Search Results (785)

Vitamin D has emerged as a modulatory factor in the pathogenesis and management of diabetes mellitus due to its influence on pancreatic β-cell function, immune regulation, and inflammatory pathways. This narrative review critically examines mechanistic and clinical evidence linking vitamin D status with type 1 diabetes (T1DM), type 2 diabetes (T2DM), and gestational diabetes (GDM). In T1DM, vitamin D’s immunomodulatory effects are thought to protect β-cells from autoimmune destruction; epidemiological studies associate vitamin D sufficiency with lower T1DM incidence and improved glycemic control, although causality remains under investigation. In T2DM, vitamin D deficiency is associated with worsened metabolic control and may contribute to disease development in at-risk individuals; however, it does not influence the initial onset of T2DM in patients who are already diagnosed. Intervention trials indicate that correcting the deficiency can modestly improve insulin sensitivity, β-cell function, and metabolic parameters. GDM has similarly been linked to hypovitaminosis D, with low maternal vitamin D levels associated with higher GDM risk and adverse perinatal outcomes; mechanistic insights suggest that adequate vitamin D supports glucose homeostasis in pregnancy, and emerging trials demonstrate improved insulin resistance with maternal vitamin D supplementation. Across these diabetes subtypes, maintaining sufficient vitamin D levels appears to confer metabolic benefits and may serve as an adjunct to current preventive and therapeutic strategies. However, definitive evidence from large-scale trials is required to establish optimal vitamin D supplementation protocols and confirm its efficacy in diabetes care. Full article

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

Background/Objectives: Physical activity is a cornerstone of diabetes mellitus (DM) management and is strongly recommended in the American Diabetes Association (ADA)’s guidelines. This study aims to investigate the self-reported physical activity levels of individuals with DM in Germany, as well as the barriers and facilitators they encounter. Methods: Individuals with type 1 DM (T1DM) and type 2 DM (T2DM) were asked to fill out an online questionnaire that was partly based on the International Physical Activity Questionnaire (IPAQ). Results: The questionnaire was completed by 338 persons with either T1DM (57.1%) or T2DM (42.9%) (females: 56.2%, males: 42.0%, gender diverse persons: 1.8%) of all age groups (at least 18 years). In total, 80.5% of respondents were aware of the current physical activity recommendations. Among the respondents, 58% reported meeting the recommendations for endurance-type physical activity, while only 30.5% reported meeting those for strength training. The three most frequently cited barriers to physical activity were lack of time, lack of motivation and current state of health. Supporting factors included coverage of costs, availability of exercise programs in close proximity to the patient’s home and target group specific exercise programs. Conclusions: The results imply that many individuals with DM in Germany do not meet ADA’s physical activity recommendations, especially considering that self-reports often overestimate actual behavior. In particular, the actual number of individuals who regularly engage in strength training may be too low. There is a clear need to better communicate the benefits of different forms of physical training and to provide physical activity programs aligned with patients’ individual needs. Full article

Background and Objectives: Ischemic stroke (IS) is a critical health issue, affecting individuals of all ages, sexes, and backgrounds. Mounting evidence suggests that sex indeed could play some distinct role in shaping the incidence, outcomes, and treatment of IS. In the context of the COVID-19 pandemic, contradictory findings from previous studies that also addressed sex differences in cerebrovascular diseases demonstrate the need for further focused research. This study aimed to evaluate the sex discrepancies in the clinical presentation of IS and its outcomes in patients admitted to Kaunas Hospital of the Lithuanian University of Health Sciences (LUHS), Lithuania. Materials and Methods: This is a retrospective record-based single-center study. All the study patients—727 men and 1082 women—enrolled between 1 January 2020, and 27 February 2022; suffered from acute IS; and had absolute contraindications against interventional IS treatment. These patients received a conservative non-interventional IS treatment at the neurological department of the LUHS’s Kaunas Hospital. The sociodemographic data; laboratory findings; comorbidities, including COVID-19; in-hospital complications; and outcome factors were obtained from the patients’ medical records and evaluated by deploying appropriate statistical tests. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated by the Cox proportional hazards regression for in-hospital lethality. Results: The mean age of IS patients was significantly higher in women compared to men (p < 0.001), as was the proportion of in-hospital deaths (19.10% and 15.36%, respectively; p < 0.05). The mean total number of in-hospital complications was again significantly higher in the group of women compared to men (p < 0.05). The prevalence of COVID-19 was higher in men compared to women (p < 0.05). COVID-19 diagnosis (HR = 1.53; p = 0.02) and acute in-hospital pulmonary complications (HR = 1.91; p = 0.008) significantly increased the risk of in-hospital lethality in men. The risk of in-hospital lethality was significantly higher in women with comorbid diabetes mellitus type 2 (DM) compared to those with comorbid isolated arterial hypertension (AH) (HR = 2.25, p = 0.007). Increased C-reactive protein elevated the risk of in-hospital lethality by more than twice in both men and women (HR = 2.46; p < 0.001 and HR = 2.28; p < 0.001, respectively). Conclusions: The following differences between men and women with IS were determined: Acute in-hospital pulmonary complications, including COVID-19, significantly increased the risk of in-hospital lethality in the male group, but not in women. However, women suffering from DM had a significantly increased risk of in-hospital lethality compared with those women IS patients with AH or chronic ischemic heart disease (IHD). Increased C-reactive protein was associated with an elevated risk of in-hospital lethality both in male and female groups. Full article

Background: Pancreas and pancreas–kidney transplantation are well-established therapeutic options for patients with type 1 diabetes mellitus (T1DM) and end-stage kidney disease (ESKD), offering the potential to restore endogenous insulin production and kidney function. It improves metabolic control, quality of life, and long-term survival. While surgical techniques and immunosuppressive strategies have advanced considerably, graft rejection and limited long-term graft survival remain significant clinical challenges. Method: To better understand these risks, the genetic and immunological factors that influence transplant outcomes are examined. Beyond traditional human leukocyte antigen (HLA) matching, non-HLA genetic variants such as gene deletions and single-nucleotide polymorphisms (SNPs) have emerged as contributors to alloimmune activation and graft failure. Result: Polymorphisms in cytokine genes, minor histocompatibility antigens, and immune-regulatory pathways have been implicated in transplant outcomes. However, the integration of such genomic data into clinical practice remains limited due to underexplored gene targets, variability in study results, and the lack of large, diverse, and well-characterized patient cohorts. Initiatives like the International Genetics & Translational Research in Transplantation Network (iGeneTRAiN) are addressing these limitations by aggregating genome-wide data from thousands of transplant donors and recipients across multiple centers. These large-scale collaborative efforts aim to identify clinically actionable genetic markers and support the development of personalized immunosuppressive strategies. Conclusions: Overall, genetic testing and genomics hold great promise in advancing precision medicine in pancreas and pancreas–kidney transplantation. Full article

More than 14% of the world’s population suffered from diabetes mellitus in 2022. This metabolic condition is defined by increased blood glucose concentrations. Among the different types of diabetes, type 1 diabetes, caused by a lack of insulin secretion, is particularly challenging to treat. In this regard, automatic glucose level estimation implements Continuous Glucose Monitoring (CGM) devices, showing positive therapeutic outcomes. AI-based glucose prediction has commonly followed a deterministic approach, usually with a lack of interpretability. Therefore, these AI-based methods do not provide enough information in critical decision-making scenarios, like in the medical field. This work intends to provide accurate, interpretable, and personalized glucose prediction using the Temporal Fusion Transformer (TFT), and also includes an uncertainty estimation. The TFT was trained using two databases, an in-house-collected dataset and the OhioT1DM dataset, commonly used for glucose forecasting benchmarking. For both datasets, the set of input features to train the model was varied to assess their impact on model interpretability and prediction performance. Models were evaluated using common prediction metrics, diabetes-specific metrics, uncertainty estimation, and interpretability of the model, including feature importance and attention. The obtained results showed that TFT outperforms existing methods in terms of RMSE by at least 13% for both datasets. Full article

Background/Objectives: Emerging evidence links diabetes to increased cancer risk. This study aimed to assess the association between diabetes mellitus (DM)(type 1, type 2, or gestational) and the development of head and neck cancer. Methods: An umbrella review was conducted using systematic searches in Cochrane, EBSCO, Wiley, ScienceDirect, and PubMed (January 2000–January 2024), registered in PROSPERO (CRD42024512151). Included were systematic reviews (SRs) and meta-analyses (MAs) of observational studies. Article selection followed the PRISMA guidelines; the quality and risk of bias of the selected studies were assessed with the Joanna Briggs Institute Checklist. The GROOVE tool was used to identify double counting. Two independent reviewers screened studies, with a third resolving disagreements. Results: Seven SRs were included. While DM has been widely examined in cancer research, few studies specifically targeted head and neck cancers. Of the 20 associations between various cancer sites and diabetes types, 9 (45%) showed a statistically significant positive correlation. The strongest evidence was for overall cancer risk (RR = 1.22, 95% CI: 1.16–1.29, p < 0.001). Oral cancer showed elevated risks (RRR = 1.13, p = 0.009; OR = 1.32, p < 0.001; HR = 1.73, p < 0.05; RR = 1.28, p < 0.05). Increased risks were also observed for oropharyngeal (RR = 1.18; HR = 1.53), head and neck (HR = 1.47), and nasopharyngeal cancer (OR = 1.40), all p < 0.05. Heterogeneity was low in two reviews, unreported in one, and high in four. Five SRs reported associated risk factors. Conclusions: While some associations between DM and cancer appear significant, evidence remains limited and inconsistent, particularly for oral cancer. Further standardized, high-quality research is needed to clarify the link across head and neck cancer subtypes. Full article

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

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

Background and Objectives: This study aimed to investigate the relationship between Maresin-1 (MaR1), Chitinase-3-like protein 1 (CHI3L1), and inflammatory as well as hematological markers in patients with type 2 diabetes mellitus (T2DM) and diabetic nephropathy (DN). Materials and Methods: This cross-sectional study included 90 participants divided into three groups: healthy controls (n = 30), patients with T2DM (n = 30), and patients with diabetic nephropathy (n = 30). The serum levels of MaR1 and CHI3L1 were measured using ELISA. Biochemical and hematological parameters were also assessed. Statistical comparisons were conducted using non-parametric tests, and correlations were analyzed via Spearman correlation. Results: Serum MaR1 levels were significantly higher in DN patients compared to both T2DM patients and controls (p < 0.01), while CHI3L1 levels were significantly lower in the DN group compared to controls (p = 0.007). MaR1 showed a positive correlation with CRP, BUN, and creatinine, and a negative correlation with GFR. CHI3L1 levels were positively correlated with GFR and negatively with BUN. Inflammatory markers such as CRP were elevated in the diabetic groups, while no significant differences were found in NLR values. Conclusions: Elevated MaR1 levels in DN patients and their correlation with renal dysfunction markers suggest that MaR1 may serve as a potential prognostic biomarker in diabetic nephropathy. The unexpected decrease in CHI3L1 levels in DN patients indicates the need for further research to clarify their role. These findings indicated that MaR1 and CHI3L1 should be further investigated in future studies as indicators for the early detection and monitoring of diabetic complications. Full article

Diabetes mellitus (DM), a chronic metabolic disease, poses a significant challenge to global health. Although type 1 diabetes mellitus (T1DM), type 2 diabetes mellitus (T2DM), gestational diabetes mellitus (GDM), and other types of diabetes mellitus differ in pathological mechanisms, they converge in that hyperglycemia is a universal clinical hallmark. Currently, the antidiabetic medications employed in clinical practice for blood glucose management require long-term administration and are associated with various side effects that can adversely impact human health. Plant heteropolysaccharides have emerged as promising candidates for anti-diabetic therapy, owing to their abundant natural sources, absence of toxicities, and confirmed hypoglycemic activities. This review aims to summarize the anti-diabetic mechanisms of plant heteropolysaccharides by dissecting the key biological pathways associated with clinical intervention in DM, including the modulation of insulin secretion, a reduction in insulin resistance, and an alteration in the composition of the gut microbiota. For these reasons, these findings provide a theoretical framework for the clinical application of plant heteropolysaccharides and indicate that they are expected to become natural agents used in treating DM. Full article

Exercise plays a key role in managing type 1 diabetes mellitus (T1DM), and virtual reality (VR)-based exercise offers an innovative solution to increase motivation and deliver meaningful health benefits to patients who are often hesitant to engage in physical activity. The purpose of this study was to assess the acceptability, usability, intention for future use, and preference of a VR-based cycling application, as well as to investigate the effects of VR-based exercise on the physiological, biochemical, and psychological parameters of individuals with T1DM compared to conventional exercise. This study represents a preliminary investigation with a small sample size of 11 patients with T1DM. Each participant underwent two 20 min low-intensity exercise trials. One session involved conventional cycling on a stationary ergometer, while the other used a VR-based cycling application. The two exercise conditions were conducted 48 h apart, without a formal washout period. According to the results, high scores were observed for preference, acceptance, and usability of the VR-based cycling application, and statistically significant improvements in mood and enjoyment were observed following the VR-based cycling compared to conventional cycling. Additionally, while no statistically significant differences were found in physiological parameters (blood glucose, blood pressure, and heart rate) between the two conditions, the VR-based session showed a trend toward greater reductions. In conclusion, the use of VR technology in the field of cycling exercise has great significance in improving the mood and engagement of T1DM patients in exercise programs, providing a user-friendly and well-accepted VR cycling application; subsequently, it has also shown preliminary potential for the regulation of biological parameters. Healthcare professionals could easily expand exercise protocols with the strengths of the VR technologies along with other health-related programs. Full article

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

Type 2 diabetes mellitus (T2DM) is a major public health concern that significantly increases the risk of diabetic retinopathy (DR), a leading cause of visual impairment worldwide. This study aimed to identify molecular markers of inflammation (INF) and angiogenesis (ANG) in the aqueous humor (AH) of patients with non-proliferative diabetic retinopathy (NPDR). We conducted an observational, multicenter, case–control study including 116 participants classified into T2DM with NPDR, T2DM without DR, and non-diabetic controls (SCG) undergoing cataract surgery. AH samples were collected intraoperatively and analyzed for 27 cytokines using multiplex immunoassay. Eighteen immune mediators were detected in AH samples, and several were significantly elevated in the NPDR group, including the interleukins (IL) -1β, -6, -8, -15, -17, as well as the granulocyte–macrophage colony stimulating factor (GM-CSF), basic fibroblast growth factor (bFGF), interferon gamma-induced protein (IP-10), macrophage inflammatory protein 1 beta (MIP-1b), monocyte chemoattractant protein-1 (MCP-1), regulated on activation, normal T cell-expressed and -secreted protein (RANTES), and the vascular endothelial growth factor (VEGF). These molecules are involved in retinal INF, blood–retinal barrier breakdown, and pathological neovascularization. Our findings reveal a distinct pro-INF and pro-ANG profile in the AH of NPDR patients, suggesting that these cytokines may serve as early diagnostic/prognostic biomarkers for DR. Targeting these molecules could provide novel therapeutic strategies to mitigate retinal damage and vision loss in diabetic patients. Full article