Search Results (2,713)

Diabetes mellitus is a growing health concern that causes numerous complications. Glycation produces advanced glycation end-products (AGEs), which promote diabetic complications. Targeting glycation is a strategy for combating the progression of diabetic complications. Pioglitazone enhances insulin sensitivity in patients with type 2 diabetes mellitus, but its impact on glycation remains unclear. This study aims to evaluate whether pioglitazone can inhibit glucose-induced glycation of human serum albumin (HSA), using in vitro assays and in silico tools. Pioglitazone inhibited >70% of early glycation products and >75% of AGEs. The treatment also reduced free lysine modification and improved biochemical markers, including carbonyl and free thiol levels. Pioglitazone exhibited moderate binding affinity for HSA, with a binding constant of 10⁴ M⁻¹. The interaction between pioglitazone and HSA was both spontaneous and entropically favourable. Molecular dynamics simulations revealed that the HSA–pioglitazone complex remained quite stable, with RMSF, RMSD, SASA, R_g, and HSA’s secondary structure showing minimal changes throughout the simulation. The overall binding energy for HSA–pioglitazone complex formation was −30.06 ± 0.31 kcal mol⁻¹, as obtained from MD simulations. The findings suggest that pioglitazone likely interacts with glycation-prone regions of HSA, as indicated by spectroscopic and docking analyses, and contributes to the reduction of glycation. Full article

Background: Postmenopausal osteoporosis is a common metabolic bone disorder characterized by decreased bone mass and microstructural deterioration, often accompanied by increased bone marrow adiposity and systemic fat accumulation. Kun-Ling Wan Formula (KLW) is a compound Chinese medicine clinically used for gynecological disorders, though its effects on postmenopausal osteoporosis and associated fat accumulation remain unclear. Distinct from previous herbal formulation studies that primarily focused on bone outcomes, our study uniquely integrates bone protection, marrow adiposity reduction, systemic metabolic improvement, and multi-omics mechanistic dissection in a high-fat diet-fed ovariectomized mouse model. Methods: KLW chemical composition was analyzed by UPLC-Q-TOF/MS. Ovariectomized (OVX) C57BL/6J mice fed high-fat or normal diet were treated with KLW at clinically equivalent or double doses, with estrogen and active compounds as controls. Bone microstructure was assessed by micro-CT, bone marrow fat by MRI-PDFF, and metabolism by OGTT, ITT, and metabolic cages. Network pharmacology, proteomics, molecular docking, and dynamics simulations identified core targets. C3H10T1/2 cells were used to assess osteogenic/adipogenic differentiation and mTOR pathway activation. Results: Twelve compounds were identified in KLW. In OVX mice, KLW significantly improved bone mineral density and trabecular microstructure, reduced adiposity and bone marrow fat, and enhanced glucose tolerance and insulin sensitivity. In vitro, KLW promoted osteogenesis and suppressed adipogenesis in C3H10T1/2 cells. Integrative analyses identified mTOR as a central target, with chrysophanol, pyrogallol, and apigenin showing high-affinity binding. KLW inhibited mTOR/S6K phosphorylation during differentiation, an effect reversible by leucine. Conclusions: KLW ameliorates osteoporosis and reduces fat accumulation in OVX mice by shifting mesenchymal stem cell differentiation toward osteogenesis via mTOR pathway modulation. Full article

Background/Objectives: Adolescence is a critical developmental period during which dietary quality and physical activity (PA) may influence insulin sensitivity and pancreatic β-cell function. This observational cohort study investigated how adherence to the Mediterranean diet (MedDiet) and participation in structured physical activity (PA) relate to metabolic changes over six months in Spanish male adolescents. Methods: A total of 78 participants (median age 11 years; IQR 10–12) were followed in a school-based study (2020–2021) and categorized by MedDiet adherence using the KIDMED index into medium (M) and high (H) groups. Metabolic health was assessed at baseline (T1) and after six months (T2) using lipid profiles, glucose, insulin, and several indirect indices of insulin resistance and β-cell function, including HOMA-IR, QUICKI, and SPINA indices. Statistical analyses included correlations and adjusted linear models, with false discovery rate correction applied. Results: At baseline, higher MedDiet adherence was associated with lower fasting insulin and improved insulin resistance markers (p ≤ 0.002). Over six months, adolescents with high adherence showed more favorable changes in insulin sensitivity (fasting insulin, HOMA-IR, QUICKI) and β-cell function (SPINA indices), with results remaining significant after correction (all pFDR < 0.05). LDL cholesterol levels also improved more markedly in participants combining high MedDiet adherence with structured PA (pFDR < 0.001). In contrast, triglycerides and TG-related indices increased across all groups, without differences between them (pFDR < 0.001). Conclusions: High MedDiet adherence combined with structured PA was associated with more favorable trajectories in insulin sensitivity, attenuated β-cell secretory demand, and a more favorable LDL-c profile. These findings support integrated lifestyle approaches for early cardiometabolic prevention in male adolescence. Full article

Background/Objectives: Type 2 diabetes mellitus (T2-DM) is a continuing national and global health challenge. Retinoic acid (RA), the major transcription-regulating ligand, plays a critical role in energy metabolism, and pancreatic β-cell homeostasis. However, human data linking circulating RA levels to T2-DM and its clinical outcomes are sparse and inconsistent. In this ethically approved cross-sectional study of consented hospital-diagnosed adult T2-DM patients (n = 292) and matched healthy controls (n = 64), variation in plasma RA levels and its relationship with disease and patient characteristics were investigated. Methods: RA concentrations assayed via specific ELISA were related to glycemic control indices [fasting blood glucose (FBG) and HbA1c], the triglyceride–glucose ratio for insulin resistance (TyG-IR), treatment modalities, and complications derived from patients’ medical records. Results: RA concentrations were substantially lower in patients with T2-DM (mean ± SD 2.63 ± 1.54 ng/mL) than in controls (5.21 ± 4.3 ng/mL; p < 0.001). Within the diabetic cohort, RA was inversely correlated with indices of glycemic dysregulation and insulin resistance. Plasma RA exhibited strong discriminatory performance for distinguishing diabetic patients from healthy adults. Its AUC is 0.870 (p < 0.0001 and 95% CI = 0.832–0.902) with a sensitivity of 79.7% and a specificity of 81.3%, at an optimal cutoff of ≤3.061 ng/mL. Conclusions: Circulating RA is associated with metabolic perturbations that define T2-DM, and therefore is promising as a clinically useful biomarker. It may reflect pathophysiological processes linking nutrient signaling, energy handling and β-cell function in T2-DM that merit further evaluation. Full article

Background: The triglyceride–glucose (TyG) index, a surrogate marker of insulin resistance, has been increasingly associated with adverse cardiometabolic outcomes. However, its relationship with acute kidney injury (AKI) across clinical settings has not been comprehensively synthesized. We performed a systematic review and meta-analysis to evaluate the association between the TyG index and AKI risk. Methods: PubMed, Embase, and Web of Science were searched through February 2026 for observational studies reporting adjusted associations between TyG and AKI. Random-effects models were used to pool categorical and continuous effect estimates. Dose–response analyses and subgroup assessments were conducted to explore consistency. Diagnostic performance was summarized when available. Results: Thirty studies involving 518,677 participants were included. Compared with the lowest-TyG category, the highest-TyG category was associated with significantly increased AKI risk (pooled OR = 1.95, 95% CI 1.66–2.28; I² = 72.7%). Associations were most consistently observed in cardiovascular disease cohorts (pooled OR = 1.86, 95% CI 1.44–2.40) and remained directionally similar across other clinical settings without significant subgroup interactions. Each 1-unit increment in TyG index was associated with higher AKI risk (OR = 1.48, 95% CI 1.30–1.69), and time-to-event analyses yielded concordant results (HR = 1.38, 95% CI 1.14–1.65). A significant non-linear dose–response association was observed (p < 0.001). The TyG index showed moderate discrimination (AUC = 0.74), with findings remaining robust in sensitivity analyses. Conclusions: Current evidence supports TyG primarily as a complementary metabolic risk marker rather than a substitute for established AKI diagnostic or prediction tools. TyG may serve as a practical marker for metabolic risk stratification in patients at risk of AKI. Full article

Growing evidence suggests that insulin resistance (IR) might be a core, unifying mechanism linking various established risk factors for bladder cancer (BC). While factors like smoking, central obesity, sedentary lifestyle, and high-fat diets are known to increase BC risk, a common thread among them is their role in driving IR due to chronic hyperinsulinemia. Hyperinsulinemia promotes BC development in several ways. It acts as a potent growth factor, stimulating the proliferation and inhibiting the programmed cell death of malignant cells by activating the insulin/IGF signaling pathway. Furthermore, IR is closely associated with chronic low-grade inflammation and oxidative stress, both of which contribute to a pro-tumorigenic microenvironment. This convergence of growth-promoting and inflammatory signals highlights the central role of IR. While more research is needed to fully elucidate these complex interactions, the available data suggest that metabolic interventions aimed at improving insulin sensitivity could be a valuable, modifiable strategy for BC prevention. Full article

Background: Supplementing aquafeeds with emulsifiers can enhance lipid utilization, yet the physiological effects of lysolecithin, derived from enzymatic lecithin conversion, remain under-explored. Objectives: This study examined the effects of lysolecithin supplementation on hepatopancreatic transcriptome and gut microbiota in largemouth bass (Micropterus salmoides) fed stearin-based high-lipid diets. Methods: Two diets were formulated: a control containing 130 g kg⁻¹ stearin fish oil (SO), and in the experimental diet (SL), 3.1 g kg⁻¹ rapeseed oil was replaced with 3.1 g kg⁻¹ lysolecithin oil. Each diet was fed to three replicate groups for 56 days. Hepatopancreas and distal intestine were sampled for transcriptome profiling, and gut microbiota were characterized at 28 and 56 days. Results: Lysolecithin supplementation resulted in 424 differentially expressed genes compared with the control (322 up- and 102 downregulated). KEGG enrichment indicated major effects on lipid metabolic processes, notably activation of the PI3K-AKT signaling pathway, enhanced adipocyte lipolysis, and modulation of adipocytokine signaling, suggesting improved insulin sensitivity and lipid mobilization. Histological analysis showed mild distal intestinal inflammation in the SO group. Gut microbiota composition shifted over time; lysolecithin increased the relative abundance of Cetobacterium and reduced potential opportunistic taxa compared with the control. Conclusions: Overall, dietary inclusion of lysolecithin improved lipid utilization in largemouth bass, likely by enhancing lipid metabolism and promoting beneficial gut microbial profiles. These findings support lysolecithin as a promising feed additive for optimizing high-lipid aquafeeds. Full article

Limosilactobacillus fermentum SHY0006 was isolated from Miao sour soup, a traditional fermented food from Guizhou, China, and systematically evaluated for its safety, metabolic functionality, and stress adaptability using phenotypic assays combined with whole-genome sequencing. SHY0006 exhibited no hemolytic activity and harbored no detectable virulence-associated or acquired antibiotic resistance genes, supporting its safety profile. Functionally, SHY0006 improved lipid metabolism and insulin resistance in both cell and animal models. In hyperlipidemic mice, hepatic triglyceride accumulation was markedly reduced, accompanied by favorable modulation of serum lipid parameters, including LDL-C, HDL-C, and free fatty acids. In diabetic mice, the strain improved insulin tolerance test (ITT) performance, indicating enhanced systemic insulin sensitivity. Whole-genome analysis revealed complete biosynthetic pathways for riboflavin and folate, along with extensive carbohydrate utilization capacity, highlighting its metabolic versatility. In addition, SHY0006 exhibited strong tolerance to environmental stress, supporting its potential viability in food matrices and gastrointestinal conditions. Collectively, these findings suggest that SHY0006 is a safe and metabolically versatile probiotic candidate with potential applications in functional foods targeting metabolic health. Full article

Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired insulin secretion, and curcumin—a polyphenolic compound derived from Curcuma longa—has shown potential anti-inflammatory and antioxidant effects. This randomized, double-blind, placebo-controlled trial evaluated the effects of 1500 mg/day curcumin supplementation for 12 months in 114 adults with T2DM, with assessments including fasting plasma glucose (FPG), glycated hemoglobin (HbA1c), insulin resistance (HOMA-IR), inflammatory cytokines (IL-6, IL-1β, TNF-α), high-sensitivity C-reactive protein (hs-CRP), neutrophil-to-lymphocyte ratio (NLR), antioxidant markers (SOD, GPx, TAS), and malondialdehyde (MDA). Curcumin supplementation was associated with significant reductions in pro-inflammatory cytokines (p < 0.001), hs-CRP and NLR (p < 0.05), and with improved antioxidant status as shown by increased TAS, SOD, and GPx together with reduced MDA levels (p < 0.001). Additionally, improvements in metabolic parameters were observed, including lower FPG (112.0 mg/dL vs. 134.5 mg/dL; p < 0.001), HbA1c (6.10% vs. 6.40%; p < 0.05), and HOMA-IR (4.88 vs. 6.71; p < 0.001). Overall, the findings suggest that long-term curcumin supplementation may contribute to improved inflammatory, antioxidant, and glycemic profiles in obese individuals with T2DM; however, further multi-center studies are needed to confirm these observations and clarify their clinical relevance. Full article

Postprandial variability in glucose and protein levels is one of the elements of insulin resistance (IR) and prediabetes, which is an area precursor to type 2 diabetes mellitus (DM). The objective of the study was a comprehensive proteomic analysis according to glucose tolerance in the general population who did not self-report DM or other diseases. We used Olink^® Reveal, a novel, high-throughput platform by Olink Proteomics based on their Proximity Extension Assay (PEA), to identify levels of 1034 circulating proteins in small volumes (4 µL) of plasma samples. The study enrolled 508 participants (mean age 52 ± 10.5 years, 47.2% men) from the population-based study, Bialystok PLUS Polish Longitudinal University Study. The study population was categorized according to glucose metabolism in comparison to impaired fasting blood glucose (IFG), impaired glucose tolerance (IGT), and newly diagnosed DM. Analysis of variance (ANOVA) adjusted for age, weight, fat mass, lean mass, and body mass index (BMI), identified 19 proteins significantly associated with categories of glucose tolerance. Of the five markers with the greatest ability to distinguish newly diagnosed diabetes from non-diabetic participants, paralemmin 2 performed best (AUC = 0.81; 77% sensitivity, 75% specificity), whereas furin was the most accurate for detecting any abnormal glucose regulation (AUC = 0.69). A linear regression model adjusted for the same confounding factors showed statistically significant associations between Hb_A1c levels and 37 proteins. Our findings highlight multiple proteins with significantly different levels across categories of glucose tolerance, especially between the healthy controls and the group with newly diagnosed DM. The consistent patterns of protein level differences, independent of body composition, suggest potential involvement in the progression of glucose metabolism disturbances and provide unique insights into pathomechanisms. These findings identify PALM2, FURIN, PDZK1, ACAA1, and IL18R1 as potential biomarkers of early dysglycemia. Full article

The global rise in obesity and metabolic disorders has intensified interest in dietary bioactives capable of improving glycemic control and metabolic health. Inositols, particularly D-pinitol, have emerged as insulin-sensitizing cyclitols with potential metabolic relevance. Carob (Ceratonia siliqua L.), one of the richest natural sources of D-pinitol, represents a promising nutritional matrix for metabolic regulation. This narrative review critically evaluates current evidence on the role of D-pinitol in glucose homeostasis and energy balance, integrating data from chemical characterization studies, mechanistic research, preclinical models, and human clinical trials assessing purified D-pinitol and D-pinitol–rich preparations, particularly from carob-derived sources. Available evidence suggests that D-pinitol may enhance insulin signaling efficiency, primarily through PI3K/Akt-dependent pathways, modulate hepatic metabolic flexibility, and influence endocrine balance without acting as a classical hypoglycemic agent. Preclinical models consistently report improvements in insulin sensitivity, lipid handling, oxidative stress parameters, and tissue-specific metabolic adaptations. In contrast, clinical trials in healthy, prediabetic, and type 2 diabetic individuals show more heterogeneous outcomes, including attenuation of postprandial glycemia, reductions in circulating insulin and HOMA-IR, and modest improvements in lipid and inflammatory markers. Overall, carob-derived D-pinitol appears to act as a potential insulin-sensitizing metabolic modulator with context-dependent effects influenced by metabolic phenotype and food matrix composition. However, available data remains limited and heterogeneous, with most data derived from preclinical studies and relatively small clinical trials. These findings should therefore be interpreted with caution. Larger, longer-term randomized controlled trials using standardized preparations are required to establish clinical relevance and translational applicability. Notably, the contribution of other bioactive components within the carob matrix cannot be excluded. Full article

Objectives: The objectives of this review are to explore the effects of various nutrition and exercise lifestyle interventions on pregnancy outcomes in individuals with, or at risk of, gestational diabetes mellitus (GDM), as well as to examine whether interventions that are culturally and/or religiously sensitive influence clinical and behavioural outcomes. Methods: This study was conducted as a narrative review. PRISMA was used solely as a reporting guide to enhance transparency in the search and study selection process. PubMed/MEDLINE, CINAHL, and Scopus were searched for studies published up to November 2025. Intervention-based studies evaluating nutrition, physical activity, or combined lifestyle interventions targeting either GDM incidence, insulin use, or glycemic outcomes were included. Forty-three studies met eligibility criteria. Study designs consisted primarily of randomized controlled trials (RCTs) with one case–control and one quasi-experimental design trial. Results: Combined lifestyle interventions generally showed the most consistent improvements in glycemic control; however, findings were not uniform across all studies, and reporting on insulin outcomes was limited. The Mediterranean, low-glycemic index (LGI) and DASH diets, along with supervised, prenatal exercise programs with low–moderate intensity, delivered at least three times per week, were effective in managing GDM. Regarding culturally or religiously sensitive interventions, only one study was identified. Conclusions: Lifestyle interventions may improve glycemic outcomes in GDM; however, further high-quality research is needed, particularly studies incorporating culturally and religiously sensitive approaches and improved reporting of insulin-related outcomes. Full article

Background: Sex-related differences in insulin sensitivity during adolescence remain incompletely understood, particularly in the context of obesity. Whether these differences reflect variations in basal insulin resistance or dynamic insulin responses remains unclear. Objective: To investigate sex differences in glucose and insulin responses during the oral glucose tolerance test (OGTT) and to explore mechanisms underlying potential dissociation between glycemic and insulinemic profiles. Methods: A cross-sectional analysis of 753 adolescents with obesity who underwent a standard oral glucose tolerance test (OGTT). Plasma glucose and insulin were measured at fasting and at 30, 60, 90, and 120 min. Mixed-effects models were used to examine glucose and insulin trajectories over time, including sex-by-time interactions, and to adjust for body mass index standard deviation score (BMI_SDS), pubertal stage (Tanner), metabolic syndrome (MetS), and body composition (resistance index). Multiple linear regression models were fitted to assess associations of sex with HOMA-IR, HOMA-β, total area under the curve (AUC), and phase-specific insulin AUCs. Results: Glucose trajectories during OGTT were similar between sexes, with no significant sex or sex-by-time interaction effects after adjustment. In contrast, insulin trajectories differed significantly by sex (sex-by-time interaction β = −0.10, p < 0.001). Boys exhibited higher baseline insulin levels and greater total insulin exposure (β = −11.2, p < 0.001), independent of BMI_SDS, pubertal stage, MetS, and body composition. Sex differences were sustained across all OGTT phases. HOMA-IR did not differ by sex, whereas HOMA-β showed a sex-related difference. BMI was positively associated with both basal and dynamic insulin measures. Conclusions: In adolescents with obesity, sex differences are characterized by altered dynamic insulin responses rather than differences in glycemic control. Boys exhibit greater compensatory insulin exposure during glucose challenge, independent of BMI-based adiposity, BIA-derived body composition and pubertal development. Full article

The global rise in obesity and cardiometabolic disease represents a major public health concern and contributes significantly to cardiovascular morbidity and mortality. Contemporary Western dietary patterns and excess adiposity are strongly associated with atherosclerotic cardiovascular disease. Although pharmacologic therapies have expanded, lifestyle interventions remain the cornerstone of prevention and management. However, identifying sustainable and effective dietary approaches continues to be challenging given the wide range of available nutrition regimens. Intermittent fasting (IF) has emerged as a promising strategy for weight reduction and metabolic improvement. In this article, we review the physiological effects of IF, including metabolic switching, ketosis, and improvements in insulin sensitivity and inflammatory regulation. We also evaluate clinical evidence regarding the impact on cardiovascular risk, as well as its safety and tolerability. We examine the hormonal responses to IF based on sex. While early studies raised concerns regarding potential reproductive and endocrine disturbances, recent data suggest beneficial effects in both males and females. IF may modestly reduce testosterone in men without impairing muscle mass or strength and may improve metabolic and reproductive outcomes in women, particularly those with hyperandrogenic conditions such as polycystic ovarian syndrome, with favorable effects also observed in postmenopausal women, especially when combined with physical activity. Full article

Background: We aimed to study the association between accelerometer-measured physical activity and metabolic markers of diabetes in a nationwide representative sample of U.S. adults. Methods: This cross-sectional analysis included 1259 adults aged ≥18 years from the 2003–2004 National Health and Nutrition Examination Survey (NHANES), the only cycle incorporating objective accelerometry. Physical activity was assessed using hip-worn accelerometers, with moderate-to-vigorous physical activity (MVPA) and sedentary time derived from validated count thresholds. Metabolic outcomes included fasting glucose, fasting insulin, glycated hemoglobin (HbA1c), and insulin resistance estimated by the Homeostatic Model Assessment (HOMA-IR). Survey-weighted linear regression models accounting for the complex sampling design were applied, with sequential adjustment for demographic, socioeconomic, anthropometric, and behavioral covariates. Sensitivity analyses tested alternative MVPA thresholds and wear-time criteria. Results: In unadjusted models, higher MVPA was inversely linked with fasting glucose and insulin concentrations; but, these associations were attenuated after full multivariable adjustment. In contrast, MVPA established a constant inverse association with insulin resistance. Higher MVPA was connected with lower HOMA-IR values, and this relationship remained statistically significant in fully adjusted models and across all sensitivity analyses (all p < 0.001). Associations between sedentary time and metabolic markers were non-sustainable after multivariable adjustment. No significant effect modification by sex was detected. Conclusions: Objectively measured moderate-to-vigorous physical activity is independently linked with lower insulin resistance in U.S. adults. These results emphasize the value of accelerometer-based assessments for identifying early metabolic risk and reinforce physical activity promotion as a key strategy for improving insulin sensitivity. Full article