OBJECTIVE:To evaluate the glycaemic outcomes of a novel calibration-free hybrid closed-loop (HCL) system in adolescents and adults with type 1 diabetes (T1D). METHODS:This multicentre pivotal trial enrolled 123 participants (21 adolescents aged 14-17 years and 102 adults aged ≥ 18 years) with T1D. All participants used the MicroTech Medical Equil S HCL system, which integrates a patch insulin pump with the AIDEX G7 calibration-free continuous glucose monitor. After a 2-week run-in period with the pump in manual mode, automated insulin delivery (auto mode) was enabled for a 12-week study phase. The primary outcome was the change in CGM-derived time in range (TIR; 70-180 mg/dL) from the run-in to the study phase. RESULTS:The median time spent in automated mode was 88.4% (IQR 76.6%-92.0%) in adolescents (mean age 15.5 ± 1.0 years) and 91.6% (IQR 87.8%-94.1%) in adults (mean age 39.4 ± 13.2 years). TIR increased significantly from 63.7% to 68.3% in adolescents (mean difference 4.6% [95% CI: 0.7-8.6]; p = 0.024) and from 69.6% to 78.0% in adults (mean difference 8.0% [95% CI: 6.3-9.8]; p < 0.001). Time below range (< 70 mg/dL) decreased from 4.1% to 3.0% in adolescents (p = 0.032) and from 3.8% to 2.7% in adults (p < 0.001). HbA1c decreased from 7.0% to 6.9% in adolescents (p = 0.011) and from 6.6% to 6.3% in adults (p < 0.001). No episodes of severe hypoglycaemia or diabetic ketoacidosis occurred. Patient-reported outcomes showed significantly higher treatment satisfaction and convenience scores at study end compared with baseline. CONCLUSIONS:In this first pivotal trial of a novel integrated HCL system, 3-month use was safe and significantly improved glycaemic control-increasing TIR while reducing HbA1c and hypoglycaemia-accompanied by enhanced treatment satisfaction in both adolescents and adults with T1D. TRIAL REGISTRATION:Chinese Clinical Trial Register Identifier: ChiCTR2300074200.

Metabolic dysfunction-associated fatty liver disease (MAFLD), which affects over 35% of the global adult population, currently lacks therapies that are safe, well tolerated, and suitable for long-term use. To enable safe and long-term intervention, we aimed to identify the optimal formulation and therapeutic value from several herbal plants while ensuring palatability for better acceptance. We evaluated the synergistic effects of Siraitia grosvenorii (monk fruit), Dimocarpus longan (longan), and Orthosiphon stamineus (misai kucing) on MAFLD. Utilizing in vivo/in vitro models, we demonstrated that the longan-misai kucing combination exhibits synergistic anti-inflammatory and hepatic lipid-clearing efficacy, surpassing that of individual monotherapies. Quinic acid and tormentic acid were further identified as key bioactive compounds of longan and misai kucing, targeting ERα and PI3K/AKT pathways via direct binding to PIK3CA, PIK3CB, and ESR1. These compounds synergistically reduced hepatic triglycerides (-59.3%) and cholesterol (-35.2%) levels, body fat mass (23.3%), and adipose tissue weight (inguinal: 39.6%; epididymal: 26.2%). This study demonstrated that the combination of longan and misai kucing activates the ERα-PI3K-AKT pathway to alleviate hepatic steatosis, which provides a pharmacodynamic basis for developing multi-herbal therapies against metabolic disorders.

Introduction and Objective: GIPR is a novel metabolic drug target, yet its role in dermal macrophages (DMs) during diabetic wound healing is unknown. We studied whether DM GIPR regulates diabetic wound via metabolic reprogramming. Methods: Myeloid GIPR KO and controls received STZ, then excisional wounds. Closure, CD31/collagen, M1/M2 markers and ROS were measured. DMs underwent RNA-seq, Seahorse, JC-1 and WB to assess metabolic profiles. Local AMPK agonist EX229 was delivered for therapy. Results: GIPR KO delayed diabetic wound closure, reduced angiogenesis and collagen, and increased inflammation. KO DMs were M1-biased with higher ROS. RNAseq, seahorse and JC-1 showed suppression of AMPK and OXPHOS. WB showed reduced p-AMPK. Local EX229 restored M2 features and rescued healing. Conclusion: DM GIPR sustains AMPK-mitochondrial homeostasis in diabetic repair. AMPK activation is a new potential therapy. Disclosure Y. Tu: None. C. Zheng: None.

ObjectivesThis study aims to provide a comprehensive analysis of the burden of Type 2 diabetes (T2D) attributable to behavioral risks.MethodsUtilizing the Global Burden of Disease (GBD) 2021 data for secondary modeling, we analyzed the burden of T2D attributable to behavioral risks, stratified by age, gender, risk factors, and regions. A Bayesian age-period-cohort (BAPC) model projected burden trajectories from 2022 to 2050 under the continuation of historical trends.ResultsFrom 1990 to 2021, global deaths and DALYs of T2D attributable to behavioral risks increased by 133.87% and 187.68%. The greatest rises in ASMR and ASDR occurred in Eastern Europe, Central Asia, and Southern Sub-Saharan Africa. Dietary risks remained the primary contributor, whereas the T2D burden attributable to high alcohol use exhibited the steepest increase from 1990 to 2021. The global ASMR and ASDR increased exponentially with age and were consistently higher in males. Projections from the BAPC model indicate that ASDR is expected to continue increasing through 2050.ConclusionT2D burden attributable to behavioral risks is increasing rapidly, underscoring the need for targeted interventions and public health education.

Wiedemann-Steiner syndrome (WSS) is an autosomal dominant disorder caused by variants in the lysine-specific methyltransferase 2 A (KMT2A) gene. It is characterized by developmental delay, intellectual disability, hypertrichosis, growth retardation, and distinctive facial appearance. Reports on adult patients with WSS remain limited. We report the case of a 26-year-old woman with WSS who presented with oligomenorrhea for 11 years and irregular menstruation for 2 years. Since birth, she had hypertrichosis on her back and extremities, growth and development retardation, and brachydactyly. She had been receiving antipsychotic treatment with risperidone and trihexyphenidyl for the past two years. Laboratory evaluation revealed hyperprolactinemia (prolactin 1062.96 mIU/L; reference range 59.00–619.00 mIU/L), hyperandrogenemia, impaired glucose tolerance, insulin resistance, and hyperuricemia. Magnetic resonance imaging showed a pituitary microadenoma, which was confirmed as non-functioning following comprehensive pituitary hormone assessment. Whole-exome sequencing identified a de novo variant in the KMT2A gene: c.173dupC (p.Ala59Glyfs*88). Regarding management, risperidone and trihexyphenidyl were switched to aripiprazole on psychiatric advice. Half a month after the medication change, prolactin decreased to 124.32 mIU/L and remained at 129.73 mIU/L six months later. Clinicians should be aware of the risk of antipsychotic-induced hyperprolactinemia in patients with WSS receiving such treatment. Moreover, endocrine-related issues warrant greater attention in the clinical management of these patients, particularly in adulthood.

INTRODUCTION:Marine n-3 polyunsaturated fatty acids (PUFAs) are proposed to have ameliorative effects on kidney function, but their role in type 2 diabetes (T2D)-related kidney disease remains uncertain. OBJECTIVES:In this study, we assessed the protective effect of marine n-3 PUFAs against worsening renal function in T2D patients and explored the underlying mechanisms. METHODS:Individuals with T2D in UK biobank were included to examine associations between circulating fatty acids and incident chronic kidney disease (CKD). The PNMD trial (NCT03708887) is a 14-month randomized, double-blind, placebo-controlled trial evaluating dose-dependent effects of marine n-3 PUFAs on renal function in T2D. RESULTS:In a cohort of 5,856 diabetic patients, higher plasma levels of n-3 PUFAs were associated with a 22% reduction in the risk of developing CKD. RCT involving 415 T2D patients reported that high-dose n-3 PUFA (3 g/day) supplementation significantly improved estimated glomerular filtration rate (eGFR) compared with placebo. The protective effect of n-3 PUFA supplementation against worsening renal function among T2D patients was primarily mediated by HDL-4-Apo-A2, a key subclass of high-density lipoproteins and was more pronounced in patients with the Apo-A1 related rs10419198 TT/CT genotype. Using the db/db/fat-1 transgenic mice, we unraveled endogenous n-3 PUFAs advances renal function by modulating lipid metabolism and promoting cholesterol efflux through the Sirt1-PGC1α-ABCA1 pathway. CONCLUSION:These findings provide novel insights into the protective role of marine n-3 PUFAs in preserving impaired kidney function in T2D, underscoring their potential as a therapeutic strategy for diabetic kidney disease.

The relationship between fat distribution, specifically visceral adipose tissue and subcutaneous fat, and the parameters of left ventricular structure has shown inconsistent findings. Interestingly, the role of neck circumference, a surrogate for upper-body subcutaneous fat, in these parameters is less explored. This research seeks to evaluate the neck-to-height ratio (NHR) as a potential phenotypic indicator for cardiac structure evaluation in type 2 diabetes patients. It particularly focuses on examining how the NHR correlates with parameters of the left ventricular structure. This observational study encompassed 1074 individuals diagnosed with type 2 diabetes, who were evaluated or treated at the Second Affiliated Hospital of the School of Medicine, Zhejiang University, from January 1, 2019, to December 31, 2020. The participants were categorized into three cohorts according to their NHR levels. Statistical analysis of normally distributed data involved one-way ANOVA, whereas the Kruskal-Wallis test was applied for data not following normal distribution. Further, multivariate linear regression analysis was utilized to explore correlations between NHR and the left ventricular mass index (LVMI). Additionally, subgroup analyses and interaction tests were conducted to further investigate these relationships. Analysis indicated the association between NHR and various parameters of left ventricular structure. Through multivariate linear regression, a significant positive correlation emerged between NHR and LVMI (LV mass/height².⁷) (β = 39.95, P = 0.003), further regression analysis, adjusting for potential confounders, confirmed a consistent positive trend between NHR and LVMI (P for trend = 0.004). Extensive subgroup analysis demonstrated that age, gender, and varying criteria for obesity assessment did not significantly alter the observed correlation between NHR and LVMI. In this cohort of Chinese patients with T2DM, a notable rise in NHR was observed to correlate positively and independently with an increase in LVMI. Not applicable.

Introduction and Objective: Obesity-induced inflammation arises from failure to resolve transient immune responses, but the mechanism remain elusive. We studied whether CAMKIIδ enforces resolution by controlling adipose macrophages (ATMs). Methods: Macrophage Camk2d knockout (CKO) and WT mice were fed HFD. We assessed metabolic phenotypes and performed scRNA-seq, proteomics and kinase assays of ATMs. Results: Camk2d KO promotes obesity. scRNA-seq revealed expansion of pathogenic ATMs co-expressing lipid-handling and inflammatory programs. CAMKIIδ directly phosphorylated EGR1 at Ser378. In CKO mice, EGR1 stabilized, converting transient signaling into persistent inflammation. ATMs-specific Egr1 silencing reversed this disorder. Conclusion: CAMKIIδ-EGR1 axis acts as a post-translational timer enforcing inflammatory resolution, establishing a therapeutic target for obesity. Disclosure Y. Tu: None. C. Zheng: None.

Background:The global prevalence of type 2 diabetes mellitus (T2DM) has risen significantly since 1990, contributing substantially to mortality and posing a major public health challenge. While overweight/obesity and insulin resistance, commonly reflected by the triglyceride-glucose (TyG) index, are established risk factors for the development of T2DM, their individual and combined effects on mortality among patients with T2DM remain incompletely elucidated. This study aimed to evaluate the associations between body mass index (BMI) and the TyG index with all-cause and cardiovascular disease (CVD) mortality in a large clinical cohort of type 2 diabetes mellitus (T2DM) patients. Methods:This retrospective cohort study included 15,796 T2DM adults (aged >18 years) from two hospitals in China (2010-2023). The primary outcome was all-cause mortality, with a mean follow-up duration of 2.8 years. BMI was categorized as normal weight (18.5-24.9 kg/m2), overweight (25-29.9 kg/m2), and obesity (≥30 kg/m2). The TyG index was calculated as ln [fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Multiple Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs) and 95% confidence intervals (CIs) for mortality. Results:Among 15,796 participants, 1,665 deaths were recorded, including 629 CVD-related deaths. Overweight and obesity were associated with lower all-cause mortality risk (aHR: 0.73, 95% CI: 0.65-0.81 and aHR: 0.86, 95% CI: 0.74-1.00, respectively). Higher TyG index quartiles (Q3 and Q4) were associated with decreased mortality risk (aHR: 0.85, 95% CI: 0.74-0.98; aHR: 0.84, 95% CI: 0.72-0.97). The protective effect of a higher BMI was more pronounced in patients aged 60 years or older. Conclusion:Our findings revealed that BMI and the TyG index are associated with mortality risk in T2DM patients, particularly in older patients. However, these findings are observational and do not imply causality or validate prognostic use. Further studies using causal inference methods are necessary to inform clinical guidelines.

Importance:The optimal long-term patterns of resistance training, including volume, consistency, and integration with other lifestyle behaviors, remain unclear. Objective:To examine the association of long-term resistance training with risk of incident type 2 diabetes (T2D) and to assess joint associations with aerobic physical activity and sedentary behavior. Design, Setting, and Participants:This prospective cohort study assessed the data from 3 ongoing US studies: the Nurses' Health Study (June 30, 2002, to June 30, 2021), the Nurses' Health Study II (June 30, 2003, to June 30, 2021), and the Health Professionals Follow-up Study (June 30, 1992, to June 30, 2021). Follow-up was completed June 30, 2021. Participants included adult health care professionals who had undergone at least 3 assessments of resistance training between 40 and 60 years of age for trajectory analysis. Data were analyzed from April 30 to September 30, 2025. Exposure:Time spent in resistance training was assessed every 2 to 4 years and categorized into 5 groups: consistently low, high to low, low to high, fluctuating, and consistently high. Long-term resistance training was characterized using cumulative means and trajectory patterns between ages 40 and 60 years in the Nurses' Health Study II. Main Outcomes and Measures:The main outcome was incident T2D. Multivariable-adjusted hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards regression models with time-varying resistance training. Results:Among 143 715 adults included in the analysis (mean [SD] age, 56.0 [10.5] years; 78.3% women), 10 038 incident T2D cases occurred during a mean (SD) follow-up of 19.2 (5.0) years. Compared with no resistance training, engaging in 2 or more hours per week of resistance training was associated with a lower T2D risk (HR, 0.73; 95% CI, 0.66-0.81). In trajectory analyses, participants with consistently high levels of resistance training (≥0.5 h/wk across midlife) had a 42% lower T2D risk (HR, 0.58; 95% CI, 0.45-0.74), and a low to high pattern was associated with a 21% lower risk (HR, 0.79; 95% CI, 0.66-0.94), compared with consistently low levels of resistance training. Participants who met recommendations for both aerobic activity (≥15 total metabolic equivalent h/wk) and resistance training (≥1 h/wk) and limited television viewing (<2 h/d) had the lowest T2D risk (HR, 0.38; 95% CI, 0.34-0.42) compared with those meeting none of the recommendations. Conclusions and Relevance:In this prospective cohort study, resistance training among US adult health care professionals was associated with substantially lower T2D risk, particularly when performed consistently over midlife and combined with adequate aerobic activity and limited sedentary television viewing. These findings support the inclusion of resistance training as a key component of lifestyle recommendations for diabetes prevention.

BACKGROUND:Long-term resistance training may influence cardiovascular health, but evidence in women, particularly in the context of aerobic activity and sedentary behavior, remains limited. OBJECTIVES:This study sought to examine the association between long-term resistance training and risk of major cardiovascular disease (CVD) in women, and to evaluate joint associations with aerobic activity, sedentary television viewing, and key training-related characteristics. METHODS:We conducted a prospective cohort study among 117,025 women from the Nurses' Health Study (N = 45,669; 2002-2020) and Nurses' Health Study II (N = 71,356; 2003-2017), with up to 5 repeated assessments of physical activity. Resistance training was reported every 4 years, and time-varying cumulative averages were calculated to represent long-term exposure. The primary outcome was incident major CVD, defined as nonfatal or fatal myocardial infarction (MI), stroke, coronary artery bypass grafting, or percutaneous coronary intervention. RESULTS:Over a mean of 14.5 years of follow-up (1,630,964 person-years), 5,459 incident major CVD events occurred. Compared with no resistance training, women performing ≥2 h/wk had a 20% lower risk of major CVD (HR: 0.80; 95% CI: 0.69-0.92; P for trend = 0.007), and each additional 1 h/wk was associated with a 5% lower risk (HR per 1 h/wk: 0.95; 95% CI: 0.92-0.99). The inverse association was stronger for MI (HR for ≥2 h/wk vs none: 0.56; 95% CI: 0.41-0.76) but not evident for stroke (HR: 0.99; 95% CI: 0.80-1.23). Women who met recommendations for aerobic activity (≥15 metabolic equivalent of task hours per week), resistance training (≥1 h/wk), and low sedentary television viewing (<2 h/d) had a lower risk of major CVD (HR: 0.60; 95% CI: 0.53-0.69), than those meeting aerobic and low sedentary television viewing recommendations but not resistance training (HR: 0.73; 95% CI: 0.67-0.80). Greater consistency in maintaining resistance training (≥75% of follow-up) and engaging in both upper and lower limb training were associated with stronger inverse associations. CONCLUSIONS:In this large prospective study of U.S. women, consistent resistance training, especially when integrated with recommended levels of aerobic activity and reduced sedentary television viewing, was associated with a substantially lower risk of major CVD, particularly MI.

Atherosclerosis, a progressive inflammatory disease and the leading cause of cardiovascular disease (CVD), remains a global health burden due to the lack of effective early therapeutic interventions. Although growing evidence highlights the involvement of plasma proteins in atherogenesis, their causal contributions to disease pathogenesis are poorly understood. To address this gap, we conducted a proteome-wide Mendelian randomization (MR) analysis using cis-pQTLs (cis-protein quantitative trait loci) from the deCODE and UKB-PPP cohorts ( 90,000 individuals) as instrumental variables. We integrated colocalization analysis, summary-data-based MR (SMR), and HEIDI tests to systematically prioritize causal plasma proteins. Key findings were replicated in the CARDIOGRAMplusC4D (coronary artery disease, CAD) and FinnGen (CVD) cohorts. Functional validation was performed through phenome-wide association studies (PheWAS), single-cell transcriptomics, histological staining, and ELISA assays to characterize protein expression patterns in specific cell types and tissues. Among 2,711 plasma proteins analyzed, 28 showed strong genetic associations with atherosclerosis. Of these, five proteins (ADK, ANGPTL4, CD4, MGAT1, SYT11) met strict validation criteria through colocalization (posterior probability of colocalization, PP.H4 > 0.8) and SMR. Subsequent replication using MR and PheWAS further confirmed the causal roles of ADK, CALB2, and COMT in CAD and other CVD outcomes. Notably, CALB2 was specifically enriched in mast cells within atherosclerotic plaques and adipose tissue, and plasma levels were significantly elevated in patients with severe carotid artery stenosis (CAS). This study identifies 28 novel therapeutic targets for atherosclerosis using a rigorous multi-omics approach. Our findings establish CALB2 as a promising biomarker and therapeutic target, particularly in severe CAS, by linking genetic evidence to cell-type-specific expression and clinical phenotypes. These insights pave the way for precision medicine approaches in the prevention and treatment of CVD.

Podocyte injury is central to diabetic kidney disease (DKD) pathogenesis, however, the mechanisms underlying podocyte loss remain unclear. Emerging evidence underscores the involvement of fibroblast growth factors (FGFs) in renal pathophysiology. Here we reveal a previously unappreciated role of podocyte-secreted FGF4 in safeguarding renal function. FGF4 expression is downregulated in renal tissues from DKD patients and animal models, correlating with disease severity. Podocyte-specific deletion of Fgf4 exacerbated podocyte loss and accelerated DKD progression in mice. Conversely, treatment with recombinant FGF4 (rFGF4) improved glomerular filtration and reduced renal injury and fibrosis in diabetic male mice. These effects are primary mediated by activating the FGFR1-AMPK-FOXO1 signaling cascade in podocytes, which mitigates oxidative stress, suppresses apoptosis, and fosters podocyte survival. Notably, rFGF4 also restores the morphology and function of human podocytes exposed to high glucose. Our findings establish FGF4 as a critical regulator of podocyte homeostasis and a potential therapeutic target for DKD.

Introduction and Objective: GLP-1(32-36), a major end-product of glucagon-like peptide 1 (GLP-1), improves diabetic limb ischemia in mice independent of its insulinotropic effect. However, the mechanisms underlying this effect and its relevance in human ischemic lesions remain unclear. Methods: We used single-cell transcriptomics on the plantar muscles of diabetic foot patients and healthy controls to investigate changes in lipid metabolism genes and pathways. We also applied cellular and spatial metabolomics to evaluate the impact of GLP-1(32-36) on lipid metabolism and lipid accumulation in the gastrocnemius microvasculature in diabetic mice. Adenovirus and lentivirus were used for gene silencing in vivo and in vitro, respectively. Cross orthogonal coupling was employed for drug modification of GLP-1(32-36). Results: High glucose induces lipid metabolism dysregulation in endothelial cells (ECs) and in diabetic mice with limb ischemia. GLP-1(32-36) binds atrial natriuretic peptide receptor A (NPRA) to regulate cholesterol transport via oxysterol-binding protein (OSBP), promoting blood flow in ischemic limbs. NPRA knockdown inhibited GLP-1(32-36)’s pro-angiogenic effects, independent of the GLP-1 receptor (GLP-1R). Single-cell RNA sequencing (scRNA seq) revealed lipid metabolism dysregulation in capillary ECs of diabetic foot patients. To prolong GLP-1(32-36)’s half-life, we synthesized the ROS-responsive prodrug tEC-cRGD-(32-36) for EC-specific delivery, enhancing blood flow recovery and reducing lipid droplet formation. Conclusion: Our findings demonstrate that GLP-1(32-36) regulates lipid metabolism via the NPRA-OSBP axis to alleviate endothelial dysfunction and promote diabetic ischemic recovery, supporting the development of EC-targeting GLP-1(32-36) for treating diabetic ischemia. Y. Zhang: None. S. Wang: None. Q. Zhou: None. C. Zheng: None.

Rationale:Heart failure (HF) is slightly more common in primary aldosteronism (PA) than in essential hypertension, but early-onset HF remains rare. In such cases, underlying genetic cardiomyopathies should be considered. Autonomously secreted aldosterone and activation of the renin-angiotensin-aldosterone system can lead to extremely high aldosterone levels, worsening cardiac function and creating major therapeutic challenges.Patient concerns:A 39-year-old male presented with progressive chest tightness and shortness of breath for 4 months. He had a 7-year history of hypertension and persistent hypokalemia. Electrocardiogram revealed a markedly reduced left ventricular ejection fraction of 18.3%.Diagnosis and interventions:The patient was diagnosed with PA based on elevated plasma aldosterone concentration, an increased aldosterone-to-renin ratio, and a positive captopril challenge test. Computed tomography and adrenal vein sampling indicated unilateral PA. After initial HF management, the patient underwent laparoscopic adrenalectomy for PA treatment.Outcomes:According to the primary aldosteronism surgical outcome consensus criteria for postoperative evaluation of PA, complete biochemical remission (normalization of aldosterone-to-renin ratio and potassium) and partial clinical remission (stable blood pressure with reduced antihypertensive medication) were achieved 1 month postoperatively and have been maintained since. At the 8-month follow-up, his left ventricular ejection fraction had improved to 45.4% and BNP levels normalized. Whole-exon sequencing revealed a missense mutation of the dystrophin (DMD) gene. Certain DMD mutations are linked to X-linked dilated cardiomyopathy with absent or subclinical skeletal muscle involvement. Sanger sequencing confirmed the hemizygous mutation in the proband. The final diagnosis was poorly controlled PA with early-onset HF, potentially influenced by a coexisting DMD gene missense mutation that may modify both the onset and severity of PA-related HF.Lessons:Early recognition and surgical treatment of PA with early-onset HF can substantially improve cardiac function, even in the presence of genetic susceptibility to cardiomyopathy. This case underscores the need to consider underlying cardiac genetic disorders in PA patients with atypical or early-onset HF and raises the hypothesis that the identified DMD variant may serve as a potential genetic modifier of HF severity in the context of PA.

Microbial dysbiosis, characterized by an imbalanced microbial community structure and function, has been linked to hypertension. While prior research has primarily focused on differential abundances, our study highlights the role of non-differential microbes in hypertension. We propose that non-differential microbes contribute to hypertension through their ecological interactions, as defined by co-abundances (pairs of microbes exhibiting correlated abundance patterns). Using gut microbiome data from the Guangdong Gut Microbiome Project, which includes 2355 hypertensive and 4644 non-hypertensive participants across 14 regions, we identified replicable hypertension-related microbial interactions. Notably, most co-abundances involved non-differential microbes, which were found to correlate with both hypertension severity and hypertension-related microbial metabolic pathways. These findings emphasize the importance of microbial interactions in hypertension pathogenesis and propose a novel perspective for microbiome-based therapeutic strategies.

AIMS:To evaluate the effectiveness and safety of a hybrid closed-loop (HCL) insulin infusion system in treating adult and adolescent patients with type 1 diabetes (T1D). MATERIALS AND METHODS:A total of 126 participants (22 adolescents and 104 adults) underwent a 2-week initial treatment phase followed by a 2-week run-in phase with the Equil® S HCL insulin pump system MTM-Z in Manual Mode with calibration-free continuous glucose monitoring (CGM) System G7, followed by a 12-week study phase with HCL Auto Mode enabled. The primary outcome was the overall mean change in CGM time in range (TIR; 70-180 mg/dL). Safety endpoints included rates of severe hypoglycaemia, hyperglycaemia and diabetic ketoacidosis (DKA). RESULTS:Compared with the baseline run-in, Auto Mode increased TIR from 69.11% to 76.72% (p < 0.001) and reduced time below range (<70 mg/dL) from 3.92% to 2.73% (p < 0.001). The mean sensor glucose (SG) decreased from 151 ± 28 to 144 ± 19 mg/dL. The proportion of achieving TIR of >70% increased from 56.03% to 77.59%. The standard deviation (SD: -5.90 mg/dL) and coefficient of variation (CV: -2.49%) reduced significantly. The greatest change in TIR (mean 20.55%), mean SG (estimated treatment difference [ETD]: -30.13, 95% confidence interval [CI]: -41.84, -18.41; p = 0.001) and SD of SG (ETD: -14.21, 95% CI: -21.17, -6.71; p = 0.004) was observed in participants with a baseline glycosylated haemoglobin A1c (HbA1c) value of >8.0%. The percentage of achieving combined recommendations for time at SG ranges increased from 25.86% to 56.90%. No severe hypoglycaemia, DKA or adverse events were observed. CONCLUSIONS:HCL therapy is safe in Chinese adolescent and adult patients with T1D. The 12-week application of the Equil® S HCL insulin pump system MTM-Z with Auto Mode increased TIR and reduced HbA1c, hyperglycaemia and hypoglycaemia.