Search Results (5,373)

Carpal tunnel syndrome (CTS) is the most common compressive mononeuropathy. In patients with type 2 diabetes mellitus (T2DM), chronic hyperglycemia, microangiopathy, and systemic inflammation increase the vulnerability of peripheral nerves to compression. This study aimed to assess the relationship between CTS severity and clinical, metabolic, inflammatory, and electrophysiological parameters in patients with T2DM. A cross-sectional study was conducted from June 2023 to June 2024, involving patients diagnosed with T2DM. Electrophysiological assessment of the upper and lower limbs was performed using a four-channel electromyography apparatus. Clinical and anthropometric data and laboratory parameters were obtained, as well as the results of nerve conduction studies (NCS). One hundred and twenty-three patients with T2DM were included in the study. The prevalence of moderate-to-severe forms of CTS was 43.9%, and bilateral involvement was present in 21.95% of patients. Patients with moderate-to-severe CTS had significantly higher hemoglobin A1c (HbA1c) (p = 0.004), glycemia (p < 0.001), and Triglyceride–Glucose Index (p = 0.018) compared with those without CTS/with mild forms. The number of monocytes was significantly higher in the group with moderate-to-severe forms (p = 0.012), suggesting a chronic inflammatory state. In the logistic regression analysis, hemoglobin HbA1c emerged as an independent predictor of CTS severity, with each 1% increase associated with approximately a 60% higher risk of moderate/severe CTS. NCS analysis showed significant correlations between median nerve parameters and those of the lower-limb peripheral nerves, particularly the tibial and sural nerves, suggesting an association with generalized diabetic peripheral neuropathy. Professional activity was significantly associated with moderate-to-severe CTS (OR = 3.5). CTS is a common complication in patients with T2DM and is associated with worse glycemic control, insulin resistance, systemic inflammation, and peripheral neuropathic damage. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) have transformed type 2 diabetes mellitus (T2DM) and obesity care, with clinical trials demonstrating weight loss exceeding 15%. However, real-world effectiveness lags trial efficacy, largely owing to high discontinuation rates. We characterize the global persistence gap and propose a framework integrating Medical Nutrition Therapy (MNT) to improve adherence. Methods: We conducted a narrative review of real-world evidence from North America, Europe, Asia, and Latin America, synthesized with physiological, nutritional, and behavioral data to distinguish established contributors to discontinuation from strategies that remain partly extrapolated from related populations. Results: Global persistence varies widely: from approximately 75–80% at 12 months in reimbursed T2DM cohorts (Sweden, Denmark) to below 10% in obesity-focused or high out-of-pocket-cost settings (Poland, Colombia), with intermediate rates in the United States and United Kingdom; in several cohorts, persistence falls below 15% by 24 months. The primary drivers are gastrointestinal intolerance and economic barriers. Meal size, dietary composition, and gastric-emptying effects influence gastrointestinal tolerability; inadequate protein intake during rapid weight loss raises concern for lean mass loss. Conclusions: Pharmacotherapy alone is unlikely to sustain long-term obesity management. Narrowing the persistence gap will require an integrated care model in which structured nutritional support—targeting protein intake, micronutrient density, and gastric-sparing feeding—is systematically offered rather than treated as an optional adjunct, while recognizing that most supporting evidence is extrapolated from primary trials in obesity and cardiometabolic disease rather than derived from GLP-1–specific randomized trials. Full article

Background/Objectives: Type 2 Diabetes Mellitus (T2DM) is characterized by insulin resistance and chronic hyperglycemia, which significantly impair vascular function. In experimental T2DM models, the vascular endothelium is compromised, showing decreased vasodilator responses. Vitamin D3 has emerged as a promising intervention for improving glycemic parameters and restoring endothelial function. This study evaluated the effects of vitamin D3 (0.25 and 0.50 µg/kg/day) administered for 4 and 8 weeks on the ex vivo aortic vascular reactivity of T2DM rats. Methods: T2DM was induced in male Wistar rats via a high-fat, normoprotein diet and streptozotocin (30 mg/kg, i.p.). Groups included normal control, diabetic control, metformin, and vitamin D3 (0.25 or 0.50 µg/kg/day). Following 4 or 8 weeks of treatment, thoracic aortic segments were isolated for ex vivo vascular reactivity studies to assess responses to vasoconstrictor and vasorelaxant agents. Results: Vitamin D3 treatment improved glycemic profiles; the 0.25 µg/kg dose reduced fasting glucose, while the 0.50 µg/kg dose lowered glycated hemoglobin at 8 weeks. Endothelium-dependent relaxation induced by acetylcholine was significantly increased in diabetic rats treated with vitamin D3 at both doses over 4 weeks compared to diabetic controls. Moreover, vitamin D3 prevented the attenuation of maximal contractile responses to phenylephrine observed in untreated diabetic rats at 8 weeks. Conclusions: Vitamin D3 supplementation restores endothelial function and improves vascular reactivity in an experimental T2DM model. These findings suggest that vitamin D3 may mitigate vascular complications by enhancing vasorelaxation and maintaining contractile integrity. Full article

Background: This study evaluated the effects of combined exercise (CE) alone and CE combined with Nigella sativa (NS) supplementation on musculoskeletal performance and blood fructosamine levels in male patients with Type 2 diabetes mellitus (T2DM). Methods: Ninety male patients were randomly allocated to one of three groups in a 1:1:1 ratio: a non-exercise comparator (Diabetes), a Diabetes + CE group, or a Diabetes + CE + NS group (n = 30 per group). NS was administered orally (2 g/day) for four weeks. Functional performance outcomes included the six-minute walk test, timed up-and-go test, handgrip strength, and sit-to-stand repetitions. Glycemic control was assessed using blood fructosamine at baseline and after four weeks. Results: Both intervention groups showed significant improvements in all functional outcomes and significant reductions in BMI and fructosamine compared with the non-exercise comparator group (p < 0.05). Post-intervention blood fructosamine was significantly lower in the CE + NS group than in the CE group (p = 0.002). Conclusions: CE significantly improved musculoskeletal performance and short-term glycemic control. The addition of NS appeared to confer additional benefits, particularly on glycemic control and upper- and lower-limb strength, although results should be interpreted with consideration of the short intervention duration, the male-only sample, and reliance on BMI as the body composition measure. Full article

Background: Diabetes mellitus remains a major public health concern, particularly in sub-Saharan Africa where type 2 diabetes predominates. In West Africa, Uvaria chamae P. Beauv. is traditionally used for diabetes management. This study investigates previously reported metabolites from Uvaria chamae using an integrated in silico approach to explore their potential antidiabetic activity and underlying mechanisms. Methods: A comprehensive literature survey identified 106 phytochemicals from stems, roots, leaves, and seeds. Diabetes-related protein targets were retrieved from the RCSB Protein Data Bank, while ligand structures were obtained from PubChem and the COCONUT database. Molecular docking, MM-GBSA rescoring, induced-fit docking, QSAR, and ADMET analyses were performed to evaluate interaction profiles, predicted activity, and developability. Results: The integrated analysis supports a polypharmacological mixture-based profile with organ-associated trends. Stem- and root-derived flavonoids, particularly isouvaretin and diuvaretin, showed the most consistent profiles for PPARγ-related pathways, while uvarinol was associated with PTP1B. Leaf alkaloids were mainly linked to DPP-4 and digestive enzyme inhibition. These compounds displayed more favorable predicted pharmacokinetic and toxicity profiles compared to acetogenins, which, despite favorable binding energies, were not prioritized as drug-like candidates due to their high lipophilicity, low QED values, and predicted toxicity liabilities, but may contribute to extract-level activity. Conclusion: These findings provide a hypothesis-generating and hierarchical framework for the prioritization of Uvaria chamae metabolites and extracts, supporting further experimental validation through enzymatic, cellular, and gene expression studies. Full article

The global burden of type 2 diabetes mellitus (T2DM) and metabolic dysfunction-associated steatotic liver disease (MASLD) continues to rise at an alarming pace, with substantial pathophysiological overlap driven by insulin resistance, visceral obesity, and chronic low-grade inflammation. MASLD may progress to metabolic dysfunction-associated steatohepatitis (MASH), with increased risk of cirrhosis and hepatocellular carcinoma. Glucagon-like peptide 1 (GLP-1)-based therapies have transformed the management of T2DM and obesity. They exert pleiotropic effects whose basis remains incompletely understood. Concurrently, Akkermansia muciniphila has emerged as a keystone gut microbiota species with demonstrated hepatoprotective potential in preclinical models of MASLD/MASH. This narrative review positions A. muciniphila simultaneously as a target of GLP-1-mediated microbiome remodeling and as an independent modulator of hepatoprotection in MASLD/MASH. A structured search of PubMed, Scopus, and Web of Science (last searched: 12 April 2026) was conducted using terms related to Akkermansia muciniphila, GLP-1 receptor agonists, MASLD/MASH and T2DM. A total of 174 records were identified. Of these, 148 were excluded due to duplication or non-relevant study design. 26 studies (23 preclinical, 3 clinical) were included in the synthesis, directly addressing A. muciniphila. Preclinical evidence demonstrates that liraglutide, semaglutide, exenatide, and tirzepatide increase A. muciniphila abundance, while A. muciniphila in turn enhances endogenous GLP-1 secretion via the P9/ICAM-2 axis, forming a hypothetical positive feedback loop. A working mechanistic model integrating these bidirectional interactions is proposed, alongside a discussion of current limitations and future research priorities, including microbiome-guided clinical trials in MASLD/MASH populations. Full article

Background: The use of estrogen-based gender-affirming hormone therapy (E-GAHT) has been associated with an increased risk of venous thromboembolism (VTE), but much of the evidence originates from data on cisgender women and from cohorts of transgender and gender diverse (TGD) individuals treated with older estrogen or estrogen/progesterone preparations, often at higher doses. Data on VTE risks associated with more modern E-GAHT regimens in TGD populations are scarce. Methods: A retrospective cohort study of adult TGD individuals who received E-GAHT within the Duke University Health System between January 1996 and June 2025 was conducted. The Duke Enterprise Data Unified Content Explorer (DEDUCE), a Duke electronic medical record search tool, was utilized to identify a cohort of TGD individuals who were prescribed E-GAHT. From this cohort, individuals who experienced a VTE during E-GAHT exposure were identified. Demographic characteristics and comorbidities were compared between the overall study cohort and those who experienced VTE using the SlicerDicer tool within Epic, supplemented by manual chart review. Results: Among 1173 adult TGD individuals prescribed E-GAHT, 16 (1.4%) experienced a VTE. Of these, 11 (68.8%) experienced a pulmonary embolism (PE with/without deep vein thrombosis [DVT]) and five (31.3%) experienced a DVT alone. Among the 16 patients with VTE, six (37.5%) had a transient surgical risk factor prior to VTE, three (18%) had significant non-surgical risk factors, and one (6%) had cancer. The remaining six (37.5%) patients experienced an unprovoked VTE. Patients with VTE were significantly older than the general population of TGD adults and were significantly more likely to experience hypertension, hyperlipidemia, and type 2 diabetes mellitus, compared to TGD patients without VTE. Conclusions: In this retrospective cohort, the proportion of TGD individuals on E-GAHT with VTE was lower than previously reported in the literature. Most events occurred in the presence of other established risk factors, suggesting that E-GAHT itself may confer a lower VTE risk than previously assumed. Larger prospective studies that evaluate both estrogen-specific and patient-specific risk factors are needed to clarify VTE risk in this population. Full article

Diabetes mellitus, particularly type 2 diabetes mellitus, is a growing global health burden characterized by chronic hyperglycemia and insulin resistance. Alpha-mangostin (AM), a xanthone from Garcinia mangostana pericarp, exhibits antioxidant, anti-inflammatory, and metabolic regulatory properties in preclinical models. We performed a systematic review and meta-analysis of controlled in vivo studies to assess AM’s anti-hyperglycemic effects. Fourteen studies (25 comparisons) in rodent models of diabetes or hyperglycemia were included. Primary outcome was blood glucose; secondary outcomes were glycated hemoglobin (HbA1c), insulin, and homeostatic model assessment of insulin resistance (HOMA-IR). Random-effects meta-analysis demonstrated that AM significantly reduced fasting blood glucose (mean difference (MD) = −8.75 mmol/L; 95% CI: −10.73 to −6.78; p < 0.001) and HbA1c (MD = −2.20%; 95% CI: −3.07 to −1.32; p < 0.001). AM did not significantly alter circulating insulin (Hedges’ g = 0.43; 95% CI: −0.62 to 1.49; p = 0.42) but improved insulin resistance as measured by HOMA-IR (MD = −0.90; 95% CI: −1.68 to −0.12; p = 0.02). Subgroup, sensitivity, and risk-of-bias analyses supported the robustness of the glucose-lowering association, although substantial between-study heterogeneity was present. Overall, this study provides preclinical evidence that AM exerts significant antihyperglycemic and insulin-sensitizing effects, supporting its potential as a multitarget metabolic modulator. Further standardized and mechanistically informed studies are warranted to facilitate translational progression. Full article

Type 2 diabetes is a multifactorial metabolic disease characterized by chronic hyperglycemia, insulin resistance, and persistent low-grade inflammation. All of these factors lead to dysregulation of the immune system. Of particular interest is the interaction between immune dysregulation in type 2 diabetes and oncogenic viruses such as Human papillomavirus (HPV) and Epstein–Barr virus (EBV), which play an essential role in the etiology of Head and neck cancer on the one hand and have mechanisms for escaping the immune response on the other. The aim of the present study is to perform an analysis of patients with head and neck cancer divided into two groups, with and without diabetes, aimed at studying the relationship between type 2 diabetes and the established viral status. It was found that for all viruses proven by us, the frequency of positive tests for them was higher in the group with type 2 diabetes compared to the group of patients without diabetes. The study provides new insights and suggestions for a significant association between type 2 diabetes mellitus, increased prevalence of EBV, and some low-risk HPV genotypes in patients with head and neck tumors. Continuing from our previous study, the association between EBV and HPV44, after strict statistical adjustment, highlights their potential biological and clinical significance within the oncogenic environment in the presence of type 2 diabetes. Full article

Background/Objectives: The rising global burden of type 2 diabetes mellitus (T2DM) demands multifaceted and more effective treatment strategies beyond monotherapy to achieve optimal metabolic control. The study aimed to evaluate the integrated effects of SGLT2 inhibitors and metformin in newly diagnosed T2DM patients on biochemical parameters, clinical outcomes and hormonal changes. Methods: This prospective longitudinal study was conducted at the Department of Biochemistry, Baqai Medical University, in collaboration with the Baqai Institute of Diabetology and Endocrinology. A total of 120 newly diagnosed T2DM patients were enrolled and stratified into three groups (n = 40): Group 1 (SGLT2 inhibitors only), Group 2 (SGLT2 inhibitors + metformin), and Group 3 (metformin only). Patients were followed for six months with data collection at baseline, at 3 months and 6 months. Anthropometric indices (weight, BMI, waist and hip circumferences, WHR), biochemical markers (FBS, HbA1c, lipid profile, uric acid, serum creatinine, HOMA-IR), and hormonal levels (insulin, glucagon) were assessed at baseline, first follow-up, and second follow-up. ANOVA, post hoc, Bonferroni and Tukey’s tests were applied; p-value < 0.05 was considered significant. Results: The findings indicate that Group 2 showed the greatest improvement in anthropometric parameters, particularly waist and hip circumferences (p < 0.01). Group 3 demonstrated the most significant improvement in glycemic indices and lipid profile (p < 0.01). HOMA-IR significantly decreased in Group 3 from baseline to the first follow-up (p < 0.01). While insulin levels remain insignificantly different among all groups. Glucagon levels declined significantly from baseline to the second follow-up in all groups, with a more pronounced decrease in Group 3 (p < 0.01). Serum creatinine and uric acid levels showed significant reductions from baseline to the second follow-up in Group 1 and Group 2 (p < 0.05). However, given the observational design, these associations should not be interpreted as causal evidence of renoprotection. Conclusions: Within the limitations of this observational study, early differences among treatment regimens were observed, though metabolic outcomes became statistically comparable across groups by six months. These hypothesis-generating findings suggest potential benefits of early combination therapy that require confirmation in randomized controlled trials. Given the substantial within-group variability and non-randomized design, no definitive conclusions about therapeutic associations can be drawn from these data. Full article

Type 2 diabetes (T2D) is a growing global health concern characterized by peripheral insulin resistance and impaired insulin secretion from pancreatic β-cells. Emerging evidence suggests that the gut microbiome, specifically gut dysbiosis, defined as an imbalance in the gut microbial composition and function, is a critical modulator of the pathophysiology of T2D. Dietary polyphenols, a diverse group of bioactive compounds that are abundant in plant-based foods, have gained increasing attention for their potential to attenuate metabolic disorders through their antioxidant and anti-inflammatory properties. These compounds work through the modulation of gut microbial composition and activity. This process effectively ameliorates dysbiosis. However, the diabetic state itself may influence polyphenol metabolism, absorption, and bioavailability, potentially limiting their therapeutic efficacy. This review examines the complex interrelationships between T2D, dietary polyphenols, and the gut microbiota and proposes a dynamic triangular interaction between these factors that might inform novel strategies for the prevention and management of metabolic disease. Full article

Background: Several studies have demonstrated that adding semaglutide to the treatment of patients with type 2 diabetes mellitus (T2DM) reduces insulin requirements and glycated hemoglobin (HbA1c) levels. This study aimed to investigate real-world evidence for the effects of semaglutide dose escalation on HbA1c, body weight, dyslipidemia, and insulin dose reduction in patients with T2DM in the Cukurova region of Türkiye. Methods: This retrospective cohort study enrolled 500 patients (255 male, 245 female; mean age 56.1 ± 10.8 years) who initiated semaglutide therapy for T2DM between 2024 and 2025. Patients were grouped according to their maximum semaglutide dose: 0.25 mg (Group I), 0.50 mg (Group II), and 1.00 mg (Group III). The primary endpoint was the change in HbA1c from baseline to end of study (30 weeks) across semaglutide dose escalation groups. Secondary endpoints included changes in body weight, frequency of insulin dose reduction, and effects on lipid parameters. Results: A total of 117 patients (23.4%) discontinued semaglutide therapy, while 383 patients (76.6%) completed the study. The primary endpoint revealed a mean HbA1c reduction of −1.03 ± 0.35% from baseline to end of study (95% CI 0.99–1.07; t = 58.644; p < 0.001). Reductions in HbA1c increased progressively from Group I to Group III (HbA1c: −0.72 ± 0.28, −1.02 ± 0.26, −1.27 ± 0.34%). Insulin dose reduction frequency increased significantly from Group I to Group III (40%, 41%, and 51%, respectively; p = 0.010), with a statistically significant difference only between Group I and Group III. At the end of follow-up, rates of hypoglycemic episodes and gastrointestinal (GI) adverse events were similar across groups. Conclusions: In a real-world population from the Cukurova region of Türkiye, semaglutide dose escalation in T2DM patients achieved clinically meaningful glycemic control, body weight reduction, LDL-cholesterol lowering, and a significant increase in insulin dose reduction frequency, without a significant increase in GI adverse events. Full article

Background and Objectives: MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression and have emerged as potential biomarkers in type 2 diabetes mellitus and its complications. This pilot exploratory study aimed to identify circulating miRNAs with differential expression in plasma from patients with newly diagnosed type 2 diabetes mellitus compared to age- and sex-matched healthy controls. Materials and Methods: Peripheral venous blood samples were collected from diabetic patients (n = 24) and controls (n = 12). Due to the exploratory nature of the study and limited sample material, samples were pooled within each group prior to plasma separation. Total RNA, including miRNAs, was extracted from plasma and analyzed using a high-throughput qPCR panel. Two normalization methods were applied to assess miRNA expression, and overlapping results were used for downstream analysis. Fold regulation was calculated using the 2^(−ΔCt) method. Results: A total of 33 and 42 miRNAs were identified as differentially expressed using the first and second normalization methods, respectively. Fourteen miRNAs were consistently downregulated across both methods. Several of these miRNAs, including hsa-miR-26a-5p, hsa-miR-146a-5p, hsa-miR-186-5p, hsa-miR-19a-3p, and hsa-miR-652-3p, have been previously associated with glucose metabolism, inflammation, and diabetic complications, such as retinopathy, neuropathy, and endothelial dysfunction. The pooling strategy enabled an efficient exploratory assessment of miRNA expression patterns while reducing inter-individual variability. Conclusions: This exploratory pilot study identifies a panel of circulating miRNAs with altered expression in pooled plasma samples from patients with newly diagnosed type 2 diabetes mellitus. These findings provide preliminary insights that warrant further validation in larger, individual-level studies to assess their diagnostic and prognostic potential. Full article

Rheumatoid arthritis (RA) is a chronic inflammatory disorder associated with a substantially increased risk of cardiovascular (CV) disease, driven by both persistent systemic inflammation and a high burden of traditional cardiometabolic risk factors. In recent years, glucagon-like peptide-1 receptor agonists (GLP-1RAs), licensed for type 2 diabetes mellitus and obesity, have attracted attention for their broader metabolic and cardiovascular benefits, raising the question of their potential role in RA. This scoping review summarizes current evidence on the impact of GLP-1RAs on RA disease activity, CV comorbidities, and the underlying immuno-metabolic mechanisms. Experimental studies suggest that GLP-1RAs could modulate key inflammatory pathways in synovial cells, reducing pro-inflammatory cytokine production, oxidative stress, and tissue-degrading enzymes, while improving mitochondrial function. Although clinical data remains limited, observational studies report improvements in disease activity, inflammatory markers, and pain in patients with RA treated with GLP-1RAs in addition to immunosuppressive treatment. Extensive evidence from randomized trials in metabolic populations demonstrates that GLP-1RAs improve glycemic control, induce significant weight loss, and reduce modestly but consistently blood pressure and atherogenic lipids, ultimately lowering major CV events and mortality. Although this evidence cannot be directly translated to RA populations, early real-world data specific to the disease suggest similar favorable trends, including reductions in cardiometabolic risk factors and thromboembolic events. Taken together, these findings suggest that GLP-1RAs may offer dual benefits in RA by addressing both metabolic dysfunction and inflammation. However, the current evidence base is heterogeneous and largely non-randomized, underscoring the need for dedicated trials. Full article

Heart failure (HF) remains associated with high morbidity and mortality, with heart failure with preserved ejection fraction (HFpEF) becoming increasingly prevalent and therapeutically challenging despite advances in pharmacological and rehabilitative care. Beyond their glucose-lowering effects, glucagon-like peptide-1 receptor agonists (GLP-1RAs) confer cardiometabolic benefits and may serve as effective adjuncts to cardiac rehabilitation (CR), particularly in obese patients with HFpEF. Obesity plays a central role in the pathophysiology of HFpEF, and GLP-1RAs promote weight loss, reduce insulin resistance and leptin signaling, and improve hemodynamic and metabolic abnormalities associated with HFpEF. Accumulating evidence suggests that the benefits of GLP-1RAs are phenotype-specific and more pronounced in patients with HFpEF than in patients with HF with reduced ejection fraction. Current clinical guidelines recommend GLP-1RAs for patients who have type 2 diabetes mellitus and established cardiovascular (CV) disease or are at high CV risk, with recent updates recognizing their potential benefits in patients with HFpEF and obesity. Cardiac rehabilitation, delivered through multidisciplinary programs, remains a cornerstone of HF management. Although caloric restriction and aerobic exercise can be beneficial in patients with HFpEF and obesity, these interventions alone are often insufficient. Sarcopenia is common in older patients with HFpEF and contributes to adverse outcomes, underscoring the importance of incorporating resistance training into CR programs. The most frequent adverse effects of GLP-1RAs are gastrointestinal events, which are generally mild to moderate but may lead to treatment discontinuation in some patients. Future studies should investigate the potential synergistic effects of GLP-1RAs and CR, clarify their long-term safety and efficacy in HF populations, and define their role beyond obese HFpEF phenotypes. Full article