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16 pages, 575 KiB  
Article
Polycystic Ovary Syndrome Attenuates TSH-Lowering Effect of Metformin in Young Women with Subclinical Hypothyroidism
by Robert Krysiak, Karolina Kowalcze, Johannes Ott, Sofia Burgio, Simona Zaami and Bogusław Okopień
Pharmaceuticals 2025, 18(8), 1149; https://doi.org/10.3390/ph18081149 - 1 Aug 2025
Viewed by 176
Abstract
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: [...] Read more.
Background/Objectives: The effect of metformin on the secretory function of thyrotropic cells is sex-dependent. The current study aimed to investigate whether the impact of this drug on activity of the hypothalamic–pituitary–thyroid axis in women is impacted by the androgen status of patients. Methods: The study population included 48 levothyroxine-naïve reproductive-aged women with subclinical hypothyroidism and prediabetes receiving 3.0 g of metformin daily. Women with (n = 24) and without (n = 24) polycystic ovary syndrome were matched for age, insulin sensitivity, TSH, and reasons for thyroid hypofunction. Circulating levels of glucose, glycated hemoglobin, insulin, TSH, thyroid hormones, gonadotropins, androgens, estradiol, SHBG, prolactin, ACTH, and IGF-1 were measured before metformin treatment and six months later. Results: At entry, women with and without polycystic ovary syndrome differed in LH, LH/FSH ratio, androgens, and estradiol. The decrease in TSH, fasting glucose and glycated hemoglobin, and the improvement in insulin sensitivity were less pronounced in women with than in women without polycystic ovary syndrome. In each group, there were no differences in the impact on TSH and thyroid hormones between patients with subclinical hypothyroidism of autoimmune and non-autoimmune origin. The changes in TSH inversely correlated with total testosterone and free androgen index. Only in women with coexisting polycystic ovary syndrome, did metformin slightly reduce LH, LH/FSH ratio, testosterone, and free androgen index. Conclusions: The results suggest that concurrent polycystic ovary syndrome attenuates metformin action on TSH secretion, which can be explained by increased androgen production. Moreover, the drug seems to alleviate PCOS-associated changes in the activity of the reproductive axis. Full article
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23 pages, 994 KiB  
Article
Correlations Between Coffee Intake, Glycemic Control, Cardiovascular Risk, and Sleep in Type 2 Diabetes and Hypertension: A 12-Month Observational Study
by Tatiana Palotta Minari, José Fernando Vilela-Martin, Juan Carlos Yugar-Toledo and Luciana Pellegrini Pisani
Biomedicines 2025, 13(8), 1875; https://doi.org/10.3390/biomedicines13081875 - 1 Aug 2025
Viewed by 134
Abstract
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 [...] Read more.
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
(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (3rd Edition))
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21 pages, 4988 KiB  
Article
Ozone Exposure Induces Prediabetic Symptoms Through Hepatic Glycogen Metabolism and Insulin Resistance
by Yuchai Tian, Xiaoyun Wu, Zhihua Gong, Xiaomin Liang, Huizhen Zhu, Jiyue Zhang, Yangcheng Hu, Bin Li, Pengchong Xu, Kaiyue Guo and Huifeng Yue
Toxics 2025, 13(8), 652; https://doi.org/10.3390/toxics13080652 - 31 Jul 2025
Viewed by 253
Abstract
(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 [...] Read more.
(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
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33 pages, 1782 KiB  
Review
Synthalin, Buformin, Phenformin, and Metformin: A Century of Intestinal “Glucose Excretion” as Oral Antidiabetic Strategy in Overweight/Obese Patients
by Giuliano Pasquale Ramadori
Livers 2025, 5(3), 35; https://doi.org/10.3390/livers5030035 - 31 Jul 2025
Viewed by 87
Abstract
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 [...] Read more.
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
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15 pages, 976 KiB  
Article
Endocannabinoid and AGE Interactions in Prediabetes: The Role of Mediterranean Diet Adherence
by Marko Grahovac, Marko Kumric, Marino Vilovic, Daniela Supe-Domic, Nikola Pavlovic, Josipa Bukic, Tina Ticinovic Kurir and Josko Bozic
Nutrients 2025, 17(15), 2517; https://doi.org/10.3390/nu17152517 - 31 Jul 2025
Viewed by 219
Abstract
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 [...] Read more.
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
(This article belongs to the Section Nutrition and Diabetes)
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21 pages, 4059 KiB  
Systematic Review
The Impact of Vitamin D Supplementation on Fasting Plasma Glucose, Insulin Sensitivity, and Inflammation in Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis
by Enny Probosari, Hertanto W. Subagio, Heri-Nugroho, Banundari Rachmawati, Siti F. Muis, Kevin C. Tjandra, Dwi Adiningsih and Tri I. Winarni
Nutrients 2025, 17(15), 2489; https://doi.org/10.3390/nu17152489 - 30 Jul 2025
Viewed by 354
Abstract
Background/Objectives: Vitamin D supplementation has shown promise in managing type 2 diabetes mellitus (T2DM), while the simultaneous impact on glycemic control and inflammation in T2DM remains poorly understood. This study aimed to investigate the potential role of vitamin D supplementation in managing [...] Read more.
Background/Objectives: Vitamin D supplementation has shown promise in managing type 2 diabetes mellitus (T2DM), while the simultaneous impact on glycemic control and inflammation in T2DM remains poorly understood. This study aimed to investigate the potential role of vitamin D supplementation in managing T2DM using fasting plasma glucose (FPG), insulin levels, HOMA-IR, HOMA-B, HbA1c, and Hs-CRP as the biomarkers. Methods: Original articles from Scopus, Pubmed, Cochrane Library, Epistemonikos, and ScienceDirect published between 2014 and 2024 were the sources. Inclusion criteria included studies conducted as clinical trials or randomized controlled trials involving adult patients diagnosed with T2DM undergoing treatment with vitamin D. The risk of bias was evaluated using the ROB-2 tool and meta-analysis was conducted to quantitatively synthesize the results across the studies using pooled effect sizes and confidence intervals. Results: Nine studies were included in the meta-analysis. Significant differences were found at 12-week follow-up in insulin level (MD(−3.59) [95% CI: −6.93, −0.25]), HOMA-B (MD(−50.35) [95% CI: −92.29, −8.41]), hs-CRP (−2.51 [95% CI: −3.45, −1.57]), and HbA1c level (MD(−0.30) [95% CI: −0.54, −0.06]) and at 24-week follow-up in HOMA-IR (MD(−0.38) [CI: −0.53, −0.24]). The quality of the included studies was generally moderate, with three showing a potential risk of bias. Conclusions: The observed trends in FPG, insulin levels, HOMA-IR, HOMA-B, HbA1c, and hs-CRP indicate that vitamin D may influence glycemic control, insulin sensitivity, and inflammation, but these effects are often modest and may diminish over time. Future studies should explore longer duration randomized trials with standardized dosing and baseline vitamin D status stratification. Full article
(This article belongs to the Section Micronutrients and Human Health)
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17 pages, 1908 KiB  
Article
BDE-47 Disrupts Gut Microbiota and Exacerbates Prediabetic Conditions in Mice: Therapeutic Potential of Grape Exosomes and Antioxidants
by Zaoling Liu, Fang Cao, Aerna Qiayimaerdan, Nilupaer Aisikaer, Zulipiya Zunong, Xiaodie Ma and Yale Yu
Toxics 2025, 13(8), 640; https://doi.org/10.3390/toxics13080640 - 29 Jul 2025
Viewed by 186
Abstract
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 [...] Read more.
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
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15 pages, 933 KiB  
Article
A Prospective Interventional Study on the Beneficial Effect of Fish Oil-Enriched High-Protein Oral Nutritional Supplement (FOHP-ONS) on Malnourished Older Cancer Patients
by Hui-Fang Chiu, Shu Ru Zhuang, You-Cheng Shen, Subramanian Thangaleela and Chin-Kun Wang
Nutrients 2025, 17(15), 2433; https://doi.org/10.3390/nu17152433 - 25 Jul 2025
Viewed by 364
Abstract
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 [...] Read more.
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
(This article belongs to the Section Nutrition and Public Health)
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15 pages, 798 KiB  
Article
Associations Between Serum Gut-Derived Tryptophan Metabolites and Cardiovascular Health Markers in Adolescents with Obesity
by Jeny E. Rivera, Renny Lan, Mario G. Ferruzzi, Elisabet Børsheim, Emir Tas and Eva C. Diaz
Nutrients 2025, 17(15), 2430; https://doi.org/10.3390/nu17152430 - 25 Jul 2025
Viewed by 293
Abstract
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 [...] Read more.
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 (VO2 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
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20 pages, 641 KiB  
Article
Associations of Serum GIP, GLP-1, and DPP-4 with Metabolic and Hormonal Profiles and Tobacco Exposure in Women with Polycystic Ovary Syndrome
by Anna Bizoń, Julia Borkowska, Grzegorz Franik and Agnieszka Piwowar
Int. J. Mol. Sci. 2025, 26(15), 7097; https://doi.org/10.3390/ijms26157097 - 23 Jul 2025
Viewed by 455
Abstract
Disorders in glucose metabolism are well-established features of polycystic ovary syndrome (PCOS) and are linked to its clinical severity and phenotypic variability. This study aimed to assess serum concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) and to [...] Read more.
Disorders in glucose metabolism are well-established features of polycystic ovary syndrome (PCOS) and are linked to its clinical severity and phenotypic variability. This study aimed to assess serum concentrations of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), and dipeptidyl peptidase-4 (DPP-4) and to examine their relationships with glucose and insulin levels, selected sex hormone concentrations, body weight, and exposure to tobacco smoke. Women with PCOS exhibited significantly elevated levels of fasting glucose, insulin, GIP, and GLP-1 compared to controls. Tobacco smoke exposure in women with PCOS was associated with reduced DPP-4 levels, which were approximately two-fold lower in smokers than in non-smokers. A significant negative correlation between DPP-4 and cotinine levels further supported this relationship. Comorbidities such as overweight/obesity or insulin resistance (IR) were also linked to elevated incretin hormone levels. However, no significant age-related trends in incretin levels were identified, despite the known association between age and glucose dysregulation. The notable alterations in incretin hormone profiles in PCOS, along with the consistent patterns of GIP or GLP-1 with metabolic and hormonal parameters, suggest that these hormones may play coordinated regulatory roles in the pathophysiology of PCOS. Full article
(This article belongs to the Special Issue Focus on Metabolic Research Priorities in PCOS)
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19 pages, 3827 KiB  
Article
A Refined Carbohydrate-Rich Diet Reduces Vascular Reactivity Through Endothelial Oxidative Stress and Increased Nitric Oxide: The Involvement of Inducible Nitric Oxide Synthase
by Karoline Neumann, Nina Bruna de Souza Mawandji, Ingridy Reinholz Grafites Schereider, Emanuelle Coutinho de Oliveira, Julia Martins Vieira, Andressa Bolsoni-Lopes, Jones Bernardes Graceli, Julia Antonietta Dantas, Lorena Silveira Cardoso, Dalton Valentim Vassallo and Karolini Zuqui Nunes
Nutrients 2025, 17(15), 2395; https://doi.org/10.3390/nu17152395 - 22 Jul 2025
Viewed by 312
Abstract
Background/Objectives: The consumption of refined carbohydrates has increased globally. It is associated with inflammation and oxidative stress, both recognized as risk factors for cardiovascular disease. This study investigated the effects of a refined carbohydrate-rich diet on the vascular reactivity of rat aorta. Methods: [...] Read more.
Background/Objectives: The consumption of refined carbohydrates has increased globally. It is associated with inflammation and oxidative stress, both recognized as risk factors for cardiovascular disease. This study investigated the effects of a refined carbohydrate-rich diet on the vascular reactivity of rat aorta. Methods: We acclimatized adult male Wistar rats for two weeks and then randomly assigned them to two experimental groups: a control (CT) group and a high-carbohydrate diet (HCD) group. The CT group received standard laboratory chow for 15 days, while the HCD group received a diet composed of 45% sweetened condensed milk, 10% refined sugar, and 45% standard chow. After the dietary exposure period, we evaluated the vascular reactivity of aortic rings, gene expression related to inflammation, superoxide dismutase activity, and biochemical parameters, including cholesterol, triglycerides, fasting glucose, and glucose and insulin tolerance. Results: The results demonstrate a reduction in vascular reactivity caused by endothelial alterations, including increased NO production, which was observed as higher vasoconstriction in the presence of L-NAME and aminoguanidine and upregulation of iNOS gene expression. In addition, increased production of free radicals, such as O2-, was observed, as well as immune markers like MCP-1 and CD86 in the HCD group. Additionally, the HCD group showed an increase in the TyG index, suggesting early metabolic impairment. GTT and ITT results revealed higher glycemic levels, indicating early signs of insulin resistance. Conclusions: These findings indicate that short-term consumption of a refined carbohydrate-rich diet may trigger oxidative stress and endothelial dysfunction, thereby increasing the risk of cardiovascular complications. Full article
(This article belongs to the Section Nutrition and Metabolism)
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17 pages, 3304 KiB  
Article
Integrating Computational Analysis of In Vivo Investigation of Modulatory Effect of Fagonia cretica Plant Extract on Letrozole-Induced Polycystic Ovary Syndrome in Female Rats
by Ayesha Qasim, Hiram Calvo, Jesús Jaime Moreno Escobar and Zia-ud-din Akhtar
Biology 2025, 14(7), 903; https://doi.org/10.3390/biology14070903 - 21 Jul 2025
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Abstract
Fagonia cretica, a medicinal herb from the Zygophyllaceae family, is traditionally utilized to treat various conditions such as hepatitis, gynecological disorders, tumors, urinary tract issues, and diabetes. The present study aimed to evaluate the therapeutic potential of Fagonia cretica in treating polycystic [...] Read more.
Fagonia cretica, a medicinal herb from the Zygophyllaceae family, is traditionally utilized to treat various conditions such as hepatitis, gynecological disorders, tumors, urinary tract issues, and diabetes. The present study aimed to evaluate the therapeutic potential of Fagonia cretica in treating polycystic ovarian syndrome (PCOS) induced in female rats. PCOS, a complex hormonal disorder, was experimentally induced by administering Letrozole (1 mg/kg) in combination with a high-fat diet for 21 days. The affected rats were then treated with hydro-alcoholic extracts of Fagonia cretica at doses of 100 mg/kg, 200 mg/kg, and 300 mg/kg for 20 days. Key biochemical parameters—including serum testosterone, insulin, fasting blood glucose, insulin resistance (HOMA-IR), cholesterol, triglycerides, and lipoprotein levels—were measured. Ultrasound imaging and histopathological analysis of ovarian tissues were also performed. The data were analyzed using computer-based statistical tools, including one-way ANOVA, Cohen’s d effect size, and Tukey’s HSD test, with graphical representations generated using Python 3.10 on the Kaggle platform. Results demonstrated a significant reduction in serum testosterone, insulin, cholesterol, and triglyceride levels (p < 0.05) in treated groups, along with improved ovarian morphology. These findings support the therapeutic potential of Fagonia cretica as a natural treatment for PCOS. Full article
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15 pages, 1920 KiB  
Article
The Absence of Bovine Serum Albumin (BSA) in Preimplantation Culture Media Impairs Embryonic Development and Induces Metabolic Alterations in Mouse Offspring
by Jannatul Ferdous Jharna, Md Wasim Bari, Norermi Firzana Alfian and Satoshi Kishigami
Int. J. Mol. Sci. 2025, 26(14), 6989; https://doi.org/10.3390/ijms26146989 - 21 Jul 2025
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Abstract
Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic [...] Read more.
Bovine serum albumin (BSA), the most commonly used protein in preimplantation embryo culture media, performs a variety of physiological functions. However, its involvement in long-term effects remains largely unclear. To investigate its physiological importance in culture media, we examined the developmental and metabolic consequences of BSA deprivation during preimplantation stages in mice. Embryos cultured in BSA-free media during specific time windows exhibited impaired blastocyst formation, with continuous deprivation from the two-pronuclei (2PN) stage significantly reducing trophectoderm (TE) and inner cell mass (ICM) cell numbers (p < 0.05), indicating compromised viability. Short-term BSA deprivation similarly disrupted lineage allocation, underscoring the sensitivity of early embryos to nutrient availability during cell fate determination. Although birth rates remained unaffected, suggesting compensatory mechanisms, longitudinal analysis revealed sex-specific metabolic dysfunction. Male offspring developed progressive glucose intolerance by 16 weeks, exhibiting elevated fasting glucose levels (p < 0.05) and impaired glucose clearance, whereas females showed no significant alterations in glucose metabolism. This study demonstrates that protein restriction during the preimplantation period not only disrupts early embryonic development but also programs long-term metabolic dysfunction, underscoring the importance of optimizing culture conditions in assisted reproductive technologies to minimize future health risks. Full article
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16 pages, 614 KiB  
Article
Diet Therapy Improves Body Composition, Blood Pressure and Glycemic Status in Individuals Living with Type 2 Diabetes: A Prospective Cohort Study
by Collins Afriyie Appiah, Harriet Wugah, Janet Adede Carboo, Mary Amoako, Michael Akenteng Wiafe and Frank Ekow Atta Hayford
Obesities 2025, 5(3), 56; https://doi.org/10.3390/obesities5030056 - 17 Jul 2025
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Abstract
Westernization of traditional diets has been implicated in the rising burden of overweight/obesity and type 2 diabetes, especially in developing countries. In recent times, diet therapy is increasingly being recognized as an essential component of diabetes care. This study assessed the effect of [...] Read more.
Westernization of traditional diets has been implicated in the rising burden of overweight/obesity and type 2 diabetes, especially in developing countries. In recent times, diet therapy is increasingly being recognized as an essential component of diabetes care. This study assessed the effect of diet therapy on body composition, antioxidant nutrient intake, and glycemic status in individuals living with type 2 diabetes (ILWT2D). In this prospective observational cohort study, 45 ILWT2D who were receiving diet therapy (personalized dietary counseling) in addition to standard medical treatment (intervention group) were compared with 45 ILWT2D receiving only standard medical treatment (comparator group). Antioxidant micronutrient intake was assessed using a 24-h dietary recall. Body composition indices, including body mass index (BMI), percentage body fat (%BF), and visceral fat (VF), were assessed. Participants’ fasting blood glucose (FBG), glycated hemoglobin (HbA1C) levels, and blood pressure (BP) were measured. All measurements were performed before and after a three-month period. There were significant improvements in BMI (27.8 ± 6.0 kg/m2 vs. 26.9 ± 5.5 kg/m2, p = 0.003), %BF (37.8 ± 11.9% vs. 35.5 ± 10.5%, p < 0.001), visceral fat (9.8 ± 3.4 vs. 9.1 ± 3.2, p < 0.001), systolic BP (136.9 ± 19.9 mmHg vs. 124.6 ± 13.0 mmHg, p < 0.001), FBG (8.8 ± 2.8 mmol/L vs. 6.7 ± 1.5 mmol/L, p < 0.001), and HbA1c (7.3 ± 1.0% vs. 6.4 ± 0.8%, p < 0.001) in the intervention group from baseline to endline, but not in the comparator group. In contrast, %BF increased within the comparator group (39.9 ± 7.8 vs. 40.7 ± 7.4; p = 0.029). Vitamin A intake increased significantly (227.5 ± 184.3 µg vs. 318.8 ± 274.7 µg, p = 0.038) within the intervention group but not in the comparator group (174.9 ± 154.3 µg, 193.7 ± 101.4 µg, p = 0.54). There were no significant changes in zinc, copper, selenium, and vitamin C intakes (p > 0.05) in the intervention group from the baseline to endline, unlike those in the comparator group who showed a significant increase in the intake of these nutrients. There was a significant increase in vitamin A intake among the ILWT2D who received dietary counseling as an intervention compared to those who did not. Additionally, the ILWT2D who received dietary counseling had significant improvements in their body composition (BMI, body fat, and visceral fat) and systolic blood pressure, compared to those who did not. The ILWT2D who received the intervention had significantly better glycemic control (FBG and HbA1c) than their counterparts who did not. Thus, this study suggests the potential of diet therapy as a viable non-pharmacological treatment approach for individuals living with type 2 diabetes. Full article
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14 pages, 1222 KiB  
Article
The Role of Endothelial Progenitor Cells (EPCs) and Circulating Endothelial Cells (CECs) as Early Biomarkers of Endothelial Dysfunction in Children with Newly Diagnosed Type 1 Diabetes
by Milena Jamiołkowska-Sztabkowska, Sebastian Ciężki, Aleksandra Starosz, Kamil Grubczak, Marcin Moniuszko, Artur Bossowski and Barbara Głowińska-Olszewska
Cells 2025, 14(14), 1095; https://doi.org/10.3390/cells14141095 - 17 Jul 2025
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Abstract
The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients’ clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children [...] Read more.
The aim of this study is to assess endothelial progenitor cells (EPCs) and circulating endothelial cells (CECs) at the time of type 1 diabetes (T1D) recognition concerning patients’ clinical state, remaining insulin secretion, and further partial remission (PR) occurrence. We recruited 45 children that were admitted to hospital due to newly diagnosed T1D (median age 10.8 yrs), and 20 healthy peers as a control group. EPC and CEC levels were measured at disease onset in PBMC isolated from whole peripheral blood with the use of flow cytometry. Clinical data regarding patients’ condition, C-peptide secretion, and further PR prevalence were analyzed. T1D-diagnosed patients presented higher EPC levels than the control group (p = 0.026), while no statistical differences in CEC levels and EPC/CEC ratio were observed. Considering only T1D patients, those with better clinical conditions presented lower EPCs (p = 0.021) and lower EPC/CEC ratios (p = 0.0002). Patients with C-peptide secretion within a normal range at disease onset presented lower EPC/CEC ratios (p = 0.027). Higher levels of EPCs were observed more frequently in patients with higher glucose, decreased fasting C-peptide, and lower stimulated C-peptide (all p < 0.05). The presence of DKA was related to higher EPC/CEC ratios (p = 0.034). Significantly higher levels of CECs were observed in patients who presented partial remission of the disease at 6 months after diagnosis (p = 0.03) only. In the study group, positive correlations of CECs with age, BMI at onset, and BMI in following years were observed. EPC/CEC ratios correlated positively with glucose levels at hospital admission and negatively with age, BMI, pH, and stimulated C-peptide level. We reveal a new potential for the application of EPCs and CECs as biomarkers, reflecting both endothelial injury and reconstruction processes in children with T1D. There is a need for further research in order to reduce cardiovascular risk in children with T1D. Full article
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