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.

Disentangling Organ-Specific Roles of Farnesoid X Receptor in Bile Acid and Glucolipid Metabolism.

Background And Aims: The farnesoid X receptor (FXR) is an attractive pharmaceutical target for metabolic dysfunction-associated steatotic liver disease (MASLD). However, its tissue-specific roles in energy metabolism remain controversial, hindering the development of effective therapies. To address this, new approaches are required.

Gut Microbiota-Butyrate-PPARγ Axis Modulates Adipose Regulatory T Cell Population.

Gut microbiota is essential for the function of peripherally-induced regulatory T (pTreg) cells. However, how commensal bacteria affect thymically derived fat-resident Treg cells that harbor a unique expression of peroxisome proliferator-activated receptor (PPAR)-γ and suppress inflammation in visceral adipose tissue (VAT), is not well defined. Here it is revealed that microbiota depletion causes a drastic decline in Treg cell population in VAT, particularly those expressing ST2 (ST2 Treg), which are largely restored after gut microbiome reconstruction.

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.

Post sleeve gastrectomy-enriched gut commensal Clostridia promotes secondary bile acid increase and weight loss.

The gut microbiome is altered after bariatric surgery and is associated with weight loss. However, the commensal bacteria involved and the underlying mechanism remain to be determined. We performed shotgun metagenomic sequencing in obese subjects before and longitudinally after sleeve gastrectomy (SG), and found a significant enrichment in microbial species in Clostridia and bile acid metabolizing genes after SG treatment.

Subcutaneous depth-selective spectral imaging with mμSORS enables noninvasive glucose monitoring.

Noninvasive blood glucose monitoring offers substantial advantages for patients, but current technologies are often not sufficiently accurate for clinical applications or require personalized calibration. Here we report multiple μ-spatially offset Raman spectroscopy, which captures Raman signals at varying skin depths, and show that it accurately detects blood glucose levels in humans. In 35 individuals with or without type 2 diabetes, we first determine the optimal depth for glucose detection to be at or below the capillary-rich dermal-epidermal junction, where we observe a strong correlation between specific Raman bands and venous plasma glucose concentrations.

Akkermansia muciniphila supplementation in patients with overweight/obese type 2 diabetes: Efficacy depends on its baseline levels in the gut.

Akkermansia muciniphila is a promising target for managing obesity and type 2 diabetes (T2D), but human studies are limited. We conducted a 12-week randomized, double-blind, placebo-controlled trial involving 58 participants with overweight or obese T2D, who received A. muciniphila (AKK-WST01) or placebo, along with routine lifestyle guidance.

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.

PI3K/AKT/mTOR Activation is Associated with Malignant Severity and Poorer Prognosis in Parathyroid Carcinomas.

Context And Objective: Parathyroid carcinoma (PCa) is a rare endocrine neoplasm known for its high recurrence. The specific molecular properties influencing the prognosis of PCa remain largely elusive. The present study was designed to explore the significance of PI3K/AKT/mTOR activation in PCa.

LGR4 is a key regulator of hepatic gluconeogenesis.

Aims/hypothesis: Emerging evidence underscored the significance of leucine-rich repeat-containing G protein-coupled receptor (LGR) 4 in endocrine and metabolic disorders. Despite this, its role in LGR4 in hepatic glucose metabolism remains poorly understood. In this study we set out to test whether LGR4 regulates glucose production in liver through a specific signaling pathway.

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.

A feeding-induced myokine modulates glucose homeostasis.

Maintaining blood glucose homeostasis during fasting and feeding is crucial for the prevention of dysregulation that can lead to either hypo- or hyperglycaemia. Here we identified feimin, encoded by a gene with a previously unknown function (B230219D22Rik in mice, C5orf24 in humans), as a key modulator of glucose homeostasis. Feimin is secreted from skeletal muscle during feeding and binds to its receptor, receptor protein tyrosine kinase Mer (MERTK), promoting glucose uptake and inhibiting glucose production by activation of AKT.

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.

A famsin-glucagon axis mediates glucose homeostasis.

Glucagon is essential for glucose homeostasis, and its dysregulation is associated with diabetes. Despite extensive research, the mechanisms governing glucagon secretion remain incompletely understood. Here, we unveil that famsin, a gut-secreted hormone, promotes glucagon release and modulates glucose homeostasis.

Standardized assessment of energy excretion in healthy adults: a novel methodology.

Background: Accurate monitoring of energy balance is essential for effective weight management, but the role of energy excretion is often neglected.

Objectives: This study aimed to develop and validate a standardized method for assessing energy excretion using dye-labeled meal replacement bars with consistent and stable ingredients.

Methods: We utilized baseline data from a registered cross-over trial involving 12 healthy adults (7 females and 5 males) with a body mass index of 18-25 kg/m.

π-HuB: the proteomic navigator of the human body.

The human body contains trillions of cells, classified into specific cell types, with diverse morphologies and functions. In addition, cells of the same type can assume different states within an individual's body during their lifetime. Understanding the complexities of the proteome in the context of a human organism and its many potential states is a necessary requirement to understanding human biology, but these complexities can neither be predicted from the genome, nor have they been systematically measurable with available technologies.

Sex Difference and Socioeconomic Inequity in Chinese People With Hypertension: National Cross-Sectional Survey Study.

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.