Search Results (10,320)

Vegetarianism has historically been associated with cardiometabolic benefits and reduced diabetes risk. Despite having the highest prevalence of vegetarians globally, the prevalence of type 2 diabetes in South Asians is amongst the highest globally. This review explores the relationship between vegetarianism and cardiometabolic measures in South Asian populations to clarify this paradoxical relationship. Five databases were searched to identify observational studies published between January 2000 and May 2025 that compared vegetarian diets with non-vegetarian diets and reported cardiometabolic measures. A total of 973 articles were identified, 590 articles were assessed, and 7 studies (n = 184,345) were ultimately included. Overall, each study utilized different dietary intake assessments and reported variable cardiometabolic measures. The three highest-quality studies found that vegetarian adherence was associated with a lower BMI, waist circumference, diastolic blood pressure, lipid levels, and fasting blood glucose compared with non-vegetarian diets. Conclusive findings were limited by the small number of studies, variability in dietary assessment methods, and heterogeneity in the reporting of cardiometabolic measures. These results underscore the importance of conducting more methodologically robust studies to assess cardiometabolic measures and demonstrate the need for culturally consistent dietary assessment tools to reduce inter-study variability and improve dietary reporting in South Asians. Full article

Type 2 diabetes mellitus (T2DM) is a prevalent and complex metabolic disorder characterized by insulin resistance, progressive β-cell dysfunction, and severe systemic complications. Advances in single-cell multi-omics—transcriptomics, chromatin accessibility profiling, and integrative analyses—have offered unprecedented insights into the cellular heterogeneity and regulatory networks of pancreatic islets. We highlight recent discoveries in islet cell heterogeneity and β-cell pathophysiology, with a particular focus on dysfunction and dedifferentiation. We further underscore the computational frameworks that enable these discoveries, spanning data preprocessing, multi-omics integration, and machine learning-driven analyses, which collectively enable the dissection of disease-relevant cell subpopulations and the reconstruction of developmental and regulatory trajectories. We also examine how impaired signaling within islets and chronic adipose inflammation contribute to T2DM pathogenesis. Finally, we discuss key challenges in clinical translation—including limited population diversity in single-cell atlases and the interpretability of computational models—and propose future directions toward precision diagnostics and therapeutic innovation in T2DM. Full article

The use of herbal medicines has gained popularity, both in science and among the public, as a natural alternative for the treatment of numerous diseases, including type 2 diabetes. Objective: The objective of this study was to evaluate peri-implant and long bone biomechanics in type 2 diabetic animals, treated or not with Bauhinia forficata. Methods: Thirty-two rats were allocated into four groups: normoglycemic (NG), normoglycemic + Bauhinia forficata (NGBf), type 2 diabetes (T2D), and T2D + Bauhinia forficata (T2DBf). Diabetes was induced using a cafeteria diet and streptozotocin (35 mg/kg). Bauhinia forficata tea (50 g/L) was administered to the NGBf and T2DBf groups. After 14 days, titanium implants were installed in the tibial metaphysis of all animals. Biomechanical analysis (removal torque), computerized microtomography, three-point bending test, confocal microscopy, and real-time PCR were performed. The results were tabulated, and a statistical test was conducted with a significance level of 5%. Results: Bauhinia forficata significantly improved the weight and blood glucose levels of the animals. In terms of biomechanics and the microarchitecture of long bones, T2D did not impair bone metabolism, and the use of the therapy did not cause significant changes in the parameters evaluated. However, T2D promoted significant impairment in the structural, biomechanical, and molecular characteristics of the peri-implant repair process, and the use of Bauhinia forficata increased the parameters evaluated in T2DBf. Conclusions: Type 2 diabetes mellitus significantly compromises peri-implant bone repair, with no influence on the metabolism of long bones, and Bauhinia forficata acts positively on both the etiopathogenesis of the disease and the tissue response to bone repair. Full article

Background/Objectives: A significantly higher fracture risk characterizes Type 2 diabetes mellitus (T2DM) patients when compared to the non-diabetic population, even though their average bone mineral density (BMD) tends to be normal or high. This elevated risk is primarily driven by defective bone quality. The trabecular bone score (TBS) and radiofrequency echographic multispectrometry (REMS) have recently been proposed to improve the assessment of bone quality in T2DM individuals. This study aimed to evaluate whether TBS and REMS can improve the identification of osteoporosis and fracture risk in these patients. Methods: BMD was measured in 223 consecutive T2DM patients (126 women and 97 man) and 102 controls. BMD values for the lumbar spine (LS), femoral neck (FN), and total hip (TH) were obtained via both dual-energy X-ray absorptiometry (DXA) and radiofrequency echographic multi-spectrometry (REMS). In all patients, TBS and Fragility Score (FS) by REMS were measured and prior major osteoporotic fractures (MOF) were assessed. Results: All BMD T-scores measured by REMS were significantly lower than those obtained by DXA at both lumbar and femoral sites. T2DM patients with previous MOF exhibited lower T-scores for both BMD-LS and BMD-TH, as assessed by DXA and REMS, compared with patients without fractures. However, these differences reached statistical significance for BMD-TH with both techniques and for BMD-LS with REMS, but not for BMD-LS with DXA. Moreover, patients with a history of MOF had significantly lower TBS values (p < 0.05) and significantly higher FS values at both lumbar (p < 0.05) and femoral (p < 0.01) sites compared with those without fractures. Conclusions: The results of this study suggest that the parameters obtained using REMS technology (BMD and FS) may be valuable tools for improving the diagnosis of osteoporosis and assessing fracture risk in patients with T2DM. Full article

Background: Hepatocellular carcinoma (HCC) is a leading cause of cancer-related deaths worldwide, increasingly arising in patients with metabolic dysfunction-associated steatotic liver disease (MASLD). Epigenetic dysregulation, particularly DNA methylation, has been implicated in MASLD-HCC development, yet the roles that the principal DNA methylation precursor metabolites, S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), play in this association are unclear. Objective: We investigated associations of circulating SAM, SAH, the SAM/SAH ratio, with MASLD-HCC. Methods: In a multi-center pilot case–control study, we evaluated 69 MASLD-HCC cases and 136 cancer-free MASLD controls. Plasma SAM and SAH levels were quantified by liquid chromatography–tandem mass spectrometry. Metabolite levels were categorized as greater than or less than the median based on distribution in controls. Logistic regression was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for age, sex, body mass index, smoking status, and type 2 diabetes. Results: MASLD-HCC cases had significantly higher plasma SAM levels (mean 121 vs. 96 nmol/L; p = 0.001) and SAM/SAH ratios (2.09 vs. 1.48; p = 6.42 × 10⁻⁷) than MASLD controls. In multivariable-adjusted models, elevated SAM levels (OR_{≥median vs. <median} = 2.76; 95% CI: 1.38–5.72) and higher SAM/SAH ratio (OR_{≥median vs. <median} = 2.30; 95% CI: 1.15–4.73) were associated with higher odds of MASLD-HCC. SAH alone was associated with MASLD-HCC. Conclusions: Higher plasma SAM levels and SAM/SAH ratios are independently linked to MASLD-HCC development. These metabolites might serve as noninvasive markers for HCC risk stratification in patients with MASLD and improve early detection efforts for MASLD-HCC. Full article

Binge eating disorder (BED) is a prevalent eating disorder lacking adequate pharmacological interventions. This review examines the therapeutic potential of glucagon-like peptide-1 receptor agonists (GLP-1RAs), medications approved for type 2 diabetes and obesity now being investigated for eating disorders through their modulation of metabolic and reward pathways. A narrative review was conducted using PubMed/MEDLINE, through May 2025, to examine GLP-1RA effects on BED, including preclinical and clinical studies, mechanistic investigations, and relevant reviews. GLP-1 receptors (GLP-1Rs) are expressed in hypothalamic nuclei, regulating energy homeostasis and mesolimbic circuits controlling food reward. Preclinical studies demonstrate that GLP-1RAs reduce food-seeking behavior, suppress dopamine signaling in reward circuits, and modulate neural transmission in key brain regions. These effects extend beyond appetite suppression to directly modify reward processing underlying compulsive eating. Emerging clinical evidence with semaglutide and liraglutide report reductions in binge eating episodes, decreased food cravings, and improved symptom scores. However, current studies remain small-scale with methodological limitations, and translating findings from animal models to human eating disorder complexity presents significant challenges. This review integrates preclinical and clinical evidence demonstrating that GLP-1RAs modulate both metabolic and reward pathways. By elucidating the underlying neurobiological mechanisms, GLP-1RAs may offer advantages over current symptom-focused therapies for BED. Full article

Intestinal dysbiosis has been linked to metabolic disorders, including insulin resistance and type 2 diabetes mellitus (T2DM). T2DM typically follows a prediabetic stage, during which insulin resistance develops. During the early stages of T2DM, its development can be corrected, thus potentially preventing or delaying the onset of the disease. This secondary, exploratory, cross-sectional comparison study aimed to contrast the gut microbiome of individuals with elevated fasting blood glucose to that of individuals with glucose levels within the normal range. This study involved 65 older adults (ages 76–83 years) enrolled from the randomized controlled trial entitled the “Generation 100 Study”, all of whom consented to provide their gut microbiome samples. We employed a high-throughput sequencing of the bacterial 16S rRNA gene to obtain metagenomic microbial profiles for all participants. These profiles were then correlated with clinical measures. Overall, microbial alpha diversity was significantly reduced in the high glucose group. We have also observed distinct patterns of microbial beta diversity between high and normal glucose groups. At the phylum level, we found that Synergistes, Elusimicobia, Euryarchaeota, Verrucomicrobia, and Proteobacteria were all significantly decreased in participants with high blood glucose. Additionally, P. copri (ASV 909561) was significantly elevated (10-fold increase) in the high glucose groups, suggesting that it may serve as an early T2DM marker. In contrast to prior reports on the Fusobacterium genus, we found that it was significantly increased in the normal glucose group, with a significant 151-fold increase compared to the high glucose group. Directly linking gut microbiota profiles with clinical indicators such as fasting blood glucose and T2DM diagnosis allows the identification of specific microbial features associated with glucose dysregulation, providing preliminary population-level evidence to guide future translational research. Our results indicate significant changes in the microbiome that may provide valuable insights for early intervention in pre-diabetic states. Full article

Sarcodon aspratus fruiting polysaccharides (SAFP) exhibit multiple therapeutic properties. In this study, a type 2 diabetes mellitus (T2DM) mouse model was established using a high-fat diet (HFD) and streptozotocin to evaluate the antidiabetic potential of SAFP. Then the benefits of SAFP on glucolipid metabolism, gut barrier integrity and intestinal microbiota were evaluated. The results indicated that SAFP alleviated disturbances in glycolipid metabolism and insulin resistance through activating Adenosine 5′-monophosphate (AMP)-activated protein kinase (AMPK) signaling pathway. Furthermore, SAFP ameliorated hepatic inflammation and hepatic steatosis, as well as restored dysbiosis in hepatic function. Notably, SAFP enhanced intestinal mucosal architecture and strengthened epithelial barrier functionality through upregulated expression of tight junction components such as Zonula occludens-1(ZO-1), Claudin-1, and Occludin proteins. The 16S rRNA analysis indicated that SAFP has the potential to restore the intestinal microbial barrier in T2DM mice through elevation of short-chain fatty acids (SCFAs) concentrations and regulation of microbial community imbalances. This research offers foundational evidence supporting the utilization of SAFP as an innovative dietary supplement or prospective prebiotic component in functional food formulations targeting diabetes management. Full article

Background/Objectives: Type 2 diabetes and obesity present escalating global health and economic challenges, highlighting the need for therapies that can effectively manage glycemic levels and reduce excess adiposity. Semaglutide, a glucagon-like peptide-1 receptor (GLP-1R) agonist available in subcutaneous or oral formulation, has quickly evolved from a theoretical concept to a crucial component of modern metabolic care. This review explores the comprehensive development journey of semaglutide, drawing on evidence from medicinal chemistry, animal studies, initial human trials, the pivotal SUSTAIN and STEP programs, and real-world post-marketing surveillance. Methods: We conducted a detailed analysis of preclinical data sets, Phase I–III clinical trials, regulatory documents, and pharmaco-epidemiological studies published between 2008 and 2025. Results: Through strategic molecular modifications, such as specific amino-acid substitutions and the addition of a C18 fatty-diacid side chain to enhance albumin binding, the half-life of the peptide was extended to approximately 160 h, allowing for weekly dosing. Studies in rodents and non-human primates showed that semaglutide effectively lowered blood glucose levels, reduced body weight, and preserved β-cells while maintaining a favorable safety profile. Phase I trials confirmed consistent pharmacokinetics and tolerability, while Phase II trials identified 0.5 mg and 1.0 mg once weekly as the most effective doses. The extensive SUSTAIN program validated significant reductions in HbA1c levels and weight loss compared to other treatments, as well as a 26% decrease in the relative risk of major adverse cardiovascular events (SUSTAIN-6). Subsequent STEP trials expanded the use of semaglutide to chronic weight management, revealing that nearly two-thirds of patients experienced a body weight reduction of at least 15%. Regulatory approvals from the FDA, EMA, and other regulatory agencies were obtained between 2017 and 2021, with ongoing research focusing on metabolic dysfunction-associated steatohepatitis, cardiovascular events, and chronic kidney disease. Conclusions: The trajectory of semaglutide exemplifies how intentional peptide design, iterative translational research, and outcome-driven clinical trial design can lead to groundbreaking therapies for complex metabolic disorders. Full article

Background/Objective: Type 2 diabetes mellitus (T2DM) is characterized by insulin resistance, β-cell dysfunction, and chronic hyperglycemia. Exercise is a cornerstone of non-pharmacological therapy, yet the optimal modalities by which different exercise prescriptions improve metabolic outcomes remain unclear. This review synthesizes evidence on the metabolic effects of aerobic, resistance, high-intensity interval (HIIT), and combined training in individuals with T2DM. Methods: The PubMed, Web of Science, and Scopus databases were searched up to March 30, 2025. A total of 26 articles were included. Articles were selected based on studies conducted on human participants diagnosed with type 2 diabetes mellitus, involving structured exercise interventions, and reporting at least one outcome related to insulin function or glycemic control. Results: This review identified five exercise programs that can improve metabolic outcomes in patients with type 2 diabetes. Evidence levels varied across the 26 studies (n = 20–98), so intensity ranges should be interpreted as indicative rather than prescriptive. Aerobic training was the primary intervention, and evidence from 13 studies (8–48 weeks) showed that moderate-to-vigorous intensity aerobic training (approximately 50–85% of maximum heart rate or 50–75% of VO₂max) was generally associated with improvements in β-cell function, insulin sensitivity, and glycated hemoglobin (HbA1c). Strength training (approximately 40–50% to <3RM, 12 weeks) was linked to better glycemic parameters in some studies, though effects on insulin resistance were inconsistent. Most studies indicated that combined aerobic training (60–85% of maximum heart rate) with resistance or other complementary exercise modalities for 8–24 weeks tended to improve HbA1c, fasting glucose, and insulin sensitivity. High-intensity interval training (HIIT, ≥85% of maximum heart rate, 8 weeks) was also associated with enhanced insulin sensitivity, β-cell function, and basal insulin levels. Conclusions: Different exercise modalities improve metabolic health through complementary mechanisms involving enhanced glucose transport, mitochondrial function, anti-inflammatory effects, and increased muscle mass. Tailoring exercise prescriptions based on individual capacity and metabolic targets may optimize outcomes in T2DM management. Full article

Background/Objectives: Insulin resistance is a major public health issue in Mexico, closely linked to obesity, prediabetes, and type 2 diabetes. The euglycemic–hyperinsulinemic clamp is the diagnostic gold standard but is impractical for routine use. The triglyceride–glucose (TyG) index has been proposed as a simple alternative validated in diverse populations. We aimed to assess the utility of TyG relative to HOMA-IR and QUICKI as an early diagnostic tool in young Mexican adults. Methods: We performed an analytical cross-sectional study in young adults. Clinical, anthropometric, and fasting biochemical variables were collected to compute TyG. We compared TyG with HOMA-IR and QUICKI and evaluated diagnostic performance using receiver operating characteristic analysis to estimate area under the curve (AUC) and identify the optimal cut-off. Results: We analyzed 115 participants; 66.9% were insulin resistant by HOMA-IR, 79.1% by QUICKI, and 42.6% by TyG. TyG showed significant associations with anthropometric and biochemical measures. Diagnostic performance was good (AUC 0.707 vs. HOMA-IR; 0.960 vs. QUICKI). The optimal cut-off was 4.38, yielding sensitivity of 70.1% and specificity of 68.4% for diagnosing insulin resistance compared with HOMA-IR. Conclusions: The TyG index appears to be a useful, accessible, and cost-effective biomarker for early detection of insulin resistance in young Mexican adults. Its implementation could facilitate earlier diagnosis and prevention of cardiometabolic complications. Longitudinal, multicenter studies are warranted to establish population-specific reference values and to confirm its predictive value for adverse outcomes. Full article

Background: Vitamin B12 deficiency, hyperhomocysteinemia, and diabetes are emerging determinants of cardiovascular risk, particularly among women. Early detection and treatment represent an important public health opportunity to reduce the burden of disease and promote health equity. Objective: We aimed to quantify the prevalence of vitamin B12 deficiency, hyperhomocysteinemia, and diabetes, and to evaluate the potential impact of detecting and addressing these conditions on reducing CVD risk in adult Mexican women. Methods: We analyzed data from 1197 women aged 20–49 years from Mexico’s 2022–2023 National Health and Nutrition Survey (ENSANUT). Serum vitamin B12, folate, and homocysteine were quantified, and 10-year CVD risk was estimated using Framingham and Globorisk models. Population-attributable fractions and cost–benefit analyses were used to assess preventable CVD cases and the economic feasibility of nationwide vitamin B12 supplementation. Results: Nationwide, 37.2% of women have vitamin B12 deficiency, and 30.6% have borderline levels. In Southern Mexico, the prevalence of vitamin B12 deficiency is higher, reaching 52.4%. Elevated homocysteine levels were detected in 12.3% of women. The predicted number of preventable CVD cases ranged from 10,000 to 14,000, and the benefit–cost ratio exceeded 1, supporting economic feasibility. Conclusions: Vitamin B12 deficiency and hyperhomocysteinemia are very common among Mexican women and are associated with an increased cardiovascular risk, especially in those aged 40 to 49. The analysis showed that implementing a national vitamin B12 supplementation strategy could be a cost-effective preventive measure, with a benefit–cost ratio ranging from 1.93 in the base case to 2.98 when broader societal savings are taken into account. These findings highlight the potential of targeted nutritional interventions to reduce the burden of cardiovascular disease in women. Full article

Background: Since the introduction of the first GLP-1 receptor agonist (GLP-1 RA) in 2005, there has been a steady increase in the number of drugs available in this group, as well as an expansion of their indications and routes of administration. Aim: The aim of the study was to assess the clinical characteristics of patients treated with GLP-1 RA in Poland in 2018–2024, with particular emphasis on the disease entities constituting indications for treatment (like obesity and diabetes), and to analyse the frequency of use of individual drugs during the study period. Methods: A cohort study was conducted based on anonymised medical data from 300 outpatient clinics the largest private healthcare facilities in Poland (Luxmed), on consecutive patients who had at least one prescription for GLP-1 RA. The analysis covered the period from 1 January 2018 to 31 December 2024. Results: The number of patients using GLP-1 RA increased from 212 in 2018 to 12,836 in 2024. Obesity was diagnosed in 78% of all patients, most often in the groups using liraglutide and tirzepatide. The highest percentage of patients with type 2 diabetes was observed in the dulaglutide group (67%), while the lowest was in the tirzepatide group (15%). From 2022, the share of oral semaglutide steadily increased, reaching 50% of all semaglutide applications in 2024 in Poland. Conclusions: In the analysed group, GLP-1 RAs were most commonly used to treat obesity. The oral form of semaglutide was more frequently used in younger females with less aggravating medical history. Full article

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely linked to comorbidities like obesity, type 2 diabetes, and cardiovascular disease. Given that liver biopsy is the diagnostic gold standard, there is a critical need for minimally invasive tests, particularly for the inflammatory form, metabolic dysfunction-associated steatohepatitis (MASH). In this discovery study, we investigated the plasma proteome to identify blood biomarkers for MASH and explored their potential tissue sources, the liver and visceral adipose tissue. Plasma low-abundance proteome profiling was performed on samples from a cohort of morbidly obese MASLD subjects (n = 90; 40 with MASH, 50 without) using Olink^® panels. Paired liver and visceral adipose biopsies were also analyzed. Data showed 34 significantly different plasma proteins between the two groups, including Pleiotrophin (PTN), Fibroblast growth factor-21 (FGF-21), and Hepatocyte growth factor (HGF), among others. While plasma-tissue correlation was only found for STX8, PTN and FGF-21 demonstrated the strongest associations with the histopathological features of MASH. A diagnostic model combining PTN, FGF-21, and AST achieved a robust AUC of 0.88 (95% CI: 0.84–0.97) for distinguishing MASH. Based on this discovery pilot study, circulating PTN and FGF-21 emerge as promising non-invasive biomarkers for improving patient stratification and supporting therapeutic evaluation in MASH, warranting validation in independent cohorts and future studies. Full article

The rapidly advancing field of gut microbiota research has revealed its pivotal role in human health, with growing evidence implicating microbial dysbiosis in the development of metabolic diseases, particularly type 2 diabetes mellitus (T2DM). This narrative review synthesizes recent findings on the complex, bidirectional relationship between the gut microbiota–metabolic axis and T2DM, drawing upon data from human and experimental studies published in the past decade. Patients with T2DM consistently demonstrate marked gut dysbiosis, characterized by reduced microbial diversity and depletion of beneficial butyrate-producing taxa such as Faecalibacterium prausnitzii and Roseburia intestinalis. In contrast, increases in pro-inflammatory bacteria including Escherichia-Shigella and Lactobacillus are commonly observed. Such compositional changes are linked to metabolic dysfunction through altered microbial metabolites, including elevated trimethylamine N-oxide (TMAO), which has been associated with insulin resistance and increased diabetes risk. Moreover, gut microbiota imbalances correlate with systemic inflammation, as indicated by higher levels of cytokines such as IFN-γ and IL-6. These findings underscore the gut microbiota’s central role in energy metabolism and inflammation in T2DM. Understanding these mechanisms could inform novel therapeutic and preventive strategies—such as microbiota-targeted dietary, probiotic, or pharmacologic interventions—to improve metabolic outcomes and enhance clinical management of diabetes. Full article