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Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D. [ABSTRACT FROM AUTHOR]

Aim: To assess the incidence and the temporal trend of type 1 diabetes (T1D) and diabetic ketoacidosis (DKA) during the period 2014–2023 in youths aged 0–14 years in the Trentino–Alto Adige region, Italy. Methods: A retrospective review of all incident cases of T1D diagnosed at the two Pediatric Diabetes Centers of Bolzano and Trento was matched with diabetes exemptions (No. 344). Demographic, clinical, and socioeconomic status (SES) data at first hospitalization were collected from subjects who agreed to participate (No. 272). Results: The incidence of T1D was 21.5/100,000 person/years, with a peak of 31.1 in 2021 during the COVID-19 pandemic. The mean age at the onset was 8.8 ± 3.9 years. Seventy-nine percent of the subjects were Italians, primarily residents in rural areas, and SES was equally represented. The mean incidence of DKA was 36.9%. The logistic regression analysis showed that the independent characteristics of the patients with DKA were of a younger age and displayed higher glycated hemoglobin (HbA1c) values. No relation of DKA with seasonality, ethnicity, or first-degree relative (FDR) with T1D or SES was detected. Conclusions: Our study revealed an incidence of T1D in the Trentino–Alto Adige region comparable to other areas in the North of Italy. The DKA rate negatively correlated with age; therefore, targeted prevention educational campaigns to increase awareness are needed. [ABSTRACT FROM AUTHOR]

Background: Our previous genome‑wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated. Methods: We assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms. Results: We identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not < 12. This variant is associated with residual islet function but not islet-specific autoantibody positivity in T1D individuals. Bioinformatics analysis indicated that rs912304 is a functional variant exhibiting spatial overlaps with enhancer active histone marks (H3K27ac and H3K4me1) and open chromatin status (ATAC-seq) in the human pancreas and islet tissues. Luciferase reporter gene assays and eQTL analyses demonstrated that the biallelic sites of rs912304 had differential allele-specific enhancer activity in beta cell lines and regulated STXBP6 expression, which was defined as the most putative causal gene based on Open Targets Genetics, GTEx v8 and Tiger database. Moreover, Stxbp6 was upregulated by T1D-related proinflammatory cytokines but not high glucose/fat. Notably, Stxbp6 over-expressed INS-1E cells exhibited decreasing insulin secretion and increasing cell apoptosis through Glut1 and Gadd45β, respectively. Conclusions: This study expanded the genomic landscape regarding late-onset T1D risk and supported islet function mechanistically connected to T1D pathogenesis. [ABSTRACT FROM AUTHOR]

Despite significant progress in the treatment of T1DM in children, achieving target levels of carbohydrate metabolism in children remains one of the most difficult tasks. The influence of the psychosocial state of the family on the ability to achieve metabolic compensation is becoming increasingly clear. However, the study of social risk factors in families with children with T1DM and their impact on metabolic control remains clearly insufficient.The purpose of the study is to determine social risk factors (SR) that are most typical for families of children with type 1 diabetes mellitus (T1DM) in our country and to analyze their relationship with compensation for T1DM based on a survey of parents.MATERIALS AND METHODS: The study was conducted in endocrinology departments of children’s hospitals and departments of medical and social care of children’s clinics in 4 regions - Vologda, Tyumen, Chelyabinsk regions and Khanty-Mansi Autonomous Okrug.A total of 325 respondents took part in the study. 1 group — experience of T1DM in children >1 year and poor metabolic control (level of glycated hemoglobin ((HbA1c) >7.5%) — 195 hours; 2 gr. — experience of T1DM in children >1 year and good metabolic control (HbA1c

Abstract Background Type 1 diabetes mellitus (T1D) is an autoimmune disease caused by destruction of pancreatic islet beta-cells. There is significant residual beta-cell function, measured through circulating C-peptide, present at the time of T1D diagnosis but this subsequently decreases with time. Higher residual beta-cell function at diagnosis associates with better glycaemic control and less glucose variability, and later in the disease course with less hypoglycaemia, lower glucose variability and fewer microvascular complications. There is therefore value in preserving residual beta cell function in new onset T1D Immunotherapeutic agents can protect residual beta-cell function in type 1 diabetes. However, clinical trials of such agents, whilst demonstrating C-peptide preservation in short term studies, have yet to be taken forward into routine clinical care due to concerns around safety and long-term efficacy. Here we report the case of a gentleman with newly diagnosed T1D whose glycaemic control and insulin requirement improved whilst on a five year infusion programme of infliximab, a monoclonal antibody against TNF-alpha, for colitis. Case presentation A 52-year-old White Caucasian man was diagnosed with T1D in August 2018. Glucose was 25.6 mmol/L, HbA1c was 98mmol/mol and GAD antibodies were strongly positive. HbA1c marginally improved to 91mmol/mol following initiation of insulin detemir 5 units at night and 1:10 g of insulin aspart (November 2018). In June 2019, he developed rectal bleeding and abdominal pain. Following colonoscopy, he was diagnosed with “indeterminate colitis” and commenced on 6-weekly infusions of 400-450 mg infliximab. Thus far, he has received 32 doses and achieved colitis remission. Following infliximab initiation there was increased frequency of mild-moderate hypoglycaemia and he was gradually weaned off and discontinued detemir in June 2020. Since then, HbA1c improved from 57mmol/mol in August 2019 to 52mmol/mol in April 2022, remaining stable at 51mmol/mol. His most recent HbA1c is 54mmol/mol in February 2024. His c-peptide was 550pmol/L in October 2022 and 442pmol/L in February 2024, suggesting well-preserved beta-cell function almost 6 years post-diagnosis. Conclusions Our patient’s improvement in glycaemic control can be explained by immunomodulation and C peptide preservation from infliximab. With the growing focus on type 1 diabetes disease modulation and working towards an ‘insulin free T1D’, our findings strengthen the evidence base for the repurposing of and long-term treatment with anti-TNF-α agents to preserve beta-cell function in new onset T1D.

Abstract Background Our previous genome‑wide association studies (GWAS) have suggested rs912304 in 14q12 as a suggestive risk variant for type 1 diabetes (T1D). However, the association between this risk region and T1D subgroups and related clinical risk features, the underlying causal functional variant(s), putative candidate gene(s), and related mechanisms are yet to be elucidated. Methods We assessed the association between variant rs912304 and T1D, as well as islet autoimmunity and islet function, stratified by the diagnosed age of 12. We used epigenome bioinformatics analyses, dual luciferase reporter assays, and expression quantitative trait loci (eQTL) analyses to prioritize the most likely functional variant and potential causal gene. We also performed functional experiments to evaluate the role of the causal gene on islet function and its related mechanisms. Results We identified rs912304 as a risk variant for T1D subgroups with diagnosed age ≥ 12 but not

The scourge of type-1 diabetes (T1D) is the morbidity and mortality it and its complications cause at a younger age. This propels the constant search for better diagnostic, treatment, and management strategies, with the ultimate quest being a cure for T1D. Recently, the therapeutic potential of exosomes has generated a lot of interest. Among the characteristics of exosomes of particular interest are (a) their regenerative capacity, which depends on their origin, and (b) their content, which determines the cell communication and crosstalk they influence. Other functional capacities, including paracrine and endocrine homeostatic regulation, pathogenic response ability resulting in insulin secretory defects or β-cell death under normal metabolic conditions, immunomodulation, and promotion of regeneration, have also garnered significant interest. Exosome specificity makes them suitable as biomarkers or predictors, and their mobility and content lend credence to drug delivery and therapeutic suitability. This review aims to highlight the functional capacities of exosomes and their established as well as novel contributions at various pathways in the onset and progression of T1D. The pathogenesis of T1D involves a complex crosstalk between insulin-secreting pancreatic β-cells and immune cells, which is partially mediated by exosomes. We also examine the potential implications for type 2 diabetes (T2D), as the link in T2D has guided T1D exploration. The collective landscape presented is expected to help identify how a deeper understanding of exosomes (and their cargo) can provide a framework for actionable solutions to prevent, halt, or change the very course of T1D and its complications.

Background: A divergent fracture pattern is seen in patients living with type 1 diabetes (T1D). These patients are at risk for fractures at unusual distal sites over and above the fractures occurring at major osteoporotic sites. Avascular necrosis (AVN) involving the talus has not been reported previously in T1D. Case Presentation: We hereby report an exceptional case of a 24-year old patient of T1D, who reported to us 3 months post-partum with swelling and pain over her right ankle. In the third trimester of her pregnancy, she encountered trivial trauma to her right ankle. One month after delivery, she developed fragility fractures over her left 2nd to 4th metatarsal heads. On further workup, she was found to have low bone mass and avascular necrosis of right talus on magnetic resonance imaging. On follow up 1 year later, she continued to have low bone mass although her bone mineral density (BMD) increased at the lumbar spine and hip. She was diagnosed with right talar AVN due to fragility fracture sustained in the third trimester with low bone mass consequent to T1D. A possible role of pregnancy- and lactation-related osteoporosis was considered in view of the chronological association with pregnancy. Conclusion: Our case highlights the fragile skeletal health of patients living with T1D making a case for greater scrutiny of declining bone health in these patients. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the prevalence of insulin autoantibody (IAA), glutamic acid decarboxylase antibody (GADA), and insulinoma-associated antigen-2 antibody (IA-2A) in type 1 diabetes (T1D) children based on the presence of predisposing HLA-II alleles. Additionally, to assess the sequence homology between autoantigens of islet cells and selected proteins derived from gut bacteria in terms of their binding capacities to HLA risk alleles, HLA-DRB1/DQB1 alleles were determined by PCR-SSOP in 111 T1D children (probands) along with 222 parents and 133 siblings. Autoantibodies were measured by ELISA, and in silico analysis was run as follows: protein extraction, homology and epitope prediction, peptide alignment, and HLA-peptide docking. Higher significant frequencies of DRB1*03:01, DQB1*02:01, and DQB1*03:02 alleles and DRB1*03:01 ~ DQB1*02:01 haplotype and lower frequencies of DRB1*11:01, DRB1*14:01, and DQB1*03:01 alleles were found in probands compared to parents and siblings. DRB1*11:01 ~ DQB1*03:01, DRB1*14:01 ~ DQB1*05:03, and DRB1*15:01-DQB1*06:02 haplotypes were significantly less frequent in the probands compared to parents. Out of 111 probands, 21 were seronegative, 90 tested positive for one autoantibody, and 15 showed the concurrent presence of three autoantibodies. Logistic regression analysis revealed that DRB1*04 ~ DQB1*03:02 haplotype was associated with the induction of GADA and IA-2A, while DRB1*11:01 ~ DQB1*03:01 was associated with seronegativity. Epitopes derived from GAD and gut bacteria showed strong binding capacities to HLA risk alleles. Due to the sequence similarities between gut bacteria-derived proteins and islet cell autoantigens and their potential for binding to HLA risk alleles, dysbiosis of gut microbiota can be considered another risk factor for the development of T1D, especially in genetically susceptible individuals. [ABSTRACT FROM AUTHOR]

Introduction: Hashimoto's thyroiditis is a prevalent autoimmune disease among the population. With the progress in diagnostic and research techniques, it has come to light that Hashimoto's thyroiditis is linked to a higher likelihood of developing other disorders that impact multiple organs and systems. Throughout the course of this disease, individuals may experience an array of complications such as sexual dysfunctions, fertility problems, specific mental disorders, cardiovascular diseases and other autoimmune diseases. Aim of the Study: The primary aim of this study is to explore the potential association between Hashimoto’s thyroiditis and its consequential effects on other physiological systems and organs. Description of the State of Knowledge: Hashimoto's thyroiditis is a complex autoimmune disease characterized by chronic inflammation of the thyroid gland. The pathogenesis of the disease is not yet completely understood. Hashimoto's thyroiditis has been associated with a range of health issues, including sexual dysfunction, fertility problems, psychiatric disorders, cardiovascular diseases, and other autoimmune disorders. Materials and methods: An unsystematic scientific literature review was conducted using specific keywords such as Hashimoto's thyroiditis, fertility problems, thyroid tumor, cardiovascular diseases, and autoimmune diseases. The review was carried out on PubMed, analyzing a total of 54 sources published until 2023. Conclusions: HT's association with psychiatric disorders, fertility issues, thyroid tumors, cardiovascular dysfunction, and comorbid autoimmune conditions underscores its broad clinical impact, necessitating integrated management approaches. Effective management of HT requires collaboration among specialists to ensure early detection, proactive intervention, and patient education, ultimately improving therapeutic outcomes and quality of life. [ABSTRACT FROM AUTHOR]

Aims: Human recombinant insulin is currently the only therapy for children and adolescents with type 1 diabetes (T1D), although not always efficient for the glycemic control of these individuals. The interrelation between the gut microbiome and the glycemic control of apparently healthy populations, as well as various populations with diabetes, is undeniable. Probiotics are biotherapeutics that deliver active components to various targets, primarily the gastrointestinal tract. This systematic review and meta-analysis examined the effect of the administration of probiotics on the glycemic control of pediatric and adolescent individuals with T1D. Materials and Methods: Randomized controlled trials employing the administration of probiotics in children and adolescents with T1D (with ≥10 individuals per treatment arm), written in English, providing parameters of glycemic control, such as mean glucose concentrations and glycosylated hemoglobin (HbA1c), were deemed eligible. Results: The search strategy resulted in six papers with contradictory findings. Ultimately, five studies of acceptable quality, comprising 388 children and adolescents with T1D, were included in the meta-analysis. Employing a random and fixed effects model revealed statistically significant negative effect sizes of probiotics on the glycemic control of those individuals, i.e., higher concentrations of glucose and HbA1c than controls. Conclusions: Children and adolescents with T1D who received probiotics demonstrated worse glycemic control than controls after the intervention. Adequately powered studies, with extended follow-up periods, along with monitoring of compliance and employing the proper strains, are required to unravel the mechanisms of action and the relative effects of probiotics, particularly concerning diabetes-related complications and metabolic outcomes. [ABSTRACT FROM AUTHOR]

Type 1 diabetes mellitus (T1D) is an incurable autoimmune disease characterized by the destruction of pancreatic islet cells, resulting in lifelong dependency on insulin treatment. There is an abundance of review articles addressing the prediction of T1D; however, most focus on the presymptomatic phases, specifically stages 1 and 2. These stages occur after seroconversion, where therapeutic interventions primarily aim to delay the onset of T1D rather than prevent it. This raises a critical question: what happens before stage 1 in individuals who will eventually develop T1D? Is there a "stage 0" of the disease, and if so, how can we detect it to increase our chances of truly preventing T1D? In pursuit of answers to these questions, this narrative review aimed to highlight recent research in the field of early detection and prediction of T1D, specifically focusing on biomarkers that can predict T1D before the onset of islet autoimmunity. Here, we have compiled influential research from the fields of epigenetics, omics, and microbiota. These studies have identified candidate biomarkers capable of predicting seroconversion from very early stages to several months prior, suggesting that the prophylactic window begins at birth. As the therapeutic landscape evolves from treatment to delay, and ideally from delay to prevention, it is crucial to both identify and validate such "stage 0" biomarkers predictive of islet autoimmunity. In the era of precision medicine, this knowledge will enable early intervention with the potential for delaying, modifying, or completely preventing autoimmunity and T1D in at-risk children. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 Diabetes (T1D) affects over 9 million worldwide and necessitates meticulous self-management for blood glucose (BG) control. Utilizing BG prediction technology allows for increased BG control and a reduction in the diabetes burden caused by self-management requirements. This paper reviews BG prediction models in T1D, which include nutritional components. Method: A systematic search, utilizing the PRISMA guidelines, identified articles focusing on BG prediction algorithms for T1D that incorporate nutritional variables. Eligible studies were screened and analyzed for model type, inclusion of additional aspects in the model, prediction horizon, patient population, inputs, and accuracy. Results: The study categorizes 138 blood glucose prediction models into data-driven (54%), physiological (14%), and hybrid (33%) types. Prediction horizons of ≤30 min are used in 36% of models, 31–60 min in 34%, 61–90 min in 11%, 91–120 min in 10%, and >120 min in 9%. Neural networks are the most used data-driven technique (47%), and simple carbohydrate intake is commonly included in models (data-driven: 72%, physiological: 52%, hybrid: 67%). Real or free-living data are predominantly used (83%). Conclusion: The primary goal of blood glucose prediction in T1D is to enable informed decisions and maintain safe BG levels, considering the impact of all nutrients for meal planning and clinical relevance. [ABSTRACT FROM AUTHOR]

BACKGROUND: Type 1 diabetes (T1D) carries a significant risk of atherosclerosis as the main driver for cardiovascular events. Atherosclerosis is initiated by the activation of the endothelium by various risk factors through the inflammation process. The anti-inflammatory cytokine TGF-β1 may inhibit the development of atherosclerosis. METHODS: In a cross-sectional study, a total of 40 patients aged 14.5±3.16 years old with T1D and 40 healthy controls aged 14.7±0.99 years old were involved. Common carotid artery IMT (CIMT) was measured by real-time M-echocardiography mode (Affinity 50G Philips) and Flow Mediated Dilatation (FMD), using high-resolution ultrasonography and Doppler flow characteristics. The TGF-B1 level was measured by indirect ELISA at Saiful Anwar Hospital Laboratory. RESULTS: There were no differences in age, gender, Body Mass Index (BMI), duration of diabetes, renal function, or nutritional status between the T1D and healthy groups (p > 0.05) A significant difference in cIMT was observed between the T1D group and the healthy group (0.567 ± 0.87 mm vs. 0.387 ± 0.57 mm, P = 0 ), FMD (7.17 ± 3.98 mm vs. 11.22 ± 5.48 mm, p = 0 ), and the level of TGF-β1 cytokine (39.83±13.51 vs. 73.67±15.34 pg/ml, P = 0 ) A significantly negative correlation between TGF-β1 and cIMT ( p = 0 ; r = - 0.685 ) a significantly positive correlation between TGF-β1 and FMD ( p = 0 ; r = 0.55 ) were found. CONCLUSION: Atherosclerosis is an inflammatory disease accelerated by diabetes. The inflammation process is more prominent in T1D patients. T1D patients show a decreased level of TGF-ẞ1, increased measurement of cIMT (>0.5 mm), and a decreased measurement of FMD. [ABSTRACT FROM AUTHOR]

Development and characterization of guinea pig anti-insulin polyclonal antibody against a target-specific insulin antigen. In India, an insulin immunogenicity kit for detecting insulin antibodies (neutralizing Nab) is an unmet medical need for diabetic patient's routine diagnosis. Type 1 diabetics rely on insulin injections daily basis for survival; if the body develops anti-insulin antibodies and neutralizes the exogenous recombinant insulin, glucose control is lost, and the patient eventually dies. Antibodies are excellent diagnostic reagents due to the specificity and sensitivity they provide in recognizing specific and unique target antigens. The paper describes the use of insulin as a target antigen and the development of target (insulin) specific antibodies in guinea pigs for use as a positive control for immunogenicity kit validation. Anti-insulin polyclonal antibody was raised against insulin in the Dunkin Hartley guinea pigs host. Anti-insulin antibody titer of all bleeds from four animals was tested using an indirect ELISA assay format. All four animals responded to the target-specific antigen but only one animal (#4) responded with a high-affinity antibody titer. The hyperimmune sera were purified using a protein A column. The purified anti-insulin antibody was characterized through SDS Page and western blot. The specificity, reactivity, and antibody binding efficiency were confirmed through immunoassays. Guinea pig anti-insulin polyclonal antibody developed in this study showed good specificity, reactivity, and efficiency in the immunoassays. This paper describes the development and characterization of anti-insulin antibodies for use as a control in developing a user-friendly insulin immunogenicity kit. [ABSTRACT FROM AUTHOR]

Objective: Pancreatic beta cell destruction is a hallmark of type 1 diabetes (T1D), a heterogeneous disorder with a wide range of potential causes. T cell activation molecules have been shown to play an important role in the development of T1D, according to the majority of studies. Some autoimmune diseases have been linked to SNPs in the 4q27 region, specifically in the KIAA1109-interleukin 2 (IL2)-IL21 block. The purpose of this research was to look into how certain polymorphic variants in the 4q27 region are linked to T1D. Methods: We investigated whether variants in the 4q27 region could be a causal factor in T1D susceptibility. Polymorphisms of ten single-nucleotide polymorphisms (SNPs) belonging to the KIAA1109/IL21/IL2 block were studied in 255 individuals from 59 families using the Sequenom MassARRAY platform. Results: The IL21/IL2 region was found to have a significant association with T1D in Tunisian cohorts. We found that the T allele of the rs2221903 marker is disproportionately passed down from parents to their children. In addition, haplotype analyses encompassing all of the SNPs under consideration show that the GACAGGA and the shortly TT haplotypes were significantly over-transmitted from parents to their children, suggesting they may be a T1D genetic susceptibility factor in our population. Conclusion: Several autoimmune disorders (ADs) have been linked to the IL2/IL21 genes, suggesting that there is a shared genetic background that confers a common genetic predisposition across ADs. More research into the genetic and functional aspects of the 4q27 region is needed to better explain the role it plays in the risk of ADs. [ABSTRACT FROM AUTHOR]

Diabetes mellitus presents a global health challenge characterized by dysregulated glucose metabolism and insulin resistance. Pancreas dysfunction contributes to the development and progression of diabetes. Cross-sectional imaging modalities have provided new insight into the structural and functional alterations of the pancreas in individuals with diabetes. This review summarizes MRI and CT studies that characterize pancreas alterations in both type 1 and type 2 diabetes and discusses future applications of these techniques. Key points: Cross-sectional imaging can detect alterations to the pancreas accompanying, and possibly presaging, the development of both type 1 diabetes (T1D) and type 2 diabetes (T2D). The smaller pancreas found in individuals with diabetes implicates exocrine involvement in the disease, as it exceeds the 1–2% of the pancreas composed of hormone-producing endocrine tissue. Pancreas fat content is associated with insulin resistance and is higher in individuals with T2D. Quantitative MRI can detect changes in pancreas composition and microstructure in individuals with diabetes that display spatial heterogeneity throughout the gland. [ABSTRACT FROM AUTHOR]

Diabetes is known to negatively affect male reproduction. Recent clinical results have confirmed that mesenchymal stem cell (MSC)–based therapies are safe and effective for the treatment of diabetes. However, the effect and potential mechanism through which MSC transplantation improves diabetes-derived male reproductive dysfunction are still unknown. In the present study, we first established a male T1D mouse model through intraperitoneal injection of streptozotocin for five consecutive days. Subsequently, we evaluated the blood glucose levels, fertility, and histology and immunology of the pancreas, testes, and penis of T1D mice with or without transplantation of menstrual blood–derived endometrial stem cells (MenSCs) or umbilical cord mesenchymal stem cells (UCMSCs). Glucose was added to the medium in which the Leydig cells were cultured to imitate high glucose–injured cell viability. Subsequently, we evaluated the cellular viability, ROS levels, and mitochondrial membrane potential of Leydig cells treated with or without MenSC-conditioned medium (MenSC-CM) using a CCK8 assay, immunofluorescence, and flow cytometry. The targeted proteins are involved in the potential mechanism underlying MenSC-derived improvements, which was further validated via Western blotting. Collectively, our results indicated that MenSC transplantation significantly ameliorated reproductive dysfunction in male T1D mice by enhancing cellular antioxidative capacity and promoting angiogenesis. This study provides solid evidence and support for the application of MSCs to improve diabetes-induced male reproductive dysfunction. [ABSTRACT FROM AUTHOR]

Introduction: Type 1 Diabetes (T1D) presents self-management challenges, requiring an additional 180 daily decisions to regulate blood glucose (BG) levels. Despite the potential, T1D-focused applications have a 43% attrition rate. This work delves into the willingness of people living with T1D (PwT1D) to use technology. Method: An online questionnaire investigated the current practices for carbohydrate estimation, nutritional tracking, and attitudes towards technology engagement, along with hypothetical scenarios and preferences regarding technology use. Results: Thirty-nine responses were collected from PwT1D (n = 33) and caregivers (n = 6). Nutrition reporting preferences varied, with 50% favoring 'type and scroll' while 30% preferred meal photographing. Concerning the timing of reporting, 33% reported before meals, 55% after, and 12% at a later time. Improved Time in Range (TIR) was a strong motivator for app use, with 78% expressing readiness to adjust insulin doses based on app suggestions for optimizing TIR. Meal descriptions varied; a single word was used in 42% of cases, 23% used a simple description (i.e., "Sunday dinner"), 30% included portion sizes, and 8% provided full recipes. Conclusion: PwT1D shows interest in using technology to reduce the diabetes burden when it leads to an improved TIR. For such technology to be ecologically valid, it needs to strike a balance between requiring minimal user input and providing significant data, such as meal tags, to ensure accurate blood glucose management without overwhelming users with reporting tasks. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is an autoimmune disease characterized by the destruction of insulin-producing β-cells in the pancreas. This destruction leads to chronic hyperglycemia, necessitating lifelong insulin therapy to manage blood glucose levels. Typically diagnosed in children and young adults, T1D can, however, occur at any age. Ongoing research aims to uncover the precise mechanisms underlying T1D and to develop potential interventions. These include efforts to modulate the immune system, regenerate β-cells, and create advanced insulin delivery systems. Emerging therapies, such as closed-loop insulin pumps, stem cell-derived β-cell replacement and disease-modifying therapies (DMTs), offer hope for improving the quality of life for individuals with T1D and potentially moving towards a cure. Currently, there are no disease-modifying therapies approved for stage 3 T1D. Preserving β-cell function in stage 3 T1D is associated with better clinical outcomes, including lower HbA1c and decreased risk of hypoglycemia, neuropathy, and retinopathy. Tumor Necrosis Factor alpha (TNF-α) inhibitors have demonstrated efficacy at preserving β-cell function by measurement of C-peptide in two clinical trials in people with stage 3 T1D. However, TNF-α inhibitors have yet to be evaluated in a pivotal trial for T1D. To address the promising clinical findings of TNF-α inhibitors in T1D, Breakthrough T1D convened a panel of key opinion leaders (KOLs) in the field. The workshop aimed to outline an optimal clinical path for moving TNF-α inhibitors to a pivotal clinical trial in T1D. Here, we summarize the evidence for the beneficial use of TNF-α inhibitors in T1D and considerations for strategies collectively identified to advance TNF-α inhibitors beyond phase 2 clinical studies for stage 3 T1D.

Clinical islet transplantation for treatment of type 1 diabetes (T1D) is limited by the shortage of pancreas donors and need for lifelong immunosuppressive therapy. A convection-driven intravascular bioartificial pancreas (iBAP) based on highly permeable, yet immunologically protective, silicon nanopore membranes (SNM) holds promise to sustain islet function without the need for immunosuppressants. Here, we investigate short-term functionality of encapsulated human islets in an iBAP prototype. Using the finite element method (FEM), we calculated predicted oxygen profiles within islet scaffolds at normalized perifusion rates of 14-200 nl/min/IEQ. The modeling showed the need for minimum in vitro and in vivo islet perifusion rates of 28 and 100 nl/min/IEQ, respectively to support metabolic insulin production requirements in the iBAP. In vitro glucose-stimulated insulin secretion (GSIS) profiles revealed a first-phase response time of

The role of the intestinal microbiota in the diagnosis and treatment of pancreatic diseases is increasingly significant. Consequently, fecal microbiota transplantation (FMT) is emerging as a promising therapeutic avenue for various pancreatic disorders, including cancer, pancreatitis, and type 1 diabetes (T1D). This innovative procedure entails transferring gut microbiota from healthy donors to individuals affected by pancreatic ailments with the potential to restore intestinal balance and alleviate associated symptoms. FMT represents a pioneering approach to improve patient outcomes in pancreatic diseases, offering tailored treatments customized to individual microbiomes and specific conditions. Recent research highlights the therapeutic benefits of targeting the gut microbiota for personalized interventions in pancreatic disorders. However, a comprehensive understanding of the intricate interplay between gut microbiota and pancreatic physiology warrants further investigation. The necessity for additional studies and research endeavors remains crucial, especially in elucidating both adult and pediatric cases affected by pathological pancreatic conditions. [ABSTRACT FROM AUTHOR]

Aims: Individuals with type 1 diabetes (T1D) do not appear to have an elevated risk of severe Coronavirus Disease 19 (COVID‐19). Pre‐existing immune reactivity to Severe Acute Respiratory Syndrome Coronavirus 2 (SARS‐CoV‐2) in unexposed individuals may serve as a protective factor. Hence, our study was designed to evaluate the existence of T cells with reactivity against SARS‐CoV‐2 antigens in unexposed patients with T1D. Materials and methods: Peripheral blood mononuclear cells (PBMCs) were collected from SARS‐CoV‐2 unexposed patients with T1D and healthy control subjects. SARS‐CoV‐2 specific T cells were identified in PBMCs by ex‐vivo interferon (IFN)γ‐ELISpot and flow cytometric assays. The epitope specificity of T cells in T1D was inferred through T Cell Receptor sequencing and GLIPH2 clustering analysis. Results: T1D patients unexposed to SARS‐CoV‐2 exhibited higher rates of virus‐specific T cells than controls. The T cells primarily responded to peptides from the ORF7/8, ORF3a, and nucleocapsid proteins. Nucleocapsid peptides predominantly indicated a CD4+ response, whereas ORF3a and ORF7/8 peptides elicited both CD4+ and CD8+ responses. The GLIPH2 clustering analysis of TCRβ sequences suggested that TCRβ clusters, associated with the autoantigens proinsulin and Zinc transporter 8 (ZnT‐8), might share specificity towards ORF7b and ORF3a viral epitopes. Notably, PBMCs from three T1D patients exhibited T cell reactivity against both ORF7b/ORF3a viral epitopes and proinsulin/ZnT‐8 autoantigens. Conclusions: The increased frequency of SAR‐CoV‐2‐ reactive T cells in T1D patients might protect against severe COVID‐19 and overt infections. These results emphasise the long‐standing association between viral infections and T1D. [ABSTRACT FROM AUTHOR]

Diabetes and its associated complications have increasingly become major challenges for global healthcare. The current therapeutic strategies involve insulin replacement therapy for type 1 diabetes (T1D) and small-molecule drugs for type 2 diabetes (T2D). Despite these advances, the complex nature of diabetes necessitates innovative clinical interventions for effective treatment and complication prevention. Accumulative evidence suggests that protein post-translational modifications (PTMs), including glycosylation, phosphorylation, acetylation, and SUMOylation, play important roles in diabetes and its pathological consequences. Therefore, the investigation of these PTMs not only sheds important light on the mechanistic regulation of diabetes but also opens new avenues for targeted therapies. Here, we offer a comprehensive overview of the role of several PTMs in diabetes, focusing on the most recent advances in understanding their functions and regulatory mechanisms. Additionally, we summarize the pharmacological interventions targeting PTMs that have advanced into clinical trials for the treatment of diabetes. Current challenges and future perspectives are also provided. [ABSTRACT FROM AUTHOR]

Islet transplantation is a curative treatment for patients suffering from type 1 diabetes and has the potential to replace current treatment strategies involving the exogenous administration of insulin. Despite this potential, there are many hurdles in achieving successful long‐term graft survival due to autoimmune and foreign body reactions leading to graft rejection coupled with donor shortage and potential adverse effects from the need for long‐term administration of immunosuppressive drugs. As a result, various approaches have been proposed to increase the viability and function of islet grafts during isolation and ex vivo culture with the use of growth factors, hormones, and other therapeutic agents. In addition, other strategies have addressed how to enhance or maintain islet graft performance after implantation with improvements on immunosuppressive drug regimens and the use of biomaterials to encapsulate and protect the cells from graft rejection. This review focuses on the recent advances in strategies to improve islet viability and function with the addition of exogenous compounds and the implementation of conformal coating as a promising tool for immunoprotection of islet transplants. [ABSTRACT FROM AUTHOR]

Aims: Sulfatide is a chaperone for insulin manufacturing in beta cells. Here we explore whether the blood glucose values normally could be associated with this sphingolipid and especially two of its building enzymes CERS2 and CERS6. Both T1D and T2D have low blood sulfatide levels, and insulin resistance on beta cells at clinical diagnosis. Furthermore, we examined islet pericytes for sulfatide, and beta‐cell receptors for GLP‐1, both of which are related to the insulin production. Materials and Methods: We examined mRNA levels in islets from the DiViD and nPOD studies, performed genetic association analyses, and histologically investigated pericytes in the islets for sulfatide. Results: Polymorphisms of the gene encoding the CERS6 enzyme responsible for synthesising dihydroceramide, a precursor to sulfatide, are associated with random blood glucose values in non‐diabetic persons. This fits well with our finding of sulfatide in pericytes in the islets, which regulates the capillary blood flow in the islets of Langerhans, which is important for oxygen supply to insulin production. In the islets of newly diagnosed T1D patients, we observed low levels of GLP‐1 receptors; this may explain the insulin resistance in their beta cells and their low insulin production. In T2D patients, we identified associated polymorphisms in both CERS2 and CERS6. Conclusions: Here, we describe several polymorphisms in sulfatide enzymes related to blood glucose levels and HbA1c in non‐diabetic individuals. Islet pericytes from such persons contain sulfatide. Furthermore, low insulin secretion in newly diagnosed T1D may be explained by beta‐cell insulin resistance due to low levels of GLP‐1 receptors. [ABSTRACT FROM AUTHOR]

Abstract Introduction - Le diabète chez l’enfant subit une mutation profonde en termes de fréquence et de recul de l’âge de début depuis une vingtaine d’années au niveau mondial. L’Algérie est particulièrement impactée par l’épidémie au point de figurer depuis 2016 dans le ‘top 10’ des pays à très forte incidence de diabète de type 1 (DT1). Notre étude a pour but de présenter l’évolution épidémiologique du DT1 de l’enfant à travers le registre de la wilaya d’Oran. Matériels et méthodes - La population de référence est celle de la wilaya d’Oran. Les nouveaux cas de DT1 proviennent des unités de première ligne et des services de pédiatrie. L’enregistrement était centralisé au niveau du service de pédiatrie «C» du CHU d’Oran depuis 1973 avec une exhaustivité proche de 100%. Résultats - Du 1er janvier 1973 au 31 décembre 2017, 2358 nouveaux cas de DT1 de moins de 15 ans au diagnostic du DT1 ont été enregistrés. L’incidence annuelle moyenne des moins de 15 ans des cinq dernières années 2013-2017 s’établit à 31,12± 3,60 cas pour 100 000 avec une évolution annuelle moyenne de 12,78% sur les 25 dernières années. Les évolutions annuelles moyennes des classes d’âge pédiatriques de [0-4], [5-9] ans et [10-14] ans sont de 15,03, 15,50 et de 9,10%, respectivement. L’incidence pour 1000 naissances vivantes des années 1998-2002 montre un risque de contracter un DT1 dans les 15 premières années de vie de 3,5 p. 1000. La prévalence était de 207 pour 100.000, soit 1 DT1 pour 482 enfants de moins de 15 ans, au 31 décembre 2017. Le sex-ratio s’établit à 0,99 pour l’ensemble des cas, mais subit des variations cycliques significatives avec des extrêmes de 0,80 et 1,14 (p=0,02). La saisonnalité hiver/été, significative de 1973 à 2014 en faveur des mois d’hiver, ne l’est plus à partir de 2015. Conclusion - L’augmentation persistante de l’incidence et le rajeunissement marqué de l’âge d’apparition du DT1 de l’enfant de la wilaya d’Oran sont une réalité depuis une vingtaine d’années. Cette évolution, liée essentiellement à l’environnement, ne va pas sans poser de nouvelles difficultés aux familles et aux équipes en charge. Abstract Introduction - Diabetes in children is undergoing a profound change in terms of fre-quency and decrease in age in the last twenty years worldwide. Algeria is particularly impacted by the epidemic to the point of appearing in the ‘top 10’ 2016 of countries with very high incidence of type 1 diabetes (T1D). Our study aims to present the epidemiological evolution of T1D in children through a recruitment of 45 years in the register of the department of Oran. Materials and Methods - The reference population is that of the department of Oran. New cases of T1D are children under 15 years old coming from front-line units and pediatric departments. Registration was centralized at the level of the «C» pediatric unit of Oran University Hospital since 1973 with an assessment close to 100%. Results - From January 1st, 1973 to December 31st, 2017, 2358 T1D new cases aged less than 15 years at T1D diagnosis have been registered. The average annual inci-dence under 15 years old for the last 5 years 2013-2017 is 31.12± 3.60 cases per 100 000 with an annual evolution average of 12.78% in the last 25 years. The annual evo-lution average of pediatric age groups are 15.03, 15.50 and 9.10%, respectively for children of [0-4], [5-9] and [10-14] years old. The incidence per 1 000 live births shows a risk of contracting T1D in the first 15 years of life of around 3.5. At December 31, 2017, the prevalence was 207 for 100 000 equivalent to 1 T1D for 482 children under 15,. The sex-ratio for all cases is 0.99 (1175 boys / 1183 girls), but undergoes cyclical variations with extremes of 0.80 and 1.14 between the periods 1978-1997 and 1998-2007 (p= 0.02). The winter/summer seasonality, significant from 1973 to 2014 in favor of winter months is no longer available starting from 2015. Conclusion - In agreement with other teams, we confirm the outsized increase in the incidence of T1D and the rejuvenation of the age at onset in children under 15 in our country. This evolution, mainly related to environmental problems poses new difficul-ties to families and teams in charge of the disease.

AbstractThe "Integrated Physiology of the Exocrine and Endocrine Compartments in Pancreatic Diseases" Workshop was a 1.5-day scientific conference at the National Institutes of Health (Bethesda, MD) that engaged clinical and basic science investigators interested in diseases of the pancreas. This report summarizes the workshop proceedings. The goal of the workshop was to forge connections and identify gaps in knowledge that could guide future research directions. Presentations were segregated into 6 major themes, including (a) Pancreas Anatomy and Physiology; (b) Diabetes in the Setting of Exocrine Disease; (c) Metabolic Influences on the Exocrine Pancreas; (d) Genetic Drivers of Pancreatic Diseases; (e) Tools for Integrated Pancreatic Analysis; and (f) Implications of Exocrine-Endocrine Crosstalk. For each theme, there were multiple presentations followed by panel discussions on specific topics relevant to each area of research; these are summarized herein. Significantly, the discussions resulted in the identification of research gaps and opportunities for the field to address. In general, it was concluded that as a pancreas research community, we must more thoughtfully integrate our current knowledge of the normal physiology as well as the disease mechanisms that underlie endocrine and exocrine disorders so that there is a better understanding of the interplay between these compartments.

Abstract Background This study investigates the association between socioeconomic status (SES) and glycemic control in individuals with type 1 diabetes (T1D) using flash glucose monitoring (FGM) devices within a public health system where these technologies are freely available and utilized according to recommended guidelines. Methods A follow-up study of 1060 adults (mean age 47.4 ± 15.0 years, 49.0% women) with T1D, receiving care at three Spanish university hospitals that regularly employ the FGM system. SES was assessed using the Spanish Deprivation Index and the average annual net income per person. Glycemic data were collected over a 14-day follow-up period, including baseline glycated hemoglobin (HbA1c) levels prior to sensor placement, the last available HbA1c levels, and FGM-derived glucose metrics. Individuals with sensor usage time

Verapamil is a well-known drug used for treating angina and hypertension. Emerging data from current clinical trials suggest that this calcium channel blocker has a potential benefit for pancreatic β-cells through the elevation and sustenance of C-peptide levels in patients with diabetes mellitus (DM). This is intriguing, given the fact that the current therapeutic options for DM are still limited to using insulin and incretins which, in fact, fail to address the underlying pathology of β-cell destruction and loss. Moreover, verapamil is widely available as an FDA-approved, cost-effective drug, supported also by its substantial efficacy and safety. However, the molecular mechanisms underlying the β-cell protective potentials of verapamil are yet to be fully elucidated. Although, verapamil reduces the expression of thioredoxin-interacting protein (TXNIP), a molecule which is involved in β-cell apoptosis and glucotoxicity-induced β-cell death, other signaling pathways are also modulated by verapamil. In this review, we revisit the historical avenues that lead to verapamil as a potential therapeutic agent for DM. Importantly, this review provides an update on the current known mechanisms of action of verapamil and also allude to the plausible mechanisms that could be implicated in its β-cell protective effects, based on our own research findings. [ABSTRACT FROM AUTHOR]

Type 1 diabetes (T1D) is characterized by the autoimmune-mediated attack of insulin-producing beta cells in the pancreas, leading to reliance on exogenous insulin to control a patient's blood glucose levels. As progress is being made in understanding the pathophysiology of the disease and how to better develop therapies to treat it, there is an increasing need for monitoring technologies to quantify beta cell mass and function throughout T1D progression and beta cell replacement therapy. Molecular imaging techniques offer a possible solution through both radiologic and non-radiologic means including positron emission tomography, magnetic resonance imaging, electron paramagnetic resonance imaging, and spatial omics. This commentary piece outlines the role of molecular imaging in T1D research and highlights the need for further applications of such methodologies in T1D. [ABSTRACT FROM AUTHOR]

Aims: This review aims to introduce research in the pancreas to a broader audience. The pancreas is a heterocrine gland residing deep within our abdominal cavity. It is the home to our islets, which play a pivotal role in regulating metabolic homeostasis. Due to its structure and location, it is an impossible organ to study, in molecular detail, in living humans, and yet, understanding the pancreas is critical if we aim to characterise the immunopathology of type 1 diabetes (T1D) and one day prevent the triggering of the autoimmune attack associated with ß‐cell demise. Methods: Over a 100 years ago, we began studying pancreatic histology using cadaveric samples and clever adaptations to microscopes. As histologists, some may say nothing much has changed. Nevertheless, our microscopes can now interrogate multiple proteins at molecular resolution. Images of pancreas sections are no longer constrained to a single field of view and can capture a thousands and thousands of cells. AI‐image‐analysis packages can analyse these massive data sets offering breakthrough findings. Conclusion: This narrative review will provide an overview of pancreatic anatomy, and the importance of research focused on the pancreas in T1D. It will range from histological breakthroughs to briefly discussing the challenges associated with characterising the organ. I shall briefly introduce a selection of the available global biobanks and touch on the distinct pancreatic endotypes that differ immunologically and in ß‐cell behaviour. Finally, I will introduce the idea of developing a collaborative tool aimed at developing a cohesive framework for characterising heterogeneity and stratifying endotypes in T1D more readily. [ABSTRACT FROM AUTHOR]

IntroductionContinue investigating Out-of-Pocket Expenses (OoPEs) and rationing of insulin and diabetes supplies, including impacts of the COVID-19 pandemic, for people with type 1 diabetes (T1D).MethodsA cross-sectional web-based survey was conducted in English and advertised by T1International’s global network of patient advocates from May through September 2022. Participants provided monthly OoPEs and rationing frequency for insulin and supplies, impacts of the COVID-19 pandemic, and open-ended comments.ResultsIn the seven most represented countries, mean monthly OoPEs were highest in the United States, followed by Panama, Canada, and India, and were much lower in the United Kingdom, Germany, and Sweden. OoPEs were highest for participants with partial healthcare coverage, followed by those with no healthcare coverage. The COVID-19 pandemic negatively impacted access and/or affordability of insulin and/or supplies for over half of participants. Globally, 19.5% reported insulin rationing and 36.6% reported rationing glucose testing supplies. Qualitative analysis of open-ended responses identified themes such as ‘mental health impacts’ and ‘limits to life choices.’DiscussionHigh OoPEs lead to rationing of insulin and supplies for many people with T1D globally. Healthcare systems improvements and price reductions of insulin and supplies are needed to ensure adequate, equitable access for all.

The research aimed to detect the roles of vitamin D (VD) and micro-ribonucleic acid (miRNA)-21-5p as potential predictors and diagnostic biomarkers for type 1 diabetes (T1D) and to determine the degree of association and predictability of them on beta (β) cells stress/death. A case-control study included three study groups: a T1D group that comprised 35 newly onset T1D patients, a first-degree relatives (FDRs) group that included a total of 35 FDRs of T1D patients, and a healthy control (HC) group that included a total of 20 subjects. All study subjects were evaluated for their serum connecting (C) peptide and VD, as well as the expression folds of serum miRNA-21-5p. The findings revealed significantly lower levels of C. peptide and VD among T1D and FDRs subjects than the HC group, whereas the folds of miRNA-21-5p were significantly higher in T1D subjects than FDRs and HC subjects. Furthermore, the level of C. peptide had a valuable positive association with VD within T1D and FDRs groups, whereas the folds of miRNA-21-5p have a valuable positive association with C. peptide and VD in FDRs and T1D groups, respectively. Vitamin D had exhibited a significantly decreased level among T1D and FDRs, and positively correlated with residual β-cells function, which indicated the possible utility of its low level as a β-cells stress/death predictive and diagnostic biomarker. Micro-RNA-21-5p indicated the possible utility of its high folds expression as β-cells stress/death predictive and diagnostic biomarker and the high level of miRNA-21-5p might play a vital role in T1D prevention.

BackgroundCaregivers of children with newly diagnosed type 1 diabetes (T1D) maintain close contact with providers for several weeks to facilitate rapid adjustments in insulin dosing regimens. Traditionally, patient glucose values are relayed by telephone for provider feedback, but digital health technology can now enable the remote sharing of glucose data via mobile apps.ObjectiveThe aim of this study was to test the feasibility of remote glucose monitoring in a population of children and adolescents with newly diagnosed T1D and to explore whether remote monitoring alters habits for self-review of glucose data or perceived ease of provider contact in this population as compared to a nonrandomized control group.MethodsData were collected from families who chose to participate in remote monitoring (intervention group) as well as from patients receiving usual care (control group). The intervention group received Bluetooth-capable glucose meters and Apple iPod Touch devices. Patient-generated glucose data were passively relayed from the meter to the iPod Touch and then to both the electronic health record (EHR) and a third-party diabetes data platform, Tidepool. The principal investigator reviewed glucose data daily in the EHR and Tidepool and contacted the participants as needed for insulin dose adjustments during the time between hospital discharge and first clinic appointment. Families in the control group received usual care, which involved keeping written records of glucose values and contacting the diabetes team daily by telephone to relay data and receive treatment recommendations. A total of 40 families (20 for the intervention group and 20 for the control group) participated in the study. All families were surveyed at 1 month and 6 months regarding self-review of glucose data and ease of contacting the diabetes team.ResultsPatient-generated glucose data were remotely accessible for 100% of the participants via Tidepool and for 85% via the EHR. Survey data indicated that families in the intervention group were more likely than those in the control group to review their glucose data using mobile health apps after 1 month (P

Type 1 diabetes (T1D) is a chronic autoimmune disease caused by the immune-mediated reduction of β cells, resulting in lifelong dependence on exogenous insulin administration. We studied the impact of M1/M2 macrophages on the β cell level. We obtained the healthy state (absence of T1D) and unhealthy state (presence of T1D). We found that in the unhealthy state, β cell levels are decreased with a continuous alternative switch between M1 and M2 macrophages. However, in the healthy state, the β cell levels increase with a high level of M2 macrophages.

BackgroundThe overarching goal of blood glucose forecasting is to assist individuals with type 1 diabetes (T1D) in avoiding hyper- or hypoglycemic conditions. While deep learning approaches have shown promising results for blood glucose forecasting in adults with T1D, it is not known if these results generalize to children. Possible reasons are physical activity (PA), which is often unplanned in children, as well as age and development of a child, which both have an effect on the blood glucose level.Materials and MethodsIn this study, we collected time series measurements of glucose levels, carbohydrate intake, insulin-dosing and physical activity from children with T1D for one week in an ethics approved prospective observational study, which included daily physical activities. We investigate the performance of state-of-the-art deep learning methods for adult data—(dilated) recurrent neural networks and a transformer—on our dataset for short-term (30 min) and long-term (2 h) prediction. We propose to integrate static patient characteristics, such as age, gender, BMI, and percentage of basal insulin, to account for the heterogeneity of our study group.ResultsIntegrating static patient characteristics (SPC) proves beneficial, especially for short-term prediction. LSTMs and GRUs with SPC perform best for a prediction horizon of 30 min (RMSE of 1.66 mmol/l), a vanilla RNN with SPC performs best across different prediction horizons, while the performance significantly decays for long-term prediction. For prediction during the night, the best method improves to an RMSE of 1.50 mmol/l. Overall, the results for our baselines and RNN models indicate that blood glucose forecasting for children conducting regular physical activity is more challenging than for previously studied adult data.ConclusionWe find that integrating static data improves the performance of deep-learning architectures for blood glucose forecasting of children with T1D and achieves promising results for short-term prediction. Despite these improvements, additional clinical studies are warranted to extend forecasting to longer-term prediction horizons.

Objective: Type 1 diabetes, a multigenic autoimmune disorder, is caused by the destruction of pancreatic beta-cells leads to insufficient insulin production and hyperglycemia, resulting in early morbidities and mortality. This study was designed to explore the genetic association of PTPN22 gene polymorphisms with T1D susceptibility among Pakistani children. Methods: Blood samples of T1D patients were obtained from the Department of Diabetes and Endocrinology of Children Hospital & University of Child Health Sciences, Lahore. Genotyping of rs2476601, rs1310182, and rs1217414 of the PTPN22 gene was performed by Tetra ARMS-PCR assay. Statistically, binary logistic regression was applied to determine variation in genotype distribution and association of PTPN22 gene polymorphism with T1D. Results: Genetic analysis showed that the A allele of rs2476601 (OR = 0.53, 95 % CI = 0.31–0.90; P

Background: Long noncoding RNA (lncRNA)-mediated posttranscriptional and epigenetic landscapes of gene regulation are associated with numerous human diseases. However, the regulatory mechanisms governing human β-cell function and survival remain unknown. Owing to technical and ethical constraints, studying the direct role of lncRNAs in β-cell function and survival in humans in vivo is difficult. Therefore, we utilized humanized mice with human islets to investigate lncRNA expression using whole transcriptome shotgun sequencing. Our study aimed to characterize lncRNAs that may be crucial for human islet cell function and survival. Methods: Human β-cell death was induced in humanized mice engrafted with functional human islets. Using these humanized mice harboring human islets with induced β-cell death, we investigated lncRNA expression through whole transcriptome shotgun sequencing. Additionally, we systematically identified, characterized, and explored the regulatory functions of lncRNAs that are potentially important for human pancreatic islet cell function and survival. Results: Human islet cell death was induced in humanized mice engrafted with functional human islets. RNA sequencing analysis of isolated human islets, islet grafts from humanized mice with and without induced cell death, revealed aberrant expression of a distinct set of lncRNAs that are associated with the deregulated mRNAs important for cellular processes and molecular pathways related to β-cell function and survival. A total of 10 lncRNA isoforms (SCYL1-1:22, POLG2-1:1, CTRB1-1:1, SRPK1-1:1, GTF3C5-1:1, PPY-1:1, CTRB1-1:5, CPA5-1:1, BCAR1-2:1, and CTRB1-1:4) were identified as highly enriched and specific to human islets. These lncRNAs were deregulated in human islets from donors with different BMIs and with type 2 diabetes (T2D), as well as in cultured human islets with glucose stimulation and induced cell death induced by cytokines. Aberrant expression of these lncRNAs was detected in the exosomes from the medium used to culture islets with cytokines. Conclusion: Islet-enriched and specific human lncRNAs are deregulated in human islet grafts and cultured human islets with induced cell death. These lncRNAs may be crucial for human β-cell function and survival and could have an impact on identifying biomarkers for β-cell loss and discovering novel therapeutic targets to enhance b-cell function and survival. [ABSTRACT FROM AUTHOR]