Search Results (167)

Type 2 diabetes (T2D) is a prevalent metabolic disorder characterized by persistent hyperglycemia, hyperinsulinemia, and long-term cardiovascular complications. Another hallmark of T2D is disrupted hormonal homeostasis—marked by elevated levels of insulin and leptin and reduced adiponectin—which plays a crucial role in modulating immune cell function. Individuals with T2D exhibit a skewed immune profile, with an elevated secretion of pro-inflammatory cytokines such as IFN-γ, TNF-α, IL17, and IL6, which are well-established drivers of vascular inflammation and dysfunction. Moreover, dysregulated metabolic hormones in T2D promote the acquisition of a pro-inflammatory phenotype in immune cells, suggesting that these hormones not only regulate energy balance but also serve as potent immune activators. Their dysregulation likely plays a significant—and perhaps underappreciated—role in the onset and progression of diabetic cardiovascular complications. Full article

Background: Low-glycemic index (GI) carbohydrates like isomaltulose (ISO) are known to enhance incretin release and to improve postprandial glucose control at the following meal (an effect known as second meal effect, or SME), which is particularly beneficial for individuals with metabolic syndrome (MetS). This study aimed to assess the most effective preprandial interval of ISO- or saccharose (SUC) snacks (1 h vs. 3 h preload) to enhance prandial incretin responses to a subsequent meal. Methods: In a randomized crossover design, 15 participants with MetS completed four experimental conditions on four non-consecutive days, combining two preload types (ISO or SUC) and two preload timings (Intervention A: 3 h preload; Intervention B: 1 h preload). Specifically, the four conditions were (1) ISO + Intervention A, (2) SUC + Intervention A, (3) ISO + Intervention B, and (4) SUC + Intervention B. The order of conditions was randomized and separated by a 3–7-day washout period to minimize carryover effects. On each study day, participants consumed two mixed meal tests (MMT-1 and MMT-2) with a standardized preload (50 g ISO or SUC) administered either 3 h or 1 h prior to MMT-2. Blood samples were collected over 9 h at 15 predefined time points for analysis of glucose, insulin, C-peptide, and incretin hormones (GLP-1, GIP, and PYY). Results: The unique digestion profile of ISO resulted in a blunted glucose ascent rate (ΔG/Δt: 0.28 vs. 0.53 mmol/L/min for SUC, p < 0.01), paralleled by synonyms PYY elevation over 540 min monitoring, compared with SUC. ISO also led to higher and more sustained GLP-1 and PYY levels, while SUC induced a stronger GIP response. Notably, the timing of ISO consumption significantly influenced PYY secretion, with the 3 h preload showing enhanced PYY responses and a more favorable SME compared to the 1 h preload. Conclusions: ISO, particularly when consumed 3 h before a meal (vs. 1 h), offers significant advantages over SUC by elevating PYY levels, blunting the glucose ascent rate, and sustaining GLP-1 release. This synergy enhances the second meal effect, suggesting ISO’s potential for managing postprandial glycemic excursions in MetS. Full article

Benign prostatic hyperplasia (BPH) is a multifactorial condition that is highly prevalent and affects aging males. It frequently results in lower urinary tract symptoms (LUTS) and a reduced quality of life. While hormonal dysregulation and chronic inflammation have long been implicated in BPH pathogenesis, recent evidence highlights the role of physical activity in modulating prostate health. In this narrative review, evidence from quantitative studies examining the effect of exercise on BPH risk and symptom severity was first synthesized. Collectively, these studies suggest that regular physical activity is associated with a lower incidence and reduced progression of BPH. The potential mechanisms through which exercise may exert protective effects on the prostate were then explored. These include modulation of sympathetic nervous system activity, alterations in hormonal profiles (e.g., testosterone and insulin), suppression of chronic inflammation and oxidative stress, and the promotion of autophagy within prostatic tissue. Central to these mechanisms is the role of myokines—signaling molecules secreted by skeletal muscle during exercise. Key myokines, such as irisin, interleukin-6 (IL-6), brain-derived neurotrophic factor (BDNF), and myostatin, are reviewed in the context of prostate health. These molecules regulate inflammatory pathways, metabolic processes, and tissue remodeling. For instance, exercise-induced reductions in myostatin are linked to improved insulin sensitivity and decreased fat accumulation, while elevated irisin and BDNF levels may exert anti-inflammatory and metabolic benefits relevant to BPH pathophysiology. Although direct causal evidence linking myokines to BPH is still emerging, their biological plausibility and observed systemic effects suggest a promising avenue for non-pharmacological intervention. Future research should focus on identifying the specific myokines involved, elucidating their molecular mechanisms within the prostate, and evaluating their therapeutic potential in clinical trials. Full article

Background/Objectives: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), which were originally developed for managing type 2 diabetes by enhancing insulin secretion and reducing appetite, have emerged as promising candidates in alcohol use disorder (AUD). These medications offer a dual mechanism of action that aligns with the multifaceted nature of addiction by targeting both peripheral metabolic and central reward pathways. This review focused on the current clinical trials and real-world evidence regarding the effects of GLP-1RAs as novel therapeutics for AUD. We also discussed early but encouraging results from clinical trials in AUD, observational and real-world evidence, safety profiles, psychiatric considerations, and future directions leading beyond GLP-1RAs. Methods: A comprehensive English-language literature search was conducted per PRISMA guidelines across PubMed, Medline, Google Scholar, Web of Science, and trial registries. Using targeted keywords, we identified relevant clinical and observational studies on GLP-1RAs for alcohol use disorder, excluding off-topic or non-English works and assessing all studies for eligibility. Results: Out of 1080 records identified, seven studies met the inclusion criteria. The findings from recent clinical trials, large-scale observational studies, and real-world evidence suggest that GLP-1RAs may significantly reduce alcohol consumption, cravings, and alcohol-related hospitalizations. Their central effect on reward processing, coupled with a generally favorable safety profile, supports their potential therapeutic role beyond metabolic disorders. Conclusions: Emerging evidence positions GLP-1RAs as a promising new pharmacologic approach for managing AUD. Ongoing and future research should prioritize larger, longer-duration randomized controlled trials that include diverse populations, with specific attention to treatment motivation, co-occurring psychiatric conditions, and long-term outcomes. Full article

Carbohydrate consumption during pregnancy represents an important source of energy; its consumption, however, can cause gestational diabetes mellitus (GDM), body weight gain, inflammation, increased glucose transport to the fetus, adiposity, and a risk of macrosomia. The objective was to research the impact of sucrose consumption during pregnancy on the metabolic, immune, and redox profile in female mice with GDM. A total of 24 female CD1 mice were used, divided into two groups: Control and GDM. Each group was subdivided into two subgroups: (a) Without sucrose and (b) With sucrose. The females were mated, and, once pregnancy was confirmed, GDM was induced by administering 230 mg/kg of streptozotocin subcutaneously. GDM was confirmed by glucose ≥ 200 mg/dL and the presence of polyphagia, polydipsia, and change in body weight. Metabolic, immune, and redox profile parameters were determined. Sucrose consumption groups increase HOMA-IR and the secretion of insulin, adiponectin, and leptin; it also increased the secretion of proinflammatory cytokines and the production of IgA and IgG antibodies, decreased the activity of the Glutathione Reductase enzyme, and increased the production of TBARS and AGE. High sucrose consumption increases the inflammatory response mediated mainly by CD8⁺ lymphocytes and the production of proinflammatory cytokines; it can trigger a compensatory humoral response and alter redox mechanisms, causing a state of Oxidant Stress. Full article

Background/Objectives: Cyclodextrins (CDs) have garnered increasing attention in pharmaceutical research due to their ability to enhance drug solubility, bioavailability, and therapeutic efficacy. Meanwhile, the gut microbiota, a key regulator of human health, has emerged as an important target in evaluating the safety and broader implications of pharmaceutical excipients. This review aims to synthesize current knowledge regarding the effects of CDs on the composition and function of the gut microbiota. Methods: A literature search following PRISMA guidelines was conducted in PubMed, ScienceDirect, and Google Scholar to identify studies on cyclodextrins and their interactions with gut microbiota. Results: Cyclodextrins, particularly α-, β-, and γ-CDs, demonstrated the capacity to modulate gut microbiota composition, promoting the growth of beneficial bacteria such as Bifidobacterium and Akkermansia. Supplementation with CDs was also associated with an increased production of short-chain fatty acids (SCFAs), which are essential for maintaining intestinal homeostasis and metabolic health. Moreover, CDs exhibited potential in lowering lipid levels and improving postprandial glycemic control without enhancing insulin secretion. Although generally recognized as safe, the toxicological profile of CDs varies depending on their type, dosage, and route of administration. Conclusions: Cyclodextrins hold considerable promise not only as pharmaceutical excipients but also as modulators of gut microbial communities, suggesting a dual therapeutic and prebiotic role. Future studies integrating metagenomic and metabolomic approaches are necessary to further elucidate the molecular mechanisms underlying CD–microbiota interactions and to optimize their application in enhancing drug delivery efficiency and promoting intestinal health. Full article

In this article, we present a case of a 49-year-old woman presenting with a recurrent metastatic neuroendocrine tumor. Background: Insulinomas are neuroendocrine tumors derived from beta cells of the pancreas that secrete insulin. Usually, they are benign tumors; however, metastatic insulinomas are an extremely rare malignant form of these tumors, carrying a significantly worse prognosis. Case Presentation: A 49-year-old woman, a patient in the University Hospital in Wroclaw in the Department of Endocrinology, Diabetes and Isotope Therapy, first presented with abdominal pain in 2009, when ultrasound and further examination led to the diagnosis of a tumor in the pancreas (a solid pseudopapillary tumor of the pancreas—meta NET G2), and the patient underwent distal pancreatectomy with splenectomy. For ten years, she was under observation, and her symptoms, such as abdominal pain, nausea, weight loss, and general weakness, reappeared in 2019. Then, magnetic resonance imaging (MRI) showed a lesion in the liver, and further histopathology revealed neuroendocrine tumor (NET) metastasis to the liver. In 2022, the patient presented with loss of consciousness and convulsion, loss of weight, and hypoglycemia after meals. In April 2022, the daily glycemic profile was recorded and a 72 h fasting test was performed; however, their results excluded insulinoma. Positron emission tomography–computed tomography (PET-CT) with 18F-fluorodeoxyglucose (18F-FDG) and PET with gallium-68-DOTA-(Tyr3)-octreotate (68Ga-DOTA-TATE) showed a metastatic proliferative process in the liver. Persistent hypoglycemia led to another hospitalization in May 2022, and repeated tests allowed for the diagnosis of insulinoma. Treatment with somatostatin analogs and diazoxide was started. A CT scan in November 2022 and a PET scan in January 2023 showed new metastases to the liver, bones, and cervical lymph nodes, and it was decided to intensify the treatment. In May 2023, the patient was qualified for Lutathera treatment for insulinoma at the University Clinical Hospital in Poznań. In June 2023, another disturbing symptom was reported by the patient, a painful lump in the breast. During diagnostics, metastases with high proliferation markers were found in both breasts. Two months later, in August 2023, the patient received another dose of Lutathera. In October 2023, significant progression of liver lesions, metastases to bones of the spine, ribs, and pelvis, and periaortic and pelvic lymphadenopathy were found as well as elevated values of neuron-specific enolase and calcitonin. The patient was also referred to the Palliative Medicine Home Hospice. In consultation with the Lower Silesian Cancer Center, the decision was made to forgo further treatment with PRRT and initiate systemic chemotherapy. Despite the chosen treatment, the patient died on 27/DEC/2023. Conclusions: This case report can serve clinicians, as it presents a case of an extremely rare and insidious tumor, metastatic insulinoma. Full article

Type 2 diabetes mellitus remains a critical global health challenge, driving the pursuit of novel therapeutic strategies. This study investigated the anti-diabetic efficacy of the peptide 1CBR, derived from sodium caseinate hydrolysate, administered orally at 25 mg/kg/day to db/db mice over a 4-week period. Glucose tolerance was evaluated via oral glucose tolerance tests (OGTT), while plasma dipeptidyl peptidase-IV (DPP-IV) activity, glucagon-like peptide-1 (GLP-1), and insulin concentrations were quantified using enzyme-linked immunosorbent assays (ELISA). Two bioactive peptides, GPFPLPD and APDSGNFR, were isolated and characterized, exhibiting half-maximal inhibitory concentrations (IC₅₀) of 99.12 µM and 73.07 µM for DPP-IV inhibition, respectively, and both significantly stimulated GLP-1 secretion in enteroendocrine cells in vitro. Pharmacokinetic analysis in Sprague–Dawley rats demonstrated oral bioavailability of 11.28% and 19.12% for these peptides, surpassing typical expectations for peptide-based agents. Collectively, these results provide compelling evidence that 1CBR-derived peptides exert glucose-lowering effects through the dual mechanisms of DPP-IV inhibition and GLP-1 stimulation, combined with favorable oral absorption profiles. These findings underscore the potential of 1CBR peptides as promising candidates for development into nutraceuticals or pharmaceutical agents for diabetes management. Full article

Infrared and related light therapies are gaining increasing interest due to their potential therapeutic properties in treating various health conditions, particularly metabolic diseases such as insulin resistance and type 2 diabetes. These diseases often coexist with dyslipidemia, obesity, non-alcoholic fatty liver disease, and cardiovascular complications. This review paper analyzes the impact, primarily of far-infrared light therapy (FIR), on improving endothelial function, reducing oxidative stress, and modulating inflammatory responses—key factors in metabolic diseases. Preliminary studies suggest that FIR may improve blood circulation, increase the secretion of VEGF, and enhance insulin sensitivity by alleviating inflammatory states and oxidative damage commonly associated with these diseases. In addition, FIR has been associated with potential benefits in blood pressure regulation and lipid metabolism, which could contribute to reduced cardiovascular risk. However, it is important to acknowledge that most current evidence is derived from preclinical models and small-scale clinical trials, limiting direct applicability to broader patient populations. Moreover, significant variability exists in exposure parameters and treatment protocols across studies. While FIR therapy holds potential as a complementary approach to the conventional management of metabolic diseases, careful monitoring is essential to mitigate potential adverse effects. Further well-designed, large-scale clinical trials are necessary to validate the therapeutic efficacy, optimize treatment parameters, and comprehensively assess the safety profile of FIR interventions in metabolic health. Full article

Background: Obesity has been defined as a true worldwide “pandemic” by the World Health Organization and represents one of the major public health problems. It is associated with a reduction in life expectancy of about 7–8 years due to related cardiovascular diseases such as arterial hypertension, metabolic syndrome, insulin resistance, type 2 diabetes mellitus, and dyslipidemia. Adipose tissue is not merely a fat storage site but a true endocrine and immunologically active organ that secretes hormones and mediators (adipokines), influencing cardiovascular risk and host physiology. Objective: This review summarizes the current understanding of the role of epicardial adipose tissue (EAT) in cardiovascular disease pathophysiology and discusses its clinical diagnostic and therapeutic implications. Methods: A narrative non-systematic review was conducted focusing on recent literature concerning the biological and clinical aspects of cardiac adipose tissue, with particular emphasis on epicardial adipose tissue. The review examined its gene expression profile, secretory function, and interaction with cardiovascular structures and diseases. Findings: There are different types of adipose tissue, including cardiac adipose tissue, which comprises epicardial and pericardial (or paracardiac) fractions. Epicardial adipose tissue is unique due to its proximity to the heart and a distinct gene expression profile compared to other adipose depots such as visceral and subcutaneous fat. EAT plays a crucial role in the development and progression of cardiovascular diseases with high morbidity and mortality, acting both as a metabolic and inflammatory mediator. Conclusion: Cardiac adipose tissue, particularly EAT, is a key player in cardiometabolic disease. Understanding its pathophysiological role and incorporating imaging tools to evaluate EAT may enhance cardiovascular risk stratification and disease management. Full article

The novel secreted protein Meteorin-β (Metrnβ) is a homologous protein of the neurotrophic regulator Meteorin, which is widely expressed in the skin, mucous membranes, and white adipose tissue upon stimulation by a variety of inflammatory mediators, including cytokines and chemokines, while, at the same time Metrnβ may also regulate the expression of these cytokines and chemokines. As a small secreted protein with low tissue specificity, Metrnβ plays vital roles in energy metabolism, insulin sensitivity regulation, neurodevelopment, white fat browning, and inflammatory response. Specifically, Metrnβ may act as an adipokine, myokine, neurotrophic factor, and cytokine, thereby being involved in the pathological and physiological processes of various human diseases, including metabolic, autoimmune and infectious/allergic diseases, and certain types of tumors. This review aims to systematically introduce the current research progress on Metrnβ, including its expression and distribution profiles, biological functions, and immunomodulatory roles in the process of human diseases. Additionally, we also discuss its potential as a biomarker, as well as a therapeutic/preventive agent for human diseases. Full article

Background/Objective: The single-nucleotide polymorphism (SNP) rs10830963 in the melatonin receptor 1B (MTNR1B) gene influences insulin secretion and glucose metabolism and has been associated with an increased risk of type-2 diabetes. This study aimed to explore the interaction between dietary intake and the MTNR1B rs10830963 polymorphism on glycemic profiles in young Brazilian adults. Methods: This cross-sectional study assessed 200 healthy young adults (19–24 years), evaluating the MTNR1B rs10830963 genotype, anthropometric parameters, glycemic markers (fasting insulin, glucose, HOMA-IR, and HOMA-β), and dietary intake via three 24 h dietary recalls. Genotype–diet interactions were tested using multivariate linear regression models adjusted for confounders. Results: The carriers of the G allele exhibited a positive association with fasting insulin levels (p = 0.003), insulin/glucose ratio (p = 0.004), HOMA-IR (p = 0.003), and HOMA-β (p = 0.018). Energy-adjusted fiber intake showed a significant genotype-specific interaction only in carriers of the G allele, where higher dietary fiber intake was significantly associated with lower fasting insulin (p_interaction = 0.034) and HOMA-IR (p_interaction = 0.028). Conclusion: Our findings indicate that the MTNR1B rs10830963 polymorphism is associated with glycemic markers, and dietary fiber intake may attenuate the adverse effects of the MTNR1B rs10830963 G allele on glycemic profiles in young Brazilian adults. This highlights the potential role of fiber in improving health outcomes for individuals carrying this risk allele. To validate these results and assess the broader implications for the Brazilian population, further intervention studies and larger-scale research are essential. Full article

Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disorder caused by impaired insulin secretion from pancreatic β-cells and insulin resistance in target tissues. Genome-wide association studies have identified over 50 genetic variants linked to T2DM, including polymorphisms associated with the disease. This study investigates the impact of the FADS1 (rs174547) polymorphism in T2DM patients compared to healthy controls and examines serum levels of omega-3 and omega-6 fatty acids, as well as D5D and D6D enzyme levels and activity. This case–control study included 120 participants: 60 newly diagnosed T2DM patients and 60 apparently healthy controls matched for age, sex, and other sociodemographic factors. Polyunsaturated fatty acid (PUFA) levels and desaturase enzyme activities in the n-3 and n-6 pathways were assessed using ELISA and gas chromatography. FADS1 gene polymorphisms were analyzed via Sanger sequencing. Genotype and allele frequencies of FADS1 (rs174547) differed significantly between groups, with higher frequencies of C-containing alleles in T2DM patients. Multivariate analysis revealed a significant association between the C-allele genotype and increased T2DM risk, independent of sociodemographic variables, lipid profile, and inflammatory markers. In conclusion; reduced serum levels of omega-3 and omega-6 fatty acids in T2DM were associated with decreased desaturase enzyme activity. The FADS1 (rs174547) polymorphism is significantly associated with T2DM risk, with the minor allele linked to lower desaturase activity. Full article

Type 2 diabetes (T2D) and cardiovascular diseases (CVDs) are major public health challenges worldwide. Metabolomics, the exhaustive assessment of metabolites in biological systems, offers important insights regarding the metabolic disturbances related to these disorders. Recent advances toward the integration of metabolomics into clinical practice to facilitate the discovery of novel biomarkers that can improve the diagnosis, prognosis, and treatment of T2D and CVDs are discussed in this review. Metabolomics offers the potential to characterize the key metabolic alterations associated with disease pathophysiology and treatment. T2D is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms; therefore, the disease-causing pathways of T2D are not completely understood. Recent studies have identified several robust clusters of T2D variants representing biologically meaningful, distinct pathways, such as the beta cell and proinsulin cluster related to pancreatic insulin secretion, obesity, lipodystrophy, the liver/lipid cluster, glycemia, and blood pressure, and metabolic syndrome clusters representing different pathways causing insulin resistance. Regarding CVDs, recent studies have allowed the metabolomic profile to delineate pathways that contribute to atherosclerosis and heart failure, as well as to the development of targeted therapy. This review also covers the role of metabolomics in integrated metabolic genomics and other omics platforms to better understand disease mechanisms, along with the transition toward precision medicine. This review further investigates the use of metabolomics in multi-metabolite modeling to enhance risk prediction models for predicting the first occurrence of major adverse cardiovascular events among individuals with T2D, highlighting the value of such approaches in optimizing the preventive and therapeutic models used in clinical practice. Full article

Human adenovirus 36 (HAdV-36) is associated with obesity, potentially by promoting adipocyte proliferation and differentiation. Although linked to increased fat storage, HAdV-36 is also correlated with improved insulin sensitivity. Given its potential role in modulating adipose tissue and promoting a less inflammatory metabolic profile, its impacts on pro- and anti-inflammatory cytokine secretion remain unclear. Methods: This nested case-control study compared cytokine levels (IL-10, IL-2, IL-6, IL-8, and TNF-α) between patients with and without HAdV-36 infection. A total of 76 participants were included, with 37 in the control group (HAdV-36 negative) and 39 classified as cases (HAdV-36 positive). Results: HAdV-36 seropositive individuals exhibited significantly lower IL-6 levels and higher IL-8 levels than seronegative participants. Additionally, they had lower glucose levels, suggesting a potential link between HAdV-36 and metabolic regulation. Conclusions: These findings support the hypothesis that HAdV-36 may influence inflammatory and metabolic responses by modulating cytokine expression and glucose levels. Further research is needed to clarify the underlying mechanisms and their implications for metabolic health. Full article