INTRODUCTION:The HSK16149-201/301 trial demonstrated short-term efficacy of the GABA analog crisugabalin for diabetic neuropathic pain. METHODS:In the current study, patients in both the crisugabalin and placebo control groups of the HSK16149-201/301 trial were invited to receive 80 mg/day crisugabalin for an additional 52 weeks. The primary end point was safety. The secondary end point was pain control as measured using the Short-Form McGill Pain Questionnaire (SF-MPQ). A total of 301 patients (mean age 59.7 years and males 58.1%) were enrolled. RESULTS:The rate of treatment-related adverse events (TRAEs) was 38.9% (117/301). The most frequent TRAEs were dizziness (27.2%), somnolence (8.3%), and peripheral edema (3.0%). The rate of Grade 3 or higher TRAEs was 1.7%. TRAEs led to dose reduction in 41 patients (13.6%), treatment interruption and discontinuation each in three patients (1.0%). At week 52, the mean difference in SF-MPQ pain rating index (PRI) and visual analog scale pain score from baseline was -2.5 (95% CI -2.9 to -2.0; paired t-test p < 0.0001) and -23.4 (95% CI -25.6 to -21.2; paired t-test p < 0.0001), respectively. The proportion of patients with SF-MPQ PPI score ≤ 1 increased by 19.0% over baseline (p < 0.0001). CONCLUSIONS:In summary, crisugabalin at 80 mg/day was well tolerated and demonstrated sustained analgesic activities. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT05890053.

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.

Diabetes mellitus (DM) remains a major health challenge in East Asia and the high-income Asia Pacific, yet systematic subtype-specific comparisons are lacking. Using Global Burden of Disease Study 2023 data, we analyzed age-standardized incidence, prevalence, mortality, and disability-adjusted life year (DALY) rates for DM subtypes from 1990 to 2023, calculated mortality-to-incidence ratios (MIRs) and population-attributable fractions, and projected outcomes to 2050. In 2023, East Asia had higher MIR (0.04) and mortality (8.26/100,000) than the high-income Asia Pacific (0.02 and 4.50/100,000), with type 2 diabetes (T2DM) comprising >94% of cases. High body-mass index was the primary T2DM risk factor (49.3%); T1DM burden was linked to temperature exposure. Under the reference scenario, T2DM mortality and DALY rates will rise by 2050, but optimized behavioral and metabolic interventions could reduce DM DALY rates by >84% in East Asia and >70% in the high-income Asia Pacific, highlighting the urgent need for targeted, risk-factor-specific diabetes control strategies.

AIMS:Glucokinase regulatory protein gene (GCKR) polymorphisms have been linked to progressive renal dysfunction in diabetic populations. However, their role in early renal injury of diabetic kidney disease (DKD) remains unclear. This study aimed to investigate the association between GCKR genetic variants and early renal impairment in newly diagnosed early-onset type 2 diabetes mellitus (T2DM). METHODS:A total of 337 newly diagnosed early-onset T2DM patients from a prospective cohort were enroled. Baseline characteristics, estimated glomerular filtration rate (eGFR), and urinary albumin-to-creatinine ratio (UACR) were collected. Seven single nucleotide polymorphisms (SNPs) in GCKR were genotyped using ASAMD microarrays. Participants were divided into normal (UACR < 30 mg/g) and elevated albuminuria (UACR ≥ 30 mg/g) groups. Logistic regression and multivariate linear regression were performed to evaluate the relationship between GCKR genotypes and UACR. RESULTS:The patients had a mean age of 33.25 ± 5.38 years. Median eGFR was 119.33 mL/min/1.73 m2, and median UACR was 14.97 mg/g; 107 patients (31.8%) presented with elevated UACR. Carriers of the GCKR rs1260326 T/T genotype exhibited significantly higher median UACR compared with C/T + C/C carriers (22.85 vs. 13.53 mg/g, p = 0.021). The rs1260326 T allele was independently associated with increased UACR under the additive genetic model (p = 0.003) adjusted for sex, age, body mass index (BMI), glycated haemoglobin (HbA1c), and systolic blood pressure (SBP). CONCLUSIONS:The GCKR rs1260326 T allele is independently associated with early renal injury in newly diagnosed early-onset T2DM. This genetic variant may serve as a predictive marker for early DKD risk stratification in this high-risk population.

This 14-day multicenter study assessed CT3 CGM accuracy and safety in 71 adults with diabetes. Key results: overall MARD 9.1% (median 7.1%), 82.4%-98.2% met %15/15-%30/30 criteria, 99.7% values in CEG zones A/B. CT3 showed strong performance, suitable for reliable 14-day wear.

Aim Monogenic diabetes is a group of disorders arising from single gene mutations with a clear pathophysiology, most of which present with impaired beta cell function rather than insulin resistance. This study aims to evaluate the ability of TyG index and polygenetic risk score (PRS) to identify multi-type beta cell monogenetic diabetes (beta-cell-MgD) in Chinese early-onset type 2 diabetes (EOD) population. Methods A prediction model for beta-cell-MgD was established by logistic regression analysis in Cohort 1 (92 beta-cell-MgD, 512 EOD). Model performance was evaluated by receiver operating characteristic curves (ROC) and validated in an independent case-control sample (Cohort 2, 35 beta-cell-MgD, 50 EOD) and a newly diagnosed drug-naive EOD cohort (Cohort 3, 7 beta-cell-MgD, 176 EOD). PRS was constructed based on Genome-wide genotyping data from participants in Cohort 3. The ability of PRS to identify beta-cell-MgD was tested by ROC. Results The TyG-MgD score based on age at diagnosis, BMI and TyG presented a good performance to distinguish beta-cell-MgD (AUC=0.769), and achieving AUCs of 0.966 and 0.754 respectively in validation cohorts. At the optimal cutoff point -16.19, the model achieved a sensitivity of 66.3% and a specificity of 75.39%, allowing one case of beta-cell-MgD identified among every three patients. -16.85 could be used as the screening threshold prioritizing 80% sensitivity (with 59% specificity). Models combining TyG-MgD with East Asian PRS and beta-cell dysfunction-high proinsulin partitioned polygenetic score showed AUCs of 0.842 and 0.834 respectively for indentifying beta-cell-MgD. Conclusion We developed a clinical prediction model as a simple screening tool for multi-type beta-cell-MgD, identifying who are most likely to benefit from next genetic sequencing in Chinese population. PRS might be helpful for further screening of MgD.

Background and Aims Steatotic liver disease (SLD) is increasingly recognized as a systemic disorder linked to cardiometabolic risk. Cardiac autonomic dysfunction may represent an early mechanistic pathway connecting hepatic steatosis with adverse cardiovascular outcomes. We investigated the associations between contemporary SLD phenotypes and cardiac autonomic function, assessed by heart rate variability (HRV). Methods and Results A total of 2,792 participants from the Pinggu Metabolic Disease Study were included. Hepatic steatosis was defined by computed tomography (liver–spleen ratio ≤1.1). Metabolic dysfunction–associated SLD (MASLD), MASLD with moderate alcohol intake (MetALD), and alcohol-associated liver disease (ALD) were classified according to the 2024 EASL–EASD–EASO criteria. HRV indices (MeanNN, SDNN, RMSSD) were derived from digitized electrocardiograms. Sex-stratified multivariable ordinal logistic regression models were used.The prevalence of MASLD, MetALD, and ALD was 17.8%, 2.1%, and 2.5%, respectively. SLD phenotypes were generally associated with adverse HRV profiles. After adjustment, SLD phenotypes remained associated with lower MeanNN. In men, MASLD and the combined MetALD/ALD group were associated with lower SDNN quartiles, with a stronger association for MetALD/ALD (OR 2.19, 95% CI 1.55–3.09), which was also associated with lower RMSSD quartiles (OR 2.08, 95% CI 1.47–2.94). In women, MASLD was associated with lower RMSSD quartiles (OR 1.57, 95% CI 1.23–2.02). Sensitivity analyses showed generally consistent findings. Conclusions SLD phenotypes were associated with higher heart rate. In men, MASLD, MetALD, and ALD were associated with impaired overall cardiac autonomic function, whereas in women, MASLD was associated with impaired cardiac parasympathetic function.

ABSTRACT Background Glycated albumin (GA) has already been introduced in clinic for decades. However, it remains unclear whether routine measurement of GA could serve as a practical tool to improve the care of patients with type 2 diabetes (T2DM). Methods This multicenter, randomized controlled trial enrolled 200 patients with newly diagnosed, poorly controlled type 2 diabetes from seven sites in China. Participants were randomly assigned (1:1) to either GA‐guided therapy (treatment intensification if GA > 16% at 4 weeks) or standard therapy, with a 12‐weeks follow‐up. The primary outcome was the proportion of patients achieving HbA1c < 7%; secondary outcomes included HbA1c < 6.5%, glycemic parameters, hypoglycemia, and β‐cell function. Results A total of 200 patients were included in this study. Therapy compliances were 97.4% (SD, 5.3%) and 98.0% (SD, 8.2%) in the GA‐guided therapy group and standard therapy group, respectively. There was no significant difference in the achievement rate of HbA1c (< 7%) between the GA‐guided therapy group (64.3%) and the standard therapy group (64.4%) after the 12‐week follow‐up (p = 0.99). In the secondary outcome, the achievement rate of HbA1c (< 6.5%) was higher in the GA‐guided therapy group than in the standard therapy group (40.5% vs. 25.3%, p = 0.034). Furthermore, the changes in HbA1c, HOMA‐β, HOMA‐IR, body weight reduction were all better in the GA guided therapy group than in standard therapy group. Conclusion GA‐guided therapy did not enhance HbA1c < 7% achievement; however, its potential benefits for more stringent glycemic targets and metabolic parameters in early diabetes management deserve further investigation. Trial Registration: ClinicalTrials.gov: NCT05227677

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have become an important option in clinical use for type 2 diabetes due to their dual benefits of glycaemic management and metabolic improvements. Efsubaglutide alfa, a novel long-acting GLP-1RA, was developed for sustained glycaemic management. This study aimed to confirm its recommended clinical dose and evaluate its efficacy and safety in drug-naive individuals with type 2 diabetes that was inadequately managed through lifestyle interventions. This two-stage Phase IIb/III trial employed an operationally seamless adaptive design and enrolled adults who had been newly diagnosed with type 2 diabetes and whose diabetes was inadequately managed by diet and exercise. In the Phase IIb stage, participants were randomised in a 2:2:2:1 ratio to receive once-weekly subcutaneous injections of efsubaglutide alfa (1, 2 or 3 mg) or placebo for 12 weeks. Based on an interim analysis, two recommended Phase III doses (RP3Ds) were selected by an independent data monitoring committee. In the Phase III stage, participants were randomised in a 2:2:1 ratio to receive efsubaglutide alfa at one of the two RP3Ds or to receive placebo. Participants, investigators and sponsors were masked to drug/placebo allocation throughout the trial. The primary endpoint was the change in HbA1c from baseline to week 24. Secondary endpoints included changes in body weight and metabolic parameters at weeks 24 and 52. Safety was monitored throughout. In the Phase IIb stage, 140 participants were randomised to efsubaglutide alfa (1 mg, n=41; 2 mg, n=39; 3 mg, n=41) or placebo (n=19). Based on interim analysis, 1 and 3 mg were selected as the RP3Ds. In the Phase III stage, 297 participants were randomised to efsubaglutide alfa (1 mg, n=118; 3 mg, n=117) or placebo (n=62). At week 24, the HbA1c reductions from baseline were −18.91 mmol/mol (1.73

The prevalence of early-onset type 2 diabetes (EOD) is rapidly increasing. This study intends to screen for early cardiovascular abnormalities in patients newly diagnosed with EOD and evaluate the cardiovascular risk across cluster phenotypes. A total of 400 patients ≤ 40 years old with newly diagnosed type 2 diabetes were enrolled from the START cohort (the Study of The newly diAgnosed eaRly onset diabeTes). Cluster classification was performed using the K-means method based on age, BMI, HbA1c, HOMA2-β, HOMA2-IR, and GAD antibodies. Echocardiography and carotid ultrasound were performed within 3 months of diabetes diagnosis. Carotid ultrasound abnormalities included intimal thickening and plaque formation, while echocardiography assessed changes in cardiac structure and systolic/diastolic function. Cluster-specific partitioned polygenic scores (pPS) were used to validate our findings from a genetic perspective. Carotid artery abnormalities were detected in 26.3

PurposeThis study investigates the incidence, predictors, and preventive strategies for microvascular complications in type 2 diabetes patients in community settings.MethodsData were collected from 3,008 type 2 diabetes patients enrolled across 31 clinics in Beijing and Hebei. Prevalence and incidence of diabetic kidney disease (DKD), diabetic retinopathy (DR), and diabetic peripheral neuropathy (DPN) were assessed. Predictors were identified using XGBoost and Cox regression, and the impact of lifestyle and multifactorial interventions (MFI) was analyzed.ResultsThe prevalence of DKD, DR, and DPN were 39.5%, 26.2%, and 27.1%, respectively, with incidences of 74, 21, and 28 per 1000-person year. XGBoost identified that diabetes duration, age, HbA1c, FBG, triglyceride, BP, serum creatinine, proteinuria, aspirin and statin use were associated with those microvascular complications. The risk of DKD increased more rapidly as HbA1c exceeded 7.5% and decreased as blood pressure was maintained below 120/70 mmHg. Cox regression models showed that community-based intervention, including lifestyle modifications, were associated with a lower risk of DR and DPN. The study also found that higher variability in HbA1c and albumin-to-creatinine ratio (ACR) was associated with an increased risk of microvascular complications.ConclusionsCommunity-based interventions significantly reduce the of DR and DPN, highlighting the need for individualized glycemic and BP management in primary care. The findings emphasize the importance of comprehensive management strategies to prevent the development and progression of microvascular complications in type 2 diabetes patients.Clinical trial registrationhttp://www.chictr.org.cn/, identifier ChiCTR-TRC-13003222.

Accumulating evidence has linked gut microbiota to bone health. However, investigations into the impacts of aging, gut microbiota, and their interactions in the development of osteoporosis remain inconclusive. We employed quantitative computed tomography to measure lumbar bone mass density (BMD) and analyzed shotgun metagenomic data in 684 Chinese adults. Our analyses revealed significant positive associations between BMD and abundances of multiple Lachnospiraceae species, including Lachnospira eligens, Blautia wexlerae, and Roseburia hominis, as well as pathways involved in L-arginine biosynthesis and butyrate production—independent of age, diet habits, and lifestyles. Moreover, we demonstrated that individuals with enterotype Bacteroides exhibited a more pronounced age-related decline in BMD compared to those with enterotype Prevotella, a pattern we validated in an independent cohort. Our findings offer valuable insights into BMD-related gut microbial features and interactions between aging, gut microbiota, and bone loss, opening potential avenues for microbiota-based prevention and treatment strategies for osteoporosis.

Aim:We aimed to assess the effects of acarbose and vildagliptin on levels of plasma trimethylamine N-oxide (TMAO) and its metabolic precursor in overweight and obese patients with type 2 diabetes mellitus and ascertain the correlation between TMAO and characteristics of diabetes. Methods:This study employed a randomized, controlled, open interventional design and recruited 100 participants who were overweight/obese and newly diagnosed with type 2 diabetes at Pinggu Hospital, Beijing Friendship Hospital, Capital Medical University, between December 2016 and December 2017. Using the sealed envelope method, participants were randomly allocated (1:1) to either the acarbose group (n = 50) or the vildagliptin group (n = 50). Participants received 6 months of treatment with oral glucose-lowering medications, acarbose, or vildagliptin. Anthropometric measurements, including height, weight, waist and hip circumferences, and blood pressure, were recorded at baseline and 3 and 6 months after the intervention. Blood samples were obtained to assess blood glucose, insulin, gut hormones, TMAO, and metabolic precursors. Data analysis focused on intragroup and intergroup variations. Results:Baseline characteristics, including weight, BMI, waist and hip circumferences, blood glucose, and gut hormone levels, were comparable between the acarbose and vildagliptin groups (all p>0.05). Intragroup analysis indicated a significant decrease in TMAO levels at 6 months compared with baseline (adjusted p<0.05). L-carnitine and γ-butyrobetaine levels significantly increased at 6 months (all adjusted p<0.05), whereas betaine and choline levels remained non-significant throughout the intervention. Intergroup analysis revealed significantly lower TMAO levels in the acarbose group at 6 months (p<0.05), without significant intergroup differences in L-carnitine, γ-butyrobetaine, choline, or betaine levels (all p>0.05). In the acarbose group, positive correlations were observed between changes in TMAO and BMI, waist circumference, postprandial glucose, fasting insulin, fasting C-peptide, and HOMA-IR from baseline to 6 months (p<0.05). Conclusions:Both acarbose and vildagliptin treatments significantly reduced TMAO levels in newly diagnosed T2DM patients, with a more pronounced reduction observed in the acarbose group. Furthermore, the decline in TMAO levels correlated significantly with improvements in insulin resistance parameters. Clinical trial registration:https://clinicaltrials.gov, identifier NCT02999841.

Aim: This study aimed to explore the relationship between visceral fat and obesity-related metabolic diseases, validate the obesity criteria from the European Association for the Study of Obesity (EASO) in the Chinese population, and propose new standards for identifying visceral fat using simple anthropometric indicators. Methods: This cross-sectional study involved 3,371 participants aged 26-76 years in Pinggu District, Beijing. Anthropometric measurements and metabolic indicators were assessed, and visceral fat area (VFA) was calculated from non-contrast abdominal computed tomography scans. The McNemar test was used to compare the diagnostic accuracy of the EASO criteria and body mass index (BMI) for identifying visceral obesity. The correlation between anthropometric indicators and VFA was analysed using Spearman's correlation coefficient. Receiver operating characteristic curves were used to compare the diagnostic efficacy and thresholds of anthropometric indicators with the EASO criteria. Results: Among 3,371 participants, 61.2% were diagnosed with visceral obesity. Metabolic disease prevalence was higher in individuals with visceral obesity, suggesting that visceral fat accumulation is a sensitive marker for identifying metabolic diseases. The EASO criteria showed higher sensitivity and lower specificity than BMI alone for diagnosing visceral obesity. Waist circumference (WC) and waist-to-height ratio correlated strongly with VFA. BMI combined with WC was the most effective tool for diagnosing visceral obesity in the Chinese population. Conclusion: Visceral fat accumulation is associated with metabolic diseases, and the EASO criteria are superior to BMI in identifying visceral obesity. BMI combined with WC is effective for diagnosing visceral obesity in the Chinese population.

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.

Background: Antiretroviral therapy (ART) effectively reduces opportunistic infections and mortality in people living with HIV (PLWH); however, some patients exhibit poor immune recovery. This study explores the connections among immune responses, metabolites, and the gut microbiota in PLWH with differing reactions to ART. Methods: We analyzed the gut microbiota composition, metabolites, and immune markers in 38 PLWH who showed an immunological response (IR) and 32 who did not (INR), as classified according to CD4+ T-cell levels after 24 months of ART. Additionally, in vitro assays using cell counting kit 8, flow cytometry, and quantitative real-time reverse transcription PCR were employed to assess the effects of the metabolites on cell viability, immune marker expression, and cytokine levels. Results: Gut microbiota and metabolic profiles differed significantly between the IR and INR groups. Enterococcus was more abundant in the INR group, whereas [Ruminococcus]_gnavus_group levels were reduced. Significant metabolic pathway alterations included decreased folate biosynthesis and biotin metabolism. We observed negative associations of Parabacteroides with activation markers on CD4+ T-cells, and positive correlations with CD4/CD8 ratios. Enterococcus showed inverse relationships with these markers. Indole-3-acetyl-beta-1-D-glucoside (area under the curve value = 0.8931), had the best discriminatory ability. Further experiments showed that Indole-3-acetyl-beta-1-D-glucoside significantly decreased the proportions of CD4+CD57+, effector CD4+, CD4+PD1+, CD8+CD57+, effector CD8+, and CD8+HLA-DR+ T cells. Moreover, mRNA expression analysis showed that Indole-3-acetyl-beta-1-D-glucoside treatment led to a suppression of pro-inflammatory cytokines. Conclusion: The multi-omics approach highlighted potential biomarkers for immune recovery in HIV, suggesting avenues for further research into treatment strategies.

Lifestyle modifications, including nutritional therapy and physical activity, are recommended as a first-line treatment for non-alcoholic fatty liver disease (NAFLD). However, both the best dietary approach and the optimal exercise pattern remain controversial. We will assess the efficacy of structured exercise and oats supplementation in NAFLD patients. Participants aged 18–65 years with intrahepatic lipid content ≥5