UNASSIGNED: The causality of autoimmune diseases with frailty has not been firmly established. We conducted this Mendelian randomization (MR) study to unveil the causal associations between autoimmune diseases with frailty.
UNASSIGNED: A MR analyses were performed to explore the relationships between autoimmune disease and frailty, using summary genome-wide association statistics.
UNASSIGNED: Through a comprehensive and meticulous screening process, we incorporated 46, 7, 12, 20, 5, and 53 single nucleotide polymorphisms (SNPs) as instrumental variables (IVs) for hypothyroidism, hyperthyroidism, rheumatoid arthritis (RA), type 1 diabetes (T1D), multiple sclerosis (MS), and overall autoimmune disease, respectively. Our analysis revealed that hypothyroidism (OR = 1.023, 95% CI: 1.008-1.038, p = 0.0015), hyperthyroidism (OR = 1.024, 95% CI: 1.004-1.045, p = 0.0163), RA (OR = 1.031, 95% CI: 1.011-1.052, p = 0.0017), T1D (OR = 1.011, 95% CI: 1.004-1.017, p = 0.0012), and overall autoimmune disease (OR = 1.044, 95% CI: 1.028-1.061, p = 5.32*10^-8) exhibited a positive causal effect on frailty. Conversely, there may be a negative causal association between MS (OR = 0.984, 95% CI: 0.977-0.992, p = 4.87*10^-5) and frailty. Cochran\'s Q test indicated heterogeneity among IVs derived from hypothyroidism, hyperthyroidism, T1D, and overall autoimmune diseases. The MR-Egger regression analyzes revealed an absence of horizontal pleiotropy in any of the conducted analyses.
UNASSIGNED: This study elucidates that hypothyroidism, hyperthyroidism, RA, T1D, and overall autoimmune disease were linked to an elevated risk of frailty. Conversely, MS appears to be associated with a potential decrease in the risk of frailty.

The immunopathogenesis of HIV infection remains poorly understood. Despite the widespread use of effective modern antiretroviral therapy (ART), people living with HIV (PLWH) are known to develop several comorbidities, including type 1 diabetes (T1DM). However, the etiology and critical mechanisms accounting for the onset of T1DM in the preceding context remain unknown. This article proposes to address this topic in order to provide further understanding and future research directions.

OBJECTIVE: Identify the relationship between a sense of belonging and psychosocial well-being in individuals with type 1 diabetes (T1D) in Iran.
BACKGROUND: Understanding this relationship is vital for tailored nursing interventions to enhance individual\'s sense of belonging and improve diabetes outcomes.
METHODS: This cross-sectional study included 205 participants selected via multi-stage cluster and simple random sampling from health centers in Iranian. Electronic surveys designed on Google Forms, using valid and reliable scales and compliant with HIPAA, assessed sense of belonging, distress, and burnout. Data were analyzed using SPSS (version 25).
RESULTS: Participants reported high sense of belonging with varying levels of diabetes distress and burnout. Multiple regression analysis of 205 participants showed that sense of belonging index (SOBI) scores significantly predicted diabetes distress (F(2,203) = 39.71, p < 0.001) and burnout (F(2, 203) = 42.319, p < 0.001). Sense of Belonging Instrument-Psychological (SOBI-P) scores were negatively correlated with both distress (r = -0.52, p < 0.001) and burnout (r = -0.53, p < 0.001), indicating higher belonging is linked to lower distress and burnout. Sense of Belonging Instrument-Antecedents (SOBI-A) scores had positive but non-significant correlations (distress: r = 0.07, p = 0.27; burnout: r = 0.10, p = 0.13). SOBI-P accounted for ∼30 % of the variance in distress (R2 = 0.275) and burnout (R2 = 0.288), with significant contributions to both models (t = -8.8, p < 0.001; t = -9.02, p < 0.001). Anticipated belonging showed no significant correlations with distress or burnout.
CONCLUSIONS: The negative correlations between personal belonging, self-reported distress, and burnout suggest that enhancing the psychological sense of belonging may be an effective strategy to mitigate diabetes-related distress and burnout Stigmatization and financial strain in Iran may exacerbate emotional burden, regimen related distress, and burnout. The lack of association between anticipated belonging and psychosocial well-being underscores differences in present and future perceptions of support, emphasizing the need for culturally sensitive nursing interventions.

BACKGROUND: Despite an increased risk for adverse outcomes from SARS-CoV-2 infection among individuals with type 1 diabetes (T1D), vaccine hesitancy persists due to safety concerns including dysglycemia. The impact of booster vaccination on individuals using automated insulin delivery (AID) systems remains unclear.
METHODS: We used continuous glucose monitoring (CGM) data from 53 individuals with T1D using insulin pump therapy who received their third and/or fourth COVID-19 vaccination. CGM data from the 14 days before and 3 and 7 days after each vaccination were compared. The primary outcome was glucose time in range (TIR) (70-180 mg/dL) 3 and 7 days post-vaccination compared with the 14 days prior. Secondary outcomes included other CGM metrics such as time below range (< 70 mg/dL), time above range (> 180 mg/dL), mean glucose, co-efficient of variation and average total daily insulin.
RESULTS: The cohort comprised 53 adults (64% women, 64% AID), totaling 74 vaccination periods (84% Pfizer-BioNTech boosters), mean ± SD age 40.0 ± 15.9 years, duration of diabetes 26.0 ± 15.4 years. There was no significant difference between pre-vaccination TIR (61.0%±18.5) versus 3 (60.5%±22.8) and 7 days post-vaccination (60.2%±21.8; p = 0.79). Level 1 hypoglycemia, time in range 54-69 mg/dL, was lower 3 (1.1%±1.7) and 7 days post-vaccination (1.1%±1.6), compared with 14 days pre-vaccination (1.4%±1.4; p = 0.021).
CONCLUSIONS: The study provides evidence that SARS-CoV-2 booster vaccination does not acutely worsen glycemia in people with T1D receiving insulin pump therapy.

BACKGROUND: Alterations in RNA splicing may influence protein isoform diversity that contributes to or reflects the pathophysiology of certain diseases. Whereas specific RNA splicing events in pancreatic islets have been investigated in models of inflammation in vitro, how RNA splicing in the circulation correlates with or is reflective of T1D disease pathophysiology in humans remains unexplored.
OBJECTIVE: To use machine learning to investigate if alternative RNA splicing events differ between individuals with and without new-onset type 1 diabetes (T1D) and to determine if these splicing events provide insight into T1D pathophysiology.
METHODS: RNA deep sequencing was performed on whole blood samples from two independent cohorts: a training cohort consisting of 12 individuals with new-onset T1D and 12 age- and sex-matched nondiabetic controls and a validation cohort of the same size and demographics. Machine learning analysis was used to identify specific isoforms that could distinguish individuals with T1D from controls.
RESULTS: Distinct patterns of RNA splicing differentiated participants with T1D from unaffected controls. Notably, certain splicing events, particularly involving retained introns, showed significant association with T1D. Machine learning analysis using these splicing events as features from the training cohort demonstrated high accuracy in distinguishing between T1D subjects and controls in the validation cohort. Gene Ontology pathway enrichment analysis of the retained intron category showed evidence for a systemic viral response in T1D subjects.
CONCLUSIONS: Alternative RNA splicing events in whole blood are significantly enriched in individuals with new-onset T1D and can effectively distinguish these individuals from unaffected controls. Our findings also suggest that RNA splicing profiles offer the potential to provide insights into disease pathogenesis.

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.
METHODS: 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.

OBJECTIVE: To assess the real-world impact of glucose-lowering drugs (GLDs) as an adjunct to insulin in Chinese patients with type 1 diabetes (T1DM).
METHODS: This dual-center, observational, retrospective study included 121 T1DM patients receiving GLDs as adjuncts and 56 participants with insulin-only drugs as comparators. Glycated hemoglobin A1c (HbA1c), daily insulin dosage, fasting blood glucose (FBG), postprandial blood glucose (PBG), nocturnal blood glucose (NBG) and the difference in trough and peak blood glucose levels on the same day (Δ TP) were assessed at baseline and at the end of the study.
RESULTS: In total, HbA1c decreased by 1.14% in the GLD+insulin group (p < 0.0001) and 0.36% in the insulin-only group (p = 0.0423, mean adjusted difference, -0.09% [95% CI, -0.55 to 0.37]). The total daily insulin concentration was reduced by 7.34 U per day in the GLD+insulin group vs. 5.55 U per day in the insulin-only group (mean adjusted difference, -2.32 U [95% CI, -4.97 to 0.33]). In particular, among patients with fasting C-peptide levels < 17 pmol/L, the total daily insulin concentration was significantly reduced by 9.22 U vs. 5.09 U per day (mean adjusted difference, -3.84 [95% CI, -6.85-0.84]; p = 0.0129). There were no notable differences in the other glycemic indices between the two groups. A gradual downward trend in changes in glycemic outcomes was observed among patients treated with various combinations of metformin, acarbose, and dipeptidyl peptidase 4 inhibitor (DPP-4i). Similar reductions in the daily insulin dose were also detected in most of the GLD+insulin group in addition to the DPP-4i-only group. No severe hypoglycemia was induced by additional GLDs.
CONCLUSIONS: The use of additional GLDs tends to improve glycemic outcomes and reduce insulin requirements in patients with T1DM. These results indicate that the use of GLDs as an adjunctive therapy may have been an effective treatment strategy among adults with T1DM in China.

OBJECTIVE: To map the glycaemic variabilities and insulin requirements across different phases of the menstrual cycle and assess the efficacy and performance of the MiniMed 780G system on mitigating glycaemic variabilities during phases of the menstrual cycle.
METHODS: A pilot study recruiting 15 adolescent and young adult females with type 1 diabetes was conducted. Only females with regular spontaneous menstruation were enrolled in the current study. Phases of each menstrual cycle were determined as either follicular phase or luteal phase. The study analysed continuous glucose monitoring metrics during two study periods: the open loop period (OLP) and the advanced hybrid closed-loop (AHCL) period; each period lasted 3 consecutive months.
RESULTS: During the OLP, the mean time in range (TIR) significantly decreased during the luteal phase compared with the follicular phase (65.13% ± 3.07% vs. 70.73% ± 2.05%) (P < .01). The mean time above range significantly increased from 21.07% ± 2.58% during the follicular phase to 24.87% ± 2.97% during the luteal phase (P < .01). After initiating the AHCL period, TIR was comparable during both phases of the menstrual cycle (P = .72), without increasing the time spent below 70 mg/dL (P > .05). Regarding insulin delivery during the AHCL period, the percentage of Auto basal and Auto correction delivered by the algorithm increased by 13.55% and 30.6%, respectively (P < .01), during the luteal phase.
CONCLUSIONS: The fully automated adaptive algorithm of the MiniMed 780G system mitigated menstrual cycle-dependent glycaemic variability, successfully attaining the recommended glycaemic outcomes with a TIR greater than 70% throughout the entire menstrual cycle.

Cardiovascular disease (CVD) is a leading cause of morbidity and mortality among individuals with type 1 diabetes (T1D), necessitating effective prevention strategies. This comprehensive review consolidates current knowledge and evidence on preventing CVD in T1D patients. It begins by exploring the pathophysiological mechanisms that link T1D to an increased risk of CVD, highlighting factors such as chronic hyperglycemia, hypertension, dyslipidemia, and inflammation. The review also examines the epidemiology and specific risk factors for CVD in this population, emphasizing the need for rigorous risk assessment and screening. Lifestyle modifications, including dietary interventions, regular physical activity, and smoking cessation, are evaluated for their effectiveness in reducing CVD risk. Additionally, the review discusses pharmacological interventions, such as insulin therapy for glycemic control, antihypertensive medications, lipid-lowering agents, and antiplatelet therapy, underscoring their critical role in CVD prevention. Emerging therapies and future research directions are explored, focusing on novel pharmacological agents, advances in insulin delivery systems, and personalized medicine approaches. The importance of integrated care models involving multidisciplinary teams and the use of technology is highlighted as essential for comprehensive management. Challenges and barriers to implementing these strategies, including healthcare system limitations, patient adherence, and socioeconomic factors, are also addressed. This review provides a detailed synthesis of current strategies and future directions for preventing CVD in individuals with T1D, serving as a valuable resource for clinicians, researchers, and policymakers dedicated to improving cardiovascular outcomes in this high-risk population.

Cutibacterium acnes, common resident of the human skin, can establish both commensal and pathogenic relations with the human host; however, long-term consequences of C. acnes-induced inflammation remained un(der)explored. To infer the capacity of triggering autoimmunity in humans via molecular mimicry, a comprehensive immunoinformatics analysis of the experimentally characterized C. acnes proteome was performed. The protocol included homology screening between the C. acnes and the human proteome, and validation of shared specificity regions against the collection of experimentally characterized T-cell epitopes, related to autoimmunity. To obtain highly reliable predictions, the results were subjected to additional cross-validation by a dedicated MHC-restriction analysis, including a docking study of C. acnes mimotopes and human counterparts with the highest degree of sequence similarity to MHCII molecules representing the highest risk for detected autoimmune pathologies. Due to mimicking of highly immunogenic, but also evolutionary conserved autoantigens from the Heat Shock protein family, association between C. acnes and the pathogenesis of highly incident autoimmune diseases: Type 1 Diabetes, Rheumatoid Arthritis, and Juvenile Idiopathic Arthritis, was found. To the best of our knowledge, this study is the first one to provide preliminary information and a mechanistic link on the putative involvement of C. acnes in the pathogenesis of autoimmunity in humans.