRF). This study aimed to investigate whether intensive BP control should be continued after WRF.

Methods: We performed a post hoc analysis of SPRINT (Systolic Blood Pressure Intervention Trial).

Circulating short-chain and branched short-chain fatty acids and the risk of incident type 2 diabetes: findings from the 4C study.

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.

Association of body roundness index with cardiovascular disease and all-cause mortality among Chinese adults.

Aims: To determine the impact of body roundness index (BRI) on the 10-year risk of cardiovascular disease (CVD) and all-cause mortality in Chinese adults.

Materials And Methods: We utilized data from a nationwide prospective cohort of 165 785 Chinese adults (aged ≥40 years, free of CVD and cancer at baseline), which was extracted from the China Cardiometabolic Disease and Cancer Cohort (4C). Cox regression and restricted cubic splines quantified BRI-outcome associations and identified optimal BRI cutoffs.

Single-cell transcriptome-wide Mendelian randomization and colocalization reveals immune-mediated regulatory mechanisms and drug targets for COVID-19.

Background: COVID-19 continues to show long-term impacts on our health. Limited effective immune-mediated antiviral drugs have been launched.

Methods: We conducted a Mendelian randomization (MR) and colocalization analysis using 26,597 single-cell expression quantitative trait loci (sc-eQTL) to proxy effects of expressions of 16,597 genes in 14 peripheral blood immune cells and tested them against four COVID-19 outcomes from COVID-19 Genetic Housing Initiative GWAS meta-analysis Round 7.

WBSCR16 is essential for mitochondrial 16S rRNA processing in mammals.

Mitochondrial rRNAs play important roles in regulating mtDNA-encoded gene expression and energy metabolism subsequently. However, the proteins that regulate mitochondrial 16S rRNA processing remain poorly understood. Herein, we generated adipose-specific Wbscr16-/-mice and cells, both of which exhibited dramatic mitochondrial changes.

Exploring age and gender disparities in cardiometabolic phenotypes and lipidomic signatures among Chinese adults: a nationwide cohort study.

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.

Effect of insulin sensitivity, insulin secretion, and beta cell function on the remission of type 2 diabetes: A post hoc analysis of the IDEATE trial.

Aims: To compare the probability of achieving diabetes remission in individuals with different phenotypes of insulin sensitivity, insulin secretion, and beta cell function and further detect the effects of diet, exercise, and lifestyle education intervention on these indexes.

Methods: Three-hundred and one participants who had glycated haemoglobin (HbA1c) data at baseline and after intervention were included for this post hoc analysis. We used the multi-way analysis of variance to assess the differences between the diabetes remission and non-remission groups or between intervention groups in changes of the indexes of insulin sensitivity, insulin secretion, and beta cell function.

Socioeconomic and mental health inequalities in global burden of type 2 diabetes: Evidence from the Global Burden of Disease Study 2021.

Aim: To explore the holistic impact of socioeconomic and mental health inequalities on the global burden of type 2 diabetes.

Materials And Methods: This cross-sectional study used data on the incidence, disability-adjusted life years (DALYs), and mortality of type 2 diabetes as well as DALYs attributable to risk factors during 1990-2021 from the Global Burden of Disease Study 2021. Average annual percent change (AAPC) was applied to assess the temporal trends from 1990 to 2021.

Heterogeneous blood pressure treatment effects on cognitive decline in type 2 diabetes: A machine learning analysis of a randomized clinical trial.

Aim: We aimed to identify the characteristics of patients with diabetes who can derive cognitive benefits from intensive blood pressure (BP) treatment using machine learning methods.

Materials And Methods: Using data from the Action to Control Cardiovascular Risk in Diabetes Memory in Diabetes (ACCORD-MIND) study, 1349 patients with type 2 diabetes who underwent BP treatment (intensive treatment targeting a systolic BP <120 mmHg vs. standard treatment targeting <140 mmHg) were included in the machine learning analysis.

Gallstones, cholecystectomy, and cancer risk: an observational and Mendelian randomization study.

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations.

Shared genetic architecture of type 2 diabetes with muscle mass and function and frailty reveals comorbidity etiology and pleiotropic druggable targets.

Background: Delineating the shared genetic architecture of type 2 diabetes with muscle mass and function and frailty is essential for unraveling the common etiology and developing holistic therapeutic strategies for these co-existing conditions.

Methods: In this genome-wide pleiotropic association study, we performed multi-level pairwise trait pleiotropic analyses using genome-wide association study summary statistics from up to 461,026 European ancestry individuals to dissect the shared genetic factors and causal relationships of type 2 diabetes and seven glycemic traits with four muscle mass- and function-related phenotypes and the frailty index.

Results: We first identified 27 pairs with significant genetic correlations through the linkage disequilibrium score regression and high-definition likelihood analysis.