Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy最新文献

Purpose: The aim of this study is to explore the changes of gut microbiota, the metabolic characteristics and sex hormones in polycystic ovary syndrome with insulin resistance (PCOS-IR), and to clarify the role of gut microbiota in the occurrence of this condition.

Methods: We established a rat model of PCOS-IR using dehydroepiandrosterone (DHEA) combined with a high-fat diet, and recruited patients who met the clinical diagnostic criteria for PCOS-IR. We measured metabolic parameters and sex hormone profiles, and analyzed gut microbiota characteristics via high-throughput 16S rRNA sequencing. We also conducted microbial transplantation experiments to verify the causal relationship between gut microbiota and PCOS-IR.

Results: In PCOS-IR rats, we observed significant endocrine-metabolic disturbances and alterations in gut microbiota β-diversity, characterized by an enrichment of Fusobacterium. Transplantation of this dysbiotic microbiota to healthy rats reproduced key PCOS-IR features, confirming a causal role. In people with PCOS-IR, we found a distinct gut microbial profile compared to both healthy individuals and those with PCOS without IR, with Fusobacterium consistently identified as a key genus across species.

Conclusion: Our findings show that gut microbiota disturbance leads to endocrine and metabolic features resembling PCOS-IR. The gut microbiota, particularly Fusobacterium, could serve as a clinical marker and potential therapeutic target for people with PCOS-IR. This study provides mechanistic insights into how gut microbiota contributes to PCOS-IR pathogenesis.

Objective: To identify risk factors for prognosis in diabetic foot patients undergoing digital subtraction angiography (DSA) intervention and analyze their correlation with ulcer severity.

Methods: This retrospective study analyzed 135 diabetic foot patients who underwent DSA-guided intervention between August 2023 and January 2025. Patients were classified good and poor prognosis groups based on 6-month outcomes. We compared demographic data and clinical laboratory indexes between groups. Statistically significant variables were analyzed using Logistic regression to identify independent risk factors. The receiver operating characteristic (ROC) curves and Pearson correlation analysis were employed to assess the diagnostic value of these factors and correlation with ulcer severity.

Results: The stratified diabetic foot ulcer risk score (SINBAD) was significantly higher in patients with poor prognosis (7.15±2.76) compared to those with good prognosis (3.24±1.81); Serum levels of procalcitonin (PCT), galactoagglutinin-3 protein (Gal-3), noncoding RNA molecule with circular structure (Hsa_circ_0057362), interleukin-6 (IL-6), and serum C-reactive protein (CRP) was significantly elevated in the poor prognosis group (P < 0.05). Pearson correlation analysis revealed positive corrections between these biomarkers and ulcer severity (r=0.283, 0.240,0.434, 0.370, 0.443, respectively; all P < 0.05); Logistic regression analysis identified PCT, Gal-3, Hsa_circ_0057362, IL-6, and CRP as independent influencing factors for poor prognosis in diabetic foot. Furthermore, ROC curve analysis demonstrated that each of these indicators possessed a certain degree of predictive value for poor prognosis following diabetic foot surgery.

Conclusion: A plethora of risk factors, including PCT, Gal-3, Hsa_circ_0057362, IL-6 and CRP, influence poor prognosis in diabetic foot patients undergoing DSA-guided intervention. These biomarkers demonstrate significant correlations with ulcer severity and hold substantial clinical utility in the predicting postoperative outcomes. Early identification of patients at risk for poor prognosis enables the implementation of targeted interventions, thereby effectively improving patient outcomes.

Purpose: Despite the pathophysiologic overlap between metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiovascular-kidney-metabolic (CKM) syndrome, MASLD has not been incorporated into the current CKM framework. This study examined the associations of MASLD and MASLD-related fibrosis with advanced CKM syndrome in Chinese and US populations.

Patients and methods: We enrolled 6186 participants in a community-based cross-sectional study conducted in China, with validation utilizing the National Health and Nutrition Examination Survey (NHANES). Advanced CKM syndrome was defined as stages 3 and 4. Hepatic steatosis and fibrosis were assessed via vibration-controlled transient elastography. Multivariable logistic regression and restricted cubic spline (RCS) analyses were employed.

Results: Advanced CKM syndrome was present in 8.8% of the Chinese and 14.9% of the US populations. MASLD participants exhibited a significantly higher prevalence of advanced CKM than those without (China: 12.6% vs 6.4%; US: 21.5% vs 9.9%). In addition, participants with MASLD were associated with increased odds of advanced CKM (China: OR 2.06, 95% CI: 1.64-2.58; US: OR 1.60, 95% CI: 1.22-2.10; both P < 0.01). Among participants with MASLD, advanced CKM syndrome was more prevalent in participants with fibrosis than without (China: 17.1% vs 11.2%; US: 28.4% vs 20.1%). MASLD-related fibrosis was also independently linked to higher odds of advanced CKM compared to non-fibrotic MASLD (China: OR 1.55, 95% CI: 1.09-2.18; US: OR 1.44, 95% CI: 1.01-2.05; both P < 0.05). Furthermore, RCS analysis revealed a positive linear relationship of controlled attenuation parameter (CAP) and liver stiffness measurement (LSM) values with the prevalence of advanced CKM syndrome (P non-linear >0.05).

Conclusion: MASLD and MASLD-related fibrosis were significantly associated with a higher prevalence of advanced CKM syndrome, and higher CAP/LSM levels showed linear associations with advanced CKM syndrome in both Chinese and US populations. These findings support evaluating liver health (eg, CAP/LSM) when risk-stratifying CKM syndrome.

Metabolic Dysfunction-Related Steatotic Liver Disease (MASLD) is a global health challenge requiring effective interventions. Although nutraceuticals possess strong hepatoprotective potential in vitro, their clinical efficacy is often hampered by fundamental formulation issues, such as poor solubility and oral bioavailability. To address these challenges, this review evaluates the translational potential of nano-based nutrient delivery systems, specifically platforms such as nanoemulsions, liposomes, and polymeric nanoparticles. Through synthesis of in vivo evidence, we analyze how these platforms modify pharmacokinetic parameters to enhance therapeutic efficacy. Preclinical evidence indicates that nanoplatforms significantly improve solubility and stability, which directly correlate with superior therapeutic outcomes in animal models (including reduced steatosis and fibrosis) compared to conventional compounds. However, the transition to clinical applications remains hampered by a lack of long-term safety data (nanotoxicity) and scalability issues. The future of this field is predicted to lie in the development of green nanotechnology utilizing sustainable and economically viable "food-grade" (GRAS) biopolymers.

Pancreatic β-cell dysfunction represents a key pathological feature in the development and progression of diabetes mellitus. Accumulating evidence has confirmed the widespread expression of vitamin D receptors in pancreatic tissue, suggesting a potential regulatory role in glucose metabolism. Epidemiological studies have consistently reported an association between vitamin D deficiency and increased diabetes incidence, impaired insulin secretion, and poor glycemic control. Vitamin D has been known to support pancreatic islet function by modulating β-cell proliferation, enhancing insulin synthesis and secretion, and mitigating inflammatory responses and oxidative stress. This review systematically discusses vitamin D metabolism and physiological functions, the role of pancreatic islet dysfunction in diabetes pathogenesis, vitamin D receptor expression and activity in pancreatic tissue, epidemiological correlations between vitamin D status and diabetes risk, and the molecular mechanisms through which vitamin D influences β-cell function. Furthermore, this review examines the therapeutic implications of vitamin D supplementation for the prevention and management of diabetes. It contributes to a growing body of knowledge that informs potential strategies to improve diabetes outcomes through vitamin D-related pathways.

Background: Dysglycemia, including prediabetes and type 2 diabetes (T2DM), is associated with an increased risk of chronic kidney disease and mortality. However, data on the relationship between estimated glomerular filtration rate (eGFR) and all-cause mortality in dysglycemic individuals remain limited.

Methods: This 10-year retrospective cohort study included 277 individuals with dysglycemia from a health check-up clinic at Srinagarind Hospital, Thailand (2007-2017). Participants were divided into three eGFR groups: ≥90, 60-<90, and <60 mL/min/1.73 m². Multivariate Cox regression models adjusted for fasting plasma glucose, body mass index, total cholesterol, and hypertension were used to estimate hazard ratios (HRs) for all-cause mortality. The association between ≥40% eGFR decline and mortality was also evaluated.

Results: Over 10 years, 37 participants (13.4%) died. Lower eGFR was associated with higher mortality risk. Compared to the ≥90 group, adjusted HRs for all-cause mortality were 1.70 (95% CI 0.82-3.52) for eGFR 60-<90 and 3.74 (95% CI 1.27-11.03) for eGFR <60. A ≥40% eGFR decline significantly increased mortality risk (adjusted HR 7.14; 95% CI 3.16-16.14).

Conclusion: Dysglycemic individuals with eGFR <60 or a ≥40% eGFR decline have a significantly higher mortality risk, highlighting the need for early detection and intervention.

Purpose: Elderly patients with diabetic peripheral neuropathy (DPN) are significantly impacted by frailty, yet frailty prediction models for this population remain underexplored. This study aims to develop and internally validate a frailty prediction model for elderly patients with DPN.

Patients and methods: A cross-sectional study design was employed, and 400 elderly DPN patients were recruited from a tertiary hospital in Guangdong Province, China, between December 2024 and July 2025. Logistic regression was employed to identify frailty risk factors and develop a prediction model and nomogram for elderly DPN patients. We evaluated the performance of the model using the area under the receiver operating characteristic (ROC) curve, abbreviated as AUC, and was further assessed through the Hosmer-Lemeshow test and calibration curves. The clinical utility of the model was assessed by decision curve analysis (DCA). Internal validation was performed using 1000 bootstrap resamples to reduce the risk of overfitting.

Results: Among the 400 patients, 113 (28.25%) patients had frailty. Six factors were identified as significant predictors: age, marital status, regular exercise, PSQI score, MNA-SF score, and HADS-D score. We constructed a nomogram based on these factors. Internal validation demonstrated good performance in both discrimination and calibration, and DCA confirmed the model's clinical applicability.

Conclusion: The nomogram developed in this study provides an effective tool for the early identification of elderly DPN patients at risk of frailty, thereby informing tailored preventive and intervention strategies. External validation will be conducted in future studies, and future studies will assess the model's generalizability across different regions and healthcare systems. The main predictors identified in this study include age, marital status, regular exercise, PSQI score, MNA-SF score, and HADS-D score, which significantly contribute to frailty risk in elderly DPN patients.

Purpose: The study aimed to explore the relationship between the monocyte-to-high-density lipoprotein cholesterol ratio (MHR) and visceral fat area (VFA) in patients with type 2 diabetes mellitus (T2DM).

Patients and methods: A total of 2156 patients with T2DM who received medical treatment at Zhejiang Provincial People's Hospital participated in this study. Patients were categorized into two groups based on VFA: the increased VFA group (VFA ≥ 100 cm², n = 1091) and the normal VFA group (VFA < 100 cm², n = 1065). Biochemical indicators were measured via blood tests, whereas VFA was measured using bioelectrical impedance analysis. Spearman correlation and linear regression analysis were conducted to examine the association between MHR and VFA. Receiver operating characteristic (ROC) curves for predicting the VFA were constructed, and areas under the ROC curves were estimated.

Results: MHR level was significantly higher in the increased VFA group (p < 0.001) than in the normal VFA group. Spearman correlation analysis showed a positive association between VFA and MHR (r = 0.366, p < 0.001). Multivariate linear regression analysis revealed that elevated MHR is an independent factor for increased VFA (β = 20.64, 95% CI 13.46-27.82, p < 0.001). After stratification by hemoglobin A1c levels and diabetes duration, MHR remained independently associated with VFA. ROC analysis indicated that MHR has a predictive effect on VFA, with an area under the curve of 0.708 (specificity = 58%, sensitivity = 73%).

Conclusion: MHR levels are associated with visceral fat area in patients with T2DM, which has a modest predictive value, and it may be useful in detecting visceral obesity.

Despite having very different underlying etiologies, an unfortunate similarity between Type 1 diabetes (T1D) and Type 2 diabetes (T2D) is the ongoing increase in incidence and prevalence in youth in both types of diabetes over the past several decades. This mini-review highlights recent studies documenting the increases in T1D and T2D in the US and worldwide. These trends underscore the need for healthcare providers and families to have a low index of suspicion for diabetes, as well as the ongoing need for improved means of preventing and treating diabetes in youth.