Search Results (13,439)

This study investigated the effects of asparagus powder supplementation on blood glucose regulation, insulin, lipid profile, and oxidative stress in overweight and obese individuals. Forty-four adults aged 18–59 years participated in a 12-week randomized controlled trial and were randomly assigned to receive either asparagus powder (40 mg/kg/day) or a placebo (maltodextrin, 40 mg/kg/day). Assessments included an oral glucose tolerance test (OGTT), fasting blood glucose (FBG), insulin, homeostasis model assessment of insulin resistance (HOMA-IR) and β-cell function (HOMA-B), lipid profile, and oxidative stress markers (malondialdehyde [MDA], protein carbonyl, and superoxide dismutase [SOD]). In the asparagus group, OGTT at 30 min and low-density lipoprotein cholesterol (LDL-C) significantly decreased, while SOD activity significantly increased (all p < 0.05). In contrast, the placebo group showed significant increases in OGTT at 30 min, insulin, HOMA-IR, HOMA-B, triglycerides (TG), the TG/high-density lipoprotein cholesterol (HDL-C) ratio, and the total cholesterol (TC)/HDL-C ratio (all p < 0.05). Between-group comparisons indicated that FBG, area under the BG curve at 30–120 min, TG, TG/HDL-C, and MDA levels were significantly lower in the asparagus group than in the placebo group (all p < 0.05), whereas OGTT, LDL-C, SOD activity, insulin, HOMA-IR, HOMA-B, and TC/HDL-C did not differ significantly. Other indices, including TC, HDL-C, and protein carbonyl, showed no significant within- or between-group differences. In conclusion, 12 weeks of asparagus powder supplementation partially improved glycemic control, lipid profile, and oxidative stress in overweight and obese individuals. These findings suggest a potential role of asparagus as a complementary nutritional strategy to reduce the risk of diabetes and cardiovascular disease in this population. Full article

An integrative approach combining network pharmacology, molecular docking, and cellular assays was used to elucidate the potential mechanisms by which the n-butanol extract of Biebersteinia heterostemon ameliorates type 2 diabetes mellitus (T2DM). Chemical constituents of the n-butanol extract were identified via ultra-high-performance liquid chromatography coupled with Q-Exactive Orbitrap mass spectrometry. Active compounds and T2DM-related targets were retrieved from public databases, and intersecting targets were identified. Protein–protein interaction (PPI) networks were constructed using the STRING database, while Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed via the DAVID database. A comprehensive “drug–compound–target–disease–pathway” network was established, and molecular docking was conducted to evaluate binding affinities of key compounds to core targets. Functional validation was performed in insulin-resistant cell models. Network pharmacology analysis identified 37 active constituents within the extract and 222 overlapping targets associated with T2DM. GO enrichment indicated involvement in protein phosphorylation, MAPK cascade activation, and negative regulation of apoptosis. Key signaling pathways included PI3K/AKT and lipid and atherosclerosis pathways. Molecular docking revealed strong binding affinities (binding energies ≤ −9.3 kcal·mol⁻¹) between core compounds—such as cheilanthifoline, glabridin, acetylcorynoline, skullcapflavone II, liquiritigenin, and dinatin—and pivotal targets including GAPDH, AKT1, TNF, SRC, EGFR, and PPARγ. In vitro experiments demonstrated that the extract significantly enhanced glucose uptake and glycogen synthesis in insulin-resistant cells, while suppressing oxidative stress and the expression of pro-inflammatory mediators such as TNF-α, MMP9, and IL-6. Collectively, B. heterostemon shows potential as an effective intervention for T2DM by targeting key molecular pathways, improving insulin sensitivity, and mitigating oxidative stress and inflammation in insulin-resistant cells. Full article

Kalanchoe pinnata, commonly known as the “miracle plant” or “life plant”, is a succulent species traditionally used for various health conditions. Recent research investigations have intensified interest in this species due to its diverse repertoire of bioactive constituents, including flavonoids, alkaloids, triterpenes, and glycosides. These compounds have been associated with multiple therapeutic effects, notably antioxidant, anti-inflammatory, and antidiabetic activities. Although several studies have highlighted the positive effects of the extracts of K. pinnata on key factors contributing to the pathophysiology and complications of diabetes mellitus, a systematic overview focusing on the use of these extracts and their bioactive constituents in the management of the disease is lacking. This literature review summarizes the phytochemical composition, traditional uses, and recent scientific data supporting the antidiabetic potential of K. pinnata, with a particular focus on its effects on glycemic control, as well as inflammatory and oxidative homeostasis, toxicity, safety, and potential clinical implications. The phytochemical constituents discussed include quercetin, kaempferol, apigenin, epigallocatechin gallate (EGCG), avicularin, and bufadienolides, along with a presentation of representative structures. The review also covers the potential mechanisms of action in diabetes mellitus. The survey of available literature highlights the effects of K. pinnata on indices of diabetes mellitus, including enhancing insulin sensitivity, mitigating oxidative stress and inflammation, lowering blood glucose levels, and the potential adverse effects. These results point to the promising prospect for K. pinnata use in the management of diabetes mellitus and its associated complications, while underscoring the need for more rigorous investigations, including well-controlled clinical trials. Full article

Objectives: Shen-Ling-Bai-Zhu-San (SLBZS) is a classical traditional Chinese herbal formula with spleen-invigorating and dampness-resolving properties. Recent pharmacological studies suggest its potential to regulate immune and metabolic disorders. Type 2 diabetes mellitus (T2D) and ulcerative colitis (UC) often coexist as comorbidities characterized by chronic inflammation, microbial imbalance, and insulin dysregulation, yet effective therapies remain limited. This study aimed to investigate the molecular mechanisms through which SLBZS may benefit T2D–UC comorbidity. Methods: An integrative multi-omics strategy was applied, combining network pharmacology, structural bioinformatics, and ensemble molecular docking–dynamics simulations. These complementary approaches were used to identify SLBZS bioactive compounds, predict their putative targets, and examine their interactions with disease-related biological networks. Results: The analyses revealed that flavonoids in SLBZS act on the SLC6A14/PI3K–AKT signaling axis, thereby modulating immune responses and improving insulin sensitivity. In addition, SLBZS was predicted to regulate the NF-$\kappa$B/MAPK signaling pathways, key hubs linking inflammation and metabolic dysfunction in T2D–UC. These dual actions suggest that SLBZS can intervene in both inflammatory and metabolic processes. Conclusions: SLBZS demonstrates promising therapeutic potential for T2D–UC by targeting interconnected immune–metabolic networks. These findings not only provide mechanistic insights bridging traditional therapeutic concepts with modern pharmacology but also establish a theoretical basis for future experimental validation and clinical application. Full article

Background: Continuous insulin infusion protocols are essential for managing decompensated diabetic dogs, but comparative data between variable and fixed infusion rates are limited. Methods: This prospective observational study evaluated the glycemic response of 21 diabetic dogs treated with a fixed-dose continuous-rate infusion (CRI) of regular insulin at 0.05 IU/kg/h for 12 h. Capillary blood glucose was measured hourly. Statistical analyses included Wilcoxon signed-rank tests, Friedman test, Mann–Whitney U, and Kruskal–Wallis tests. Results: A significant reduction in glucose concentration occurred during the first five hours of infusion (p < 0.0001), followed by a stabilization phase with no further significant changes. No differences in glycemic response were found by sex or breed. The protocol was well tolerated, with no hypoglycemic events observed. Conclusions: A fixed-dose CRI of 0.05 IU/kg/h offers a safe and effective option for acute glycemic control in diabetic dogs, including those with early ketoacidosis. The standardized approach simplifies management without compromising efficacy and supports its inclusion in emergency treatment protocols. Full article

Introduction: After total pancreatectomy, patients inevitably develop pancreatogenic diabetes with marked glycemic variability and high risk of malnutrition due to both endocrine and exocrine insufficiency. Weight loss and malnutrition can occur even in those with adequate dietary intake and plausible pancreatic enzyme replacement. We hypothesized that glycemic variability is associated with nutritional decline. Methods: We retrospectively analyzed 14 patients who underwent continuous glucose monitoring (CGM) after total pancreatectomy. Nutritional status was assessed using the Geriatric Nutritional Risk Index (GNRI), and patients were classified into malnutrition-risk progression or nutrition-maintaining groups. Then, we evaluated glycemic indices, dietary intake, anthropometry, and pancreatic enzyme replacement therapy (PERT). Results: Insulin use, PERT dose, and dietary intake were approximately comparable between groups. In contrast, the malnutrition-risk progression group showed significantly higher mean glucose and time above range, and lower time in range (TIR). Importantly, TIR consistently showed an inverse association with malnutrition-risk progression across models adjusted for clinical covariates, including time since pancreatectomy, primary diagnosis, insulin regimen, and pancrelipase dose. These findings indicate that the observed relationship between lower TIR and worsening GNRI was independent of dietary intake and adequacy of enzyme replacement therapy, underscoring TIR as a clinically meaningful indicator of nutritional decline in this population. Conclusions: Hyperglycemia and reduced TIR were significantly associated with worsening GNRI after total pancreatectomy, independent of dietary intake or PERT. CGM-based glycemic metrics may help identify patients at risk of malnutrition and guide postoperative management. Full article

Type 2 diabetes mellitus (T2DM) is a chronic disease that has become a serious health problem worldwide. Moreover, increased systemic and cerebrovascular inflammation is one of the major pathophysiological features of T2DM, and a growing body of evidence emphasizes T2DM with memory and executive function decline. Bioactive sphingolipids regulate a cell’s survival, inflammatory response, as well as glucose and insulin signaling/metabolism. Moreover, current research on the role of sphingosine kinases (SPHKs) and sphingosine-1-phosphate receptors (S1PRs) in T2DM is not fully understood, and the results obtained often differ. The aim of the present study was to evaluate the effect of metformin (anti-diabetic agent, MET) on the brain’s sphingosine-1-phosphate-related signaling and ultrastructure in diabetic mice. Our results revealed elevated mRNA levels of genes encoding sphingosine kinase 2 (SPHK2) and sphingosine-1-phosphate receptor 3 (S1PR3), which was accompanied by downregulation of sphingosine-1-phosphate receptor 1 (S1PR1) in the hippocampus of diabetic mice. Simultaneously, upregulation of genes encoding pro-inflammatory cytokines interleukin 6 (IL-6) and tumor necrosis factor α (TNF-α) was observed. Administration of MET significantly reversed changes in mRNA levels in the hippocampus and reduced Sphk2, Il6, and Tnf, with concomitant upregulation of S1pr1 gene expression. Ultrastructural analysis of diabetic mice hippocampus revealed morphological alterations in neurons, neuropil, and capillaries that were manifested as mitochondria swelling, blurred synaptic structure, and thickened basal membrane of capillaries. The use of MET partially reversed those changes. Our research emphasizes the important role of insulin sensitivity modulation by metformin in the regulation of SPHKs and S1PRs and inflammatory gene expression in a murine model of T2DM. Full article

Background/Objectives: Accurate blood glucose forecasting is critical for closed-loop insulin delivery systems to support effective disease management in people with type 1 diabetes (T1D). While long short-term memory (LSTM) neural networks have shown strong performance in glucose prediction tasks, the relative performance of individualized versus aggregated training remains underexplored. Methods: In this study, we compared LSTM models trained on individual-specific data to those trained on aggregated data from 25 T1D subjects using the HUPA UCM dataset. Results: Despite having access to substantially less training data, individualized models achieved comparable prediction accuracy to aggregated models, with mean root mean squared error across 25 subjects of 22.52 ± 6.38 mg/dL for the individualized models, 20.50 ± 5.66 mg/dL for the aggregated models, and Clarke error grid Zone A accuracy of 84.07 ± 6.66% vs. 85.09 ± 5.34%, respectively. Subject-level analyses revealed only modest differences between the two approaches, with some individuals benefiting more from personalized training. Conclusions: These findings suggest that accurate and clinically reliable glucose prediction is achievable using personalized models trained on limited individual data, with important implications for adaptive, on-device training, and privacy-preserving applications. Full article

Given that type 2 diabetes mellitus is common in several ciliopathies, the NME7 gene (non-metastatic cells 7), encoding a recognized member of the ciliome, was studied in connection with glucose metabolism. The aim was to find out whether the variability in the gene is associated with the response to administered glucose during the 3 h oral glucose tolerance test. The study included 1262 individuals with different levels of glucose tolerance. Glycemic curves were categorized according to their shape as monophasic, biphasic, triphasic, and more complex multiphasic. The analysis showed a significant association of five linked NME7 polymorphisms with the biphasic course of the glycemic curve, a shape that has been shown to be metabolically protective. Specifically, minor alleles of rs4656659 and rs2157597 in combination with wild-type alleles of rs10732287, rs4264046, and rs10800438 were more frequent within the biphasic category. Moreover, haplotype analysis confirmed higher insulin sensitivity in carriers of this specific haplotype. In conclusion, a cluster of five linked NME7 polymorphisms showed an association with a biphasic glycemic curve. Considering the health benefits of the biphasic curve in terms of glycoregulation and taking into account the demonstrated link of the NME7 haplotype with insulin sensitivity, variability in the NME7 gene represents another piece of the complex mosaic influencing healthy energy processing. Full article

Fluoride is a widespread environmental toxin that disrupts metabolic and endocrine functions, but its impact on pancreatic inflammation and hormone secretion remains unclear. This study examined how chronic fluoride exposure affects pancreatic inflammation and secretory function in rats. Pregnant Wistar rats received sodium fluoride (NaF) at 50 mg/L in drinking water during gestation and lactation. Male offspring continued exposure until 3 months old. Controls received fluoride-free water. Pancreatic tissue and serum were collected. Fluoride levels were measured potentiometrically. Eicosanoids were quantified by SPE and HPLC. Serum insulin, glucagon, and somatostatin were measured by ELISA. Histological and biochemical markers of inflammation and oxidative stress were assessed. Fluoride exposure did not lead to significant accumulation in the pancreas or serum. However, fluoride-exposed rats exhibited a significant decrease in serum insulin and somatostatin concentrations, while glucagon levels remained unchanged. Additionally, the pancreas of fluoride-treated animals showed markedly elevated levels of pro-inflammatory eicosanoids, including prostaglandin E2, leukotrienes A4 and B4, and HETE/HODE derivatives, indicating activation of cyclooxygenase and lipoxygenase pathways. Sustained low-dose fluoride exposure induced pancreatic inflammation and disrupted endocrine homeostasis in rats. These findings suggest that chronic fluoride intake may impair insulin secretion and promote pre-diabetic alterations, warranting further research. Full article

Background: Spexin is a neuropeptide involved in various physiological functions, including energy metabolism, appetite regulation, and weight loss. This study aimed to identify correlations between circulating spexin levels, obesity, and insulin resistance (IR) in Korean children and adolescents. Methods: We included 128 Korean children and adolescents in the study. Among them, 69 individuals (53.9%) were classified as obese, 43 (33.6%) were considered overweight, and 16 (12.5%) had a normal weight. We recorded participants’ anthropometric parameters, fasting biochemical parameters, and homeostasis model assessment for insulin resistance (HOMA-IR), and assessed their correlations with plasma spexin levels. Results: Plasma spexin levels were significantly lower in obese subjects than in controls (mean, 163.1 vs. 198.4 pg/mL; p = 0.01). Subjects with IR had lower spexin levels than those without IR (mean, 145.3 vs. 185.1 pg/mL; p < 0.001). Spexin levels were negatively correlated with the BMI SDS (r = −0.30; p < 0.001), systolic blood pressure (r = −0.33; p < 0.001), fasting insulin (r = −0.41; p < 0.001), HOMA-IR value (r = −0.41; p < 0.001), triglyceride (TG) level (r = −0.38; p < 0.001), and plasma leptin level (r = −0.26; p = 0.004). In multivariate analysis, HOMA-IR and TG levels were independently associated with plasma spexin levels (p < 0.001 for both). Mediation analyses suggest a potential bidirectional relationship between obesity-related reductions in circulating spexin and insulin resistance. Conclusions: Decreased circulating spexin levels were associated with obesity and IR among Korean children and adolescents. Our findings suggest a link between circulating spexin, obesity, and IR in this population. Full article

Spontaneous intracerebral hemorrhage (ICH) is a devastating form of stroke, disproportionately affecting older adults and is associated with high rates of mortality, functional dependence, and long-term cognitive decline. Aging profoundly alters the structure and function of the cerebral vasculature, predisposing the brain to both covert hemorrhage and the development of cerebral microbleeds (CMBs), small, often subclinical lesions that share common pathophysiological mechanisms with ICH. These mechanisms include endothelial dysfunction, impaired cerebral autoregulation, blood–brain barrier breakdown, vascular senescence, and chronic inflammation. Systemic factors such as age-related insulin-like growth factor 1 (IGF-1) deficiency further exacerbate microvascular vulnerability. CMBs and ICH represent distinct yet interconnected manifestations along a continuum of hemorrhagic small vessel disease, with growing recognition of their contribution to vascular cognitive impairment and dementia (VCID). Despite their increasing burden, older adults remain underrepresented in clinical trials, and few therapeutic approaches specifically target aging-related mechanisms. This review synthesizes current knowledge on the cellular, molecular, and systemic drivers of ICH and CMBs in aging, highlights diagnostic and therapeutic challenges, and outlines opportunities for age-sensitive prevention and individualized care strategies. Full article

Over the past century of research, it has become increasingly evident that glucagon should no longer be regarded solely as a counter-regulatory hormone to insulin. Its role in the pathophysiology of metabolic disorders—including diabetes, obesity, and non-alcoholic fatty liver disease—appears to be critical. Hyperglucagonemia is a common feature across several metabolic conditions, not only in adults but also in pediatric populations, suggesting that glucagon may represent both a pathogenic factor and a potential therapeutic target in metabolic disease. Accordingly, therapeutic strategies have been developed that either inhibit or enhance glucagon activity, depending on the clinical context, and some of these approaches are being applied in pediatric care as well. This review aims to provide a comprehensive overview of the pathophysiological role of glucagon in metabolic diseases, synthesizing recent findings that support novel hypotheses for the management and prevention of these conditions. Full article

Background and Objectives: Albuminuria is a key clinical marker for early detection of diabetic kidney disease (DKD) in individuals with type 2 diabetes mellitus (T2DM). The triglyceride-glucose (TyG) index, a simple surrogate of insulin resistance, has been increasingly investigated for its potential association with renal complications. This study aimed to evaluate the relationship between the TyG index and albuminuria in patients with T2DM and assess its clinical utility as an accessible metabolic marker reflecting early renal involvement. Materials and Methods: This retrospective cross-sectional study included 570 adult patients with confirmed T2DM who were followed at a tertiary internal medicine outpatient clinic between January and December 2024. Participants were classified as albuminuric or non-albuminuric based on spot urine albumin-to-creatinine ratio (ACR) values. Clinical and biochemical parameters were collected from medical records, and the TyG index was calculated as ln [fasting triglyceride (mg/dL) × fasting glucose (mg/dL)/2]. Logistic regression models were used to identify independent factors associated with albuminuria. ROC analysis was performed to evaluate the discriminatory accuracy of the TyG index. Results: The median TyG index was significantly higher in the albuminuric group compared to the non-albuminuric group (10.0 vs. 9.1; p < 0.001) and increased progressively with albuminuria severity (p < 0.001). In multivariate logistic regression analysis, elevated TyG index, hyperlipidemia, and reduced estimated glomerular filtration rate were independently associated with albuminuria. When evaluated as a continuous variable, the TyG index showed strong discriminatory ability (area under curve (AUC) = 0.949; 95% confidence interval (CI): 0.933–0.964). Using the optimal cut-off threshold of 9.6, the TyG index maintained high diagnostic performance (AUC = 0.870; 95% CI: 0.839–0.902; sensitivity 87.7%, specificity 86.3%). Subgroup analyses confirmed the robustness of this association across clinical and demographic variables. Conclusions: In this study, higher TyG index values were significantly associated with the presence and severity of albuminuria in individuals with T2DM. While causality cannot be inferred, the findings suggest that the TyG index may serve as a practical, cost-effective tool for identifying patients at increased risk for early diabetic kidney involvement. Prospective longitudinal studies are needed to confirm its predictive value and clinical applicability. Full article

Background/Objectives: The triglyceride–glucose index (TyG) and conicity index (CI) are markers of insulin resistance and abdominal obesity, respectively. However, their joint impact on stroke remains unclear. This study aimed to assess the association between the novel composite TyG–conicity index (TyG-CI = TyG × CI) and stroke risk. Methods: This prospective cohort study enrolled 8011 participants aged 45 years or older with no history of stroke at baseline, from the China Health and Retirement Longitudinal Study. Cox proportional hazards regression models were used to estimate the impact of TyG-CI on the risk of incident stroke. Restricted cubic spline regressions were applied to estimate possible nonlinear associations. The predictive performance was evaluated using the area under the receiver operating characteristic curve (AUC) and time-dependent Harrell ‘s C-index. Results: Over a mean follow-up of 8.36 years, 753 participants (9.4%) experienced stroke. After adjusting for potential confounders, compared with the lowest quartile, the adjusted HRs of incident stroke for participants with the highest quartile of TyG, CI, and TyG-CI were 1.36 (95%CI 1.05–1.76), 1.43 (95%CI 1.15–1.78), and 1.69 (95%CI 1.31–2.17), respectively. Restricted cubic spline analysis confirmed a linear relationship between TyG-CI and stroke risk (p for nonlinearity = 0.90). The AUC was highest for TyG-CI (0.594), exceeding TyG (0.575) and CI (0.575) with statistically significant differences (all p < 0.05). Conclusions: Elevated TyG-CI indicates a higher stroke risk, with superior predictive value compared to its components alone, providing a promising indicator that is simple, reliable, and inexpensive for identifying stroke risk in clinical practice. Full article