This study aims to perform an updated meta-analysis evaluating the efficacy and safety of metformin adjunct therapy in type 1 diabetes mellitus (T1DM) patients.

Cochrane, PubMed and Embase were searched for randomised controlled trials (RCTs) that reported the efficacy and safety of metformin in T1DM patients. Statistical analyses were performed using STATA software.

Twenty-nine placebo-controlled RCTs enrolling 2051 T1DM patients were included. Adolescents experienced a notable reduction in total insulin daily dose (TIDD) (mean difference [MD] = -0.61 [95% confidence interval (CI): -1.02, -0.20] units/kg per day) and levels of haemoglobin A1c (HbA1c) (MD = -0.45 [95% CI: -0.79, -0.11]), total cholesterol (TC) (MD = -0.78 [95% CI: -1.54, -0.02]), and low-density lipoprotein (LDL) (MD = -0.69 [95% CI: -1.36, -0.02]) at 3 months of follow-up with metformin. In adults, metformin significantly reduced Body Mass Index (BMI) (MD = -0.71 [95% CI: -1.23, -0.19]), TIDD (MD = -0.44 [95% CI: -0.73, -0.16]), and levels of HbA1c (MD = -0.70 [95% CI: -1.10, -0.30]) and TC (MD = -0.60 [95% CI: -1.09, -0.10]) at 6 months. The risk of gastrointestinal adverse events (GIAEs) was significantly higher in both adolescents (Relative Risk [RR] = 1.74 [95% CI: 1.38, 2.21]) and adults (RR = 3.24 [95% CI: 1.49, 7.02]). All of the above had p-values less than 0.05. The metformin group showed no differences in BMI Z-score, high-density lipoprotein (HDL) level, or diabetic ketoacidosis (DKA) risk. No statistical difference was identified for any of the outcomes at other follow-up endpoints.

Metformin may reduce TIDD and levels of HbA1c, TC, triglycerides (TG), and LDL in T1DM adolescents. BMI, TIDD, and levels of HbA1c and TC may decrease in adults. Moreover, it may raise the risk of GIAEs in both age groups.

Type 1 diabetes mellitus (T1DM) is a chronic disease with an increasing global incidence. The mortality associated with T1DM complications emphasizes the urgency of developing therapeutic strategies to prevent or delay the onset of T1DM. Historically, T1DM was solely described as a T cell-mediated disease. However, the role of β-cells as active participants in the immune-mediated damage is now well appreciated. Indeed, heterogeneity, vulnerability to stressors and the ability of β-cells to act as antigen-presenting cells has altered the perspective of what is necessary for effective disease prevention and ongoing β-cell preservation. Currently, teplizumab, an Fc-receptor non-binding humanized CD3-specific monoclonal antibody, is the only therapy approved by the FDA for the delay of T1DM onset. The intravenous administration, generalized immunosuppression and adverse effects mean that the transition to routine clinical practice is not without challenges. However, teplizumab could lead to the development of more accessible therapies. In this Review, we explore current and potential therapeutics for T1DM prevention. We offer alternative approaches, such as targeting the receptor for advanced glycation end products (RAGE). RAGE is a pattern recognition receptor that engages a wide range of ligands, including advanced glycation end products (AGEs; a family of molecules that includes the well described marker of long-term glucose concentrations, HbA1c).

Incidence of type 1 diabetes is increasing globally, which is hypothesized to be due to environmental influences. We leverage Swedish nationwide registers linked to all children (n = 2,928,704) born in 1982-2010 to investigate if the heritability of childhood-onset type 1 diabetes has changed over time and how alterations in environmental factors have contributed to the rising type 1 diabetes incidence. The heritability is estimated at 0.83 (95% confidence interval: 0.79, 0.86) and stable over the observation period (0.80 [0.71, 0.86] in 1982, 0.83 [0.79, 0.86] in 2000, and 0·83 [0.79, 0.86] in 2010, respectively). Environmental factors including maternal smoking during pregnancy and childhood adiposity explain <10% of the increasing type 1 diabetes incidence. In this work, the heritability of childhood-onset type 1 diabetes has remained high and stable over the last 30 years. Our findings indicate that the available environmental factors are not the major contributors to the rise in type 1 diabetes in Sweden.

NETosis, the process through which neutrophils release neutrophil extracellular traps (NETs), has emerged as a crucial mechanism in host defense and the pathogenesis of autoimmune responses. During the SARS-CoV-2 pandemic, this process received significant attention due to the central role of neutrophil recruitment and activation in infection control. However, elevated neutrophil levels and dysregulated NET formation have been linked to coagulopathy and endothelial damage, correlating with disease severity and poor prognosis in COVID-19. Moreover, it is known that SARS-CoV-2 can induce persistent low-grade systemic inflammation, known as long COVID, although the underlying causes remain unclear. It has been increasingly acknowledged that excessive NETosis and NET generation contribute to further pathophysiological abnormalities following SARS-CoV-2 infection. This review provides an updated overview of the role of NETosis in autoimmune diseases, but also the relationship between COVID-19 and long COVID with autoimmunity (e.g., latent and overt autoimmunity, molecular mimicry, epitope spreading) and NETosis (e.g., immune responses, NET markers). Finally, we discuss potential therapeutic strategies targeting dysregulated NETosis to mitigate the severe complications of COVID-19 and long COVID.

This article explores Italy's pioneering national paediatric screening initiative for type 1 diabetes (T1D), the first of its kind to be mandated by the Italian law for the general population aged 1-17 years. This initiative is designed to facilitate early detection and secondary prevention of T1D and coeliac disease (CD), aiming to identify children in presymptomatic stages of T1D, regardless of family history. Emphasis is placed on autoantibody screening for T1D and CD to refine risk prediction and enhance secondary prevention efforts. Furthermore, the anti-CD3 + T cell monoclonal antibody teplizumab, which may be considered at present for compassionate use only, represents a step forward in delaying T1D onset in stage 2 patients. Italy's comprehensive screening law, passed in 2023, allows for early detection of T1D minimising the risk of consequences such as DKA at diagnosis. The screening will also advance our understanding of T1D disease pathogenesis and progression. These insights advocate for tailored prevention strategies, thus improving the design of clinical trials.

Type 1 diabetes mellitus (T1DM) is an autoimmune disease characterized by β-cell damage and absolute insulin deficiency. We consider combining immune intervention and β-cell replacement by biological scaffold to treat T1DM. Zinc transporter 8 (ZnT8) is known to be a pancreatic islet-specific autoantigen. Studies have shown that ZnT8(107-115)/HLA-A2 dimers can be used as antigen-specific immunosuppressants for T1DM. Mesenchymal stem cells (MSCs) can be induced to differentiate into insulin-producing cells (IPCs) under certain conditions in vitro. In recent years, the development of biomaterials has provided a more suitable three-dimensional microenvironment for cell transplantation. Our research group previously prepared gelatin/polylactic acid (PLLA/G) nanofiber scaffold by electrospinning technology, fixed GLP-1 analogues on the scaffold by surface modification with polydopamine (pDA) and confirmed the scaffold can promote bone mesenchymal stem cells (BMSCs) proliferation and improve cell survival rate. In addition, the scaffold can promote the differentiation of BMSCs into IPCs. Subsequently, ZnT8(107-115)/HLA-A2 dimer was constructed and loaded on the scaffold and confirmed the scaffold loaded with immunosuppressants can inhibit the proliferation and cytotoxicity of specific CD8+ T cells in vitro. This study used the above scaffold to co-load ZnT8(107-115)/HLA-A2 dimer and IPCs and implanted the scaffold into T1DM mice to study the blood glucose control and immunomodulatory effects on T1DM.

First, the PLLA/G scaffold was modified with pDA and fixed with Liraglutide (LIR) to obtain the PLLA/G-pDA-LIR scaffold. Rat BMSCs were loaded on the scaffold and the 'three-step induction method' was used to induce differentiation in vitro. The insulin expression of IPCs was detected by Dithizone (DTZ) staining, glucose stimulate insulin secretion (GSIS) in vitro and intraperitoneal glucose tolerance test (IPGTT) in vivo. Then, non obese diabetes mice were modelled with T1DM and randomly divided into 5 groups. Blank control group was not treated; negative control group underwent sham surgery; positive control group was injected with IPCs through tail vein; single load scaffold group was subcutaneously transplanted with PLLA/G-pDA-LIR scaffold loaded with IPCs; double load scaffold group was subcutaneously transplanted with PLLA/G-pDA-LIR scaffold loaded with IPCs and ZnT8(107-115)/HLA-A2 dimer. Blood glucose and body weight were measured weekly before and after transplantation. At 2, 4 and 6 W after transplantation, some mice were taken from each group to detect serum insulin and C-peptide, spleen lymphocyte subsets and Tregs and pancreatic Th1/Th2 cell inflammatory factors.

The results of insulin expression in induced differentiated IPCs show that cells with insulin expression can be obtained through the "three-step induction method", and transplanting IPCs can effectively reduce blood glucose and improve glucose tolerance. Compared with non-scaffold induced IPCs, fixing Liraglutide scaffolds can improve the insulin expression level of IPCs and promote the induction of differentiation. The results after scaffold transplantation showed that compared with the positive control group and the single load scaffold group, the blood glucose was significantly reduced, and the serum insulin and C-peptide were significantly increased and lasted longer. In addition, the pathogenic T cells and inflammatory factors in the double load scaffold group were significantly reduced, and Tregs and anti-inflammatory factors were significantly increased.

The results show that the biological scaffold with IPCs and ZnT8(107-115)/HLA-A2 dimers has the dual functions of controlling blood glucose and regulating immunity, and may effectively treat T1DM.

Stem cell-derived islet cell therapy can effectively treat type 1 diabetes, but its efficacy is hindered by low oxygen supply post-transplantation, particularly in subcutaneous spaces and encapsulation devices, leading to cell dysfunction. The response to hypoxia and effective strategies to alleviate its detrimental effects remain poorly understood. Here, we show that β cells within stem cell-derived islets gradually undergo a decline in cell identity and metabolic function in hypoxia. This is linked to reduced expression of immediate early genes (EGR1, FOS, and JUN), which downregulates key β cell transcription factors. We further identified genes important for maintaining β cell fitness in hypoxia, with EDN3 as a potent player. Elevated EDN3 expression preserves β cell identity and function in hypoxia by modulating genes involved in β cell maturation, glucose sensing and regulation. These insights improve the understanding of hypoxia's impact on stem cell-derived islets, offering a potential intervention for clinical applications.

Ketone bodies are key products of fat metabolism, primarily consisting of acetoacetate (AcAc), β-hydroxybutyrate (BHB), and acetone (acetone). Monitoring the concentration of ketone bodies in sweat can reflect the metabolic status of the body; it is also particularly significant in areas such as diabetes management, exercise monitoring, and the evaluation of the ketogenic diet. This paper presents a microfluidic patch for sweat collection and multiplex detection of AcAc, BHB and glucose. The microfluidic patch can achieve time-sequential sensing through Tesla valves, hydrophilic coatings, and unique chamber structural design. The concentrations of the three substances are quantified using colorimetric methods. Additionally, this study has designed a colorimetric app which can achieve automatic framing and detect the grayscale value of the colored area. Experimental results show that the patch can accurately detect changes in the concentrations of the three substances within specific ranges. The linear detection range for AcAc is 0.25 mM to 8 mM, the limit of detection (LOD) is 0.08 mM; for BHB, the linear detection range is 0.05 mM to 0.80 mM, the LOD is 0.02 mM; and for glucose, the linear detection range is 62.50 μM to 1000 μM, the LOD is 20.83 μM. In the future, this technology is expected to be applied to portable metabolic monitoring devices, offering a convenient solution for personal health management.

Type 1 diabetes (T1D) is an autoimmune condition characterized by the destruction of insulin-producing beta cells in the pancreas. Anti-Thymocyte Globulin (ATG) has emerged as a promising immunomodulatory therapy aimed at preserving beta-cell function and altering the disease course. This systematic review synthesizes current evidence from the clinical trials evaluating the efficacy and safety of low-dose ATG in individuals with T1D.

We conducted a comprehensive literature search of electronic databases, including PubMed (MEDLINE), Science Direct, Scopus, EMBASE, and ClinicalTrials.gov, to identify studies investigating ATG in T1D in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The Joanna Briggs Institute (JBI) Critical Appraisal Tools for randomized clinical trials and case-control studies were used to assess the quality and evaluate the risk of bias in the eligible studies.

The primary outcomes assessed were preservation of C-peptide levels, glycemic control, and adverse events. Results indicated that ATG showed potential in preserving beta-cell function and improving clinical outcomes in recent-onset T1D. However, the incidence of adverse events, such as cytokine release syndrome and lymphopenia, necessitated careful monitoring and management.

Low-dose ATG presents a promising therapeutic approach for modifying the progression of T1D. While early-phase trials demonstrate potential benefits in preserving beta-cell function, further large-scale, long-term studies are essential to establish optimal dosing regimens, long-term efficacy, and safety profiles. This review highlights the importance of continued research to fully elucidate the role of ATG in T1D management.

We investigated whether the peripheral co-administration of leptin and liraglutide (a glucagon-like peptide-1 receptor agonist) improved glucose metabolism in a mouse model of insulin-dependent diabetes mellitus (IDDM). Twelve-week-old male C57BL/6J mice were injected intraperitoneally with a high dose of streptozotocin to induce IDDM or vehicle-treated. Mice with IDDM were divided into four groups: leptin treatment alone (LEP), liraglutide treatment alone (LIRA), co-administration of leptin and liraglutide treatment (LEP+LIRA), untreated mice (UNT). Vehicle-treated mice were the healthy controls (HC). The blood glucose (BG) levels were measured, and a glucose tolerance test (GTT) was performed to compare the five groups. Leptin was administered peripherally at 20 μg/day using an osmotic pump, while liraglutide was administered subcutaneously at 1000 μg/kg/day. Monotherapy with leptin or liraglutide significantly improved glucose metabolism, as assessed by comparing BG levels and GTTs with those of the UNT group. Mice in the LEP+LIRA group showed even greater improvements in glucose metabolism than the monotherapy groups. Notably, glucose metabolism in the LEP+LIRA group improved comparably with the HC group. Thus, the peripheral co-administration of leptin and liraglutide effectively improved glucose metabolism in mice with IDDM without the use of insulin.

In recent years, the incidence of type 1 diabetes has been rising steadily, positioning its prevention and treatment as a central focus of global public health initiatives. Previous Mendelian randomization (MR) studies have investigated the relationship between proteomics and type 1 diabetes. Consequently, this study aims to identify prospective therapeutic targets for type 1 diabetes through a comprehensive multi-omics analysis.

This study primarily utilized the MR method, drawing on genetic data from several large-scale, publicly accessible genome-wide association studies. Within this framework, we applied two-sample MR to evaluate the relationship between five omics components and type 1 diabetes. Finally, we conducted various sensitivity analyses and bidirectional MR to ensure the robustness and reliability of our findings.

The inverse variance weighted method revealed that, following false discovery rate correction, 39 plasma proteins and 3 plasma protein ratios exhibited significant associations with type 1 diabetes. The genetically predicted risk of type 1 diabetes ranged from 0.05 for RBP2 to 394.51 for FMNL1. Furthermore, 4-chlorobenzoic acid levels demonstrated a potential association with type 1 diabetes.

Our research identified numerous omics components associated with type 1 diabetes. These findings offer novel insights into the disease's etiology, diagnosis, and treatment.

Physical activity plays an essential role in a healthy lifestyle. For children, the development of an encouraging attitude toward exercise can define a positive life-long behaviour. Type 1 diabetes mellitus (T1DM) is a metabolic disorder that usually develops in early childhood and severely affects glucose metabolism. Associated hypo- and hyperglycaemic conditions can dramatically interfere with the patient's everyday life. Since exercise significantly alters the glucose consumption of the body, this might influence how T1DM patients view physical activity. As parental guidance is critical in their children's behaviour, we investigate how parents of T1DM children relate to the engagement in physical activity of their children as compared to parents of healthy children.

A self-reported survey was conducted among those parents whose T1DM children were cared for at the Paediatric Clinic of the University of Debrecen, Hungary. All together, 318 children, 140 with T1DM and 178 healthy peers, participated in the study.

We found no significant difference in the body mass index of healthy and T1DM children and, furthermore, no significant difference was observed in HbA1c levels in exercising and non-exercising T1DM children. Nevertheless, while 67.6% of the healthy children regularly engage in physical activity, only 57.5% of T1DM children do so (p = 0.044). Importantly, parents whose T1DM child exercised regularly believed that daily PhysEd classes improved their children's health and had positive effects on their attitude toward exercise. In contrast, parents of children who did not regularly exercise were significantly less convinced.

These findings highlight the importance of targeted educational efforts to foster positive attitudes toward physical activity among families with T1DM children and contribute valuable insights into how parental perceptions may influence children's engagement in exercise.

Diabetes is a complex metabolic disorder affecting over 37 million people in the United States. Without proper management, diabetes can lead to a myriad of complications, including cardiovascular disease, kidney failure, and vision loss. Obesity is a major contributor to type 2 diabetes, but genetic and physiological factors make weight loss difficult, necessitating medication management for both conditions. Government-approved weight loss medications, including glucagon-like peptide-1 agonists and amylin analogs, have proven to be effective for both conditions. However, intensive glycemic control involving antidiabetic medications, while beneficial for reducing diabetic complications, can often precipitate hypoglycemic events, which are characterized by cardiac arrhythmias, coma, confusion, and even mortality. A new drug under investigation, CagriSema, combines cagrilintide, an amylin analog, with semaglutide, a glucagon-like peptide-1 agonist. This drug is being marketed as a safe and potentially superior medication to lower both Hemoglobin A1c and body weight. In this article, the pathophysiology, current guidelines, and management of diabetes will be reviewed, with an emphasis on the clinical evidence for tight glucose control and avoiding hypoglycemic events. Following this, an overview of recent trials on antidiabetic medications, including those involving CagriSema, will be presented, along with prospects for future trials in this promising area of research.

Real-time continuous glucose monitoring (rtCGM) is now the standard care for people with type 1 diabetes. However, whilst its impact on glycaemic outcomes is well-documented, its psychosocial effects, particularly in young adults experiencing extreme hyperglycaemia, remain poorly understood.

We aimed to explore the psychosocial impact of rtCGM on young adults with extreme hyperglycaemia who thus far have not been studied extensively.

A qualitative study employing semi-structured interviews was undertaken. Young adults 18-25 years (HbA1c >75mmol/mol (9.0%)), naïve to rtCGM, were provided with rtCGM for 6-months. Interviews (centred on barriers to self-management and experience of rtCGM use) were conducted within 2-weeks of recruitment and at the end. An inductive, thematic analysis of interviews was undertaken.

Eight participants (median age (IQR) 23.0 (22.0-24.5) years, 100% non-white ethnicity) were recruited with median HbA1c 94 (88-107) mmol/mol [DCCT 10.8 (10.2-12.1)%.]. All participants used multiple daily insulin injections. Despite low rtCGM wear-time (32.2 (23.1-59.4)%), significant improvements were observed in time in range, but no change in HbA1c. Thematic analysis indicated that high levels of disease burden were reported, with rtCGM-related themes identified: 1) interaction with rtCGM data, 2) feelings of control and trust from using rtCGM, and 3) frustration of technology and alarms. Although participants reported that knowledge of glucose levels on their smartphone was convenient and led to 'greater control', this was countered by alarm-fatigue, technical difficulties and feeling overwhelmed. Three participants prematurely stopped using rtCGM.

Young adults with high-risk hyperglycaemia have complex relationships with rtCGM. rtCGM may have benefits in this high-risk group, but are likely to require additional support and must be determined on a case-by-case basis as associated effort may contribute to feelings of distress and/or burnout. Implementing structured educational, psychosocial, and technical support, alongside alternative care models such as more frequent check-ins, should be considered in order to enhance self-management practices with rtCGM and address technology-related challenges.

To evaluate the prevalence of autoimmune diseases in patients with type 1 diabetes mellitus.

This scoping review was conducted following the Joanna Briggs Institute guidelines and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews (PRISMA-ScR) tool to ensure methodological rigor. We systematically searched PubMed, Embase, Scopus, Lilacs, and Web of Science databases to identify relevant literature published between 2018 and 2023.

Twenty-four studies were included, mostly single-center studies from six continents, with varying study designs: 16 cross-sectional, seven retrospective, and one prospective cohort. The most prevalent autoimmune diseases found among patients with type 1 diabetes mellitus enrolled in these studies were autoimmune thyroiditis (5.5-41.2%), celiac disease (0.45-24.8%), rheumatoid arthritis (0.4-5.1%), and primary adrenal insufficiency (0.6-2.6%).

Autoimmune thyroiditis and celiac disease were the most prevalent autoimmune diseases in patients with type 1 diabetes mellitus. As the complexity of managing type 1 diabetes mellitus increases in the presence of multiple autoimmune comorbidities, further studies are required to elucidate the relationship between type 1 diabetes mellitus and different autoimmune pathologies. A deeper understanding of these associations will guide the development of public health policies, screening strategies, and educational initiatives tailored to the specific needs of this population.

Accurate understanding of type 1 diabetes risk is critical for optimisation of counselling, monitoring and interventions, yet even within established staging classifications, individual time to clinical disease varies. Previous work has associated IA-2A positivity with increased type 1 diabetes progression but a comprehensive assessment of the impact of screening for IA-2A positivity across the natural history of autoantibody positivity has not been performed. We asked whether IA-2A would consistently be associated with higher risk of progression within and across established stages of type 1 diabetes in a large natural history study.

Genetic, autoantibody and metabolic data from adult and paediatric autoantibody-negative (n=192) and autoantibody-positive (n=4577) relatives of individuals with type 1 diabetes followed longitudinally in the Type 1 Diabetes TrialNet Pathway to Prevention Study were analysed. Cox regression was used to compare cumulative incidences of clinical diabetes by autoantibody profiles and disease stages.

Compared with IA-2A- individuals, IA-2A+ individuals had higher genetic risk scores and clinical progression risk within single-autoantibody-positive (5.3-fold increased 5 year risk), stage 1 (2.2-fold increased 5 year risk) and stage 2 (1.3-fold increased 5 year risk) type 1 diabetes categories. Individuals with single-autoantibody positivity for IA-2A showed increased metabolic dysfunction and diabetes progression compared with people who were autoantibody negative, those positive for another single autoantibody, and IA-2A- stage 1 individuals. Individuals at highest risk within the single-IA-2A+ category included children (HR 14.2 [95% CI 1.9, 103.1], p=0.009), individuals with IA-2A titres above the median (HR 3.5 [95% CI 1.9, 6.6], p<0.001), individuals with high genetic risk scores (HR 1.4 [95% CI 1.2,1.6], p<0.001) and individuals with HLA DR4-positive status (HR 3.7 [95% CI 1.6, 8.3], p=0.002). When considering all autoantibody-positive individuals, progression risk was similar for euglycaemic IA-2A+ individuals and dysglycaemic IA-2A- individuals.

IA-2A positivity is consistently associated with increased progression risk throughout the natural history of type 1 diabetes development. Individuals with single-autoantibody positivity for IA-2A have a greater risk of disease progression than those who meet stage 1 criteria but who are IA-2A-. Approaches to incorporate IA-2A+ status into monitoring strategies for autoantibody-positive individuals should be considered.

Executive functions (EFs) are important for the Type 1 diabetes mellitus (T1DM) self-care perspective. This study aimed to investigate whether patients with T1DM have poorer EFs than healthy controls (HCs) and whether there are differences in EFs between childhood-onset and adult-onset T1DM.

This study included 94, 110, and 100 participants with childhood-onset and adult-onset T1DM and HCs, respectively. All participants completed the Wisconsin Card Sorting Test to assess EFs. The Chinese version of the WAIS and BDI-II were performed to determine IQ and emotion in all participants.

The childhood-onset group made lower scores of WCST total errors (P = 0.015), perseverative errors (P = 0.038) than the HC group, and the adult-onset group made lower scores of WCST total errors (P = 0.025) than the HC group. In the diabetes group, after controlling diabetes duration, the childhood-onset group made significantly higher scores of WCST total errors (P = 0.040), perseverative errors (P = 0.038), and non-perseverative errors (P = 0.013). In the childhood-onset group, perseverative errors were significantly associated with duration of T1DM (β = -0.24, t = -2.34, P = 0.021), and the history of severe hypoglycemia affects the non-perseverative errors(β = -0.26, t = -2.55, P = 0.013).

T1DM is associated with EF decrements, and there are differences in EFs between childhood-onset and adult-onset T1DM. These findings indicate that we should consider detecting and intervening in EF deficits in the T1DM population according to the age of onset.

The global COVID-19 pandemic has necessitated the widespread use of N95 masks, yet their impact on children with chronic conditions like type 1 diabetes (T1DM) remains underexplored.

This study investigates the effects of N95 mask usage on clinical outcomes in children with T1DM.

This study enrolled 34 children aged 10-18 with T1DM. Study participants' systemic symptoms and physiological parameters were assessed before and after wearing N95 masks for one hour. Blood glucose levels and capillary blood gas analyses were performed, and any symptoms reported were documented.

Nearly half of the participants (47 %) experienced symptoms such as difficulty breathing (41.2 %), ear pain (26.5 %), and runny nose (20.6 %). Despite these symptoms, no significant changes were observed in laboratory values or vital signs, including blood glucose levels, pH, pCO2, HCO3, base excess, lactate, blood pressure, respiratory rate, pulse rate, and oxygen saturation.

The findings suggest that N95 masks may cause discomfort but do not adversely affect physiological parameters in children with T1DM. The study highlights the importance of balancing mask-related discomfort with the protective benefits of mask usage in this population. To confirm these findings, more extensive studies with extended mask use durations are needed.

Nurses are crucial in educating children and their families about proper mask usage, addressing potential discomfort, and implementing strategies to improve adherence. These may include ensuring an appropriate mask fit and advising on brief, safe breaks when needed.

The EarLy Surveillance for Autoimmune (ELSA) study aims to explore the feasibility and acceptability of UK paediatric general population screening for type 1 diabetes.

We aim to screen 20,000 children aged 3-13 years for islet-specific autoantibodies through dried blood spot sample collection at home, hospital or community settings. Children with two or more autoantibodies are offered metabolic staging via oral glucose challenge testing. Feasibility assessments will compare recruitment modalities and uptake according to demographic factors (age, gender, ethnicity, level of deprivation and family history of diabetes) to determine optimal approaches for general population screening. The study is powered to identify 60 children (0.3%) with type 1 diabetes (stage 1-3). Parents are invited to qualitative interviews following ELSA completion (child screened negative or positive, single autoantibody or multiple, stage 1-3) to share their screening experience, strengths of the programme and any areas for improvement (acceptability assessments). Parents who decline screening or withdraw from participation are invited to interview to explore any concerns. Finally, we will interview professional stakeholders delivering the ELSA study to explore barriers and facilitators to implementation.

Early detection of type 1 diabetes allows insulin treatment to be started sooner, avoids diagnosis as an emergency, gives families time to prepare and the opportunity to benefit from future prevention trials and treatments. ELSA will provide essential feasibility and acceptability assessments for UK general population screening to inform a future national screening programme for paediatric type 1 diabetes.

To assess cardiovascular risk management among Australians with diabetes.

Retrospective analysis of clinical audit data collected from diabetes centres participating in the Australian National Diabetes Audit in 2022. Adults (≥18 years) with type 1 or type 2 were included. Clinical performance was assessed by comparing modifiable cardiovascular risk factors against evidence-based clinical targets at the national and diabetes centre level for the total cohort, with sub-analyses by diabetes type, and by cardiovascular disease (CVD) status.

There were 4341 people included; 32.4 % with type 1 and 67.6 % with type 2 diabetes. Of the total cohort, 25.9 % met the HbA1c target (≤7% or 53 mmol/mol), 45.5 % met the low-density lipoprotein cholesterol target (<2 mmol/L), 43.4 % met the systolic blood pressure target (<130 mmHg), 19.8 % met the body mass index target (<25 kg/m2), 30.2 % met the physical activity target (≥150 mins/week of moderate-to-vigorous intensity), and 85.0 % were non-smokers. Compared to patients with type 1 diabetes, patients with type 2 diabetes were less likely to meet targets. Compared to patients without existing CVD, patients with CVD were less likely to meet targets.

Management of cardiovascular risk in adults with diabetes is sub-optimal, increasing the risk of preventable adverse health outcomes.

Type 1 diabetes (T1D) arises from an autoimmune attack on pancreatic beta cells, leading to a reliance on external insulin to maintain glucose levels. In recent years, research has increasingly focused on preventive strategies for individuals at high risk. A promising new intervention in this field is Teplizumab, the first approved disease-modifying therapy for T1D. Teplizumab is designed to delay progression to stage 3 T1D in adults and children aged 8 years and older who are diagnosed with stage 2 T1D.

Type 1 diabetes (T1D) is an autoimmune condition characterized by the destruction of insulin-producing pancreatic beta cells, leading to lifelong insulin dependence and significant complications. Early detection of T1D is essential to delay disease onset and improve outcomes. Recent advancements in artificial intelligence (AI) and machine learning (ML) have provided powerful tools for predicting and diagnosing T1D. This systematic review evaluates the current landscape of AI/ML-based approaches for early T1D detection. A comprehensive search across PubMed, EMBASE, Science Direct, and Scopus identified 1447 studies, of which 10 met the inclusion criteria for narrative synthesis after screening and full-text review. The studies utilized diverse ML models, including logistic regression, support vector machines, random forests, and artificial neural networks. The datasets encompassed clinical parameters, genetic risk markers, continuous glucose monitoring (CGM) data, and proteomic and metabolomic biomarkers. The included studies involved a total of 49,172 participants and employed case-control, retrospective cohort, and prospective cohort designs. Models integrating multimodal data achieved the highest predictive accuracy, with area under the curve (AUC) values reaching up to 0.993 in sex-specific models. CGM data and plasma biomarkers, such as CXCL10 and IL-1RA, also emerged as valuable tools for identifying at-risk individuals. While the results highlight the potential of AI/ML in revolutionizing T1D risk stratification and diagnosis, challenges remain. Data heterogeneity and limited model generalizability present barriers to widespread implementation. Future research should prioritize the development of universal frameworks and real-world validation to enhance the reliability and clinical integration of these tools. Ultimately, AI/ML technologies hold transformative potential for clinical practice by enabling earlier diagnosis, guiding targeted interventions, and improving long-term patient outcomes. These advancements could support clinicians in making more informed, timely decisions, thus reducing diagnostic delays and paving the way for personalized prevention strategies in both pediatric and adult populations.

Type 1 diabetes (T1D) is an autoimmune condition affecting approximately 1.5 million children and adolescents worldwide, with an incidence of approximately 2-3% each year and rising. During the recent COVID-19 pandemic, a significant increase in incidence of T1D in children and adolescents was observed in numerous countries worldwide, with an increased number of newly-diagnosed cases presenting with diabetic ketoacidosis. The increased frequency of T1D presenting with diabetic ketoacidosis has been attributed not only to the SARS-CoV-2 virus itself but also to the restrictions imposed by the pandemic. The shift to telemedicine and unwillingness to seek medical care due to fear of infection contributed to delayed diagnosis and more severe disease presentation. Furthermore, the periods of lockdown that were implemented during the pandemic presented multiple challenges for children and adolescents living with T1D and disrupted the management of their condition. Changes in physical activity and diet as well as shortage of medical supplies during that period have been linked to worsening of glycemic control, which were at least partly offset by increased parental involvement and use of telemedicine.

[This corrects the article DOI: 10.36469/jheor.2024.124604.].

Type 1 diabetes (T1D) is a significant global health concern, characterized by the autoimmune destruction of insulin-producing pancreatic β-cells, resulting in lifelong dependence on insulin therapy. Although genetic predisposition plays a crucial role in the pathogenesis of T1D, environmental factors also contribute to its onset and progression. Recent research has identified a number of genetic polymorphisms, particularly in the protein tyrosine phosphatase non-receptor 22 gene (PTPN22), that are strongly associated with an increased risk of T1D and may serve as potential biomarkers for early diagnosis and prevention. Despite this, studies investigating the relationship between PTPN22 rs2476601 and T1D risk have consistently demonstrated an association in certain populations, whereas research on rs1310182 has yielded conflicting and less conclusive results. This study presents an updated meta-analysis of two key PTPN22 polymorphic loci - rs2476601 (C1858T) and rs1310182 (A852G) - with the aim of clarifying their associations with T1D. The analysis revealed a significant association between PTPN22 rs2476601 and an increased risk of T1D. In contrast, no significant correlation was found for rs1310182. These findings suggest that PTPN22 rs2476601 as a marker for T1D susceptibility, offering insights into the development of early intervention strategies. However, further research is required to validate these associations and deepen our understanding of the genetic factors involved in T1D pathogenesis.

No therapy confers complete β-cell protection at any of the 3 stages of type 1 diabetes (T1D). Disease-modifying therapies in type 1 diabetes aim to prolong the preclinical (stages I and II) and the post-diagnostic partial clinical remission (PR) phases of T1D to reduce its short- and long-term complications. These therapies are focused on mitigating β-cell apoptosis by reducing autoimmune attacks on surviving β-cells through several pathways; as well as improving β-cell function to enable the production of functional endogenous insulin and C-peptide through the reduction of proinsulin to C-peptide ratios and other measures. These therapies target the 3 stages of T1D as monotherapy or combination therapy. Stage I of T1D is marked by the presence of at least one diabetes-associated autoantibody in an individual with normoglycemia; stage II is marked by the presence of diabetes-associated autoantibodies and dysglycemia; stage III is marked by the clinical diagnosis of T1D in an individual with antibodies, hyperglycemia, and symptoms. Conventional thinking suggests that the long-term complications of diabetes are principally rooted in early-stage hyperglycemia at the time of diagnosis of the disease, i.e., stage III of T1D. However, this theory of hyperglycemic memory is limited as it does not address the dichotomy in lipid-based atherosclerotic cardiovascular disease (ASCVD) risk in those with T1D. Given the current limitations to developing disease-modifying therapies in T1D because of the limited impact of current agents on β-cell preservation, we introduce the theory of hyperlipidemic memory of type 1 diabetes. This theory was developed by the author in 2022 using the same population as in this article to address the shortcomings of the theory of hyperglycemic memory and explain that the dichotomy in ASCVD risk is based on PR history. In this Review, the theory presents new pathways for disease-modifying therapies in T1D that focus on preventing early-phase dyslipidemia. It is hoped that including this theoretical framework in designing disease-modifying therapies in T1D will help move the field forward. This new theory supports the hypothesis that PR is an imprimatur rather than a process. It hypothesizes that pre-diagnostic interventions, at stages I or II of T1D, to ensure the occurrence of PR may be more effective in the long term than post-diagnostic interventions, at stage III, to prolong PR. This paradigm shift in approach to disease-modifying therapy in T1D is discussed in this review.

Autoinflammation and autoimmunity are almost "opposite" phenomena characterized by chronic activation of the immune system, 'innate' in the first and 'adaptive' in the second, leading to inflammation of several tissues with specific protean effectors of tissue damage. The mechanism of involvement of multiprotein complexes called 'inflammasomes' within autoimmune pictures, differently from autoinflammatory conditions, is yet undeciphered. In this review we provide a comprehensive overview on NLRP3 inflammasome contribution into the pathogenesis of some autoimmune diseases. In response to autoantibodies against nucleic acids or tissue-specific antigens the NLRP3 inflammasome is activated within dendritic cells and macrophages of patients with systemic lupus erythematosus. Crucial is NLRP3 inflammasome to amplify tissue inflammation with interleukin-1 overexpression and matrix metalloproteinase production at the joint level in rheumatoid arthritis. A deregulated NLRP3 inflammasome activation occurs in the serous acini of salivary and lacrimal glands prone to Sjogren's syndrome, but also in the inflammatory process involving endothelial cells, leucocyte recruitment, and platelet plugging of vasculitides. Furthermore, organ-specific autoimmune diseases such as thyroiditis and hepatitis may display hyperactive NLRP3 inflammasomes at the level of resident immune cells within thyroid or liver, respectively. Therefore, it is not unexpected that preclinical studies have shown how specific inflammasome inhibitors may significantly overthrow the severity of different autoimmune diseases and slow down their trend towards an ominous progression. Specific markers of inflammasome activation could also reveal subclinical inflammatory components escaping conventional diagnostic approaches or improve monitoring of autoimmune diseases and personalizing their treatment.

Background and Aims: The age-at-onset is of great importance in the heterogeneity of Type 1 diabetes mellitus (T1DM). This study was designed to define clinical and laboratory differences between child-adolescent-onset and adult-onset T1DM at presentation and during follow-up and determine the predicting factors for developing microvascular and macrovascular complications. Material and Methods: This retrospective observational study evaluated T1DM patients who were followed in the diabetes outpatient clinic between January 1, 2000, and December 31, 2019. Results: The study cohort included 490 individuals with T1DM (54.3% female, 58.8% adult-onset, and median follow-up: 5 years). In the adult-onset group, baseline C-peptide and GADA prevalence were higher, whereas presentation with ketoacidosis was 2.3-fold lower compared to the child-adolescent-onset group (p < 0.001). During follow-up, the adult-onset group had a 2.4-fold higher overweight/obesity (p < 0.001) and 1.7-fold higher dyslipidemia/hyperlipidemia (p = 0.002) than the child-adolescent-onset group. In multivariate analysis, fasting glucose (p = 0.024) in adult-onset, dyslipidemia/hyperlipidemia (p = 0.037) in child-adolescent-onset, and diabetes duration (p = 0.008 and p = 0.007) and hypertension (p = 0.001 and p = 0.01) in both groups were associated with increased risk of microvascular complications, whereas age-at-onset (p = 0.024), dyslipidemia/hyperlipidemia (p = 0.03), nephropathy (p = 0.003), and neuropathy (p = 0.001) in adult-onset and age (p = 0.002) and triglycerides (p = 0.013) in child-adolescent-onset groups were associated with increased risk of macrovascular complications. The cutoff C-peptide levels at baseline predicted microvascular complications in the whole cohort and adult-onset group were defined as 0.383 ng/mL (p < 0.001) and 0.41 ng/mL (p = 0.001), respectively. In the Kaplan-Meier analysis, C-peptide (< 0.383 ng/mL) but not age-at-onset predicted future development of microvascular and macrovascular complications (p = 0.003 and p = 0.032). Conclusion: Clinical presentation and prognosis differ in adult-onset and child-adolescent-onset T1DM. Low initial C-peptide may predict the development of microvascular and macrovascular complications.

Background/Objectives: Periodontitis is an inflammatory disease associated with many systemic disorders such as diabetes and cardiovascular disease. The aim was to evaluate the usefulness of the CDC/AAP and the EFP/AAP criteria to detect subclinical atherosclerosis in subjects with diabetes and severe periodontal disease. Methods: This was a cross-sectional study. Atheroma plaque was evaluated by high-resolution carotid and femoral ultrasonography. A dental examination protocol was implemented by a trained periodontist. A full-mouth periodontal clinical examination was carried out at six sites by automated computerized Florida Probe Periodontal Probing. Periodontal disease was defined by CDC/AAP and EFP/AAP criteria. Results: In total, 98 patients were included (60.2% women), of which 50% had diabetes. Subjects with diabetes showed a high prevalence of severe cases of periodontal disease. Both criteria were useful to detect the presence of atheroma plaque only in the presence of diabetes. However, the CDC/AAP criteria had higher correlation with atheroma plaques than EFP/AAP criteria (r = 0.522 vs. r = 0.369, p < 0.001). Conclusions: The CDC/AAP and the EFP/AAP criteria are a useful tool to identify subclinical atherosclerosis in subjects with severe periodontal disease and diabetes. These results show the potential role of the oral healthcare team in the dental office for the identification of subjects with diabetes at risk of developing cardiovascular disease.

The relationship between viral infection and autoimmune manifestations has been emerging as a significant focus of study, underscoring the intricate interplay between viral infections and the immune system. Influenza infection can result in a spectrum of clinical outcomes, ranging from mild illness to severe disease, including mortality. Annual influenza vaccination remains the most effective strategy for preventing infection and its associated complications. The complications arising from acute influenza infection are attributable not only to the direct effects of the viral infection but also to the dysregulated immune response it elicits. Notably, associations between influenza and various autoimmune diseases, such as Guillain-Barré Syndrome (GBS), Type 1 Diabetes (T1D), and antiphospholipid syndrome, have been reported. While viral infections have long been recognized as potential triggers of autoimmunity, the underlying mechanisms remain to be elucidated. Here, we described the pathophysiology caused by influenza infection and the influenza-associated autoimmune manifestations. Current advances on the understanding of the underlying immune mechanisms that lead to the potential strategies were also summarized.

Precision medicine in diabetes care requires a dedicated focus on hypoglycemic symptoms. This study explored the associations between clustering of hypoglycemic symptoms, psychological characteristics, and problem-solving capabilities in adults with type 1 diabetes (T1D).

A total of 251 adults with T1D participated in this survey. Hierarchical clustering was used to analyze 11 hypoglycemic symptoms (Edinburgh scale). The data included diabetic complications, fear of hypoglycemia, depressive symptoms, hypoglycemia problem-solving scale (HPSS), and treatment details. For predicting clusters and identifying feature importance, we utilized a machine learning approach.

Three distinct clusters were observed; individuals not sensitive to autonomic or neuroglycopenic symptoms (cluster 1, n = 138), those sensitive to both autonomic and neuroglycopenic symptoms (cluster 2, n = 19), and those sensitive to autonomic but not neuroglycopenic symptoms (cluster 3, n = 94). Compared to cluster 1, individuals from clusters 2 and 3 were of younger age, had higher fear of hypoglycemia, increased depressive symptoms, and greater use of continuous subcutaneous insulin infusion. Cluster 2 displayed enhanced HPSS scores, indicating better detection control and a more proactive approach to seeking preventive strategies than cluster 1. The accuracy for classifying into 3 clusters using machine learning was 88.2%. The feature importance of random forest model indicated that hunger, shaking, palpitation, sweating, and confusion were the top five important factors for predicting clusters.

This study identified three distinct clusters of adults with T1D. These findings may provide valuable insights for diabetes professionals seeking to educate these individuals on how to manage hypoglycemia effectively.

University Hospital Medical Information Network (UMIN) Center: UMIN000039475); approval date: February 13, 2020.

Identification of circulating proteins that may play a role in the pathogenesis of type 1 diabetes can provide promising targets for biomarker and drug target identification. Supported by multiple lines of evidence, circulating abundances of CTSH, IL27RA, SIRPG, and PGM1 were associated with the risk of type 1 diabetes. Tissues and cell types with enrichment of target protein-coding gene expression were identified. CTSH, IL27RA, SIRPG, and PGM1 may be explored as biomarkers or drug targets for type 1 diabetes.

To achieve glucose-activated transcriptional regulation of insulin analogue in skeletal muscle of T1D mice, thereby controlling blood glucose levels and preventing or mitigating diabetes-related complications.

We developed the GANIT (Glucose-Activated NFAT-regulated INSA-F Transcription) system, an innovative platform building upon the previously established intramuscular plasmid DNA (pDNA) delivery and expression system. In the GANIT system, skeletal muscle cells are genetically engineered to endogenously produce the insulin analogue INSA-F (Insulin Aspart with Furin cleavage sites). The transcription of INSA-F is precisely controlled by a glucose-responsive promoter containing NFAT (Nuclear Factor of Activated T-cells) regulatory motifs, which can be activated in response to changes in extracellular glucose concentrations. This design enables glucose-dependent regulation of insulin analogue expression, mimicking physiological glucose-responsive insulin secretion.

T1D mice that received two GANIT treatments over a 2-month experimental period demonstrated significant improvements in glucose homeostasis, glucose tolerance and glycated haemoglobin (HbA1c) levels. Additionally, the treatment effectively reduced oxidative stress and alleviated cardiac and renal fibrosis, while maintaining a favourable biosafety profile.

The GANIT system provides significant advantages in terms of efficiency, convenience and cost-effectiveness, making it a promising approach for regulating blood glucose levels and alleviating diabetes-related complications in insulin-deficient diabetes.

To investigate the association between chronic inflammation and subclinical left ventricular dysfunction in type 1 diabetes (T1D).

In a cross-sectional study of individuals with T1D without known heart disease, interleukin-6 (IL-6), soluble-urokinase-plasminogen-activator-receptor (suPAR), and high-sensitivity C-reactive-protein (hsCRP) were examined for associations with echocardiographic E/e' (primary outcome) and global longitudinal strain (GLS) (secondary outcome). We adjusted for several clinical variables in linear regression analysis, including N-terminal pro-B-type natriuretic peptide (NT-proBNP). The biomarkers were categorized as elevated/non-elevated based on their upper quartiles.

Of 962 individuals (52 % male, mean age 49 ± 14 years), mean E/e' was 7 ± 3 and GLS 18 ± 3. In fully adjusted models, all biomarkers were each associated with increased E/e': beta coefficients for IL-6 0.2 (95 % confidence intervals: 0.1-0.3, P = 0.001), suPAR 0.5 (0.1-0.7, P = 0.011), and hsCRP 0.1 (0.0-0.2, P = 0.023). Combining biomarkers showed stronger associations: elevated IL-6 and suPAR 1.3 (0.7-2.0, P < 0.001), elevated all three 1.9 (1.1-2.7, P < 0.001). Results were similar for decreased GLS with IL-6-0.4 (-0.7 to 0.0, P = 0.039), IL-6 and hsCRP -1.0 (-1.7 to -0.4, P = 0.007), all three -1.1 (-2.0 to -0.3, P = 0.009).

Inflammatory biomarkers are independently associated with subclinical left ventricular dysfunction. Chronic inflammation may contribute to the development of myocardial dysfunction in T1D.

Type 1 and type 2 diabetes are metabolic disorders that require one to manage one's blood glucose levels on a daily basis through a series of behaviorally complex tasks. Research shows that psychosocial factors, including mood, stress, and social relationships, have a significant influence on one's ability to maintain these disease management routines and achieve healthy blood glucose levels. However, researchers have typically approached these questions from a between-person perspective. Here, we argue for greater consideration of short-term, within-person links of psychosocial factors-including mood, stress, and social interactions-to glucose outcomes. Drawing from existing social and health psychology theories, we put forth an organizing theoretical framework describing how psychosocial experiences may operate on glucose outcomes over subsequent hours. We then review the small but burgeoning literature of intensive longitudinal studies that have examined the short-term effects of negative affect, positive affect, stress, and social interactions on glucose outcomes. Findings showed somewhat stronger links for negative affect and stress compared to positive affect and social interactions, but studies varied greatly in their methodologies, making direct comparisons challenging. A number of findings, particularly in the social interaction literature, depended on dispositional or contextual factors, further complicating interpretation. There was little investigation of the mechanistic pathways that may connect psychosocial factors to glucose outcomes, and few studies conducted lagged analyses to probe the directionality of these links. We conclude by proposing best practices for future research that will address the key weaknesses in the extant literature.

Type 1 diabetes (T1D) is a chronic and costly disease that is often diagnosed in childhood. Achieving excellent glycaemic control during this period requires attention to multiple factors. Advances in technology now allow clients (patients/family members) to fine-tune their insulin delivery, necessitating support from highly skilled nurses, dietitians and physicians (clinicians). Despite quarterly team-based appointments, interim issues and questions often arise, and families may not always reach out for support. The incidence of T1D is rising, and yet barriers exist to expanding the clinical team. Additionally, clinicians are not necessarily colocated, making timely and efficient communication challenging. We postulated that offering texting as a communication modality would increase client interactions by 20%, and that clients and clinicians would find it a desirable tool in the delivery of efficient and timely ambulatory care.

A prospective interventional quality improvement project was conducted between July 2022 and August 2023. Baseline data were obtained for the number of interactions. Parents, caregivers and age-appropriate patients were then registered onto the texting platform (N=125) and received a weekly check-in message. The number of interactions and clinical time spent texting and providing care because of a text interaction were collected.

There were approximately 30 interactions per week, an increase of >2300%. The average additional clinical time required was 56 min per week (average of 30 s/interaction). Qualitatively, 100% of our clients expressed a desire to continue texting with the team. 97% of clients felt that texting was an important way for them to contact their diabetes team. Our clinicians also wished to continue texting, valuing the improved efficiency of communication and experiencing a greater degree of connection with their clients.

Texting is a welcome modality of communication between clients and their clinical care team in the setting of ambulatory T1D care, resulting in increased engagement.

Type 1 diabetes (T1D) is generally viewed as an etiologic subtype of diabetes caused by the autoimmune destruction of the insulin-secreting β-cells. It has been known that autoreactive T cells unfortunately destroy healthy β-cells. However, there has been a notion of etiologic heterogeneity around the world implicating a varying incidence of a non-autoimmune subgroup of T1D related to insulin deficiency associated with decreased β cell mass, in which the β-cell is the key contributor to the disease. Beta cell dysfunction, reduced mass, and apoptosis may lead to insufficient insulin secretion and ultimately to the development of T1D. Interestingly, Korean as well as other ethnic genetic results have also suggested that genes related with insulin deficiency, let alone those of immune regulation, were associated with the risk of T1D in the young. Genes related with insulin secretion may influence the phenotype of diabetes differentially and different genes may be working on different steps of T1D development. Although we admit the consensus that islet autoimmunity is an essential component in the pathogenesis of T1D, however, dysfunction might occur not only in the immune system but also in the β-cells, the defect of which may induce further dysfunction of the immune system. These arguments stem from the fact that the β-cell might be the trigger of an autoimmune response. This emergent view has many parallels with the fact that by their nature and function, β-cells are prone to biosynthetic stress with limited measures for self-defense. Beta cell stress may induce an immune attack that has considerable negative effects on the production of a vital hormone, insulin. If then, both β-cell stress and islet autoimmunity can be harnessed as targets for intervention strategies. This also may explain why immunotherapy at best delays the progression of T1D and suggests the use of alternative therapies to expand β-cells, in combination with immune intervention strategies, to reverse the disease. Future research should extend to further investigate β-cell biology, in addition to studies of immunologic areas, to find appropriate biomarkers of T1D susceptibility. This will help to decipher β-cell characteristics and the factors regulating their function to develop novel therapeutic approaches.

Diabetes mellitus, a global health challenge, influences millions worldwide by leading to severe complications and premature death. A key factor in its pathogenesis is immune cell dysfunction, which aggravates both type 1 and type 2 diabetes. The important role that immune cell dysregulation plays in the emergence of diabetes complications is investigated in this research. It highlights the manner in which diabetes compromises the immune system's adaptive as well as innate responses. Key defects in innate immunity include impaired pathogen recognition, and dysfunctional behavior of macrophages, neutrophils, and natural killer (NK) cells. Additionally, the complement system is dysregulated, and cytokine production is altered, affecting overall immune signaling. The study investigates the dysfunction of several T and B cell subsets, such as CD4+ T cells, CD8+ T cells, regulatory T cells, and B cells, in relation to adaptive immunity. These dysfunctions collectively contribute to chronic inflammation, reduced pathogen clearance, and increased susceptibility to infections, ultimately exacerbating diabetes complications. Developing targeted therapies to reduce diabetes complications and enhance patient outcomes requires an understanding of these mechanisms.