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

Background: Insulin resistance (IR) is a pivotal pathological feature in the development of type 2 diabetes mellitus (T2DM). MicroRNA-199a (miR-199a) has been implicated in various metabolic disorders, but its precise role and mechanism in hepatic IR remain largely unexplored. This study aimed to investigate the role of miR-199a in IR and inflammation and to determine whether its effects are mediated through DDIT4 and the PI3K/AKT pathway.

Methods: An in vitro IR model was established in HepG2 cells using palmitic acid, and an in vivo T2DM model was induced in mice using a high-fat diet combined with streptozotocin injection. Functional assays, including glucose uptake and ELISA, were employed to assess metabolic and inflammatory responses. The interaction between miR-199a and its putative target, DDIT4, was validated by luciferase reporter and RNA immunoprecipitation assays. Key proteins in the PI3K/AKT signaling pathway were analyzed by Western blotting.

Results: We found that miR-199a was significantly upregulated, while DDIT4 was downregulated in both IR HepG2 cells and diabetic mice. Mechanistically, we identified DDIT4 as a direct target of miR-199a. Knockdown of miR-199a ameliorated insulin resistance and suppressed inflammation, whereas concomitant depletion of DDIT4 abolished these protective effects. Furthermore, miR-199a inhibition activated the PI3K/AKT pathway, as evidenced by increased phosphorylation of PI3K, AKT, and AS160, and decreased phosphorylation of FOXO1. These signaling changes were also dependent on DDIT4. In vivo, inhibition of miR-199a improved glucose homeostasis, attenuated systemic inflammation, and activated pancreatic PI3K/AKT signaling in T2DM mice.

Conclusion: Our findings reveal a novel miR-199a/DDIT4 axis that regulates insulin sensitivity and inflammation via the PI3K/AKT pathway, suggesting miR-199a as a potential therapeutic target for T2DM.

Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder indicated by hyperglycemia. The potential for adverse effects occurring in conventional therapies necessitates the exploration of natural alternatives.

Aim: This study aimed to evaluate the protective effect of mermelosin in a high-fat diet and streptozotocin (STZ) induced rat model of T2DM.

Methods: Twenty-four rats were randomly allocated to four experimental groups (n=6) for a 28-day study. Group 1 served as the control, receiving 0.5 mL of normal saline. Group 2 (T2DM control) received 35 mg/kg STZ and HFD to induce diabetes. Groups 3 and 4 received 10 mg and 20 mg of marmelosin orally, respectively. After 28 days, biochemical analyses were performed to assess pancreatic oxidative stress, insulin levels, and essential biochemical markers, including a lipid profile, liver function, inflammatory responses, oxidative stress levels, and apoptotic activity.

Results: Marmelosin significantly improved fasting blood glucose (FBG) and hemoglobin A1c (HbA1c) levels in rats with T2DM. It also enhanced insulin sensitivity, as evidenced by increased plasma insulin levels and decreased HOMA-IR values. Marmelosin effectively mitigated dyslipidemia by lowering total cholesterol and serum triglycerides while elevated HDL cholesterol. Furthermore, it acted as a potent antioxidant, as indicated by the elevation of SOD, GSH, CAT, and reduced cytokines (TNF-α, IL-1β, IL-6). Marmelosin also reduced apoptosis by downregulating caspase-3 expression.

Conclusion: These findings collectively suggest that marmelosin acts as a multifaceted protective effect, including metabolic regulation, anti-inflammatory, antioxidant, and anti-apoptotic activities, highlighting its potential as a promising therapeutic agent for the management of T2DM.

Purpose: Dumping syndrome (DS) is a postsurgical complication of bariatric procedures. It is classified into early and late dumping based on occurrence within different postprandial timeframes. This study measures the prevalence of DS among adult patients and its association with social determinants and nutrition knowledge.

Patients and methods: This cross-sectional study used a convenience sampling method via distributing an online validated questionnaires to patients who underwent sleeve gastrectomy or gastric bypass surgery in ≥3 months.

Results: Out of 352 participants, 237 (67.3%) had a modified Sigstad weighted DS score of ≥3.26, indicating the presence of DS; 182 (76.8%) had early DS (symptoms within 1 hour postprandially) and 55 (23.2%) had late DS (symptoms 1-3 hours postprandially). Only gender and monthly income showed statistically significant differences between early and late DS patients. No statistically significant associations were found between the DS subtypes and sociodemographic characteristics, although participants' age approached significance (p = 0.052). Type 1 diabetes was significantly associated with DS and affected patients were 6.7 times more likely to experience symptoms. The mean nutrition knowledge score among all the participants was 60.88 (SD = 14.76) suggesting moderate nutrition knowledge.

Conclusion: There is a high prevalence of DS (67.3%) among post-bariatric surgery patients in Saudi Arabia, and early DS is more common than late DS. The findings suggest a strong correlation between type 1 diabetes and DS. Nutrition knowledge was moderate but insufficient in key areas that affect postoperative outcomes. The study is novel in reporting a high prevalence of DS among post-bariatric patients in Saudi Arabia and uniquely explores the association of DS with social determinants, nutrition knowledge, and type 1 diabetes-areas less examined in previous research. It emphasizes the imperative need for comprehensive patient education and continuous dietary counseling to improve long-term management and outcomes for bariatric surgery patients.

Objective: To search, evaluate and summarize the evidences of health management in middle-aged and elderly patients with type 2 diabetes with traditional Chinese medicine (TCM) characteristics, so as to provide evidence-based basis for improving patients' participation initiative and implementing personalized health management practice for community medical staff.

Methods: Based on evidence-based nursing methods, The domestic and foreign evidence-based resource databases including UpToDate, Elsevier, Web of Science and Cochrane were searched Library, RNAO, PubMed, Medline, CINAHL, Embase, BMJ British Medical Journal, Medical Pulse Guide Network, Chinese Medical Association, Diabetes Society, CMA Chinese Medical Association, OVID database, JBI evidence-based Health Care Center database, Chinese Traditional Medicine Database, Chinese Biomedical Literature Xian database, Wanfang database, VIP database and China National Knowledge Infrastructure. Two researchers based on the critical appraisal for summaries of evidence, CASE) appraisal of guidelines for research and evaluationII (AGREEII) independently assessed the quality of the included literature, and extracted and summarized the literature evidence that met thecriteria.

Results: A total of 10 guidelines, 6 expert consensus, 3 evidence summaries, and 2 Meta-analysis summarized four dimensions, namely nutrition management, exercise management, TCM diet management, and TCM emotional management, with a total of 35 pieces of evidence.

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.