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30 pages, 3316 KiB  
Systematic Review
Preclinical Evidence of Curcuma longa Linn. as a Functional Food in the Management of Metabolic Syndrome: A Systematic Review and Meta-Analysis of Rodent Studies
by Samuel Abiodun Kehinde, Zahid Naeem Qaisrani, Rinrada Pattanayaiying, Wai Phyo Lin, Bo Bo Lay, Khin Yadanar Phyo, Myat Mon San, Nurulhusna Awaeloh, Sasithon Aunsorn, Ran Kitkangplu and Sasitorn Chusri
Biomedicines 2025, 13(8), 1911; https://doi.org/10.3390/biomedicines13081911 - 5 Aug 2025
Abstract
Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active [...] Read more.
Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active compound curcumin, has shown therapeutic promise in preclinical studies. This systematic review and meta-analysis evaluated the effects of Curcuma longa and its derivatives on MetS-related outcomes in rodent models. Methods: A comprehensive search was conducted across six databases (PubMed, Scopus, AMED, LILACS, MDPI, and Google Scholar), yielding 47 eligible in vivo studies. Data were extracted on key metabolic, inflammatory, and oxidative stress markers and analyzed using random-effects models. Results were presented as mean differences (MD) with 95% confidence intervals (CI). Results: Meta-analysis showed that curcumin significantly reduced body weight (rats: MD = −42.10; mice: MD = −2.91), blood glucose (rats: MD = −55.59; mice: MD = −28.69), triglycerides (rats: MD = −70.17; mice: MD = −24.57), total cholesterol (rats: MD = −35.77; mice: MD = −52.61), and LDL cholesterol (rats: MD = −69.34; mice: MD = −42.93). HDL cholesterol increased significantly in rats but not in mice. Inflammatory cytokines were markedly reduced, while oxidative stress improved via decreased malondialdehyde (MDA) and elevated superoxide dismutase (SOD) and catalase (CAT) levels. Heterogeneity was moderate to high, primarily due to variations in curcumin dosage (ranging from 10 to 500 mg/kg) and treatment duration (2 to 16 weeks) across studies. Conclusions: This preclinical evidence supports Curcuma longa as a promising functional food component for preventing and managing MetS. Its multi-faceted effects warrant further clinical studies to validate its translational potential. Full article
(This article belongs to the Special Issue The Role of Cytokines in Health and Disease: 3rd Edition)
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30 pages, 15481 KiB  
Article
Effects of 12 Weeks of Chromium, Phyllanthus emblica Fruit Extract, and Shilajit Supplementation on Markers of Cardiometabolic Health, Fitness, and Weight Loss in Men and Women with Risk Factors to Metabolic Syndrome Initiating an Exercise and Diet Intervention: A Randomized Double-Blind, Placebo-Controlled Trial
by Victoria Martinez, Kay McAngus, Broderick L. Dickerson, Megan Leonard, Elena Chavez, Jisun Chun, Megan Lewis, Dante Xing, Drew E. Gonzalez, Choongsung Yoo, Joungbo Ko, Heather Rhodes, Hudson Lee, Ryan J. Sowinski, Christopher J. Rasmussen and Richard B. Kreider
Nutrients 2025, 17(12), 2042; https://doi.org/10.3390/nu17122042 - 19 Jun 2025
Viewed by 2599
Abstract
Background: Exercise and nutritional interventions are often recommended to help manage risk related to metabolic syndrome (MetSyn). The co-ingestion of Phyllanthus emblica (PE) with trivalent chromium (Cr) has been purported to improve the bioavailability of chromium and enhance endothelial function, reduce platelet aggregation, [...] Read more.
Background: Exercise and nutritional interventions are often recommended to help manage risk related to metabolic syndrome (MetSyn). The co-ingestion of Phyllanthus emblica (PE) with trivalent chromium (Cr) has been purported to improve the bioavailability of chromium and enhance endothelial function, reduce platelet aggregation, and help manage blood glucose as well as lipid levels. Shilajit (SJ) has been reported to have anti-inflammatory, adaptogenic, immunomodulatory, and lipid-lowering properties. This study evaluated whether dietary supplementation with Cr, PE, and SJ, or PE alone, during an exercise and diet intervention may help individuals with risk factors to MetSyn experience greater benefits. Methods: In total, 166 sedentary men and women with at least two markers of metabolic syndrome participated in a randomized, placebo-controlled, parallel-arm, and repeated-measure intervention study, of which 109 completed the study (48.6 ± 10 yrs., 34.2 ± 6 kg/m2, 41.3 ± 7% fat). All volunteers participated in a 12-week exercise program (supervised resistance and endurance exercise 3 days/week with walking 10,000 steps/day on non-training days) and were instructed to reduce energy intake by −5 kcals/kg/d. Participants were matched by age, sex, BMI, and body mass for the double-blind and randomized supplementation of a placebo (PLA), 500 mg of PE (PE-500), 1000 mg/d of PE (PE-1000), 400 µg of trivalent chromium (Cr) with 6 mg of PE and 6 mg of SJ (Cr-400), or 800 µg of trivalent chromium with 12 mg of PE and 12 mg of SJ (Cr-800) once a day for 12 weeks. Data were obtained at 0, 6, and 12 weeks of supplementation, and analyzed using general linear model multivariate and univariate analyses with repeated measures, pairwise comparisons, and mean changes from the baseline with 95% confidence intervals (CIs). Results: Compared to PLA responses, there was some evidence (p < 0.05 or approaching significance, p > 0.05 to p < 0.10) that PE and/or Cr with PE and SJ supplementation improved pulse wave velocity, flow-mediated dilation, platelet aggregation, insulin sensitivity, and blood lipid profiles while promoting more optimal changes in body composition, strength, and aerobic capacity. Differences among groups were more consistently seen at 6 weeks rather than 12 weeks. While some benefits were seen at both dosages, greater benefits were more consistently observed with PE-1000 and Cr-800 ingestion. Conclusions: The results suggest that PE and Cr with PE and SJ supplementation may enhance some exercise- and diet-induced changes in markers of health in overweight individuals with at least two risk factors to MetSyn. Registered clinical trial #NCT06641596. Full article
(This article belongs to the Section Phytochemicals and Human Health)
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29 pages, 2167 KiB  
Review
Coffee and Its Major Polyphenols in the Prevention and Management of Type 2 Diabetes: A Comprehensive Review
by HwiCheol Kim, Sang Ryong Kim and Un Ju Jung
Int. J. Mol. Sci. 2025, 26(12), 5544; https://doi.org/10.3390/ijms26125544 - 10 Jun 2025
Viewed by 2939
Abstract
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired glucose metabolism and affects a substantial portion of the global population. Over the past few decades, numerous studies have investigated lifestyle factors, including diet and physical activity, [...] Read more.
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder characterized by insulin resistance and impaired glucose metabolism and affects a substantial portion of the global population. Over the past few decades, numerous studies have investigated lifestyle factors, including diet and physical activity, as preventive measures or adjunctive treatments for T2DM. Among the dietary factors, coffee consumption has garnered attention because of its potential to mitigate the risk and progression of T2DM. This review examines the current evidence on the relationship between coffee consumption and T2DM, with particular focus on the major polyphenols found in coffee, such as chlorogenic acid and related hydroxycinnamic acids (caffeic acid, ferulic acid, p-coumaric acid, and sinapic acid). These bioactive compounds are thought to exert anti-diabetic effects through several mechanisms, including improvements in glucose homeostasis, insulin sensitivity, inflammation, and oxidative stress. This review aimed to clarify the scientific rationale behind the potential therapeutic effects of coffee on T2DM and proposed directions for future studies. However, significant knowledge gaps remain, including limited clinical evidence, unclear optimal dosages, low bioavailability, and an incomplete understanding of molecular mechanisms. Addressing these gaps through well-designed clinical trials and advanced molecular studies is essential to fully establish the therapeutic potential of coffee and its polyphenols in T2DM. Full article
(This article belongs to the Collection Latest Review Papers in Bioactives and Nutraceuticals)
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20 pages, 1718 KiB  
Review
Cyclodextrins as Modulators of Gut Microbiota: Pharmaceutical Applications and Impact on Intestinal Health
by Renata Maria Varut, Mircea Sorin Ciolofan, Maria Elena Veronica, Kristina Radivojević, Diana Maria Trasca, Cristina Popescu, Oana Diaconu and Cristina Elena Singer
Pharmaceutics 2025, 17(6), 752; https://doi.org/10.3390/pharmaceutics17060752 - 7 Jun 2025
Viewed by 681
Abstract
Background/Objectives: Cyclodextrins (CDs) have garnered increasing attention in pharmaceutical research due to their ability to enhance drug solubility, bioavailability, and therapeutic efficacy. Meanwhile, the gut microbiota, a key regulator of human health, has emerged as an important target in evaluating the safety [...] Read more.
Background/Objectives: Cyclodextrins (CDs) have garnered increasing attention in pharmaceutical research due to their ability to enhance drug solubility, bioavailability, and therapeutic efficacy. Meanwhile, the gut microbiota, a key regulator of human health, has emerged as an important target in evaluating the safety and broader implications of pharmaceutical excipients. This review aims to synthesize current knowledge regarding the effects of CDs on the composition and function of the gut microbiota. Methods: A literature search following PRISMA guidelines was conducted in PubMed, ScienceDirect, and Google Scholar to identify studies on cyclodextrins and their interactions with gut microbiota. Results: Cyclodextrins, particularly α-, β-, and γ-CDs, demonstrated the capacity to modulate gut microbiota composition, promoting the growth of beneficial bacteria such as Bifidobacterium and Akkermansia. Supplementation with CDs was also associated with an increased production of short-chain fatty acids (SCFAs), which are essential for maintaining intestinal homeostasis and metabolic health. Moreover, CDs exhibited potential in lowering lipid levels and improving postprandial glycemic control without enhancing insulin secretion. Although generally recognized as safe, the toxicological profile of CDs varies depending on their type, dosage, and route of administration. Conclusions: Cyclodextrins hold considerable promise not only as pharmaceutical excipients but also as modulators of gut microbial communities, suggesting a dual therapeutic and prebiotic role. Future studies integrating metagenomic and metabolomic approaches are necessary to further elucidate the molecular mechanisms underlying CD–microbiota interactions and to optimize their application in enhancing drug delivery efficiency and promoting intestinal health. Full article
(This article belongs to the Section Drug Delivery and Controlled Release)
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24 pages, 1226 KiB  
Review
From Soil to Brain: Olive Oil Attributes, Consumer Choices, Intermittent Fasting, and Their Impact on Health
by Ion-Bogdan Dumitrescu, Cristina Manuela Drăgoi and Alina Crenguța Nicolae
Nutrients 2025, 17(11), 1905; https://doi.org/10.3390/nu17111905 - 1 Jun 2025
Viewed by 1630
Abstract
Olive oil (OO) has longstanding significance in human history, particularly in the Mediterranean region, where it has been a cornerstone of diet, economy, and culture. This history adds to modern evidence-based knowledge. Background: The Mediterranean diet (MD), rich in plant-based foods and [...] Read more.
Olive oil (OO) has longstanding significance in human history, particularly in the Mediterranean region, where it has been a cornerstone of diet, economy, and culture. This history adds to modern evidence-based knowledge. Background: The Mediterranean diet (MD), rich in plant-based foods and OO, has been extensively associated with improved cardiometabolic and cognitive health. Recent interest has emerged in understanding how intermittent fasting protocols may enhance these effects. Still, the quality of OO does not only lie in the extraction process; it is also dependent on the tree variety, the soil, and the agricultural practices, ending with the way in which the finished product is stored and consumed. Objectives: This review explores the synergistic potential between OO consumption and intermittent fasting, focusing on their combined impact on metabolic health, oxidative stress, and inflammatory pathways. Methods: A literature search was conducted using multiple databases to identify studies addressing the health effects of OO, fasting, and the MD. Both human and relevant preclinical studies were considered, with emphasis on those evaluating inflammatory markers, lipid metabolism, insulin sensitivity, and neuroprotective mechanisms. Results: Evidence suggests that the bioactive compounds in EVOO may potentiate the benefits of fasting by enhancing antioxidant capacity, reducing postprandial inflammation, and modulating gene expression related to cellular metabolism. Combined, these factors may support improved insulin sensitivity, reduced oxidative damage, and delayed onset of age-related diseases. Conclusions: Understanding the integrative role of OO and fasting within the MD framework could offer valuable insights for nutritional strategies aimed at preventing metabolic syndrome, type 2 diabetes, and neurodegeneration. These findings also support the need for future clinical trials exploring the timing, dosage, and dietary context in which these interventions are most effective. Full article
(This article belongs to the Special Issue Intermittent Fasting: Health Impacts and Therapeutic Potential)
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31 pages, 1499 KiB  
Review
Plant-Based Diet for Glycemic Control, Insulin Sensitivity, and Lipid Profile in Type 2 Diabetes: A Systematic Review
by Siwatt Thaiudom, Kakanang Posridee, Sunthara Liangchawengwong, Chantira Chiaranai, Saranya Chularee, Aoitip Samanros, Anant Oonsivilai, Naruemol Singha-Dong and Ratchadaporn Oonsivilai
Foods 2025, 14(11), 1919; https://doi.org/10.3390/foods14111919 - 28 May 2025
Viewed by 1314
Abstract
Background/Objective: Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder characterized by hyperglycemia. Plant-based interventions have gained attention as potential complementary treatments alongside conventional therapies. This systematic review evaluates the efficacy of plant-based interventions in improving glycemic control, insulin sensitivity, lipid profiles, [...] Read more.
Background/Objective: Type 2 diabetes mellitus (T2D) is a chronic metabolic disorder characterized by hyperglycemia. Plant-based interventions have gained attention as potential complementary treatments alongside conventional therapies. This systematic review evaluates the efficacy of plant-based interventions in improving glycemic control, insulin sensitivity, lipid profiles, and other outcomes such as GLUT-4, Tumor Necrosis Facto-alpha, dietary inflammation index, plasma lipopolysaccharide, total antioxidant capacity, and malondialdehyde in individuals with T2D. Methods: We conducted a systematic search of PubMed, Scopus, and ScienceDirect databases to identify randomized controlled trials (RCTs) and observational studies. RCTs were used as an additional screening criterion. The review included studies on the effects of plant-based interventions, encompassing fruits, vegetables, herbs, spices, and their extracts. We analyzed data on glycemic control, insulin sensitivity, lipid profiles, and other metabolic markers. Results: Twenty-six studies were included in our analysis. Various interventions showed potential benefits, with improved glycemic control, insulin sensitivity, and lipid profiles. Specific interventions such as Ziziphus jujuba juice, black tea, caper fruit extract, and balanced diets were linked with positive outcomes. Based on the Functional Food Claim framework, all 26 studies met the quality criteria for novel foods. However, the novel food score varied, and results were inconsistent across different interventions. Conclusion: Although some plant-based interventions appear promising in managing T2D, the evidence remains inconclusive due to variability in study quality and methodology. Further high-quality RCTs are necessary to confirm these findings and to establish the optimal dosage, duration, and combinations of interventions for effective T2D management. Despite inconclusive results, few plant-based diets have promising outcomes. Healthcare providers, especially nurse case managers, can incorporate the findings of this study into their practice protocol to support self-management for individuals with TD2. Full article
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12 pages, 294 KiB  
Review
Corticosteroid Use in Musculoskeletal and Neuraxial Interventions: Effects on Glycemic Control
by Brian Singer, Dovid Chaimovitz, Thomas Bucek, Eli Dayon, Aimee Abbott-Korumi, Moshe Spatz, Tejaswi Makkapati, Hayk Petrosyan and Laurent Delavaux
Medicina 2025, 61(5), 936; https://doi.org/10.3390/medicina61050936 - 21 May 2025
Viewed by 743
Abstract
Effective multidisciplinary pain management involves an in-depth knowledge not only of diagnosis and treatment but of how interventional procedures affect patients across all health domains. One of the most common pharmacological tools utilized in patients suffering from chronic pain disorders is corticosteroids. Corticosteroids [...] Read more.
Effective multidisciplinary pain management involves an in-depth knowledge not only of diagnosis and treatment but of how interventional procedures affect patients across all health domains. One of the most common pharmacological tools utilized in patients suffering from chronic pain disorders is corticosteroids. Corticosteroids are leveraged for their anti-inflammatory properties across a wide range of disorders. This review examines the role of corticosteroids and pain management with a specific focus on their metabolic impact regarding glucose metabolism. Corticosteroids have been shown to increase gluconeogenesis, resulting in reduced insulin sensitivity and an impaired peripheral glucose uptake. These varied responses to corticosteroids are especially concerning given the high prevalence of diabetes mellitus in chronic pain patients. There is well-documented evidence of not only transient hyperglycemia but emerging literature on prolonged glycemic disturbances that may have a greater effect on patients than previously recognized. A review of the available literature reveals variations in hyperglycemia depending on corticosteroid type, dose, and various patient-specific factors. Some research does suggest that lower corticosteroid dosages can provide similar therapeutic benefits and potentially reduce glycemic aberrations. Given the current evidence, clinicians should closely monitor patients’ hemoglobin A1C levels when determining the risks and benefits of an interventional procedure and consider alternative pain management strategies when appropriate. Future research should focus on optimizing corticosteroid selection and dosing to balance the safety, particularly in diabetic or prediabetic patient populations. Full article
(This article belongs to the Special Issue Physiotherapy in Musculoskeletal Pain: Assessment and Management)
25 pages, 2037 KiB  
Review
The Potential of Edible Bird’s Nests in Reducing Cardiovascular Disease Risk Factors: A Narrative Review
by Nina Diyana Rusanuar, Amilia Aminuddin, Adila A. Hamid, Jaya Kumar, Chua Kien Hui, Mohd Kaisan Mahadi and Azizah Ugusman
Int. J. Mol. Sci. 2025, 26(10), 4619; https://doi.org/10.3390/ijms26104619 - 12 May 2025
Viewed by 1134
Abstract
Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with dyslipidemia, obesity, diabetes mellitus, and hypertension being major modifiable risk factors. Functional foods with antioxidant and anti-inflammatory properties have gained attention for their potential for reducing CVD risk. Edible bird’s nest (EBN), [...] Read more.
Cardiovascular disease (CVD) remains a leading cause of mortality worldwide, with dyslipidemia, obesity, diabetes mellitus, and hypertension being major modifiable risk factors. Functional foods with antioxidant and anti-inflammatory properties have gained attention for their potential for reducing CVD risk. Edible bird’s nest (EBN), a functional food rich in bioactive compounds such as sialic acid, lactoferrin, and glycoproteins, has been shown to exhibit antioxidant and anti-inflammatory effects. This review explores the potential of EBN in mitigating CVD risk factors, focusing on its role in improving lipid profiles, managing obesity, and enhancing glucose metabolism. EBN has been shown to improve the lipid profile by regulating the hepatic cholesterol metabolism and gut–liver axis interactions. Additionally, EBN reduces body weight gain and visceral fat accumulation, improves adipokine regulation, and enhances insulin sensitivity, which may collectively support cardiovascular health. Despite promising findings, clinical evidence remains limited. Future research should focus on clinical trials to validate its efficacy, determine optimal dosages, and assess its long-term safety. Additionally, further studies on EBN’s effects on hypertension and its interaction with conventional therapies could enhance its potential role in CVD prevention and management. Full article
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14 pages, 692 KiB  
Review
The Anti-Mullerian Hormone as a Biomarker of Effectiveness of Metformin Hydrochloride Therapy in Polycystic Ovarian Syndrome and Insulin Resistance
by Nikoleta Parahuleva, Anna Mihaylova, Stanislava Harizanova, Yana Merdzhanova, Mariya Koleva, Vasil Madzharov, Gergana Strikova and Ekaterina Uchikova
Healthcare 2025, 13(8), 884; https://doi.org/10.3390/healthcare13080884 - 11 Apr 2025
Cited by 1 | Viewed by 934
Abstract
Background/Objectives: Among the therapeutic options available for managing PCOS, metformin improves insulin sensitivity, reduces androgen levels, and helps restore menstrual regularity and ovulation. While primarily used for its metabolic effects, metformin therapy may also influence reproductive parameters, including AMH levels, which are [...] Read more.
Background/Objectives: Among the therapeutic options available for managing PCOS, metformin improves insulin sensitivity, reduces androgen levels, and helps restore menstrual regularity and ovulation. While primarily used for its metabolic effects, metformin therapy may also influence reproductive parameters, including AMH levels, which are pivotal in improving ovarian function and predicting therapeutic outcomes in PCOS. The aim of this study was to search the scientific literature and analyze the correlation between AMH levels and metformin hydrochloride therapy in women with PCOS and IR. Methods: A systematic review of the scientific literature was conducted using the following keywords: polycystic ovarian syndrome, anti-Mullerian hormone, insulin resistance, metformin, treatment, biomarker, and metabolic syndrome. This review was aimed at investigating the potential of AMH as a biomarker of the effectiveness of metformin therapy in patients with PCOS and IR. Results: Metformin treatment in PCOS patients has shown significant reductions in serum AMH levels with prolonged therapy. As an insulin sensitizer, metformin improves insulin sensitivity, reduces hyperinsulinemia, and suppresses hyperandrogenism. This process inhibits the growth of antral follicles, which is reflected in decreased AMH levels. Conclusions: Reductions in AMH levels and improvements in insulin sensitivity can serve as indicators of treatment efficacy and enhancements in reproductive function for these patients. AMH could be considered a prognostic marker for evaluating the effectiveness of metformin therapy. A decrease in AMH levels following treatment may indicate improved ovarian function and a reduction in polycystic morphology. However, further research is necessary to confirm these findings and to determine the optimal dosages and duration of treatment. Full article
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34 pages, 831 KiB  
Review
Improving Fat Graft Survival Using Soluble Molecule Preconditioning
by Nabil Amraoui, Isabelle Xu, Jorge Robles Cortés, Chanel Beaudoin Cloutier and Julie Fradette
Biomolecules 2025, 15(4), 526; https://doi.org/10.3390/biom15040526 - 3 Apr 2025
Cited by 1 | Viewed by 1380
Abstract
Fat grafting is widely used in plastic surgery to correct soft tissue deformities. A major limitation of this technique is the poor long-term volume retention of the injected fat due to tissue remodeling and adipocyte death. To address this issue, various optimizations of [...] Read more.
Fat grafting is widely used in plastic surgery to correct soft tissue deformities. A major limitation of this technique is the poor long-term volume retention of the injected fat due to tissue remodeling and adipocyte death. To address this issue, various optimizations of the grafting process have been proposed. This scoping review focuses on preclinical and clinical studies that investigated the impact of various classes of soluble molecules on fat grafting outcomes. Globally, we describe that these molecules can be classified as acting through three main mechanisms to improve graft retention: supporting adipogenesis, improving vascularization, and reducing oxidative stress. A variety of 18 molecules are discussed, including insulin, VEGF, deferoxamine, botulinum toxin A, apocynin, N-acetylcysteine, and melatonin. Many biomolecules have shown the potential to improve long-term outcomes of fat grafts through enhanced cell survival and higher volume retention. However, the variability between experimental protocols, as well as the scarcity of clinical studies, remain obstacles to clinical translation. In order to determine the best preconditioning method for fat grafts, future studies should focus on dosage optimization, more sustained delivery of the molecules, and the design of homogenous experimental protocols and specific clinical trials. Full article
(This article belongs to the Section Molecular Medicine)
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21 pages, 2412 KiB  
Review
Role of γ-Aminobutyric Acid (GABA) as an Inhibitory Neurotransmitter in Diabetes Management: Mechanisms and Therapeutic Implications
by Hassan Barakat and Thamer Aljutaily
Biomolecules 2025, 15(3), 399; https://doi.org/10.3390/biom15030399 - 11 Mar 2025
Cited by 7 | Viewed by 2512
Abstract
GABA (γ-Aminobutyric Acid), a well-established inhibitory neurotransmitter in the central nervous system, has garnered considerable interest for its potential role in diabetes management, particularly due to its presence in pancreatic islets. This review aims to explore the therapeutic role of GABA in diabetes [...] Read more.
GABA (γ-Aminobutyric Acid), a well-established inhibitory neurotransmitter in the central nervous system, has garnered considerable interest for its potential role in diabetes management, particularly due to its presence in pancreatic islets. This review aims to explore the therapeutic role of GABA in diabetes management and its potential mechanisms for antidiabetic effects. Relevant studies were searched across databases such as PubMed and ScienceDirect, applying strict eligibility criteria focused on GABA administration methods and diabetic models. The collective results showed that the administration of GABA in diabetic models resulted in remarkable enhancements in glucose and insulin homeostasis, favorable modifications in lipid profiles, and amelioration of dysfunctions across neural, hepatic, renal, and cardiac systems. The findings from the literature demonstrated that GABAergic signaling within pancreatic tissues can significantly contribute to the stimulation of β cell proliferation through the facilitation of a sustained trans-differentiation process, wherein glucagon-secreting α cells are converted into insulin-secreting β-like cells. In addition, activated GABAergic signaling can trigger the initiation of the PI3K/AKT signaling pathway within pancreatic tissues, leading to improved insulin signaling and maintained glucose homeostasis. GABAergic signaling can further function within hepatic tissues, promoting inhibitory effects on the expression of genes related to gluconeogenesis and lipogenesis. Moreover, GABA may enhance gut microbiota diversity by attenuating gut inflammation, attributable to its anti-inflammatory and immunomodulatory properties. Furthermore, the neuroprotective effects of GABA play a significant role in ameliorating neural disorders associated with diabetes by facilitating a substantial reduction in neuronal apoptosis. In conclusion, GABA emerges as a promising candidate for an antidiabetic agent; however, further research is highly encouraged to develop a rigorously designed framework that comprehensively identifies and optimizes the appropriate dosages and intervention methods for effectively managing and combating diabetes. Full article
(This article belongs to the Special Issue Therapeutic Potential of Natural Products in Metabolic Diseases)
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12 pages, 249 KiB  
Article
Association Between Hypertension, Dipping Status, and ACE and AGTR1 Gene Polymorphisms in Adolescents with Type 1 Diabetes
by Smiljka Kovacevic, Maja Jesic, Vera Zdravkovic, Stefan Djordjevic, Jelena Miolski, Vladimir Gasic, Marina Jelovac, Milena Ugrin, Sonja Pavlovic and Branko Subosic
Biomedicines 2025, 13(3), 615; https://doi.org/10.3390/biomedicines13030615 - 3 Mar 2025
Viewed by 1229
Abstract
Objectives: This study aims to show the distribution of angiotensin-converting enzyme (ACE) rs1799752 (I>D) gene insertion/deletion (I/D) polymorphism and angiotensin II receptor type 1 (AGTR1) rs5186 (A>C) gene polymorphism in adolescents with hypertension (HT) and type [...] Read more.
Objectives: This study aims to show the distribution of angiotensin-converting enzyme (ACE) rs1799752 (I>D) gene insertion/deletion (I/D) polymorphism and angiotensin II receptor type 1 (AGTR1) rs5186 (A>C) gene polymorphism in adolescents with hypertension (HT) and type 1 diabetes (T1D), as well as its association with hypertension and the diurnal variation of mean blood pressure (dipping phenomenon). Methods: A cross-sectional study was conducted involving 118 adolescents diagnosed with T1D who underwent clinical and laboratory investigations, genetic analyses, and 24 h ambulatory blood pressure monitoring. The genotype frequencies were compared between adolescents with HT and those with normal blood pressure. Additionally, the genotype frequencies were compared between dippers and non-dippers. Results: Patients with HT were more likely to be female and exhibited significantly poorer glycemic control and higher triglycerides, along with increased body mass index and daily insulin dosage. The prevalence of ACE rs1799752 genotypes in the hypertensive group was 20% II, 66.7% ID, and 13.3% DD, which did not significantly differ from the normal blood pressure group with 29.1% II, 53.4% ID, and 17.5% DD (p = 0.625). The prevalence of AGTR1 rs5186 genotypes in the hypertensive group was 53.3% AC, 40% AA, and 6.7% CC, which also did not significantly differ from the normal blood pressure group with 39.8% AC, 52.4% AA, and 7.8% CC (p = 0.608). A total of 46% of the patients exhibited non-dipping phenomena. The prevalence of non-dippers among the ACE genotypes was 13% DD, 33.3% II, and 53.7% ID (p = 0.369), while for the AGTR1 genotypes, it was 50% AA, 42.6% AC, and 7.4% CC (p = 0.976). Conclusions: Our results indicate that in our adolescents with T1D, clinical and metabolic factors such as higher body mass index, triglycerides, suboptimal glycemic control, and female gender are more indicative of the development of hypertension than ACE and AGTR1 gene polymorphisms. A potential reason for this finding could be the young age of the patients or the relatively small size of the study group. Future research involving larger sample sizes is needed to further investigate the genetic predisposition for the development of hypertension. Full article
(This article belongs to the Special Issue Diabetes: Comorbidities, Therapeutics and Insights (2nd Edition))
23 pages, 7563 KiB  
Article
Hesperetin-Enhanced Metformin to Alleviate Cognitive Impairment via Gut–Brain Axis in Type 2 Diabetes Rats
by Danyang Zhang, Xiaoshi He, Yinbo Wang, Xiaoyu Wang, Xiao Han, Haodong Liu, Yan Xing, Bo Jiang, Zhilong Xiu, Yongming Bao and Yuesheng Dong
Int. J. Mol. Sci. 2025, 26(5), 1923; https://doi.org/10.3390/ijms26051923 - 23 Feb 2025
Cited by 1 | Viewed by 1271
Abstract
Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and cognitive decline. The use of metformin for treating cognitive impairment remains controversial. The present study found that hesperetin, a flavanone derived from citrus [...] Read more.
Diabetes constitutes a risk factor for cognitive impairment, whereas insulin resistance serves as the shared pathogenesis underlying both diabetes and cognitive decline. The use of metformin for treating cognitive impairment remains controversial. The present study found that hesperetin, a flavanone derived from citrus peel, enhanced metformin’s efficacy in reducing blood sugar levels, improving insulin sensitivity, and ameliorating cognitive impairment in diabetic rats. Additionally, it reduced the required dosage of metformin to one-third of its conventional dose. Transcriptome analysis and 16S rRNA sequencing revealed that the activation of insulin and cyclic-adenosine monophosphate response element binding protein (CREB)/brain-derived neurotrophic factor (BDNF) pathways benefited from the regulation of gut microbiota and the promotion of short-chain fatty acid (SCFA) producers such as Romboutsia. Furthermore, this study demonstrated that hesperetin supplementation counteracted the upregulation of β-site amyloid precursor protein cleaving enzyme 1 (BACE1), a pathological factor of Alzheimer’s disease (AD) that was induced by metformin. Our findings reveal that hesperetin can be used in supplementary treatment for cognitive impairment associated with diabetes. Full article
(This article belongs to the Special Issue Plant Phenolic Accumulation and Application in Human Diseases)
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8 pages, 211 KiB  
Article
Serum Carnosinase 1 Is Not Associated with Insulin Resistance or Glucose Metabolism in a Type 1 Diabetes Cohort
by Jiedong Qiu, Benito A. Yard, Bernhard K. Krämer, Harry van Goor, Peter R. van Dijk and Aimo Kannt
Biomedicines 2025, 13(2), 366; https://doi.org/10.3390/biomedicines13020366 - 5 Feb 2025
Viewed by 835
Abstract
Background/Objectives: Preclinical studies suggest that the deleterious effect of a high serum carnosinase 1 (CN1) concentration is attributed to its adverse effects on insulin sensitivity and glucose metabolism. However, there is little evidence for a modulating role of CN1 in glucose metabolism [...] Read more.
Background/Objectives: Preclinical studies suggest that the deleterious effect of a high serum carnosinase 1 (CN1) concentration is attributed to its adverse effects on insulin sensitivity and glucose metabolism. However, there is little evidence for a modulating role of CN1 in glucose metabolism in humans. Methods: We measured serum CN1 concentration in an observational type 1 diabetes cohort of 172 patients in whom glucose variability (MAGE, MODD, SD of individual blood glucose, mean, and CV) was recorded by blinded continuous glucose monitoring for 5–7 days. Furthermore, insulin dose per kg body weight was compared. Results: Insulin sensitivity (insulin dosage) and glucose variability parameters did not differ between different CN1 tertiles (p > 0.05). Conclusions: There was no association of serum CN1 with indices of glucose variability in this type 1 diabetes cohort. Full article
(This article belongs to the Special Issue Diabetic Nephropathy and Diabetic Atherosclerosis)
19 pages, 1337 KiB  
Article
Exploiting Personalized Observation Frequency for Proportional Integral Derivative-Based Diabetes Management
by Phuwadol Viroonluecha, Esteban Egea-Lopez and Jose Santa
Electronics 2025, 14(3), 560; https://doi.org/10.3390/electronics14030560 - 30 Jan 2025
Viewed by 816
Abstract
People with type 1 diabetes (T1D) need to monitor their blood glucose level frequently and use insulin to regulate it. T1D typically develops in young individuals and requires lifelong insulin injections for glycemic control. High or low blood glucose levels can lead to [...] Read more.
People with type 1 diabetes (T1D) need to monitor their blood glucose level frequently and use insulin to regulate it. T1D typically develops in young individuals and requires lifelong insulin injections for glycemic control. High or low blood glucose levels can lead to serious health issues. To address the challenges posed by regular monitoring and manual insulin injections, automated glucose control methods have been developed. Various insulin regimes are used to manage blood sugar levels, such as traditional regimes that involve one or two injections per day or multiple daily injection therapy, which offers more flexibility in the diet and dosage but still requires patients to monitor their carbohydrate intake and insulin injections. A proportional integral derivative (PID) controller is an automated glucose control method that is commonly used in commercial and research settings due to its simplicity and robustness. However, despite its effectiveness, this method can be affected by external factors like food, exercise, and illness. This study proposes to set an individualized observation frequency (OF) per user for the PID controller for blood glucose control in T1D. Optimizing the OF improves the PID controller’s performance, maintaining or elevating median glucose levels. Tuning the OF offers a simple and effective enhancement for the widely used PID controller. Full article
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