Diabetic neuropathy (DN) is a debilitating complication of diabetes mellitus (DM), characterized by progressive neuronal damage, sensory dysfunction, and impaired quality of life. Recent advances in exosome research have elucidated their crucial role in DN's pathogenesis, diagnosis, and treatment. Exosomes-nanoscale extracellular vesicles-function as vehicles for molecular cargo, including microRNAs (miRNAs), proteins, and lipids, which mediate intercellular communication and regulate key biological processes. Pathologically, hyperglycemia and hyperlipidemia induce the release of exosomes enriched with pathogenic miRNAs, such as miR-130a and miR-20b-3p, which disrupt neuronal function, axonal regeneration, and inflammatory pathways. Conversely, diagnostic studies highlight the utility of exosomal biomarkers like miR-7 and miR-221 in the early detection and monitoring of DN. Therapeutically, Schwann cell-derived and mesenchymal stromal cell (MSC)-derived exosomes demonstrate neuroprotective and reparative effects by enhancing mitochondrial function, modulating inflammation, and promoting axonal repair. Emerging approaches, including engineered exosomes and miRNA-enriched vesicles, further expand their therapeutic potential. Despite these advances, challenges such as standardization, large-scale production, and clinical validation remain in translating these findings into clinical practice. This review underscores the multifaceted roles of exosomes in DN and highlights their potential as innovative tools for precision diagnostics and targeted therapies, paving the way for future research and clinical applications.

Probiotic and synbiotic supplementation has garnered attention for its potential to modulate metabolic parameters, including glycemic control, in individuals with prediabetes and type 2 diabetes mellitus (T2DM). This systematic review and dose-response meta-analysis aims to evaluate the effectiveness of these supplements on glycemic indices, synthesizing evidence from randomized controlled trials (RCTs) with grade-assessed methodologies. A comprehensive search of scientific databases was conducted from inception through January 2025 to identify RCTs assessing the effects of probiotic and synbiotic supplementation on glycemic indices, including fasting blood glucose (FBG), fasting insulin (FI), hemoglobin A1c (HbA1c), and homeostatic model assessment for insulin resistance (HOMA-IR). Eligible studies were screened; relevant data were extracted, and the quality of evidence was evaluated using the GRADE approach. Statistical analyses were performed using STATA to generate pooled results. The pooled analysis of 48 RCTs demonstrated that probiotics and synbiotics supplementation significantly decreased FBG (WMD: - 7.00 mg/dL), FI (WMD: - 1.72 µIU/mL), HbA1c levels (WMD: - 0.34%), and HOMA-IR (WMD: - 0.91), with a substantial heterogeneity across all outcomes (p < 0.001). Subgroup analyses indicated reductions in FBG, FI, HbA1c, and HOMA-IR across varying baseline characteristics, including glycemic levels, trial durations, and participant health status. Both probiotics and synbiotics were effective, with notable benefits for patients with T2DM, longer intervention durations, and higher baseline BMI. Meta-regression and dose-response analyses revealed no significant association between the duration of probiotic and synbiotic supplementation and changes in glycemic indices. Probiotic and synbiotic supplements significantly reduce FBG, FI, HbA1c, and HOMA-IR, leading to improvements in glycemic markers in individuals with prediabetes and T2DM. These supplements can be used as effective adjunctive strategies to enhance glycemic control, highlighting the promising role of gut microbiota modulation in diabetes management.

Diabetes is often associated with dyslipidemia, increasing the risk of cardiovascular complications. Studies have shown that Vitamin E, as a potent antioxidant, may improve serum lipid profile by reducing oxidative stress and inflammation. However, findings on its effects on diabetic patients remain inconsistent. To address this gap, this meta-analysis aims to evaluate the impact of vitamin E on serum lipid parameters in individuals with diabetes. A search was conducted on databases from inception to June 2025 to identify relevant randomized controlled trials (RCTs). Pooled effect sizes were estimated using weighted mean differences (WMDs) with 95% confidence intervals (CIs), applying a random-effects model. All statistical analyses were performed using STATA (V. 11.2). The pooled analysis of 28 RCTs found that overall vitamin E administration in diabetic patients significantly reduced total cholesterol (TC) (WMD: - 5.20 mg/dL, 95% CI: [- 7.60, - 2.80], p < 0.001) and low-density lipoprotein cholesterol (LDL-C) (WMD: - 4.21 mg/dL, 95% CI: [- 7.32, - 1.09], p = 0.008). While no significant change was observed in triglyceride (TG) (WMD: - 6.19 mg/dL, 95% CI: [- 13.13, 0.75], p = 0.081) and high-density lipoprotein cholesterol (HDL-C) serum levels (WMD: 0.57 mg/dL, 95%CI: [- 0.11, 1.24], p = 0.99). Subgroup analysis showed that vitamin E reduced TG with longer durations, lowered TC and LDL-C in participants with high baseline levels, higher doses, or longer interventions, and increased HDL-C only in studies lasting over 8 weeks. Linear regression analysis found no significant associations between vitamin E dose or duration and serum lipids. In contrast, non-linear dose-response analysis showed a significant inverse relationship between vitamin E dose and TC levels. Vitamin E administration may improve lipid profiles in diabetic patients, with significant reductions in TC and LDL-C, while effects on TG and HDL-C were not statistically significant but showed potential clinical relevance. Subgroup analysis highlighted greater benefits with higher doses (> 400 IU/day) and longer intervention durations (> 8 weeks), particularly in individuals with elevated baseline lipid levels. Further large-scale studies are needed to confirm these findings and establish optimal dosing strategies for clinical application.

Chronic diseases and inflammation are often linked to elevated liver enzymes and inflammatory markers. Studies suggest that curcuminoid and piperine co‐supplementation (Cur + Pip), which enhances bioavailability, may offer beneficial effects. However, previous findings have been inconsistent. This meta‐analysis aims to evaluate the effectiveness of Cur + Pip on liver enzymes and inflammation in adults. A comprehensive search of scientific databases was conducted until April 2025 to identify relevant randomized controlled trials (RCTs) involving adults. Included studies compared Cur + Pip with placebo, control, or no treatment, focusing on changes in liver enzymes and inflammatory markers as main outcomes. Data from eligible studies were extracted, and pooled effect sizes were calculated using weighted mean differences (WMDs) with 95% confidence intervals (CIs) under a random‐effects model. The pooled analysis of 18 RCTs showed that Cur + Pip significantly reduced AST (WMD: −2.29 IU, p = 0.019) and IL‐6 (WMD: −5.59, p < 0.001), whereas changes in ALT (WMD: −3.88 IU, p = 0.053), ALP (WMD: −15.74 IU, p = 0.095), CRP (WMD: −1.53 mg/dL, p = 0.222), and TNF‐α (WMD: −0.77, p = 0.314) were not statistically significant. Subgroup analysis revealed that reductions in ALT were significant in individuals with metabolic dysfunction (WMD: −4.64 IU, p = 0.044) and adults with overweight (WMD: −4.89 IU, p = 0.048). AST reductions were more pronounced in prolonged supplementation (≥ 12 weeks) (WMD: −4.08 IU, p < 0.001) and in overweight participants (WMD: −3.04 IU, p = 0.020). Cur + Pip demonstrated beneficial effects on liver enzymes, particularly AST, and showed a positive trend for ALT, especially in overweight or metabolically at‐risk individuals. The observed reduction in IL‐6 supports their potential anti‐inflammatory properties, although no significant effects were seen for CRP or TNF‐α. These findings suggest therapeutic promise in specific populations, but further large‐scale, long‐duration trials are necessary to confirm efficacy and establish clinical significance.

Background: Alcohol use disorder (AUD) affects nearly half a billion people globally and is associated with significant physical and psychiatric comorbidities. Glucagon-like peptide-1 receptor agonists (GLP-1RAs), approved for diabetes and obesity, have shown promise in modulating reward-related brain pathways, suggesting potential benefits in the management of AUD. Methods: This systematic review and meta-analysis, registered in PROSPERO and conducted per PRISMA guidelines, assessed the effects of GLP-1RA use on AUD and alcohol-related outcomes in adults with obesity or type 2 diabetes mellitus. Five databases (PubMed, Embase, Web of Science, Scopus, and Cochrane Library) were searched up to September 30, 2025. Random-effects models were applied, and sensitivity analyses examined result stability. No subgroup or meta-regression analyses were performed owing to the small number of eligible studies. Results: Five observational cohort studies (three on AUD diagnosis, two on alcohol-related hospitalization) were included, with sample sizes ranging from 4,321 to > 53,000 participants. GLP-1RA use was associated with a 28% lower risk of AUD diagnosis (HR = 0.72, 95% CI 0.59–0.89; I² = 65%). For alcohol-related hospitalization, a non-significant reduction was observed (HR = 0.76, 95% CI 0.57–1.01; I² = 77%). Leave-one-out sensitivity analyses confirmed the direction and magnitude of the AUD finding but highlighted the limited evidence base for hospitalization. Conclusion: GLP-1RA use was associated with a reduced risk of AUD diagnosis, with a possible but non-significant reduction in alcohol-related hospitalization. Effects may be mediated through modulation of mesolimbic reward pathways and the gut–brain axis. Further large-scale trials are warranted to confirm these findings. Graphical