Search Results (1,714)

Objective: To evaluate the efficacy of Roux-en-Y gastric bypass (RYGB) in improving glucose regulation and metabolic parameters in feline diabetes mellitus (FDM). Methods: FDM was experimentally induced via partial pancreatectomy, splenectomy, and dexamethasone administration. Following insulin stabilization, the RYGB cohort underwent gastric bypass, while the medical management group received glargine insulin. Untreated diabetic controls were monitored for 12 weeks. Blood glucose (GLU), fructosamine (FRU), biochemical profiles, and metabolic hormones were evaluated pre- and post-intervention. Hepatic and pancreatic tissues were collected for histopathological examination. Results: GLU and FRU concentrations in the RYGB group were significantly lower than in diabetic controls (p < 0.05), remaining comparable to the insulin-treated group (p > 0.05). Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities were significantly reduced post-RYGB (p < 0.05), closely matching insulin therapy outcomes (p > 0.05). Hormonal assays demonstrated decreased gastric inhibitory polypeptide (GIP) and elevated glucagon-like peptide-1 (GLP-1) in RYGB cats. Histopathologically, the RYGB group exhibited attenuated hepatic steatosis and a higher density of pancreatic islet cells with abundant cytoplasm compared to the control groups. Conclusions: RYGB effectively restores glycemic control and metabolic hormone balance in FDM, promoting morphological improvements in pancreatic islets and offering a highly promising alternative therapy for diabetic felines. Full article

Glucagon-like peptide-1 (GLP-1) and dual GLP-1 and glucose-dependent insulinotropic polypeptide (GIP) receptor agonists are highly effective therapies for overweight and obesity due to their potent ability to provide significant amounts of weight loss. There is also increasing evidence in their medium- to long-term benefits to metabolic outcomes in those with obesity, due to improvements in weight and glycemia, as well as direct action of GLP-1 on multiple organ systems. This narrative review examines the literature behind the metabolic effects in those with overweight and obesity, as well as the implications of long-term use in regard to the safety and cost-effectiveness of these agents. Improvement and prevention of metabolic disease with GLP-1 therapies remains promising, although studies of longer duration are required to further expand indications and confirm safety of therapy. Full article

Diabetic neuropathy is a frequent and disabling complication of diabetes, encompassing distal symmetric polyneuropathy and cardiovascular autonomic neuropathy, both associated with reduced quality of life and increased cardiovascular risk. Beyond its traditional interpretation as a direct consequence of chronic hyperglycaemia, oxidative stress has emerged as a central integrative mechanism linking metabolic overload, inflammation, mitochondrial dysfunction, and microvascular injury to progressive neural damage. These processes converge within the neurovascular unit, promoting a self-perpetuating cycle of axonal degeneration, impaired nerve perfusion and altered neuronal excitability. This narrative review synthesises experimental and clinical evidence on oxidative stress-related pathways implicated in diabetic neuropathy, including hyperglycaemia-activated metabolic routes, mitochondrial dysfunction, endoplasmic reticulum stress, and chronic inflammatory signalling. Classical antioxidant and mitochondrial-supportive interventions are evaluated alongside pleiotropic glucose-lowering agents, with particular emphasis on sodium–glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists, integrating mechanistic insights with biomarker and clinical outcome data. Conventional antioxidant strategies, such as α-lipoic acid, acetyl-L-carnitine, coenzyme Q10 and N-acetylcysteine, show reproducible benefits on neuropathic symptoms and oxidative stress markers, but evidence for sustained structural or disease-modifying effects remains limited. In contrast, incretin-based therapies and sodium–glucose cotransporter-2 inhibitors exert broader pleiotropic actions by attenuating oxidative and inflammatory signalling, improving mitochondrial homeostasis and endothelial function, with emerging evidence for modest but consistent neurophysiological and autonomic benefits. Overall, oxidative stress emerges as a key mechanistic hub in diabetic neuropathy. Future progress will depend on mechanism-aligned, neuropathy-specific clinical trials incorporating multidimensional endpoints and validated biomarkers. Full article

Whether the risk of gastric neoplasm is modified by newer glucose-lowering therapies—dipeptidyl peptidase-4 inhibitors (DPP4is), glucagon-like peptide-1 receptor agonists (GLP1RAs), and sodium–glucose cotransporter 2 inhibitors (SGLT2is)—remains uncertain. Given their global uptake and long-term use in populations already predisposed to malignancy, decision-grade comparative safety evidence is needed. We conducted a systematic review and network meta-analysis (NMA) of randomized controlled trials (RCTs) in adults without baseline gastric neoplasms. PubMed, Embase, Cochrane CENTRAL, Web of Science, ClinicalTrials.gov, ClinicalKey, ProQuest, and ScienceDirect were searched from inception to 10 January 2026, without language restrictions. The primary outcome was incident gastric neoplasms (benign or malignant). Random-effects frequentist NMA estimated risk ratios (RRs) with 95% confidence intervals (CIs); Bayesian NMA served as sensitivity analysis. Certainty of evidence was assessed using GRADE adapted for NMA (PROSPERO CRD420261282728). Fifty-two RCTs (171,165 participants; mean age 63.6 years; 36.9% women; mean follow-up 141.8 weeks) were included. At the class level, GLP1RAs were associated with lower gastric neoplasm risk versus controls (RR = 0.51, 95% CI = 0.28–0.92), whereas DPP4is were associated with higher risk (RR = 1.77, 95% CI = 1.09–2.85). These signals persisted in prespecified subgroup analyses among participants with diabetes mellitus, in trials with duration ≥52 weeks (GLP1RA: RR = 0.52, 95% CI = 0.28–0.95; DPP4i: RR = 2.05, 95% CI = 1.19–3.55), and in older populations (age ≥60 years; DPP4i: RR = 2.08, 95% CI = 1.15–3.77). No class showed a significant association in younger participants (<60 years) or shorter trials (<52 weeks). Across available RCT evidence, GLP1RA prescription generally had a relatively lower gastric neoplasm risk than controls. In contrast, among patients with diabetes mellitus receiving longer-term therapy, GLP1RAs may be the preferable option from the perspective of gastric neoplasm risk, while DPP4is warrant heightened vigilance and mechanistic clarification. These findings support improved neoplasms ascertainment in future trials rather than immediate prescribing changes. Full article

Background: Incretin-based therapies, including glucagon-like peptide-1 (GLP-1) receptor agonists and dual GLP-1/glucose-dependent insulinotropic polypeptide (GIP) receptor co-agonists, advance obesity treatment by promoting weight loss and lowering the risk of type 2 diabetes and cardiovascular disease. Methods: This narrative review synthesizes clinical evidence to highlight the role of dietitians in obesity management when incretin-based therapies are used. Results: GLP-1 receptor agonists and dual GLP-1/GIP receptor co-agonists achieve 15–21% weight loss and reduce cardiometabolic risk. Their effectiveness and safety are optimized when integrated with medical nutrition therapy (MNT) and personalized nutrition strategies. In Italy’s aging population, the rising burden of sarcopenic obesity requires dietitian-led care to preserve fat-free mass while reducing fat mass. Dual GLP-1/GIP co-agonists show superior reductions in visceral adiposity, but effects on fat-free mass remain inconclusive, underscoring the need for dietitian oversight to prevent adverse body-composition changes. Sarcopenic obesity is associated with increased mortality and functional decline. Dietitians are uniquely qualified to ensure adequate protein intake and protect muscle during pharmacologic interventions. In Italy, role clarity in clinical nutrition remains limited; however, under national law (DM 744/94; Law 42/1999), dietitians are recognized as the professionals authorized to provide medical nutrition therapy (MNT). Conclusions: The dietitian’s expertise maximizes therapeutic efficacy, minimizes adverse effects, and safeguards long-term outcomes. Integrating dietitians into pharmacological treatment pathways is essential to optimize outcomes, ensure patient safety, and safeguard long-term metabolic health. Full article

There is cumulative evidence that glucagon-like peptide-1 receptor agonists (GLP-1 RAs) can offer cardiovascular protection extending beyond glucose-lowering and weight reduction, but the underlying mechanisms contributing to these effects remain incompletely understood. Modulation of platelet function might contribute to the aforementioned benefits. In the current literature review article, we synthesized available preclinical and clinical data evaluating the effects of GLP-1 RAs on platelet activation and function. Preclinical data indicate that GLP-1 RAs might decrease platelet activation via both GLP-1 receptor-dependent and -independent mechanisms with the involvement of cyclic adenosine monophosphate signaling, increase in nitric oxide bioavailability, and suppression of thromboxane-mediated pathways, particularly under inflammatory or shear-stress conditions. Additionally, clinical studies, despite being limited and heterogeneous, support a reduction in platelet activation markers, even independently of glycemic control or weight loss. However, most of them are characterized by small sample sizes and significant heterogeneity among them. In summary, existing evidence suggests that GLP-1 RAs exhibit potential antiplatelet effects that could contribute to their cardioprotective profile. Larger, well-designed clinical studies are crucial to better understand the clinical importance of platelet modulation by GLP-1 RAs and their potential implications for cardiovascular risk reduction. Full article

Background/Objectives: The use of GLP-1 RAs has dramatically increased with expanded indications for diabetes mellitus and obesity. Delayed gastric emptying due to these medications can lead to increased residual gastric content (RGC). While previous studies have focused on Esophagogastroduodenoscopy (EGD), few have specifically analyzed the impact of GLP-1 RAs on residual gastric content in patients undergoing concurrent colonoscopy with adequate bowel preparation. Methods: A retrospective, case–control study was conducted at Shanghai East Hospital from January 2023 to June 2025. Adult patients with increased RGC were identified as cases. Controls without increased RGC were randomly selected at a 1:2 ratio, matched for age and sex. Multivariable logistic regression was used to assess the independent association between GLP-1 RAs use and increased RGC. Results: Among 131,255 procedures screened, 3746 patients were included (1257 with increased RGC and 2489 controls). GLP-1 RAs users had higher odds of increased RGC in both unadjusted [OR 15.20 (95% CI 5.98–38.61)] and adjusted analyses [aOR = 13.31 (95% CI 5.07–34.93)]. Other significant risk factors for RGC included diabetes-related complications [aOR = 8.89 (3.15–25.12)]. Interestingly, among the enrolled patients who used GLP-1 RAs and underwent concurrent colonoscopy, 19 of the 22 patients (86.4%) exhibited increased RGC, whereas only 3 (13.6%) did not. Conclusions: Perioperative use of GLP-1 RAs is associated with an increased residual gastric content in patients undergoing EGD alone or with concurrent colonoscopy. There was no aspiration event related to residual gastric content. Our study highlights the need for vigilant preoperative assessment and individualized periprocedural management in patients on GLP-1 RAs undergoing endoscopic procedures, despite having standardized adequate bowel preparation. Full article

Background/Objectives: The coexistence of chronic obstructive pulmonary disease (COPD) and type 2 diabetes mellitus (T2D) poses significant clinical challenges due to overlapping mechanisms of systemic inflammation, oxidative stress, hypoxia, and metabolic dysregulation. Patients with both conditions face higher risks of exacerbations, prolonged hospitalizations, cardiovascular events, and reduced quality of life. This review aims to summarize current evidence on the pathophysiological interplay between COPD and T2D and to evaluate the impact of lifestyle and pharmacologic interventions. Methods: A narrative review of the literature was conducted to evaluate the pathophysiological links between COPD and T2D, assess the effects of pharmacologic and lifestyle interventions, and highlight key gaps and priorities for future research, with an emphasis on integrated, evidence-based management for this high-risk population. Results: Lifestyle interventions, including smoking cessation and structured physical activity, remain foundational to management. Emerging evidence indicates that antidiabetic therapies, such as glucagon-like peptide-1 receptor agonists (GLP-1RAs) and sodium–glucose cotransporter-2 inhibitors (SGLT-2is), may confer additional pulmonary, metabolic, and cardiovascular benefits. These agents modulate systemic inflammation, oxidative stress, endothelial function, and insulin sensitivity, potentially reducing COPD exacerbations, improving lung function, and enhancing survival. Safety concerns, including glucocorticoid-induced hyperglycaemia and hypoxia-related metabolic complications, underscore the need for careful monitoring and individualized therapy COPD patients. Conclusions: Optimal care requires a multidisciplinary, patient-centred approach integrating pulmonology, endocrinology, primary care, nutrition, and rehabilitation, alongside shared decision-making and patient education. Despite promising findings, critical knowledge gaps remain. Large, well-designed randomized controlled trials and standardized definitions are needed to guide personalized therapeutic strategies. Full article

Background: Atrial fibrillation (AF) is a prevalent arrhythmia closely associated with cardiometabolic disorders and systemic inflammation. Epicardial adipose tissue (EAT), located in direct contact with the atrial myocardium, has emerged as a biologically active tissue involved in atrial remodeling through inflammatory, fibrotic, and electrophysiological mechanisms. The objective of this review is to summarize current translational and clinical evidence on the role of EAT in AF pathophysiology and to discuss its implications for diagnostic assessment, interventional management, and cardiometabolic therapeutic strategies. Methods: A narrative, structured review of experimental, translational, and clinical studies was conducted using major biomedical databases. The literature was evaluated with a focus on mechanisms linking EAT to atrial remodeling, noninvasive imaging techniques for EAT characterization, echocardiographic and electroanatomical markers of atrial disease, outcomes of catheter ablation strategies, and pharmacological interventions targeting metabolic and inflammatory pathways. Results: The available evidence indicates that increased EAT volume and altered inflammatory activity are associated with atrial fibrosis, conduction abnormalities, and impaired atrial function, contributing to AF initiation and persistence. Multimodality imaging, including cardiac computed tomography and cardiac magnetic resonance, enables quantitative and qualitative assessment of EAT and supports clinical phenotyping. Clinical studies report an association between higher EAT burden and increased AF recurrence after pulmonary vein isolation, particularly in patients with persistent AF. Emerging cardiometabolic therapies, such as glucagon-like peptide-1 receptor agonists and dual GIP/GLP-1 agonists, have been shown to reduce EAT volume and inflammatory markers, although direct evidence linking these interventions to improved AF outcomes remains limited. Conclusions: EAT represents a relevant pathophysiological interface between metabolic disease and AF with potential clinical implications. Incorporating EAT assessment into routine evaluation may enhance risk stratification and support personalized AF management. Further prospective studies are required to define its role as a therapeutic target in clinical practice. Full article

Background/Objectives: Insulin and glucagon are key hormones in metabolic regulation. There are limited comparative data on how common rodent anesthetic regimens influence hormone secretion, leading to misinterpretation of results. We aimed to compare the effects of several anesthetic regimens on insulin and glucagon secretion using the physiologically relevant isolated perfused rat pancreas model. Methods: Six commonly used rodent anesthetic regimens were assessed for their ability to induce surgical depth of anesthesia. Once achieved, the pancreas was vascularly isolated and perfused. After euthanasia, the pancreas was stimulated with glucose and glucagon-like peptide-1 (GLP-1). Insulin and glucagon were measured in the effluent using radioimmunoassay. Results: Anesthesia with Hypnorm^® (fentanyl/fluanisone)/midazolam produced the most physiological responses, meaning that insulin was secreted in response to hyperglycemia and GLP-1, and glucagon was secreted under hypoglycemia. Ketamine/dexmedetomidine anesthesia abolished insulin dynamic secretion and blunted glucagon secretion. Isoflurane/buprenorphine anesthesia partially suppressed insulin secretion, but it still followed a physiological pattern in response to glucose fluctuations. However, it abolished the dynamic glucagon responses to glucose. Three additional anesthetic regimens failed to produce surgical depth anesthesia and were therefore not further analyzed. Conclusions: Different anesthetic regimens altered pancreatic hormone secretion. Fentanyl/fluanisone/midazolam was associated with dynamic insulin and glucagon secretion, whereas ketamine/dexmedetomidine and isoflurane/buprenorphine altered the pattern and/or magnitude of hormone secretion. Overall, the choice of anesthesia is a critical variable in animal experimentation for metabolic studies and may confound the interpretation of results. Full article

Background: This study investigated the effects of Laurocerasus officinalis Roem (cherry laurel; CL), a traditionally consumed fruit, on cognitive performance and selected neurobiochemical and metabolic pathways in a nontransgenic streptozotocin (STZ)-induced Alzheimer’s disease (i.c.v. STZ) model and an STZ-induced type 2 diabetes mellitus (T2DM; i.p. STZ) model. Method: Fifty-seven adult male Sprague–Dawley rats were allocated to control, T2DM, and Alzheimer (ALZ) model groups, with subgroup interventions including CL supplementation and, in the T2DM model, metformin as a comparator. Spatial learning and memory were assessed using the Morris Water Maze. Serum and brain tissue levels of GSK3-β, glutathione (GSH), interleukin-1 (IL-1), GLUT4, GLP-1, β-amyloid (Aβ), and acetylcholinesterase (AChE) were quantified. Results: Serum GSK3-β levels did not differ significantly between groups, whereas brain tissue GSK3-β showed significant between-group differences. CL increased GSH levels in both models, with significant elevations in serum and brain tissue GSH in the ALZ model following CL administration; in the T2DM model, GSH increased after both CL and metformin. In the ALZ model, CL was associated with decreased serum Aβ and AChE levels and improved Morris Water Maze performance, reflected by reduced escape latencies. Conclusions: CL supplementation was associated with antioxidant enhancement and modulation of amyloid- and cholinergic-related measures, alongside improved spatial learning performance in the STZ-induced nontransgenic ALZ model. In addition, CL reduced blood glucose in the T2DM model. Given the likely contribution of fruit phytochemicals (including total phenolics), further studies are warranted to better define the bioactive composition and mechanisms underlying these effects. Full article

Data suggest that both pancreatic and intestinally produced glucagon-like peptide-1 (GLP-1) increases in response to inflammation. Here, we set out to determine the tissue-specific function of increased GLP-1 during inflammatory stimuli. Using our innovative mouse model of tissue-specific Gcg (the gene that encodes GLP-1) expression, we explored the function of GLP-1 under severe inflammatory conditions induced by lipopolysaccharide (LPS) administration in lean and obese mice. High-fat diet (HFD) increased the LPS-induced suppression of feeding and increased the plasma levels of pro-inflammatory cytokines and GLP-1. Both pancreatic and intestinal Gcg expression contribute to LPS-induced increases in GLP-1, but Gcg was not necessary for the glucoregulatory or suppressed feeding responses to LPS. While Gcg was not necessary for systemic cytokine increases with LPS in either chow- or HFD-fed mice, whole-body Gcg-null animals had increased macrophage accumulation and an increased expression of genes reflecting pro-inflammatory signaling in the pancreas. We then performed flow cytometry on the pancreas from mice expressing a fluorescent marker on the GLP-1 receptor (GLP-1R). In response to LPS, we found that pancreatic CD64+/CD11b+ macrophages expressed the GLP-1R. We conclude that under severe inflammatory conditions, pancreatic production of GLP-1 functions in an immunological rather than a metabolic role to directly regulate local macrophage accumulation. Full article

Background: Short bowel syndrome (SBS) is the leading cause of chronic intestinal failure and is frequently associated with long-term dependence on parenteral nutrition (PN) and intravenous fluids. Teduglutide, a glucagon-like peptide-2 (GLP-2) analogue, promotes intestinal adaptation and has been demonstrated to reduce parenteral support requirements. However, real-world data from the Greek population are scarce. Methods: We conducted a non-interventional, multicenter, retrospective cohort study across 5 centers in Greece, including adult patients with SBS receiving teduglutide therapy. Demographic and clinical characteristics, parenteral nutrition and intravenous fluid requirements, body mass index (BMI), laboratory parameters, and adverse events were recorded at baseline and during follow-up at weeks 4, 12, 26, and 52. Results: Eight adult patients with SBS were included (75% female), with a median age of 53 years (range 19–71). Over 52 weeks of treatment, mean parenteral nutrition requirements decreased by approximately 45% compared with baseline (from 1430 to 788 kcal/day), while mean intravenous hydration requirements decreased by approximately 80% (from 5170 to 1000 mL/week). Complete independence from parenteral nutrition was achieved in 2 of 8 patients (25%). Nutritional status improved, with a 10.6% increase in mean BMI at Week 52. Teduglutide was generally well tolerated; mild adverse events occurred in 3 of 8 patients, were predominantly gastrointestinal, and did not lead to treatment discontinuation. Conclusions: This study provides data from the Greek population and supports the effectiveness and favorable safety profile of teduglutide in adult patients with SBS and chronic intestinal failure. Further prospective studies are warranted to better define predictors of response and optimize long-term management strategies. Full article

Background/Objectives: Collagen hydrolysates are widely used as nutritional ingredients for skin and joint health; however, growing evidence indicates that collagen may also exert beneficial effects on cardiometabolic pathways. Short peptides have been shown to modulate angiotensin-converting enzyme (ACE) and dipeptidyl peptidase IV (DPP-IV), key regulators of blood pressure and glucose homeostasis. This study aimed to assess the dual ACE- and DPP-IV inhibitory and GLP-1 stimulation activities, respectively of a tripeptide-enriched formulation (CH). The study was performed using a benchmark collagen hydrolysate (BCH) as reference. Methods: ACE and DPP-IV inhibitory activities were evaluated using in vitro enzymatic assays. Cellular compatibility and in situ DPP-IV inhibition were assessed in Caco-2 intestinal cells, while glucagon-like peptide-1 (GLP-1) secretion was measured in STC-1 enteroendocrine cells. The degree of hydrolysis was determined by OPA assay, and nanoLC–HRMS was used to characterize and compare the proteomic profiles of the samples. Results: Both hydrolysates exhibited dose-dependent ACE and DPP-IV inhibition; however, CH showed significantly higher inhibitory activity at comparable concentrations. CH also reduced cellular DPP-IV activity in Caco-2 cells and stimulated GLP-1 secretion in STC-1 cells, whereas BCH showed limited or non-significant cellular effects. Peptidomic analysis revealed an enrichment of short- and medium-length peptides in CH, while BCH contained a higher proportion of long peptides (>2000 Da). Consistently, CH exhibited a 1.7-fold higher degree of hydrolysis than BCH. Conclusions: The tripeptide-enriched collagen hydrolysate demonstrated superior enzymatic and cellular bioactivity compared with the benchmark formulation, supporting its potential as a multifunctional bioactive ingredient for health applications. Full article

Diabetes mellitus (DM) is highly prevalent among patients undergoing foot and ankle surgery and is associated with substantially increased perioperative and postoperative risk. This narrative review synthesizes the current literature on optimization of DM patients undergoing foot and ankle surgery. Complications of chronic hyperglycemia, including neuropathy and peripheral vascular disease, make the foot and ankle particularly vulnerable to ulceration, infection, and deformity, contributing to high rates of both operations and postoperative complications such as surgical site infection and readmission. Glycemic control and obesity are modifiable predictors of surgical outcomes and represent key targets for preoperative optimization. Lifestyle modification and pharmacologic therapy play central roles in DM optimization. Traditional agents such as metformin, sulfonylureas, thiazolidinediones, and dipeptidyl peptidase-4 inhibitors remain foundational therapies, while newer therapies such as sodium–glucose cotransporter-2 inhibitors (SGLT2is) and glucagon-like peptide-1 (GLP-1) agonists offer meaningful improvements to glycemic control and weight loss. Pharmacologic regimens must be individualized, and many agents require careful perioperative management. Despite advances in medical therapy, high-quality evidence specific to foot and ankle surgery remains limited. Future research should focus on developing procedure- and agent-specific guidelines to reduce the substantial clinical and economic burden of DM in foot and ankle surgical patients. Full article