Search Results (189)

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

Diabetes mellitus, both type 1 (T1D) and type 2 (T2D), has become the epidemic of the century and a major public health concern given its rising prevalence and the increasing adoption of a sedentary lifestyle globally. This multifaceted disease is characterized by impaired pancreatic beta cell function and insulin resistance (IR) in peripheral organs, namely the liver, skeletal muscle, and adipose tissue. Additional insulin target tissues, including cardiomyocytes and neuronal cells, are also affected. The advent of stem cell research has opened new avenues for tackling this disease, particularly through the regeneration of insulin target cells and the establishment of disease models for further investigation. Human-induced pluripotent stem cells (iPSCs) have emerged as a valuable resource for generating specialized cell types, such as hepatocytes, myocytes, adipocytes, cardiomyocytes, and neuronal cells, with diverse applications ranging from drug screening to disease modeling and, importantly, treating IR in T2D. This review aims to elucidate the significant applications of iPSC-derived insulin target cells in studying the pathogenesis of insulin resistance and T2D. Furthermore, recent differentiation strategies, protocols, signaling pathways, growth factors, and advancements in this field of therapeutic research for each specific iPSC-derived cell type are discussed. Full article

Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits. Full article

Objectives: This study explored perceptions, experiences, and outcomes associated with the choice of insulin therapies among pediatric patients with type 1 diabetes mellitus (T1D). Methods: This study included 20 adolescents (8 male and 12 female) with T1D, with a mean age of 15.05 ± 0.91 years, a mean diabetes duration of 5.19 ± 1.2 years, and a mean most recent HbA1c of 7.03 ± 0.16%. Ten of the participants were using an insulin pump (n = 10) and another 10 had either refused (n = 7) or discontinued (n = 3) insulin pump therapy. A qualitative inductive method was employed, using in-depth individual interviews. The interview material was transcribed verbatim and grounded theory was used to analyze the verbal material. Results: Four main thematic categories were identified from the narrations that captured both common and divergent perceptions of insulin pump users versus non-users: (1) adjusting to the lifelong diagnosis, (2) exposing diabetes versus hiding it, (3) becoming autonomous and integrating insulin pump therapy into daily life, and (4) worrying over the pump. The third theme, capturing autonomy and integration, surfaced as the core thematic category of this study. Conclusions: This grounded theory study revealed that, by using insulin pump therapy, adolescent T1D patients can enhance their autonomy and facilitate the integration of insulin treatment into their life. This study identified processes that inform diabetes education and contribute to ameliorating gaps in the uptake and maintenance of pump therapy in pediatric care. Full article

Background: The education process for newly diagnosed Type 1 diabetes mellitus (T1D) patients and their families, primarily led by diabetes specialist nurses, is essential for gaining knowledge about the disease and its management. However, few assessment tools have been employed to evaluate long-term knowledge retention among T1D patients years after diagnosis. Methods: We developed a 20-question test to assess the knowledge of patients and their families at the conclusion of the initial education process and again 6–12 months later. Demographic and clinical data were also collected. Statistical analyses included comparisons between the first and second test results, as well as evaluation of potential contributing factors. The internal consistency and construct validity of the questionnaire were evaluated. Results: Forty-four patients completed both assessments, with a median interval of 11.5 months between them. The average score on the first test was 88.6, which declined to 82.7 on the second assessment (p < 0.001). In univariate analysis, factors positively associated with higher scores included Jewish ethnicity, lower HbA1c levels, and shorter hospitalization duration. Multivariate analysis revealed that parents had lower odds of experiencing a significant score decline compared to patients. Cronbach’s alpha was 0.69, and Principal Component Analysis (PCA) identified eight components accounting for 67.1% of the total variance. Conclusions: Healthcare providers should consider offering re-education to patients and their families approximately one year after diagnosis, with particular attention to high-risk populations during the initial education phase. Further studies are needed to examine this tool’s performance in larger cohorts. Full article

Introduction: Emerging research indicates that alterations in the methylation of retrotransposons may contribute to genomic instability and cellular aging in various autoimmune disorders and diabetes mellitus (DM). As relevant information for people with type 1 diabetes mellitus (PwT1D) is limited, we aimed to investigate long interspersed nuclear element-1 (LINE-1) methylation status in this population. Methods: DNA methylation levels and patterns of LINE-1 were examined in the peripheral blood of 35 PwT1D and 28 healthy controls (age- and sex-matched), by using the COmbined Bisulfite Restriction Analysis methodology (COBRA). Results: Total LINE-1 methylation rate (mC) was higher in PwT1D compared to controls [47.3% (46.6–47.8%) vs. 46.5% (44.7–47.3%), p < 0.05]. The partial LINE-1 methylation pattern (uCmC) was less frequently observed in patients vs. controls [28.4% (24.7–33.3%) vs. 33.1% (27.8–37.9%), p < 0.05]. Prevalence of other methylation patterns [partially methylated (mCuC), hypermethylated (mCmC) and hypomethylated (uCuC)] was similar in the two groups. Furthermore, levels of fasting glucose and glycated hemoglobin (HbA1c) were positively associated with total methylation (mC) [Spearman’s rho = 0.380, p = 0.002 and rho = 0.342, p = 0.006, respectively], but negatively associated with the partially methylated (uCmC) pattern [Spearman’s rho = −0.383, p = 0.002 and rho = −0.270, p = 0.033, respectively]. The LINE-1 (uCmC) methylation pattern was negatively associated with the age at diagnosis of T1D [Spearman’s rho = −0.341, p = 0.049], but positively associated with disease duration [Spearman’s rho = 0.388, p = 0.021]. Conclusions: PwT1D were found to have higher total LINE-1 methylation rate (mC) compared to healthy controls. The partial methylation pattern (uCmC) was less frequently observed in these patients and was negatively associated with the glycemic status and the age at diagnosis of T1D, while demonstrating a positive correlation with disease duration. Full article

Type 1 diabetes mellitus (T1D) is increasingly recognised not only as an autoimmune metabolic disorder but also as a condition associated with accelerated biological ageing. Among the hallmarks of ageing, telomere shortening has emerged as a key feature, driven by multiple molecular pathological pathways linked to T1D onset and progression. This review explores the molecular mechanisms contributing to telomere attrition in T1D, including cytokine-induced β-cell damage, ROS-mediated DNA damage, impaired mitochondrial dynamics, and dysregulated DNA damage response pathways. Empirical evidence supports a consistent association between shortened telomeres and T1D, vascular complications, nephropathy, and mortality in T1D patients. Furthermore, the bidirectional relationship between telomere biology and immune-metabolic stress suggests novel directions for intervention. Understanding these pathways may enhance the predictive value of telomere length as a biomarker and inform targeted therapeutic strategies aimed at mitigating premature ageing and disease progression in T1D. Full article

Diabetes Mellitus (DM) is highly prevalent and carries a significant self-management burden and elevated risk of biopsychosocial sequelae. Psychological flexibility (PF) has been shown to benefit living with and managing chronic health conditions. The present scoping review aimed to synthesize the available evidence on the relationship between PF and factors central to living with and managing DM. A systematic literature search was conducted. Studies were included if they measured psychological (in)flexibility (PI/PF) and/or one of its component processes and sampled individuals with type 1 or type 2 DM. A total of 48 articles were included. Eighteen (37.5%) sampled individuals with T2D, 16 (33.3%) sampled individuals with T1D, and 14 (29.2%) had mixed diagnostic samples. Twenty-nine (60.4%) reported observational studies, and 19 (39.6%) reported 18 intervention studies. Studies were conducted across 17 countries and broadly found that PI/PF were associated with many clinically meaningful DM variables (e.g., HbA1c, diabetes distress, quality of life, and self-management). Intervention studies including individual, group, and digital Acceptance and Commitment Therapy (ACT) interventions showed trends for beneficial change in PI/PF and diabetes outcomes, but some findings were mixed, and many studies were underpowered. Only two studies tested change in PI/PF as a mediator of diabetes-related outcomes, and most studies used the Acceptance and Action Questionnaire, which has been increasingly criticized for poor discriminant validity. Overall, findings show PI/PF are associated with most aspects of living with and managing diabetes and are generally amenable to change through ACT interventions. However, more methodologically rigorous studies are needed to determine whether PI/PF are active change processes in improving diabetes management and outcomes. Six key calls to action are presented to expand and strengthen this important area of research. Full article

Background/Objectives: Parental involvement is essential in managing type 1 diabetes mellitus (T1DM) in children, particularly with the growing use of continuous glucose monitoring (CGM). Validated tools assessing parental self-efficacy in this context remain limited. This study aimed to validate the Parental Self-Efficacy Scale for Diabetes Management (PSESDM) among parents of children using a CGM sensor and to examine its associations with diabetes outcomes and parental characteristics. Methods: A cross-sectional study was conducted involving 106 parent–child dyads at a university pediatric diabetes center. Parents completed the Hungarian PSESDM. Data regarding children’s HbA1c level were recorded, along with standard measures of their general and diabetes-specific quality of life (EQ-5D-Y-3L, PedsQL Diab); data regarding parents’ health literacy (Chew), fear of hypoglycemia (HFS), health-related quality of life (EQ-5D-5L), and capability well-being (ICECAP-A) were also collected. The PSESDM’s reliability, internal consistency, and discriminant and criterion validity were assessed using standard statistical methods. Results: The PSESDM demonstrated good internal consistency (Cronbach’s α = 0.857) and strong item–total correlations (range: 0.678–0.791). Higher parental self-efficacy was significantly associated with better glucose control (lower HbA1c, r_s = −0.50) and weakly correlated with the child’s diabetes-specific quality of life (r_s = 0.20). Among parental characteristics, self-efficacy correlated strongly with capability well-being (r_s = 0.52), moderately with health literacy (r_s = −0.30), and showed no difference between socio-demographic subgroups, except for the subgroup related to income. Conclusions: The PSESDM is a valid and reliable tool for measuring self-efficacy in parents of children with T1DM using CGM sensors. Its associations with children’s HbA1c levels, diabetes-specific quality of life, and parental characteristics support its clinical relevance and potential use in identifying families at risk for poorer diabetes outcomes. Full article

Objective: to assess the association between attention-deficit/hyperactivity disorder (ADHD), type 1 diabetes mellitus (T1D), and cardiovascular comorbidities in adults. Methods: The Adult Self-Report Scale V1.1 (ASRS) for ADHD symptoms was electronically sent to 2069 adults with T1D. Cardiometabolic conditions, laboratory measurements, and PHQ-2/PHQ-9 depression scores were obtained from the electronic medical record. Results: In total, 292 (14.1%) individuals responded and 279 consented to medical records extraction. The average age was 47.4 years (SD: ±18.9), 64.2% were women, 95.7% were non-Hispanic white, and the mean HbA1c level was 7.7% (±1.5%). Of 273 completing ASRS, 87 med ADHD criteria (ASRS positive, 31.9%), and 42 (15.4%) had an ADHD diagnosis or medication. Women had higher scores than men. ADHD symptoms decreased with age, but remained significantly higher than the general population levels. HbA1c levels were positively associated with the ASRS scores (Spearman’s r = 0.28, p < 0.0001). ASRS positive individuals had worse glycemic control (HbA1c ≥ 8.0%, adjusted OR 2.3, 95%CI: 1.3–4.1, p < 0.0001) and higher PHQ-9 scores (10 ± 7.3 vs. 6.1 ± 6, χ²₍₁₎ = 9.2, p = 0.002) than the ASRS negative group. No associations were found between ASRS scores and cardiometabolic diseases, or other laboratory or clinical measurements. Conclusions: Many adults with T1D exhibit undiagnosed ADHD symptoms, which correlate with poorer glycemic control and depression. Further research with larger samples is needed to investigate ADHD prevalence and impacts in this group. Full article

Type 1 Diabetes Mellitus (T1D) is a disease characterized by the destruction of pancreatic beta cells. The subsequent loss of insulin production results in hyperglycemia, muscle wasting, and vascular dysfunction. Due to an inability to appropriately maintain glucose homeostasis, patients afflicted with T1D suffer from increased morbidity and early mortality. Skeletal muscle is the body’s largest metabolic reservoir, absorbing significant amounts of glucose from the bloodstream and physical exercise is known to improve and prevent the progression of pathological outcomes, but many T1D patients are unable to exercise at a level that conveys benefit. Thus, directly targeting muscle mass and function may prove beneficial for improving T1D patient outcomes, independent of exercise. A potent negative regulator of skeletal muscle has been identified as being upregulated in T1D patients, namely the myokine myostatin. Our hypothesis is that targeting myostatin (via genetic deletion) will prevent glucose dysfunction in a T1D model, preserve skeletal muscle function, and protect against vascular and renal dysfunction. Our methods utilized adult male mice with (WT) and without myostatin (Myo KO), in combination with the chemical induction of T1D (streptozotocin). Experimental outcomes included the assessment of glucose homeostasis (plasma glucose, HbA1c, IGTT), metabolism, muscle function (in vivo plantarflexion), and skeletal muscle vascular function (ex vivo pressure myography). Our results described systemic benefits from myostatin deletion in the T1D model, independent of insulin, including the following: inhibition of T1D-induced increases in plasma glucose, prevention of functional deficits in muscle performance, and preservation of fluid dynamics. Further, endothelial function was preserved with myostatin deletion. Taken together, these data inform upon the use of myostatin inhibition as a therapeutic target for effective treatment and management of the cardiometabolic and skeletal muscle dysfunction that occurs with T1D. Full article

Polycystic ovary syndrome (PCOS), a common and multifactorial endocrine disorder in reproductive-aged women, is strongly associated with insulin resistance (IR) and type 2 diabetes mellitus (T2DM), and also affects up to one in four women with type 1 diabetes mellitus (T1DM). The current study explored the potential of Plantago ovata (P. ovata) seed ethanol extract (POEE) to modulate oxidative stress (OS), inflammatory responses, metabolic profiles, and hormonal levels in rat Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. Phytochemical analysis measured total phenolic content (TPC) and total flavonoid content (TFC) using HPLC-DAD-ESI MS for compound identification. POEE’s antioxidant activity was evaluated in vitro through DPPH, H₂O₂, FRAP, and NO scavenging assays. Rats received POEE, metformin, or Trolox (TX) for 10 days. PCOS confirmation was achieved via ultrasound and histopathology. Serum levels of OS markers (TOS, TAC, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, and SH), inflammatory markers (NF-κB, IL-1β, IL-18, Gasdermin D, and IL-10), metabolic parameters (fasting blood glucose, lipid profile, and liver enzymes), and hormone levels (LH, FSH, estrogen, testosterone, and insulin) were assessed. Additionally, the Triglyceride–Glucose index (TyG) and HOMA-IR were calculated. POEE had a medium content of polyphenols and a good in vitro antioxidant effect. In vivo, POEE administration in diabetic rats led to a reduction in OS markers and an increase in antioxidant levels, alongside decreases in inflammatory cytokines, blood glucose levels, and transaminase activity and improvements in lipid profile. In the PCOS model, POEE treatment effectively reduced total OS and lowered levels of LH, FSH, and testosterone, while elevating estrogen concentrations and reducing insulin resistance. These therapeutic effects were dose-dependent, with higher doses producing more pronounced outcomes, comparable to those observed with metformin and TX treatment. Full article

Type 1 diabetes mellitus (T1DM) is a multifactorial disease in which environmental factors and genetic predisposition interact to induce an autoimmune response against pancreatic β-cells. Vitamin D promotes immune tolerance through immunomodulatory and anti-inflammatory functions. The aim of this study is to provide a narrative review about the association between vitamin D status in the pathogenesis of T1DM and the role of vitamin D supplementation in the prevention and treatment of T1DM. Although vitamin D deficiency is more prevalent in children/adolescents with new-onset T1DM than in healthy individuals, there does not appear to be an association between vitamin D status before diagnosis and the onset of T1DMD later in life. The results of vitamin D as adjuvant therapy have, at best, a positive short-term effect in newly diagnosed T1DM patients. Intervention studies have been conducted in the clinical phase of T1DM, but it would be desirable to do so in the early stages of the autoimmune process (pre-diabetes). Full article

Polycystic ovary syndrome (PCOS) and diabetes mellitus (DM) are prevalent endocrine disorders with overlapping pathophysiological mechanisms. Type 2 diabetes mellitus (T2DM) is commonly associated with PCOS, with both conditions strongly linked to insulin resistance (IR), while recent studies have also reported an increased prevalence of PCOS among women with type 1 diabetes mellitus (T1DM). This study evaluated the potential of Lythrum salicaria L. ethanol extract (LSEE) to mitigate oxidative stress (OS), inflammation, and metabolic and hormonal imbalances in separate experimental models of Streptozotocin (STZ)-induced DM and Letrozole (LET)-induced PCOS. LSEE underwent phytochemical analysis to quantify total phenolic and flavonoid content and HPLC-MS for polyphenols identification. In vitro, antioxidant capacity was investigated through FRAP, DPPH, NO, and H₂O₂ scavenging assays. Subsequently, in vivo, studies utilized STZ-induced DM and LET-induced PCOS rat models, with 10-day treatments of LSEE, metformin, or trolox (TX) administered by gavage. Dysregulation of hormonal profiles, ultrasound, and histological examinations confirmed PCOS development. At the end of the treatment period, serum samples were collected to assess OS markers (TOS, OSI, MDA, AOPP, 8-OHdG, NO, 3-NT, AGEs, TAR, SH) in both models. Inflammatory markers were also measured (IL-1β, NF-κB, IL-18, and Gasdermin D in DM and IL-1β, NF-κB, IL-18, and IL-10 in PCOS). Additionally, metabolic markers (glucose, lipids, TG-glucose index, liver enzymes) were assessed in DM rats, and hormones (LH, FSH, estrogen, testosterone, insulin, HOMA-IR) were determined in PCOS rats. LSEE demonstrated a high polyphenolic content and notable in vitro antioxidant activity. In vivo, it effectively reduced OS by lowering oxidant levels and enhancing antioxidant defenses, reduced inflammatory markers and blood glucose levels, and improved lipid profiles along with the TyG index and liver injury markers in diabetic rats. In PCOS rats, LSEE lowered the total oxidants, increased antioxidants, reduced LH, FSH, testosterone, and insulin, and increased estrogen levels. The effects exhibited a dose-dependent pattern, with higher doses producing more pronounced benefits comparable to those observed with metformin and TX. In conclusion, LSEE may be a promising complementary treatment for DM and PCOS. Full article