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Search Results (351)

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Keywords = diabetes mellitus type II

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19 pages, 427 KiB  
Review
The Role of Viral Infections in the Immunopathogenesis of Type 1 Diabetes Mellitus: A Narrative Review
by Ioanna Kotsiri, Maria Xanthi, Charalampia-Melangeli Domazinaki and Emmanouil Magiorkinis
Biology 2025, 14(8), 981; https://doi.org/10.3390/biology14080981 (registering DOI) - 2 Aug 2025
Viewed by 266
Abstract
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells, resulting in lifelong insulin dependence. While genetic susceptibility—particularly human leukocyte antigen (HLA) class II alleles—is a major risk factor, accumulating evidence implicates viral infections [...] Read more.
Type 1 diabetes mellitus (T1DM) is a chronic autoimmune disorder characterized by the destruction of insulin-producing pancreatic beta cells, resulting in lifelong insulin dependence. While genetic susceptibility—particularly human leukocyte antigen (HLA) class II alleles—is a major risk factor, accumulating evidence implicates viral infections as potential environmental triggers in disease onset and progression. This narrative review synthesizes current findings on the role of viral pathogens in T1DM pathogenesis. Enteroviruses, especially Coxsackie B strains, are the most extensively studied and show strong epidemiological and mechanistic associations with beta-cell autoimmunity. Large prospective studies—including Diabetes Virus Detection (DiViD), The environmental determinans of diabetes in the young (TEDDY), Miljøfaktorer i utvikling av type 1 diabetes (MIDIA), and Diabetes Autoimmunity Study in the Young (DAISY)—consistently demonstrate correlations between enteroviral presence and the initiation or acceleration of islet autoimmunity. Other viruses—such as mumps, rubella, rotavirus, influenza A (H1N1), and SARS-CoV-2—have been investigated for their potential involvement through direct cytotoxic effects, immune activation, or molecular mimicry. Interestingly, certain viruses like varicella-zoster virus (VZV) and cytomegalovirus (CMV) may exert modulatory or even protective influences on disease progression. Proposed mechanisms include direct beta-cell infection, molecular mimicry, bystander immune activation, and dysregulation of innate and adaptive immunity. Although definitive causality remains unconfirmed, the complex interplay between genetic predisposition, immune responses, and viral exposure underscores the need for further mechanistic research. Elucidating these pathways may inform future strategies for targeted prevention, early detection, and vaccine or antiviral development in at-risk populations. Full article
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14 pages, 1040 KiB  
Article
Diabetes Worsens Outcomes After Asphyxial Cardiac Arrest in Rats
by Matthew B. Barajas, Takuro Oyama, Masakazu Shiota, Zhu Li, Maximillian Zaum, Ilija Zecevic and Matthias L. Riess
Diabetology 2025, 6(8), 78; https://doi.org/10.3390/diabetology6080078 - 1 Aug 2025
Viewed by 163
Abstract
Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function [...] Read more.
Background: Diabetes mellitus is associated with worse outcomes after cardiac arrest. Hyperglycemia, diabetes treatments and other long-term sequalae may contribute to this association. We sought to determine the acute effect of diabetes on the return of spontaneous circulation (ROSC) and post-arrest cardiac function in a rat cardiac arrest model. Methods: Eighteen male Wistar rats were utilized, and 12 underwent the induction of type II diabetes for 10 weeks through a high-fat diet and the injection of streptozotocin. The carotid artery flow and femoral arterial pressure were measured. Seven minutes of asphyxial cardiac arrest was induced. An external cardiac compression was performed via an automated piston. Post-ROSC, epinephrine was titrated to a mean arterial pressure (MAP) of 70 mmHg. Data was analyzed using the Mann–Whitney test. The significance was set at p ≤ 0.05. Results: The rate of the ROSC was significantly lower in animals with diabetes, 50% compared to 100% in non-diabetics. Additionally, it took significantly longer to achieve the ROSC in diabetics, p = 0.034. In animals who survived, the cardiac function was reduced, as indicated by an increased epinephrine requirement, p = 0.041, and a decreased cardiac output at the end of the experiment, p = 0.017. The lactate, venous and arterial pressures, heart rate and carotid flow did not differ between groups at 2 h. Conclusions: Diabetes negatively affects the survival from cardiac arrest. Here, the critical difference was the rate of the conversion to a life-sustaining rhythm and the achievement of the ROSC. The post-ROSC cardiac function was depressed in diabetic animals. Interventions targeted at improving defibrillation success may be important in diabetics. Full article
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20 pages, 656 KiB  
Review
Culinary Medicine in Type II Diabetes Mellitus Management: A Narrative Review of Randomized Clinical Trials on Dietary Interventions (Nutritional Profiles of Meals and Snacks, Timing, Preparation and Key Considerations)
by Maria Dimopoulou, Odysseas Androutsos, Michail Kipouros, Alexandra Bargiota and Olga Gortzi
Diabetology 2025, 6(8), 72; https://doi.org/10.3390/diabetology6080072 - 31 Jul 2025
Viewed by 306
Abstract
According to the National Institutes of Health, approximately 465 million individuals are affected by type II diabetes mellitus (T2DM) and could benefit from managing their condition with a high-quality diet based on proper, nutrient-rich food choices. A plant-based diet not only has health [...] Read more.
According to the National Institutes of Health, approximately 465 million individuals are affected by type II diabetes mellitus (T2DM) and could benefit from managing their condition with a high-quality diet based on proper, nutrient-rich food choices. A plant-based diet not only has health benefits but also helps mitigate climate change by reducing greenhouse gas emissions, but the Mediterranean diet has the most beneficial effect on overall health. In contrast, ultra-processed foods have a negative impact on T2DM outcomes. Reviewing the nutritional profile of different meals, snacks and desserts would be helpful in enhancing their quality, strengthening the role of dietitians and doctors and protecting against T2DM complications. This approach would also increase simplification and education for consumers. The PubMed-Medline, Web of Science, Scopus and Cochrane Library databases were searched for relevant articles published up to May, from 2000 (based on publication date). The results support the need to reinforce health claims and highlight public demand for food choices while also improving patient quality of life. Full article
(This article belongs to the Special Issue Obesity and Diabetes: Healthy Lifestyle Choices)
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20 pages, 3927 KiB  
Review
A Historical and Epistemological Review of Type 1 Diabetes Mellitus
by Eugenio Cavalli, Giuseppe Rosario Pietro Nicoletti and Ferdinando Nicoletti
J. Clin. Med. 2025, 14(14), 4923; https://doi.org/10.3390/jcm14144923 - 11 Jul 2025
Viewed by 548
Abstract
Over the past century, the understanding of type 1 diabetes mellitus (T1DM) has evolved significantly, transitioning from a fatal metabolic disorder to a well-characterized autoimmune disease. This review explores the historical developments and scientific milestones that have reshaped the perception of T1DM, highlighting [...] Read more.
Over the past century, the understanding of type 1 diabetes mellitus (T1DM) has evolved significantly, transitioning from a fatal metabolic disorder to a well-characterized autoimmune disease. This review explores the historical developments and scientific milestones that have reshaped the perception of T1DM, highlighting key discoveries and shifts in medical paradigms. Methods: A comprehensive narrative review was conducted, examining literature spanning from ancient medical texts to contemporary research up to 2024. Emphasis was placed on pivotal moments such as the discovery of insulin in 1921, the recognition of autoimmune mechanisms in the 1970s, and recent advancements in immunotherapy. Results: The reclassification of T1DM as an autoimmune disease was supported from multiple lines of evidences including the presence of islet cell autoantibodies, the identification of lymphocytic infiltration in pancreatic islets, and the associations of the disease with certain HLA class II alleles. The development of animal models and large-scale cohort studies facilitated the establishment of disease staging and risk prediction models. Notably, the approval of immunotherapies like teplizumab underscores the translational impact of these scientific insights. Conclusions: The historical trajectory of T1DM exemplifies the dynamic nature of medical knowledge and the interplay between clinical observations and scientific research. Recognizing these developments enhances our comprehension of disease mechanisms and informs current approaches to diagnosis and treatment. Full article
(This article belongs to the Section Clinical Guidelines)
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17 pages, 2986 KiB  
Article
Modulatory Role of Hesperetin–Copper(II) on Gut Microbiota in Type 2 Diabetes Mellitus Mice
by Xi Peng, Yushi Wei, Deming Gong and Guowen Zhang
Foods 2025, 14(13), 2390; https://doi.org/10.3390/foods14132390 - 6 Jul 2025
Viewed by 495
Abstract
Background: Exploring new strategies to improve type 2 diabetes mellitus (T2DM) is one of the frontier hotspots in the field of healthy food. Flavonoid–metal complexes have become one of the research hotspots in the field of health foods due to their unique structural [...] Read more.
Background: Exploring new strategies to improve type 2 diabetes mellitus (T2DM) is one of the frontier hotspots in the field of healthy food. Flavonoid–metal complexes have become one of the research hotspots in the field of health foods due to their unique structural and functional properties. Methods: In this study, the effect of hesperetin–copper(II) complex [Hsp–Cu(II)] on the gut microbiota of mice with T2DM was investigated by the 16S rRNA high-throughput sequencing. Results: The analyses of α and β diversity indicated that the richness and diversity of gut microbiota in the T2DM mice decreased and the community structure was significantly different from the normal mice. Hsp–Cu(II) increased the abundances of the beneficial bacteria (Lactobacillus, Ligilactobacillus, Romboutsia, Faecalibaculum, and Dubosiella), and decreased the amounts of the harmful bacteria (Desulfobacterota, Corynebacterium, and Desulfovibrio) and the ratio of Firmicutes/Bacteroidetes (from 44.5 to 5.8) in the T2DM mice, which was beneficial for regulating the composition of intestinal microbiota. The linear discriminant analysis effect size analysis showed that the intervention of Hsp–Cu(II) made the short-chain fatty acid (SCFA) producers (o_Lachnospirales, f_Lachnospiraceae, g_Faecalibaculum, g_Romboutsia, and g_Turicibacter) and the lactic acid bacteria producers (f_Lactobacillaceae and o_Lactobacillales) highly enriched, and the production of its metabolite SCFAs (acetic acid, propionic acid, butyric acid, and valeric acid) were increased in a dose-dependent manner, promoting the SCFA metabolism. Conclusions: Hsp–Cu(II) may improve glucose metabolic disorders and alleviate T2DM by modulating gut microbiota composition, promoting probiotics proliferation and SCFAs production, restoring intestinal barrier integrity, and suppressing local inflammation. These research findings may provide a theoretical basis for developing Hsp–Cu(II) as a new hypoglycemic nutritional supplement, and offer new ideas for the dietary food nutritional regulation to alleviate T2DM. Full article
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10 pages, 190 KiB  
Article
Type II Diabetes Mellitus and COVID-19: Exploring Insulin Management in Patients from Family Medicine Clinics
by Chinemerem Opara, Annesha White, Kimberly G. Fulda, Somer Blair, Clare Aduwari, Nihitha Nukala and Yan Xiao
Pharmacy 2025, 13(4), 93; https://doi.org/10.3390/pharmacy13040093 - 4 Jul 2025
Viewed by 340
Abstract
The COVID-19 pandemic disrupted routine care for individuals with type 2 diabetes mellitus (T2DM), raising concerns about its impact on glycemic control and medication management. This study evaluated the relationship between insulin use and glycemic control among T2DM patients during the pandemic. A [...] Read more.
The COVID-19 pandemic disrupted routine care for individuals with type 2 diabetes mellitus (T2DM), raising concerns about its impact on glycemic control and medication management. This study evaluated the relationship between insulin use and glycemic control among T2DM patients during the pandemic. A retrospective analysis was conducted using deidentified clinical and prescription data from two family medicine clinics, comparing data from the pre-COVID-19 period (1 March 2019–13 March 2020) and during the COVID-19 pandemic (14 March 2020–31 March 2021). Patients included had at least two A1c values before the COVID and one during the COVID. A1c control was defined as less than 8%. Among 992 patients, 238 experienced a change in A1c status: 128 improved and 110 worsened. Mean A1c remained stable at 8.2 across both periods. A majority of patients who improved were using insulin during the COVID-19 era, although some discontinued insulin at some point during the study period. These findings suggest that consistent insulin therapy may have helped maintain glycemic control despite healthcare disruptions. This study highlights the importance of sustained medication management and suggests that integrating telehealth and pharmacist-led care could support diabetes control during future healthcare system challenges. Full article
(This article belongs to the Collection New Insights into Pharmacy Teaching and Learning during COVID-19)
14 pages, 919 KiB  
Article
The Association Between Uterine Artery Pulsatility Index at Mid-Gestation and the Method of Conception: A Cohort Study
by Antonios Siargkas, Ioannis Tsakiridis, Dimitra Kappou, Apostolos Mamopoulos, Ioannis Papastefanou and Themistoklis Dagklis
Medicina 2025, 61(6), 1093; https://doi.org/10.3390/medicina61061093 - 16 Jun 2025
Viewed by 649
Abstract
Background and Objectives: Pregnancies resulting from assisted reproductive technology (ART) have been associated with placenta-related adverse outcomes. Uterine artery Doppler pulsatility index (UtA-PI) reflects placental function. This study aimed to examine whether second-trimester UtA-PI differs according to the conception method after adjusting [...] Read more.
Background and Objectives: Pregnancies resulting from assisted reproductive technology (ART) have been associated with placenta-related adverse outcomes. Uterine artery Doppler pulsatility index (UtA-PI) reflects placental function. This study aimed to examine whether second-trimester UtA-PI differs according to the conception method after adjusting for potential confounding factors. Materials and Methods: In this retrospective cohort study, we included data from February 2015 to August 2024, at the third Department of Obstetrics and Gynecology, School of Medicine, Faculty of Health Sciences, Aristotle University of Thessaloniki, Greece, on singleton pregnancies presenting for their routine antenatal care, including a second-trimester anomaly scan. Pregnancies conceived via ART, including those conceived via ovulation induction/intrauterine insemination (OI/IUI) or in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI), were compared to those conceived spontaneously. Multiple linear regression was employed to investigate the association between the mode of conception and log10 UtA-PI values, adjusting for various confounders, including gestational age at the time of the scan, maternal weight, height, age, parity, mode of delivery, smoking status, pre-existing diabetes mellitus (type I or II), and pre-existing thyroid disease. Results: The study included 15,552 singleton pregnancies, of which 82 (0.5%) were conceived via OI/IUI and 690 (4.4%) were conceived via IVF/ICSI. The median UtA-PI values were 0.99 (IQR: 0.85–1.17) for spontaneous conception (SC), 1.00 (IQR: 0.86–1.16) for OI/IUI, and 0.90 (IQR: 0.76–1.12) for IVF/ICSI. The Kruskal–Wallis test indicated a statistically significant difference among these groups (p < 0.001). Pairwise comparisons using the Wilcoxon rank-sum test with Bonferroni correction revealed that UtA-PI values in IVF/ICSI pregnancies were significantly lower compared to both SC and OI/IUI pregnancies (p < 0.001 for both). No significant difference was observed between the SC and OI/IUI groups. In the multivariable linear regression model, IVF/ICSI conception was independently associated with lower log10 UtA-PI values (estimate = −0.076, 95% CI: −0.096, −0.056) while no association was found for OI/IUI conception. Conclusions: Although ART has been associated with placental-related complications, mid-trimester UtA flow was found to be lower in IVF/ICSI pregnancies, suggesting better utero-placental flow in ART pregnancies and other possible mechanisms in the maternal–placental interplay for the development of pregnancy complications. Full article
(This article belongs to the Section Obstetrics and Gynecology)
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15 pages, 773 KiB  
Article
The Role of Neutrophil-to-Lymphocyte Ratio and Platelet-to-Lymphocyte Ratio in Predicting Atrial Fibrillation and Its Comorbidities
by Evelina Maria Gosav, Daniela Maria Tanase, Anca Ouatu, Oana Nicoleta Buliga-Finis, Diana Popescu, Cristina Gena Dascalu, Nicoleta Dima, Minerva Codruta Badescu and Ciprian Rezus
Life 2025, 15(6), 960; https://doi.org/10.3390/life15060960 - 16 Jun 2025
Cited by 1 | Viewed by 619
Abstract
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias encountered globally, characterized by a pro-inflammatory pattern. This analysis evaluated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with AF alongside chronic kidney disease (CKD) and/or type 2 diabetes mellitus [...] Read more.
Atrial fibrillation (AF) is one of the most common cardiac arrhythmias encountered globally, characterized by a pro-inflammatory pattern. This analysis evaluated the neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) in patients with AF alongside chronic kidney disease (CKD) and/or type 2 diabetes mellitus (T2DM). This retrospective cohort study included 6077 patients admitted to the Third Medical Clinic of Saint Spiridon Hospital in Iasi from 2018 to 2023, all diagnosed with AF, CKD, and T2DM. After applying the exclusion criteria, 1066 AF patients remained eligible. For a multivariate comparative analysis, the patients were divided into groups: I. control group (non-AF patients); II. AF patients; III. T2DM group; IV. CKD-only group; V. AF+CKD group; VI. AF+T2DM group; and VII. AF+T2DM+CKD group. The Mann–Whitney/Kruskal–Wallis test demonstrated a statistically significant difference in NLR and PLR values between the AF group and the non-AF group (H = 70.627, p < 0.001). The receiver operating characteristic (ROC) analysis identified statistical significance and predictive power for NLR (AUC = 0.722; sensitivity = 63.6%; specificity = 76.9%) and neutrophil count in diagnosing AF, T2DM, and CKD. In conclusion, this study illustrated the utility of NLR and PLR as readily available and predictive biomarkers of inflammation in patients with AF, with or without comorbidities. Full article
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13 pages, 531 KiB  
Article
Study of MicroRNA-192 as an Early Biomarker for Diagnosis of Diabetic Nephropathy
by Mohamad Motawea, Mayada S. Khalel, Ismail Kandil, Ahmed Mohsen Faheem, Maysaa El Sayed Zaki, Mostafa Abdelsalam and Fady Kyrillos
Diagnostics 2025, 15(12), 1504; https://doi.org/10.3390/diagnostics15121504 - 13 Jun 2025
Viewed by 931
Abstract
Background/Objectives: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. This clinical condition is diagnosed through the detection of microalbuminuria. Molecular biomarkers such as MicroRNA-192 may play a role in the early diagnosis of this condition. This study aims to compare the [...] Read more.
Background/Objectives: Diabetic nephropathy (DN) is a serious complication of diabetes mellitus. This clinical condition is diagnosed through the detection of microalbuminuria. Molecular biomarkers such as MicroRNA-192 may play a role in the early diagnosis of this condition. This study aims to compare the serum concentrations of MicroRNA-192 in diabetic patients with and without DN and in healthy individuals. Methods: This study was a retrospective case-control study that included three groups. Group I included diabetic patients without DN, Group II included patients with DN, and Group III included healthy control subjects. Blood samples were obtained from each participant and subjected to a full biochemical study including creatinine, albumin, and the detection of MicroRNA-192 by real-time polymerase chain reaction. Results: There were significant differences among the MicroRNA-192 levels in the three groups (p-0.001). There was a significant increase in the MicroRNA-192 level in Group I (1.35 ± 7 0.5) compared with Group II (0.65 ± 7 0.2, p3 = 0.001) and Group III (0.83 ± 7 0.3, p1-0.001). There was a significant reduction in the MicroRNA-192 level in Group II compared with Group III (p2-0.001). Conclusions: This study highlights the potential role of serum miR-192 as a noninvasive biomarker for the early detection of DN in patients with type 2 DM. Our findings demonstrated that serum miR-192 levels were significantly reduced in patients with DN compared with diabetic patients without nephropathy and healthy controls, suggesting the possible protective role of miR-192 in early disease stages. Full article
(This article belongs to the Section Pathology and Molecular Diagnostics)
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9 pages, 776 KiB  
Brief Report
Increased O-GlcNAcylation in Leukocytes from Overweight Pediatric Subjects: A Pilot Study
by Alessia Remigante, Sara Spinelli, Gianluca Rizzo, Daniele Caruso, Angela Marino, Elisabetta Straface, Silvia Dossena and Rossana Morabito
Int. J. Mol. Sci. 2025, 26(12), 5665; https://doi.org/10.3390/ijms26125665 - 13 Jun 2025
Viewed by 450
Abstract
Type II diabetes mellitus (T2D) is a metabolic disorder. Childhood overweight or obesity raises the risk for developing T2D later in life. Early identification of at-risk individuals is fundamental for disease prevention and patient management. The scope of this pilot study was to [...] Read more.
Type II diabetes mellitus (T2D) is a metabolic disorder. Childhood overweight or obesity raises the risk for developing T2D later in life. Early identification of at-risk individuals is fundamental for disease prevention and patient management. The scope of this pilot study was to explore whether leukocyte protein O-GlcNAc modification is elevated in an overweight pediatric cohort. Eight overweight and eight normal-weight children aged 3–13 years were recruited at the Papardo General Hospital (Messina, Italy). Physical exams, complete blood tests, and determination of leukocyte protein O-GlcNAcylation were carried out. Protein O-GlcNAcylation was higher in leucocytes from overweight children compared to normal-weight children, and was significantly correlated with BMI, metabolic markers (LDL-cholesterol/triglycerides), and the inflammatory marker CRP. This study suggests that leukocyte protein O-GlcNAcylation may represent a novel biomarker for the early detection of metabolic abnormalities that may lead to the development of pre-diabetes or T2D later in life. Full article
(This article belongs to the Section Molecular Pathology, Diagnostics, and Therapeutics)
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12 pages, 811 KiB  
Review
Retatrutide—A Game Changer in Obesity Pharmacotherapy
by Vasiliki Katsi, Georgios Koutsopoulos, Christos Fragoulis, Kyriakos Dimitriadis and Konstantinos Tsioufis
Biomolecules 2025, 15(6), 796; https://doi.org/10.3390/biom15060796 - 30 May 2025
Viewed by 5280
Abstract
Obesity and type 2 diabetes mellitus (T2DM) are global health crises with significant morbidity and mortality. Retatrutide, a novel triple receptor agonist targeting glucagon-like peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors, represents a groundbreaking advancement in obesity and T2DM pharmacotherapy. This [...] Read more.
Obesity and type 2 diabetes mellitus (T2DM) are global health crises with significant morbidity and mortality. Retatrutide, a novel triple receptor agonist targeting glucagon-like peptide-1 (GLP-1), Glucose-Dependent Insulinotropic Polypeptide (GIP), and glucagon receptors, represents a groundbreaking advancement in obesity and T2DM pharmacotherapy. This review synthesizes findings from preclinical and clinical studies, highlighting retatrutide’s mechanisms, efficacy, and safety profile. Retatrutide’s unique molecular structure enables potent activation of GLP-1, GIP, and glucagon receptors, leading to significant weight reduction, improved glycemic control, and favorable metabolic outcomes. Animal studies demonstrate retatrutide’s ability to delay gastric emptying, reduce food intake, and promote weight loss, with superior efficacy compared to other incretin-based therapies. Phase I and II clinical trials corroborate these findings, showing dose-dependent weight loss, reductions in Glycated Hemoglobin (HbA1c) levels, and improvements in liver steatosis and diabetic kidney disease. Common adverse effects are primarily gastrointestinal and dose-related. Ongoing Phase III trials, such as the TRIUMPH studies, aim to further evaluate retatrutide’s long-term safety and efficacy in diverse patient populations. While retatrutide shows immense promise, considerations regarding cost and the quality of weight loss beyond BMI reduction warrant further investigation. Retatrutide heralds a new era in obesity and T2DM treatment, offering hope for improved patient outcomes. Full article
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11 pages, 632 KiB  
Article
Age-Dependent Loss of Sirtuin1 (Sirt1) Correlates with Reduced Autophagy in Type 2 Diabetic Patients (T2DM)
by Julia Fischer, Nina Judith Hos, Sophie Tritschler, Joel Schmitz-Peters, Raja Ganesan, Chiara Calabrese, Petra Schiller, Hannah Brunnert, Angela Nowag, Sandra Winter, Ruth Hanßen, Katja Römer, Nazifa Qurishi, Isabelle Suarèz, Norma Jung, Clara Lehmann, Georg Plum, Michael Faust, Pia Hartmann and Nirmal Robinson
Diabetology 2025, 6(6), 45; https://doi.org/10.3390/diabetology6060045 - 23 May 2025
Viewed by 679
Abstract
Aims and Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 [...] Read more.
Aims and Background: Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder frequently associated with increased inflammation and dysregulated innate immune responses. Thus, patients with T2DM are predisposed to bacterial infections. However, the underlying mechanism is poorly understood. The NAD+-dependent deacetylase Sirtuin1 (SIRT1) plays an important role in regulating cellular metabolism, including T2DM and aging. Furthermore, we have recently demonstrated that SIRT1 critically regulates inflammatory pathways and autophagy during infection. Thus, we aimed to investigate SIRT1 expression and its correlation with autophagy in peripheral blood mononuclear cells (PBMCs) from patients with T2DM compared to non-diabetic patients. Methods: Clinical characteristics of the study subjects were obtained. SIRT1 and autophagic markers such as p62 and LC3-I/II were determined using Western blot analysis followed by densitometric analysis. Results: We found that SIRT1 levels were decreased in PBMCs of diabetic patients in an age-dependent manner. Importantly, reduced SIRT1 expression correlated with reduced LC3-II/I ratios, indicating reduced autophagy. Reduced SIRT1 also corresponded to decreased autophagic adaptor protein Sequestome-1/p62. Conclusions: In summary, our results suggest a potential role of SIRT1 in regulating autophagy in PBMCs from T2DM patients. Full article
(This article belongs to the Special Issue Feature Papers in Diabetology 2024)
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25 pages, 5232 KiB  
Article
Oral Sulforaphane Intervention Protects Against Diabetic Cardiomyopathy in db/db Mice: Focus on Cardiac Lipotoxicity and Substrate Metabolism
by Pan Wang, Ziling Wang, Xinyuan Jin, Mengdi Zhang, Mengfan Shen and Dan Li
Antioxidants 2025, 14(5), 603; https://doi.org/10.3390/antiox14050603 - 16 May 2025
Viewed by 918
Abstract
The protective effect of cruciferae-derived sulforaphane (SFN) on diabetic cardiomyopathy (DCM) has garnered increasing attention. However, no studies have specifically explored its mechanistic involvement in cardiac substrate metabolism and mitochondrial function. To address this gap, Type 2 diabetes mellitus (T2DM) db/db mice were [...] Read more.
The protective effect of cruciferae-derived sulforaphane (SFN) on diabetic cardiomyopathy (DCM) has garnered increasing attention. However, no studies have specifically explored its mechanistic involvement in cardiac substrate metabolism and mitochondrial function. To address this gap, Type 2 diabetes mellitus (T2DM) db/db mice were orally gavaged with vehicle or 10 mg/kg body weight SFN every other day for 16 weeks, with vehicle-treated wild-type mice as controls. SFN intervention (SFN-I) alleviated hyperglycemia, dyslipidemia, HOMA-IR, serum MDA levels, and liver inflammation. Furthermore, SFN-I improved the lipotoxicity-related phenotype of T2DM cardiomyopathy, manifested as attenuation of diastolic dysfunction, cardiac injury, fibrosis, lipid accumulation and peroxidation, ROS generation, and decreased mitochondrial complex I and II activities and ATP content, despite having no effect on ceramide abnormalities. Protein expression data revealed that the model mice exhibited upregulated cardiac CD36, H-FABP, FATP4, CPT1B, PPARα, and PDK4 but downregulated GLUT4, with unchanged MPC1 and MPC2. Notably, SFN-I significantly attenuated the increase in CD36, H-FABP, CPT1B, and PPARα. These results suggest that chronic oral SFN-I protects against DCM by mitigating overall metabolic dysregulation and inhibiting cardiolipotoxicity. The latter might involve controlling cardiac fatty acid metabolism and improving mitochondrial function, rather than promoting glucose metabolism. Full article
(This article belongs to the Section Health Outcomes of Antioxidants and Oxidative Stress)
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12 pages, 639 KiB  
Article
Elevated Leukocyte Glucose Index (LGI) Is Associated with Diabetic Ketoacidosis (DKA) Severity and Presence of Microvascular Complications
by Mircea Cătălin Coșarcă, Raluca Maria Tilinca, Nicolae Alexandru Lazăr, Suzana Vasilica Șincaru, Bogdan Corneliu Bandici, Cosmin Carașca, Ráduly Gergő, Adrian Vasile Mureșan and Mariana Cornelia Tilinca
Medicina 2025, 61(5), 898; https://doi.org/10.3390/medicina61050898 - 15 May 2025
Viewed by 564
Abstract
Background and Objectives: Diabetic ketoacidosis (DKA) represents the most prevalent hyperglycemic emergency and poses a significant life-threatening metabolic risk for individuals with diabetes. The present study examines the predictive role of the leukocyte glucose index (LGI) values at baseline in diagnosing the [...] Read more.
Background and Objectives: Diabetic ketoacidosis (DKA) represents the most prevalent hyperglycemic emergency and poses a significant life-threatening metabolic risk for individuals with diabetes. The present study examines the predictive role of the leukocyte glucose index (LGI) values at baseline in diagnosing the severity of DKA and their correlation with the presence of diabetes-related microvascular complications. Materials and Methods: A retrospective observational study was conducted involving a total of 94 patients who had previously confirmed diagnoses of either Type I or Type II diabetes mellitus and presented with ketoacidosis upon emergency admission to the Department of Diabetology, Nutrition, and Metabolic Disease. Demographic information, values of arterial systolic and diastolic pressure, known duration and type of diabetes, severity of ketoacidosis, routine laboratory results, and blood gas analyses were retrieved from the hospital’s electronic database. Results: Higher diastolic blood pressure (DBP) values were observed in both mild (p = 0.021) and severe DKA (p = 0.035) compared to moderate DKA. When examining laboratory data, elevated white blood cell (WBC) counts were observed in severe DKA when compared to mild DKA (p = 0.009), as well as increased neutrophil counts in both moderate (p = 0.038) and severe (p = 0.011) DKA relative to mild DKA. Furthermore, patients with severe DKA exhibited lower values of venous blood pH, partial pressure of carbon dioxide (pvCO2), base excess (BE), and bicarbonate than the other groups (all p < 0.05), alongside higher levels of lactate, anion gap, and LGI (all p < 0.05). Regarding the parameters of arterial blood gas, we identified a negative correlation between LGI values and venous blood pH (r = −0.383, p < 0.001), serum bicarbonate (r = −0.352, p < 0.001), pCO2 (r = −0.271, p = 0.009), and BE (r = −0.330, p < 0.001). At univariate analysis, elevated LGI values are associated with the severity of DKA (OR: 1.87, p = 0.016) and diabetes-related microvascular complications (OR: 2.16, p = 0.010). Conclusions: The positive correlation between LGI and DKA severity and between LGI and diabetes microvascular complications highlights the potential utility of LGI as a predictive marker, facilitating early risk stratification and clinical decision-making. Full article
(This article belongs to the Section Endocrinology)
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Article
Interplay of PAK1 and CAMKII in Pancreatic Beta Cell Insulin Secretion
by Nely Gisela López-Desiderio, Genaro Patiño-López, Citlaltépetl Salinas-Lara, Carlos Sánchez-Garibay, Olga Villamar-Cruz, Alonso Vilches-Flores, José de Jesús Peralta-Romero, Leonel Armas-López, Jazmín García-Machorro, Luis Enrique Arias-Romero and Héctor Iván Saldívar-Cerón
Diabetology 2025, 6(5), 39; https://doi.org/10.3390/diabetology6050039 - 7 May 2025
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Abstract
Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major global health challenge, primarily driven by insulin resistance and beta-cell dysfunction. This study investigated the roles of p21-activated kinase 1 (PAK1) and calcium/calmodulin-dependent protein kinase II (CAMKII) in insulin secretion, aiming to elucidate their [...] Read more.
Background/Objectives: Type 2 diabetes mellitus (T2DM) is a major global health challenge, primarily driven by insulin resistance and beta-cell dysfunction. This study investigated the roles of p21-activated kinase 1 (PAK1) and calcium/calmodulin-dependent protein kinase II (CAMKII) in insulin secretion, aiming to elucidate their involvement in this process and their implications in T2DM pathophysiology. Methods: Using the Beta-TC-6 insulinoma cell line, we assessed colocalization and interaction of PAK1 and CAMKII under glucose stimulation through indirect immuno-fluorescence (IFI) and proximity ligation assays (PLA). To examine their expression dynamics in a physiological context, we performed immunohistochemistry (IHC) on pancreatic sections from wild-type (WT), prediabetic, and T2DM murine models. Additionally, bioinformatic analysis of publicly available RNA sequencing (RNA-Seq) data from human islets of healthy donors, prediabetic individuals, and T2DM patients provided translational validation. Results: High glucose conditions significantly increased PAK1-CAMKII colocalization, correlating with enhanced insulin secretion. Pharmacological inhibition of these kinases reduced insulin release, confirming their regulatory roles. Murine and human islet analyses showed a progressive increase in kinase expression from prediabetes to T2DM, highlighting their relevance in disease progression. Conclusions: The coordinated function of PAK1 and CaMKII in insulin secretion suggests their potential as biomarkers and therapeutic targets in T2DM. Further studies are warranted to explore their mechanistic roles and therapeutic applications in preserving beta-cell function. Full article
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