BACKGROUND In China, the prevalence of prediabetes is alarmingly high, affecting approximately 35.7% of adults. Although lifestyle interventions can reduce diabetes onset, the manifestations of prediabetes vary across individuals with age, body composition, insulin resistance, and beta-cell function. Therefore, current diagnostic approaches based solely on glucose thresholds are not sufficient, necessitating improved risk stratification through data-driven, unsupervised clustering methods. AIM To investigate the metabolic heterogeneity of prediabetes in Chinese individuals and its association with lifestyle intervention outcomes. METHODS A prospective, multicenter cohort study was conducted in China with 2527 adults aged 18-70 years, at high risk for diabetes. Centers were assigned to either enhanced lifestyle management or standard health education. Enhanced management included individualized dietary energy prescriptions, wearable activity trackers, a mobile co-management app, and structured follow-up. Unsupervised K-means clustering identified four metabolic subtypes. Longitudinal outcomes, including incident diabetes and reversion to normoglycemia, were analyzed using Cox models adjusted for intervention and demographic covariates. RESULTS Four distinct prediabetes subtypes were identified: Mild obesity-related dysmetabolism (MOD, n = 177), mild age-related dysmetabolism (MARD, n = 190), severe insulin resistance (n = 95), and severe insulin deficiency (n = 159). Of 621 participants, 367 (59.1%) contributed longitudinal data; although attrition differed significantly across subtypes (P < 0.001), inverse probability of censoring weighting confirmed the robustness of all estimates. After a median follow-up of 735 days, MOD had a lower risk of diabetes progression than MARD [adjusted hazard ratio (aHR) = 0.52, P = 0.028] and a greater likelihood of reversion to normoglycemia (aHR = 2.08, P = 0.049). Adjusted for subtype and sex, enhanced lifestyle management reduced diabetes progression risk (aHR = 0.52, 95% confidence interval: 0.30-0.89; P = 0.017), but not reversion to normoglycemia (P = 0.159). CONCLUSION Data-driven prediabetes subtyping improved risk stratification. The MOD subtype showed more favorable metabolic trajectories than the MARD subtype. Enhanced lifestyle management was associated with reduced diabetes progression risk.
BACKGROUND Type 2 diabetes mellitus is a global health challenge that often leads to complications such as diabetic foot ulcers (DFUs). Although malnutrition is a common feature of hospitalized patients with type 2 diabetes mellitus, data on malnourished patients also diagnosed with DFUs are limited. AIM To determine the clinical features of malnutrition in this high-risk population. METHODS This retrospective study included patients diagnosed with DFUs who were hospitalized between January 2020 and December 2025. We analyzed clinical data derived from electronic medical records, with patients being categorized into malnutrition and non-malnutrition groups based on nutritional status at admission and compared with respect to demographic, clinical, and outcome variables. Univariate and multivariate logistic regression analyses were performed to identify factors of interest, and receiver operating characteristic curves were used to evaluate the predictive value of significant risk factors. RESULTS In total, 268 eligible patients were enrolled in this study, of whom 96 and 172 were assigned to the malnutrition and non-malnutrition groups, respectively. Univariate analysis identified significant between-group differences for six factors, namely, age, duration of diabetes, serum albumin, triglycerides, hemoglobin, glycated hemoglobin, and multidrug-resistant organisms (MDROs; P < 0.05). Multivariate analysis revealed that age (> 65 years; P = 0.004), serum albumin (< 36.6 g/L; P = 0.014), hemoglobin (< 111.2 g/L; P < 0.001), glycated hemoglobin (> 7.1%; P < 0.001), and MDROs (P < 0.006) were independent risk factors for malnutrition. Furthermore, compared with the non-malnutrition group, patients in the malnutrition group had a longer mean hospital stay and lower rates of wound healing within 60 days (P < 0.05). CONCLUSION To improve the clinical outcomes of malnourished hospitalized patients with DFUs, early intervention should be provided to those with risk factors such as older age, depleted hemoglobin, and MDRO infections.
BACKGROUND Diabetic ulcer is a prevalent chronic refractory wound and a severe complication of diabetes that drastically undermines patients' quality of life and causes heavy economic burdens. Local dressing therapy is a core diabetic ulcer intervention, but existing functional hydrogel dressings are plagued by single-target action and insufficient antioxidant components and have become key bottlenecks in dressing research and development. AIM To develop a novel thermosensitive composite hydrogel dressing that overcomes the limitations of existing hydrogel dressings for effective diabetic ulcer management. METHODS A thermosensitive composite hydrogel [PF/polyhexamethylene biguanide (PHMB)-nicotinamide mononucleotide (NMN)] was successfully fabricated by integrating NMN, which is a potent antioxidant, as the functional ingredient with Pluronic F127 and PHMB, an antibacterial agent. In this preclinical study, the effect of this hydrogel in the treatment of diabetic wounds was evaluated by both in vitro and in vivo experiments. RESULTS The PF/PHMB-NMN hydrogel possessed excellent sustained drug release, antibacterial and antioxidant properties; in vitro experiments confirmed that the hydrogel could effectively inhibit bacteria, promote cell migration and angiogenesis. In mouse models, the NMN-loaded hydrogel significantly accelerated diabetic wound healing, with upregulated expression levels of vascular endothelial growth factor and transforming growth factor-beta 1. CONCLUSION The NMN-PHMB-loaded Pluronic F127 thermosensitive composite hydrogel safely and effectively facilitates diabetic wound healing in a mouse model, offering a potential therapeutic strategy and promising a candidate dressing for further investigation in clinical diabetic foot ulcer management.
BACKGROUND Metabolic dysfunction-associated steatotic liver disease (MASLD) is the most common chronic liver disease worldwide, but non-invasive biomarkers for its detection remain limited. The high-sensitivity C-reactive protein-triglyceride-glucose index (CTI), which integrates inflammatory and metabolic parameters, has emerged as a potential marker. However, its association with MASLD and diagnostic performance across different glycemic states remain unclear. AIM To investigate the association between CTI and MASLD and to evaluate its diagnostic performance across different glycemic states. METHODS This study included 7413 adults who underwent routine health examinations between January 2020 and March 2024. Participants were categorized into three groups according to glycemic status: Normal glucose regulation (NGR; n = 2933), prediabetes mellitus (pre-DM; n = 3549), and diabetes mellitus (DM; n = 931). CTI was calculated as 0.412 & times; ln(high-sensitivity C-reactive protein) + ln(triglycerides & times; fasting plasma glucose/2). The Boruta algorithm was applied to identify variables relevant to MASLD. Multivariable logistic regression assessed CTI-MASLD associations, restricted cubic spline analyses were performed to examine dose-response relationships, and diagnostic performance was evaluated using receiver operating characteristic curves. RESULTS After multivariable adjustment, each unit increase in CTI was significantly associated with MASLD in the NGR (adjusted OR = 3.07; 95%CI: 2.19-4.31) and pre-DM groups (adjusted OR = 3.26; 95%CI: 1.70-6.23), but not in the DM group (adjusted OR = 1.58; 95%CI: 0.65-3.84). CTI achieved an overall area under the curve (AUC) of 0.808 (95%CI: 0.798-0.817), with AUCs of 0.792, 0.783, and 0.749 in the NGR, pre-DM, and DM groups, respectively. Optimal CTI thresholds increased progressively with worsening glycemic status (NGR: 8.596; pre-DM: 8.908; DM: 9.456). CONCLUSION CTI was significantly associated with MASLD in normoglycemic and prediabetic populations but not in diabetic individuals, with optimal thresholds varying by glycemic status.
BACKGROUND Type 2 diabetes mellitus (T2DM) is not only a disorder of glucose and lipid metabolism, but also closely associated with disturbances in amino acid metabolism. Dangua Fang (DGF) is a traditional Chinese medicine formula used for the treatment of diabetes and has been shown to regulate amino acid metabolism. The nicotinamide phosphoribosyltransferase (NAMPT)/nicotinamide adenine dinucleotide (NAD+)/sirtuin 1 (SIRT1) axis is closely linked to amino acid metabolism and plays an important role in maintaining metabolic homeostasis.AIM To investigate the regulatory effects of DGF on the hepatic NAMPT/NAD+/SIRT1 axis and amino acid metabolism in T2DM rats. METHODS A T2DM rat model was established by a high-glucose and high-fat diet combined with streptozotocin injection. Rats were randomly assigned into four groups, namely the control group, model group, DGF group (DFG, 20 g/kg), and metformin group (0.11 g/kg), with eight rats in each group. After 14 weeks of intervention, glucolipid metabolism-related indicators, expression of the NAMPT/NAD+/SIRT1 axis, and hepatic amino acid metabolism were evaluated. RESULTS Compared with the model group, the DFG and metformin groups exhibited significantly increased body weight and high-density lipoprotein cholesterol levels (P < 0.05 and P < 0.01), accompanied by reductions in fasting and postprandial blood glucose, liver weight, liver index, haemoglobin A1c, total cholesterol, triglycerides, low-density lipoprotein cholesterol, and free fatty acid levels (P < 0.05 and P < 0.01), along with alleviated hepatic histopathological damage and significantly upregulated NAMPT and SIRT1 mRNA and protein expression (P < 0.05 and P < 0.01), as well as elevated NAD+ content (P < 0.01). In the DFG group, several key metabolic pathways were significantly modulated, including riboflavin metabolism, pentose and glucuronate interconversions, purine metabolism, glycolysis/gluconeogenesis, and vitamin B6 metabolism, indicating significant modulation of amino acid metabolism. CONCLUSION DGF significantly ameliorates glucolipid metabolism in T2DM rats, an effect that may be mediated by regulation of the hepatic NAMPT/NAD+/SIRT1 axis and amino acid metabolism disorders.
