Purpose Both hyperuricemia and high urinary uric acid excretion (UUAE) are strongly associated with obesity and metabolic syndrome (MetS). However, few studies have examined the joint association of these two conditions with obesity and MetS. This study was aimed at investigating whether the concomitant presence of high serum uric acid (SUA) and high UUAE was associated with higher odds of obesity and MetS in patients with Type 2 diabetes mellitus (T2DM). Methods This cross‐sectional study included 7051 Chinese patients with T2DM in a real‐world setting. Participants were divided into four groups, including patients with normal SUA and UUAE (Group 1), normal SUA and high UUAE (Group 2), high SUA and normal UUAE (Group 3), and high SUA and UUAE (Group 4). The clinical characteristics and prevalence of obesity and MetS were compared among these groups. Results After adjustment, compared with Group 1, both Groups 2 and 3 had a significantly elevated prevalence of obesity (42.6%, 63.2%, and 62.6%, respectively, p < 0.001 for trend), abdominal obesity (62.4%, 76.5%, and 81.3%, respectively, p < 0.001 for trend), and MetS (66.4%, 78.3%, and 87.8%, respectively, p < 0.001 for trend). Moreover, the prevalence of obesity, abdominal obesity, and MetS further increased in Group 4 (84.6% for obesity, 93.6% for abdominal obesity, and 88.5% for MetS). Additionally, serum CRP levels and HOMA2‐IR values were significantly higher in the other three groups than in Group 1, with the highest values in Group 4 ( p < 0.001 for trend). Conclusion The concomitant presence of elevated SUA and UUAE was associated with higher odds of both obesity and MetS among patients with T2DM. Thus, the combined consideration of SUA and UUAE levels may help to identify those T2DM patients with a greater burden of obesity and MetS.
Background Type 1 diabetes mellitus (T1DM) cardiomyopathy is a severe complication that typically follows an insidious onset and then progresses rapidly to heart failure and premature death. AGEs accumulate in the myocardium under hyperglycemic conditions and have emerged as important mediators of this diabetic complication, although the full signaling cascades engaged by AGEs remain largely unresolved. In the present study, we therefore investigated whether AGEs induce myocardial injury in T1DM via NLRP3 inflammasome activation. Methods A T1DM mouse model was established using streptozotocin (STZ) injections, and an in vitro model was generated by treating primary neonatal mouse cardiomyocytes with AGEs. Cardiac performance and morphological changes were examined via echocardiography and histopathological staining. Expression and activation of the NLRP3 signaling cascade were evaluated by Western blotting, ELISA, and immunofluorescence. Pyroptotic cell death was assessed by SYTOX green staining, PI uptake, and lactate dehydrogenase (LDH) release assay. Correlations between whole‐blood RAGE gene expression and inflammatory cytokine levels (IL‐1 β and IL‐18) in T1DM patients, along with myocardial abundance of RAGE, NLRP3, and N‐GSDMD in the experimental mice, were analyzed as exploratory descriptive observations. Results STZ‐induced T1DM mice exhibited sustained hyperglycemia (fasting blood glucose ≥ 11.1 mmol/L) and impaired cardiac function. Myocardial tissue from T1DM animals showed marked engagement of the NLRP3 signaling cascade, as evidenced by elevated NLRP3, cleaved caspase‐1 P20, and N‐GSDMD, enhanced ASC speck formation, and increased serum IL‐1 β levels. In vitro, AGEs treatment directly triggered the NLRP3 pathway and drove cardiomyocyte pyroptosis. Mechanistically, AGEs binding to RAGE triggered a burst of intracellular ROS, which led to NF‐ κ B activation and subsequent NLRP3 activation. These effects were suppressed by either the RAGE inhibitor FPS‐ZM1 or the ROS scavenger N‐acetylcysteine (NAC). Furthermore, MCC950 treatment significantly attenuated AGE‐induced caspase‐1 activation, IL‐1 β /IL‐18 secretion, and N‐GSDMD expression, confirming that NLRP3 is a necessary mediator of this signaling cascade. SYTOX green staining, PI uptake, and LDH release assays further demonstrated that AGE‐induced pyroptotic cell death was blocked by FPS‐ZM1, NAC, and MCC950, indicating that pyroptosis occurs specifically through the RAGE/ROS/NLRP3 axis. Correlation analyses revealed that RAGE transcript levels in whole blood from T1DM patients positively correlated with circulating IL‐1 β and IL‐18. In the diabetic mouse heart, RAGE, NLRP3, and N‐GSDMD protein levels were analyzed as exploratory descriptive observations and showed a consistent pattern of coexpression at the individual level. Conclusion AGEs promote NLRP3 inflammasome activation in cardiomyocytes via the RAGE/ROS/NF‐ κ B signaling axis, driving inflammatory responses and pyroptosis, thereby contributing to the progression of T1DM cardiomyopathy. These observations imply that modulating this signaling axis could serve as a promising therapeutic strategy for treating T1DM cardiomyopathy.
Background Diabetes mellitus (DM) is a metabolic disorder characterized by a consistently elevated blood sugar level. DM poses a major risk factor for many neurodegenerative diseases, causing a decline in cognitive function. BDNF (brain‐derived neurotrophic factor) is a neurotrophin in the central and peripheral nervous systems that plays a crucial role in the development of brain circuits. Hence, disturbance in levels of BDNF is linked to the occurrence of neurodegenerative diseases and cognitive decline in diabetic patients. Physical exercise has emerged as a nonpharmacological intervention in elevating BDNF levels. Our systematic review and meta‐analysis evaluate the relationship between a globally affecting metabolic disorder, diabetes, with decreased BDNF levels, and explore exercise as a promising potential intervention. Methods After screening 37 articles, 4 studies have been included in the systematic review and meta‐analysis, out of which 3 of them are randomized controlled trials (RCTs), and 1 is a crossover trial. The search was conducted on PubMed (MEDLINE), ScienceDirect, Embase, Scopus, and Cochrane Central databases from inception to June 2025. PRISMA (Preferred Reporting Items for Systematic Reviews and Meta‐Analyses) guidelines were followed to conduct a systematic review. Cochrane risk‐of‐bias tool was used to assess the quality of the studies. Data were pooled using a random effect model. The protocol for this systematic review was registered in PROSPERO. Results A total of 37 articles were screened, 3 RCTs and 1 crossover trial with 131 participants were included in the meta‐analysis. Serum BDNF levels were higher in the exercise group compared with controls (MD = 73.50; p = 0.05). A small reduction in body fat percentage in the exercise group compared with the control was found (MD = −1.24 % ; p = 0.17), which was not statistically significant. Body weight and fasting blood glucose (FBG) showed no statistically significant differences between the exercise and control groups (MD = 0.97; p = 0.65), (MD = −27.20; p = 0.31). Moderate to high heterogeneity was noticed across the data analyzed. Conclusion This meta‐analysis overall concludes that regular exercise positively affects serum BDNF levels in diabetics. However, the small number of trials and small sample sizes has limited the conclusions. Further large‐scale RCTs are required to determine the long‐term neurological effects of exercise in diabetics.
Background This study employed a high‐energy diet and streptozotocin (STZ) injection to establish a rat model of diabetic peripheral neuropathy (DPN), focusing on inflammatory responses. The aim was to investigate the mechanism by which electroacupuncture (EA) improves the neuroinflammatory microenvironment in diabetic rats and attenuates DPN development. Method Twenty‐four male SD rats were randomly assigned using a random number table into control, model, and EA groups, with eight rats in each group. A DPN model was established using a high‐energy diet combined with STZ injection. The EA group received intervention immediately after successful diabetic modeling, whereas intervention ceased once DPN modeling was established in the model group. During the intervention period, random blood glucose levels and paw withdrawal latency (PWL) were recorded weekly for rats in each group. After intervention, the neurophysiological status of rats was assessed. The ultrastructure of Schwann cells in the sciatic nerve was observed using transmission electron microscopy. Western Blot and RT‐PCR were employed to detect the protein levels and mRNA expression of ASC, caspase‐1, NLRP3, and P62. ELISA was implemented to measure IL‐18 and IL‐1 β levels. Results Compared with the control, model rats exhibited significantly elevated random blood glucose and PWL levels ( p < 0.0001, p < 0.0001), markedly reduced motor nerve conduction velocity (MNCV) ( p < 0.0001), and pronounced damage to Schwann cell structure. ASC, caspase‐1, NLRP3, and P62 levels were markedly elevated ( p < 0.01, p < 0.0001, p < 0.0001, p < 0.001; p < 0.001, p < 0.01, p < 0.05, p < 0.001), whereas IL‐18 and IL‐1 β levels were notably elevated ( p < 0.0001, p < 0.0001). Compared with the model group, rats in the EA group displayed no marked difference in random blood glucose ( p > 0.05), but reduced PWL ( p < 0.0001), increased MNCV ( p < 0.0001), and milder structural damage to Schwann cells. ASC, caspase‐1, NLRP3, and P62 levels were considerably reduced ( p < 0.01, p < 0.0001, p < 0.001, p < 0.001; p < 0.05, p < 0.05, p < 0.05, p < 0.05), whereas IL‐18 and IL‐1 β levels were notably diminished ( p < 0.001, p < 0.0001). Conclusion EA may protect peripheral nerve tissue morphology and function by suppressing NLRP3 inflammasomes, thereby alleviating inflammatory responses and potentially attenuating the onset and progression of DPN. This process may be associated with autophagy; but further mechanistic studies are needed to establish causality.
Objective The aim of this study is to compare the standardized associations, cross‐sectional discrimination, and distributional robustness of 13 routinely derived metabolic indices for International Diabetes Federation (IDF)‐defined metabolic syndrome (MetS). Methods We included 9660 Chinese adults who underwent routine health examinations at Peking University Shenzhen Hospital between August 2024 and March 2026. Associations were assessed using logistic regression with standardized indices and restricted cubic splines, and overall and prespecified subgroup discrimination were evaluated using receiver operating characteristic analyses. Fully adjusted analyses included age, sex, low‐density lipoprotein cholesterol, total bilirubin, blood urea nitrogen, creatinine, and uric acid. Robustness was examined after 1st–99th percentile winsorization using self‐standard deviation (self‐SD) and fixed main‐sample standard deviation (fixed main‐SD) standardization. Results Among 9660 participants, 1635 had MetS (16.93%). The cardiometabolic index (CMI) showed the strongest standardized association (odds ratio (OR) per standard deviation increment, 19.437), followed by the triglyceride‐glucose waist circumference index (TyG‐WC; OR, 16.332). TyG‐WC had the highest overall area under the receiver operating characteristic curve (AUC, 0.934; 95% confidence interval (CI), 0.929–0.939) and the highest AUC in 9 of 11 prespecified strata. After winsorization, TyG‐WC retained strong standardized associations under self‐SD and fixed main‐SD scaling (ORs, 17.181 and 18.638, respectively) and stable discrimination (AUC, 0.935), whereas CMI, the lipid accumulation product (LAP), visceral adiposity index (VAI), and triglyceride‐total cholesterol‐body weight index (TCBI) showed substantial scale dependence. All indices showed nonlinear associations ( p < 0.001). Conclusion The 13 indices differed in association strength, discrimination, and distributional robustness. TyG‐WC showed the most balanced overall profile and maintained strong discrimination across most prespecified subgroups. These findings support the further evaluation of TyG‐WC in routine health examination settings. Further validation in independent multicenter populations is required.
