Search Results (1,712)

Background: Alcohol-associated liver disease (AALD) represents significant health burdens worldwide. This study aims to provide a comprehensive overview of the AALD outcomes that were incompletely understood. Methods: The current study utilizes data from the National Health and Nutrition and Examination Survey (NHANES) from 2011–2020, using a stratified, multistage probability cluster design. AALD in the NHANES was defined using clinical laboratory data and self-reported alcohol use, among which fibrosis-4 score of >2.67. Analysis is conducted using weighted, logistic, and Cox linear regression. Results: The initial sample included 23,206 participants aged 20 and older, with recorded cardiovascular status and AST/ALT levels. Participants reporting AALD had a higher percentage of college degrees (p < 0.001) and were more likely to be daily smokers. Asians exhibited the highest rates of AALD compared to other demographics (p < 0.001). The prevalence in private insurance is significantly greater than Medicaid, but the usage trends have been increasing in Medicaid. The trends of advanced fibrosis have been increasing in blacks and Asians, while they have been decreasing among whites and Mexicans. Those with AALD also had higher mean systolic and diastolic blood pressure, as well as elevated fasting glucose levels (p < 0.001). The mortality rate among AALD participants with heart diseases was 25%, compared to 3% among those without (p < 0.001). After adjusting for potential confounding variables, no statistically significant associations were found between AALD status and HF or CAD. However, a clinically significant increase in the odds of stroke was observed within the AALD group (p < 0.001). Conclusions: Our findings indicate Asians have the highest rates of AALD. The trends of advanced fibrosis have been increasing in blacks and Asians. There is an increased prevalence of AALD with heart diseases and a significant increase in mortality with stroke. Full article

Blood flow restriction training (BFRT) offers notable advantages, including simplicity and time efficiency. However, no meta-analysis has yet comprehensively evaluated its effects on glucose and lipid metabolism in overweight or obese adults. This meta-analysis examines the potential efficacy of BFRT in improving glycemic and lipid control in overweight/obese adults. The literature was searched in six databases, with the search period up to 31 March 2025. A total of eight randomized controlled trials involving 267 participants were identified. Data were analyzed using Stata 18.0 and RevMan 5.4 with random effects models. Outcomes included fasting blood glucose (FBG), homeostasis model assessment of insulin resistance (HOMA-IR), and lipid profiles, and risk of bias and publication bias (Egger’s test) were assessed. BFRT significantly reduced FBG (Hedges’ g = −1.13, 95% CI: −1.65 to −0.62, p < 0.01; I² = 66.34%) and HOMA-IR (Hedges’ g = −0.98, 95% CI: −1.35 to −0.61, p < 0.01; I² = 17.33%) compared with the controls. However, no significant changes were observed in lipid profiles. Our analysis demonstrates that BFRT exhibits the favorable effect of improving glucose metabolism in overweight/obese adults; however, current evidence does not support significant advantages of BFRT for lipid metabolism improvement. Full article

Background: The consumption of coffee has been widely debated regarding its effects on health. This study aims to analyze the correlations between daily coffee intake and sleep, blood pressure, anthropometric measurements, and biochemical markers in individuals with type 2 diabetes (T2D) and hypertension over a 12-month period. Methods: An observational study was conducted with 40 participants with T2D and hypertension, comprising 20 females and 20 males. Participants were monitored for their daily coffee consumption over a 12-month period, being assessed every 3 months. Linear regression was utilized to assess interactions and relationships between variables, providing insights into potential predictive associations. Additionally, correlation analysis was performed using Pearson’s and Spearman’s tests to evaluate the strength and direction of linear and non-linear relationships. Statistical significance was set at p < 0.05. Results: Significant changes were observed in fasting blood glucose (FBG), glycated hemoglobin (HbA1c), body weight, body mass index, sleep duration, nocturnal awakenings, and waist-to-hip ratio (p < 0.05) over the 12-month study in both sexes. No significant differences were noted in the remaining parameters (p > 0.05). The coffee consumed by the participants was of the “traditional type” and contained sugar (2 g per cup) for 100% of the participants. An intake of 4.17 ± 0.360 cups per day was found at baseline and 5.41 ± 0.316 cups at 12 months (p > 0.05). Regarding correlation analysis, a higher coffee intake was significantly associated with shorter sleep duration in women (r = −0.731; p = 0.037). Conversely, greater coffee consumption correlated with lower LDL cholesterol (LDL-C) levels in women (r = −0.820; p = 0.044). Additionally, a longer sleep duration was linked to lower FBG (r = −0.841; p = 0.031), HbA1c (r = −0.831; p = 0.037), and LDL-C levels in women (r = −0.713; p = 0.050). No significant correlations were observed for the other parameters in both sexes (p > 0.05). Conclusions: In women, coffee consumption may negatively affect sleep duration while potentially offering beneficial effects on LDL-C levels, even when sweetened with sugar. Additionally, a longer sleep duration in women appears to be associated with improvements in FBG, HbA1c, and LDL-C. These correlations emphasize the importance of a balanced approach to coffee consumption, weighing both its potential health benefits and drawbacks in postmenopausal women. However, since this study does not establish causality, further randomized clinical trials are warranted to investigate the underlying mechanisms and long-term implications—particularly in the context of T2D and hypertension. Full article

(1) Background: Epidemiological studies link ozone (O₃) exposure to diabetes risk, but mechanisms and early biomarkers remain unclear. (2) Methods: Female mice exposed to 0.5/1.0 ppm O₃ were assessed for glucose tolerance and HOMA (homeostasis model assessment) index. Genes related to impaired glucose tolerance and insulin resistance were screened through the Comparative Toxicogenomics Database (CTD), and verified using quantitative real-time PCR. In addition, liver histopathological observations and the determination of basic biochemical indicators were conducted, and targeted metabolomics analysis was performed on the liver to verify glycogen levels and gene expression. In vitro validation was conducted with HepG2 and Min6 cell lines. (3) Results: Fasting blood glucose and insulin resistance were elevated following O₃ exposure. Given that the liver plays a critical role in glucose metabolism, we further investigated hepatocyte apoptosis and alterations in glycogen metabolism, including reduced glycogen levels and genetic dysregulation. Metabolomics analysis revealed abnormalities in fructose metabolism and glycogen synthesis in the livers of the O₃-exposed group. In vitro studies demonstrated that oxidative stress enhances both liver cell apoptosis and insulin resistance in pancreatic islet β cells. (4) Conclusions: O₃ triggers prediabetes symptoms via hepatic metabolic dysfunction and hepatocyte apoptosis. The identified metabolites and genes offer potential as early biomarkers and therapeutic targets. Full article

After the first release of synthalin B (dodecamethylenbiguanide) in 1928 and its later retraction in the 1940s in Germany, the retraction of phenformin (N-Phenethylbiguanide) and of Buformin in the USA (but not outside) because of the lethal complication of acidosis seemed to have put an end to the era of the biguanides as oral antidiabetics. The strongly hygroscopic metformin (1-1-dimethylbiguanide), first synthesized 1922 and resuscitated as an oral antidiabetic (type 2 of the elderly) compound first released in 1959 in France and in other European countries, was used in the first large multicenter prospective long-term trial in England in the UKPDS (1977–1997). It was then released in the USA after a short-term prospective trial in healthy overweight “young” type 2 diabetics (mean age 53 years) in 1995 for oral treatment of type 2 diabetes. It was, however, prescribed to mostly multimorbid older patients (above 60–65 years of age). Metformin is now the most used oral drug for type 2 diabetes worldwide. While intravenous administration of biguanides does not have any glucose-lowering effect, their oral administration leads to enormous increase in their intestinal concentration (up to 300-fold compared to that measured in the blood), to reduced absorption of glucose from the diet, to increased excretion of glucose through the stool, and to decrease in insulin serum level through increased hepatic uptake and decreased production. Intravenously injected F18-labeled glucose in metformin-treated type 2 diabetics accumulates in the small and even more in the large intestine. The densitometry picture observed in metformin-treated overweight diabetics is like that observed in patients after bowel-cleansing or chronically taking different types of laxatives, where the accumulated radioactivity can even reach values observed in colon cancer. The glucose-lowering mechanism of action of metformin is therefore not only due to inhibition of glucose uptake in the small intestine but also to “attraction” of glucose from the hepatocyte into the intestine, possibly through the insulin-mediated uptake in the hepatocyte and its secretion into the bile. Furthermore, these compounds have also a diuretic effect (loss of sodium and water in the urine) Acute gastrointestinal side effects accompanied by fluid loss often lead to the drugs’ dose reduction and strongly limit adherence to therapy. Main long-term consequences are “chronic” dehydration, deficiency of vitamin B12 and of iron, and, as observed for all the biguanides, to “chronic” increase in fasting and postprandial lactate plasma level as a laboratory marker of a clinical condition characterized by hypotension, oliguria, adynamia, and evident lactic acidosis. Metformin is not different from the other biguanides: synthalin B, buformin, and phenformin. The mechanism of action of the biguanides as antihyperglycemic substances and their side effects are comparable if not even stronger (abdominal pain, nausea, vomiting, diarrhea, fluid loss) to those of laxatives. Full article

Objectives: To determine whether plasma concentrations of anandamide (AEA) and 2-arachidonoylglycerol (2-AG) are elevated in adults with prediabetes, we explored their association with tissue advanced glycation end-products (AGEs) and assessed the influence of Mediterranean diet adherence. Methods: This cross-sectional single-centre study included 92 adults with prediabetes and 86 age-/sex-matched normoglycaemic controls. Anthropometry, blood pressure, biochemical indices, and skin autofluorescence-derived AGEs were measured. Serum AEA and 2-AG were quantified by competitive ELISA, while Mediterranean diet adherence was assessed using the Mediterranean Diet Serving Score (MDSS). Results: Prediabetes was associated with higher AEA (p = 0.004) but not 2-AG (p = 0.520). Also, AEA correlated positively with AGE values (r = 0.36; p = 0.002) and increased across AGE-based cardiovascular risk categories. In multivariable models, both prediabetes status and AGE burden independently predicted AEA. Participants achieving MDSS ≥ 14 exhibited lower AEA (p = 0.038); 2-AG remained unaffected. Finally, the multivariable analysis confirmed that both prediabetes (β = 11.9; p = 0.005) and AGE values (β = 0.25; p = 0.003) are positively associated with plasma AEA levels, independent of age, sex, BMI, and fasting plasma glucose levels. Conclusions: Circulating AEA, but not 2-AG, is elevated in prediabetes and independently linked to cumulative AGE burden, suggesting early endocannabinoid activation contributes to cardiometabolic risk. High adherence to a Mediterranean diet may mitigate this dysregulation. Full article

Background: Chronic stress in childhood and adolescence leads to excessive cortisol secretion, adipokines production and obesity with all the negative mental and physical effects on the health of individuals and adulthood. Objectives: The aim of the present non-randomized controlled trial was to investigate the effect of a stress management protocol with diaphragmatic breathing (DB) and physiotherapy exercise on stress, body composition, cardiorespiratory and metabolic markers of children and adolescents with morbid obesity. Methods: The study included 31 children and adolescents (5–18 years old) with morbid obesity (22 in the intervention arm and 9 controls). All participants completed anxiety questionnaires and a self-perception scale. Forced expiratory volume in the first second (FEV1), forced vital capacity (FVC), blood pressure (BP) and SpO₂ were measured. Fasting glucose, uric acid, triglycerides, HbA1c, (AST/SGOT), (ALT/SGPT), HDL, LDL, insulin, ACTH, cortisol, HOMA-IR, 17-OH, S-DHEA, SHBG were assessed, and anthropometric measurements were also performed. Results: In the intervention group, 4 months after the treatment, an improvement was noted in the BMI, BMI z-score, waist-to-height ratio, FEV1, SpO₂, pulse and systolic BP. HDL increased, ALT/SGPT and insulin resistance improved. Positive changes were observed in temporary and permanent stress and self-esteem of children in the intervention group, including anxiety, self-perception, physical appearance, etc. Conclusions: A combined exercise and DB protocol has a positive effect on stress, by improving body composition, reducing insulin resistance, and ameliorating physical and mental health and quality of life of pediatric patients with morbid obesity. Full article

Background and Objectives: This study investigated whether the interaction between heavy alcohol use and depression amplifies the risk of hyperglycemia in psychiatric patients. Materials and Methods: We conducted a cross-sectional study on 172 patients (aged 18–65) hospitalized at the “Elisabeta Doamna” Clinical Psychiatric Hospital, Romania. The data included fasting blood glucose, gamma-glutamyl transferase (GGT), Beck Depression Inventory (BDI), and Alcohol Use Disorders Identification Test (AUDIT) scores. Results: Moderate positive correlations were observed between depression scores and blood glucose (r = 0.44) and between alcohol consumption and blood glucose (r = 0.43). The interaction term (BDI × AUDIT) was statistically significant in multiple regression (β = 0.012, p = 0.001), and the model explained 39.1% of glucose variability. Logistic regression analysis revealed that neither high alcohol consumption (OR = 1.38, p = 0.441) nor severe depression alone (OR = 1.30, p = 0.582) were significantly associated with hyperglycemia. However, their interaction demonstrated a strong and statistically significant effect (OR = 19.3, 95% CI: 3.22–115.81, p = 0.001). The prevalence of hyperglycemia reached 95.8% in patients with both risk factors. Conclusions: The combined presence of high alcohol consumption and severe depression significantly increases the risk of hyperglycemia. These findings highlight the importance of integrated screening and interventions in psychiatric settings. Full article

Background: BDE-47, a pervasive environmental pollutant detected in >90% of human serum samples, is increasingly linked to metabolic disorders. This study investigates the specific impact of BDE-47 exposure on the gut microbiota in prediabetic mice and evaluates the efficacy of therapeutic interventions in mitigating these effects. Objectives: To determine whether BDE-47 exposure induces diabetogenic dysbiosis in prediabetic mice and to assess whether dietary interventions, such as grape exosomes and an antioxidant cocktail, can restore a healthy microbiota composition and mitigate diabetes risk. Methods: In this study, a prediabetic mouse model was established in 54 male SPF-grade C57BL/6J mice through a combination of high-sugar and high-fat diet feeding with streptozotocin injection. Oral glucose tolerance tests (OGTT) were conducted on day 7 and day 21 post-modeling to assess the establishment of the model. The criteria for successful model induction were defined as fasting blood glucose levels below 7.8 mmol/L and 2 h postprandial glucose levels between 7.8 and 11.1 mmol/L. Following confirmation of model success, a 3 × 3 factorial design was applied to allocate the experimental animals into groups based on two independent factors: BDE-47 exposure and exosome intervention. The BDE-47 exposure factor consisted of three dose levels—none, high-dose, and medium-dose—while the exosome intervention factor included three modalities—none, Antioxidant Nutrients Intervention, and Grape Exosomes Intervention. Fresh fecal samples were collected from mice two days prior to sacrifice. Cecal contents and segments of the small intestine were collected and transferred into 1.5 mL cryotubes. All sequences were clustered into operational taxonomic units (OTUs) based on defined similarity thresholds. To compare means across multiple groups, a two-way analysis of variance (ANOVA) was employed. The significance level was predefined at α = 0.05, and p-values < 0.05 were considered statistically significant. Bar charts and line graphs were generated using GraphPad Prism version 9.0 software, while statistical analyses were performed using SPSS version 20.0 software. Results: The results of 16S rDNA sequencing analysis of the microbiome showed that there was no difference in the α diversity of the intestinal microbiota in each group of mice (p > 0.05), but there was a difference in the Beta diversity (p < 0.05). At the gate level, the abundances of Proteobacteria, Campylobacterota, Desulfobacterota, and Fusobacteriota in the medium-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Patellar bacteria was lower than that of the model control group (p < 0.05). The abundances of Proteobacteria and Campylobacterota in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Planctomycetota and Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Campylobacterota in the grape exosome group was higher than that of the model control group (p < 0.05). The abundance of Patescibacteria was lower than that of the model control group (p < 0.05), while the abundance of Firmicutes and Fusobacteriota in the antioxidant nutrient group was higher than that of the model control group (p < 0.05). However, the abundance of Verrucomicrobiota and Patescibacteria was lower than that of the model control group (p < 0.05). At the genus level, the abundances of Bacteroides and unclassified Lachnospiraceae in the high-dose BDE-7 group were higher than those in the model control group (p < 0.05). The abundance of Lachnospiraceae NK4A136_group and Lactobacillus was lower than that of the model control group (p < 0.05). The abundance of Veillonella and Helicobacter in the medium-dose BDE-7 group was higher than that in the model control group (p < 0.05), while the abundance of Lactobacillus was lower (p < 0.05). The abundance of genera such as Lentilactobacillus and Faecalibacterium in the grape exosome group was higher than that in the model control group (p < 0.05). The abundance of Alloprevotella and Bacteroides was lower than that of the model control group (p < 0.05). In the antioxidant nutrient group, the abundance of Lachnospiraceae and Hydrogenophaga was higher than that in the model control group (p < 0.05). However, the abundance of Akkermansia and Coriobacteriaceae UCG-002 was significantly lower than that of the model control group (p < 0.05). Conclusions: BDE-47 induces diabetogenic dysbiosis in prediabetic mice, which is reversible by dietary interventions. These findings suggest that microbiota-targeted strategies may effectively mitigate the diabetes risk associated with environmental pollutant exposure. Future studies should further explore the mechanisms underlying these microbiota changes and the long-term health benefits of such interventions. Full article

Time-restricted eating (TRE), a dietary strategy that aligns food intake with circadian rhythms, has emerged as a promising non-pharmacological approach for improving glycemic control in patients with type 2 diabetes. This systematic review and meta-analysis evaluated the effects of TRE on glycemic outcomes by analyzing eight randomized controlled trials involving 312 participants with type 2 diabetes or impaired fasting glucose. Meta-analyses of six eligible studies demonstrated that TRE significantly reduced fasting glucose (mean difference [MD]: −0.74 mmol/L; 95% CI: −1.13 to −0.36) and glycated hemoglobin (ΔHbA1c) (MD: −0.11%; 95% CI: −0.15 to −0.07) and increased time in range (TIR) for blood glucose (MD: +10.51%; 95% CI: 6.81 to 14.21). Improvements in fasting glucose and HbA1c were modest but consistent, while the increase in TIR showed no between-study heterogeneity, suggesting a robust and reproducible benefit of TRE on glycemic stability. These findings support the clinical feasibility and effectiveness of TRE as a dietary intervention in diabetes management. However, further high-quality trials with standardized protocols and longer follow-up are needed to confirm long-term efficacy and inform guidelines. Full article

Background: Metabolic syndrome (MetS) is a multifactorial condition involving central obesity, dyslipidemia, hypertension, and impaired glucose metabolism, significantly increasing the risk of type 2 diabetes and cardiovascular disease. Objectives: Given the clinical heterogeneity of MetS, this study aimed to identify distinct metabolic phenotypes, referred to as metabotypes, using validated biomarkers and to examine their association with MetS. Materials and Methods: A total of 1245 Korean adults aged 19–79 years were selected from the 2016–2023 Korea National Health and Nutrition Examination Survey. Metabotype risk clusters were derived using k-means clustering based on five biomarkers: body mass index (BMI), uric acid, fasting blood glucose (FBG), high-density lipoprotein cholesterol (HDLc), and non-HDL cholesterol (non-HDLc). Multivariable logistic regression was used to assess associations with MetS. Results: Three distinct metabotype risk clusters (low, intermediate, and high risk) were identified. The high-risk cluster exhibited significantly worse metabolic profiles, including elevated BMI, FBG, HbA1c, triglyceride, and reduced HDLc. The prevalence of MetS increased progressively across metabotype risk clusters (OR: 5.46, 95% CI: 2.89–10.30, p < 0.001). In sex-stratified analyses, the high-risk cluster was strongly associated with MetS in both men (OR: 9.22, 95% CI: 3.49–24.36, p < 0.001) and women (OR: 3.70, 95% CI: 1.56–8.75, p = 0.003), with notable sex-specific differences in lipid profiles, particularly in HDLc. Conclusion: These findings support the utility of metabotyping using routine biomarkers as a tool for early identification of high-risk individuals and the development of personalized prevention strategies in clinical and public health settings. Full article

Background: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine disorder characterized by excess body weight, hyperandrogenism, hyperglycemia, and insulin resistance often resulting in hirsutism and infertility. Dietary strategies have been shown to ameliorate metabolic disturbances, hormonal imbalances, and inflammation associated with PCOS. Recent evidence indicates that intermittent fasting (IF) could effectively enhance health outcomes and regulate circadian rhythm; however, its impact on PCOS remain unclear. Objective: Therefore, this systematic review and meta-analysis aims to examine the effect of IF on women diagnosed with PCOS. Methods: Comprehensive research was conducted across three major databases including PubMed, Scopus, and Web of Science without date restrictions. Meta-analysis was performed using Cochrane Review Manager Version 5.4 software. Results: Five studies fulfilled the inclusion criteria. IF significantly reduced body weight (MD = −4.25 kg, 95% CI: −7.71, −0.79; p = 0.02), BMI (MD = −2.05 kg/m², 95% CI: −3.26, −0.85; p = 0.0008), fasting blood glucose (FBG; MD = −2.86 mg/dL, 95% CI: −4.83, −0.89; p = 0.004), fasting blood insulin (FBI; MD = −3.17 μU/mL, 95% CI: −5.18, −1.16; p = 0.002), insulin resistance (HOMA-IR; MD = −0.94, 95% CI: −1.39, −0.50; p < 0.0001), triglycerides (TG; MD = −40.71 mg/dL, 95% CI: −61.53, −19.90; p = 0.0001), dehydroepiandrosterone sulfate (DHEA-S; MD = −33.21 μg/dL, 95% CI: −57.29, −9.13; p = 0.007), free androgen index (FAI; MD = −1.61%, 95% CI: −2.76, −0.45; p = 0.006), and C-reactive protein (CRP; MD = −2.00 mg/L, 95% CI: −3.15, −0.85; p = 0.006), while increasing sex hormone-binding globulin (SHBG; SMD = 0.50, 95% CI: 0.22, 0.77; p = 0.004). No significant changes were observed in waist-to-hip ratio (WHR), total cholesterol (TC), LDL, HDL, total testosterone (TT), or anti-Mullerian hormone (AMH). Conclusions: IF represents a promising strategy for improving weight and metabolic, hormonal, and inflammatory profiles in women with PCOS. However, the existing evidence remains preliminary, necessitating further robust studies to substantiate these findings. Full article

Background: Malnutrition and cancer-related fatigue (CRF) are prevalent in cancer patients, significantly impacting prognosis and quality of life. Oral nutritional supplements (ONSs) enriched with protein and ω-3 fatty acids may improve nutritional status and mitigate CRF. This study evaluates the effects of a high-protein, fish oil-enriched ONS (FOHP-ONS) on nutritional intake, body composition, fatigue, and quality of life in malnourished cancer patients. Methods: Cancer patients with malnutrition or inadequate food intake received 8 weeks of FOHP-ONS (2 cans/day, providing 4.2 g/day of ω-3 fatty acids). Dietary intake, body weight, handgrip strength, serum biochemical markers, nutritional status (PG-SGA), fatigue (BFI-T), and quality of life (EORTC QLQ-C30) were assessed at baseline, week 4, and week 8. Results: Of the 33 enrolled patients, 30 completed the study. Energy and protein intake significantly increased (p < 0.05), and body BMI and handgrip strength showed significant improvements (p < 0.05), while muscle mass did not change significantly. Nutritional status, assessed by PG-SGA, improved, with the proportion of severely malnourished patients (Stage C) decreasing from 46.7% to 13.3%, and moderately malnourished patients (Stage B) improving to well-nourished status (Stage A) from 10.0% to 30.0% (p < 0.001). Serum albumin levels increased significantly (p < 0.05), while fasting blood glucose significantly decreased (p < 0.05). Additionally, triglyceride levels significantly decreased (p < 0.05), while total cholesterol and LDL-C showed a downward trend. Cancer-related fatigue scores improved across all domains (p < 0.05), and quality of life significantly increased, particularly in physical and role functioning (p < 0.05). Conclusions: FOHP-ONS supplementation improved nutritional intake, body composition, and muscle strength while alleviating CRF and enhancing quality of life in malnourished cancer patients. These findings support its potential role in nutritional intervention for malnourished cancer patients. Full article

Background/Objectives: Gut-derived tryptophan (Trp) metabolites play important roles in metabolic and cardiovascular regulation. Although animal studies suggest their protective effects against metabolic dysfunction, data in adolescents, particularly those with obesity, remain limited. The objective of this study was to evaluate associations between circulating gut-derived Trp metabolites and markers of cardiometabolic, vascular, and platelet health in adolescents with obesity. Methods: Data were analyzed from 28 adolescents (ages 13–18; mean BMI = 36 ± 6.4 kg/m²). Fasting blood was collected to assess lipid profiles using a clinical analyzer and insulin resistance using the homeostatic model assessment for insulin resistance (HOMA-IR). Gut-derived Trp metabolites were measured by UPLC–mass spectrometry, peak oxygen uptake (VO_{2 peak}) by gas exchange during an incremental cycle ergometer test, and body composition by dual-energy X-ray absorptiometry. Platelet spare respiratory capacity (SRC), endothelial function, and liver fat were measured using high-resolution respirometry, flow-mediated dilation (FMD) of the brachial artery, and magnetic resonance imaging respectively. Results: Indole-3-propionic acid was inversely associated with diastolic blood pressure (rho = −0.39, p = 0.047), total cholesterol (rho = −0.55, p = 0.002), and LDL-C (rho = −0.57, p = 0.0014), independent of sex and obesity severity. Indoxyl sulfate was positively correlated with fasting glucose (rho = 0.47, p = 0.012), and adolescents with impaired fasting glucose had 1.6-fold higher IS levels. Indole-3-acetaldehyde declined with age (rho = −0.50, p = 0.007), and Indole-3-acetic acid and indole were higher in Hispanics vs. non-Hispanics. No significant associations were observed between Trp metabolites and FMD, VO₂ peak, or SRC. Conclusions: Gut-derived Trp metabolites, particularly indole-3-propionic and indoxyl sulfate, are associated with markers of cardiometabolic risk in adolescents with obesity. These findings support their potential relevance in early-onset cardiovascular disease risk. Full article

Background: Sodium–glucose cotransporter 2 (SGLT2) inhibitors have transformed type 2 diabetes mellitus (T2DM) management by promoting glucosuria, lowering glycated hemoglobin (HbA1c), blood pressure, and weight; however, their use is limited by genitourinary infections and ketoacidosis. Phytocannabinoids—bioactive compounds from Cannabis sativa—exhibit multi-target pharmacology, including interactions with cannabinoid receptors, Peroxisome Proliferator-Activated Receptors (PPARs), Transient Receptor Potential (TRP) channels, and potentially SGLT2. Objective: To evaluate the potential of phytocannabinoids as novel modulators of renal glucose reabsorption via SGLT2 and to compare their efficacy, safety, and pharmacological profiles with synthetic SGLT2 inhibitors. Methods: We performed a narrative review encompassing the following: (1) the molecular and physiological roles of SGLT2; (2) chemical classification, natural sources, and pharmacokinetics/pharmacodynamics of major phytocannabinoids (Δ⁹-Tetrahydrocannabinol or Δ⁹-THC, Cannabidiol or CBD, Cannabigerol or CBG, Cannabichromene or CBC, Tetrahydrocannabivarin or THCV, and β-caryophyllene); (3) in silico docking and drug-likeness assessments; (4) in vitro assays of receptor binding, TRP channel modulation, and glucose transport; (5) in vivo rodent models evaluating glycemic control, weight change, and organ protection; (6) pilot clinical studies of THCV and case reports of CBD/BCP; (7) comparative analysis with established synthetic inhibitors. Results: In silico studies identify high-affinity binding of several phytocannabinoids within the SGLT2 substrate pocket. In vitro, CBG and THCV modulate SGLT2-related pathways indirectly via TRP channels and CB receptors; direct IC₅₀ values for SGLT2 remain to be determined. In vivo, THCV and CBD demonstrate glucose-lowering, insulin-sensitizing, weight-reducing, anti-inflammatory, and organ-protective effects. Pilot clinical data (n = 62) show that THCV decreases fasting glucose, enhances β-cell function, and lacks psychoactive side effects. Compared to synthetic inhibitors, phytocannabinoids offer pleiotropic benefits but face challenges of low oral bioavailability, polypharmacology, inter-individual variability, and limited large-scale trials. Discussion: While preclinical and early clinical data highlight phytocannabinoids’ potential in SGLT2 modulation and broader metabolic improvement, their translation is impeded by significant challenges. These include low oral bioavailability, inconsistent pharmacokinetic profiles, and the absence of standardized formulations, necessitating advanced delivery system development. Furthermore, the inherent polypharmacology of these compounds, while beneficial, demands comprehensive safety assessments for potential off-target effects and drug interactions. The scarcity of large-scale, well-controlled clinical trials and the need for clear regulatory frameworks remain critical hurdles. Addressing these aspects is paramount to fully realize the therapeutic utility of phytocannabinoids as a comprehensive approach to T2DM management. Conclusion: Phytocannabinoids represent promising multi-target agents for T2DM through potential SGLT2 modulation and complementary metabolic effects. Future work should focus on pharmacokinetic optimization, precise quantification of SGLT2 inhibition, and robust clinical trials to establish efficacy and safety profiles relative to synthetic inhibitors. Full article