Effectiveness of the MyDiaMate application in reducing diabetes distress in adults with type 1 diabetes: Study protocol of the multi-national, randomised-controlled MyREMEDY trial.

AIMS: Diabetes distress is common among people with type 1 diabetes (T1D), negatively affecting quality of life, self management, and diabetes outcomes. E-health-based interventions could be an effective and low-cost way to improve the psychological care for people with T1D experiencing diabetes distress. The MyREMEDY study aims to test the effectiveness of the online unguided self-help intervention MyDiaMate in decreasing diabetes distress in adults with T1D. MyDiaMate is based on Cognitive Behavioural Therapy and consists of eight modules, each focusing on a different aspect of living with T1D that is often experienced as burdensome (e.g. hypoglycaemia, fatigue). METHODS: The effectiveness of MyDiaMate will be tested through a randomised-controlled trial across four European countries (the Netherlands, Germany, Spain and the United Kingdom). Six hundred and sixty adults (N = 165 per country) with T1D will be recruited and randomised with a balance of 2:1 into the intervention and care as usual groups. Intervention group members receive access to MyDiaMate for 6 months, care as usual group members receive access after 3 months for 3 months. Participants fill in questionnaires at 0 (baseline), 3 (effectiveness) and 6 months (follow-up). Primary outcome is diabetes distress at 3 months. Secondary outcomes are emotional well-being, psychological self-efficacy in relation to diabetes, social engagement, fatigue, and glycaemic outcomes. Moreover, logdata of MyDiaMate use is passively collected. Linear mixed model analyses will be used to test the effectiveness of MyDiaMate along with identifying which user subgroup benefits most from MyDiaMate use. TRIAL REGISTRATION: Clinicaltrials.gov NCT06308549.

Modified streptozotocin-induced diabetic model in rodents.

Streptozotocin (STZ)-induced type I diabetes mellitus (DM) models have been pivotal in diabetes research due to their ability to mimic the insulin-dependent hyperglycemia akin to human type I diabetes. However, these models often suffer from poor induction rates and low survival post-STZ induction, especially in long-term experiments, necessitating insulin supplementation, which introduces additional variables to experiments. To address this, we present a novel modification to the STZ-induced DM model in C57BL/6J mice to improve survival rates without insulin supplementation. Our method involves non-fasting, low-dose STZ injections dissolved in pH-neutral phosphate buffer saline instead of acidic sodium citrate buffer, administered over 5 days. We observed hyperglycemia induction in 94.28% of mice within a week post-injection, with stable high blood glucose levels, stable body weight, and minimal mortality up to 21 weeks. Notably, omitting 10% sucrose in water and fasting did not affect hyperglycemia induction. Our findings suggest that the modified protocol not only decreases the experimental effort of the researchers, but reduces animal stress and mortality, thus enhancing experimental outcomes and animal welfare. By optimizing the STZ-induced DM model in C57BL/6J mice, our study provides a valuable resource for researchers aiming to study diabetes and its complications while minimizing experimental variability and animal usage.

Ccl2-Induced Regulatory T Cells Balance Inflammation Through Macrophage Polarization During Liver Reconstitution.

Inflammation is highlighted as an initial factor that helps orchestrate liver reconstitution. However, the precise mechanisms controlling inflammation during liver reconstitution have not been fully elucidated. In this study, a clear immune response is demonstrated during hepatic reconstitution. Inhibition of the hepatic inflammatory response retards liver regeneration. During this process, Ccl2 is primarily produced by type 1 innate lymphoid cells (ILC1s), and ILC1-derived Ccl2 recruits peripheral ILC1s and regulatory T cells (Tregs) to the liver. Deletion of Ccl2 or Tregs exacerbates hepatic injury and inflammatory cytokine release, accelerating liver proliferation and regeneration. The adoption of Tregs and IL-10 injection reversed these effects on hepatocyte regenerative proliferation. Additionally, Treg-derived IL-10 can directly induce macrophage polarization from M1 to M2, which alleviated macrophage-secreted IL-6 and TNF-α and balanced the intrahepatic inflammatory milieu during liver reconstitution. This study reveals the capacity of Tregs to modulate the intrahepatic inflammatory milieu and liver reconstitution through IL-10-mediated macrophage polarization, providing a potential opportunity to improve hepatic inflammation and maintain homeostasis.

Relationship between type 1 diabetes and autoimmune diseases in european populations: A two-sample Mendelian randomization study.

Background: Previous studies have suggested an association between Type 1 diabetes (T1D) and autoimmune diseases (AIDs), but the causal relationship remains unclear. Therefore, this study utilizes publicly available Genome-Wide Association Studies (GWAS) databases and employs a two-sample Mendelian Randomization (MR) approach to explore the causal relationships between T1D and systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and inflammatory bowel disease (IBD). Methods: Summary GWAS data for T1D, SLE, RA, and IBD were downloaded from open GWAS databases and the International Inflammatory Bowel Disease Genetics Consortium (IIBDGC). We employed a series of methods to select instrumental variables closely related to T1D. To enhance the reliability of our conclusions, we applied multiple robust analytical methods, with the inverse variance weighted (IVW) method as the primary approach. Validation and meta-analysis were conducted using the FinnGen consortium. Additionally, we assessed heterogeneity, pleiotropy, and sensitivity to ensure the robustness of our conclusions. Results: A potential causal association was found between T1D and SLE (OR = 1.37, 95% CI = 1.26 - 1.49, P < 0.001), which was further confirmed by meta-analysis. Similarly, a potential causal association was found between T1D and RA (OR = 1.32, 95% CI = 1.17 - 1.50, P < 0.001), and this was also confirmed by meta-analysis. Although the association between T1D and IBD showed P < 0.05, the leave-one-out test did not pass, and further meta-analysis indicated no significant statistical association between them. Conclusion: Our study reveals the relationships between T1D and three clinically common autoimmune diseases (SLE, RA, and IBD). This research supplements previous studies and provides a reference for future clinical work.

Whitaker syndrome: A case report of autoimmune polyendocrine syndrome type 1 with dilated cardiomyopathy.

Key Clinical Message: This case report highlights dilated cardiomyopathy as a cardiovascular complication in autoimmune polyendocrine syndrome type 1 (APS-1), emphasizing the need for early recognition and a multidisciplinary approach. Comprehensive care and regular follow-up are crucial in managing these atypical presentations to optimize patient outcomes. Abstract: APS-1, also known as Whitaker syndrome, is characterized by a triad of mucocutaneous candidiasis, adrenal insufficiency, and hypoparathyroidism. This rare autosomal recessive disorder results from mutations in the autoimmune regulator (AIRE) gene. Cardiovascular and pulmonary manifestations in APS-1 are infrequently reported in the literature. We present a case of a 28-year-old male who presented with shortness of breath and pedal edema. Physical examination revealed alopecia, absence of eyebrows, hyperpigmentation on joints, oral candidiasis, and nail dystrophy. Echocardiography demonstrated dilated cardiomyopathy (DCM) and pericardial effusion. Chest x-ray showed left-sided pleural effusion. Laboratory investigations revealed hypocalcemia, hyperphosphatemia, low parathyroid hormone (PTH), low cortisol, and high adrenocorticotropic hormone (ACTH) levels. The combination of chronic mucocutaneous candidiasis (CMC), hypoparathyroidism, and adrenal insufficiency confirmed the diagnosis of APS-1. To the best of our knowledge, this is the first Pakistani and second worldwide reported case of APS-1 presenting with such a combination of manifestations. Early recognition and multidisciplinary management are crucial for improving outcomes in these patients.

Regulatory CD4+ T cells redirected against pathogenic CD8+ T cells protect NOD mice from development of autoimmune diabetes.

Introduction: In this study, we report a novel therapeutic approach redirecting antigen-specific CD4+ T cells recognizing a hybrid insulin peptide (BDC2.5 T cell receptor (TCR) transgenic CD4+ T cells) to attract and suppress islet-specific CD8+ T cells T cells in the non-obese diabetic (NOD) mouse model, and prevent the development of autoimmune diabetes. Methods: Purified BDC2.5 CD4+ T cells were induced to differentiate into regulatory T cells (Tregs). The Tregs were then electroporated with mRNA encoding chimeric human ß2 microglobulin (hß2m) covalently linked to insulin B chain amino acids 15-23 (designated INS-eTreg) or islet-specific glucose-6-phosphatase related protein (IGRP) peptide 206-214 (designated IGRP-eTreg). Immunoregulatory functions of these engineered regulatory T cells (eTregs) were tested by in vitro assays and in vivo co-transfer experiments with ß-cell-antigen-specific CD8+ T cells in NOD.Scid mice or by adoptive transfer into young, pre-diabetic NOD mice. Results: These eTregs were phenotyped by flow cytometry, and shown to have high expression of FoxP3, as well as other markers of Treg function, including IL-10. They suppressed polyclonal CD4+ T cells and antigen-specific CD8+ T cells (recognizing insulin or IGRP), decreasing proliferation and increasing exhaustion and regulatory markers in vitro. In vivo, eTregs reduced diabetes development in co-transfer experiments with pathogenic antigen-specific CD8+ T cells (INS-CD8+ or IGRP-CD8+ cells) into NOD.Scid mice. Finally, when the eTreg were injected into young NOD mice, they reduced insulitis and prevented spontaneous diabetes in the recipient mice. Conclusion: Our results suggest a novel therapeutic strategy to protect NOD mice by targeting antigen-specific cytotoxic CD8+ T cells, using redirected antigen-specific CD4+ Treg cells, to suppress autoimmune diabetes. This may suggest an innovative therapy for protection of people at risk of development of type 1 diabetes.

Autoimmune diseases refractory to corticosteroids and immunosuppressants.

Corticosteroids and immunosuppressive drugs can alleviate the symptoms of most autoimmune diseases and induce remission by restraining the autoimmune attack and limiting the damage to the target tissues. However, four autoimmune non-degenerative diseases-adult advanced type 1 diabetes mellitus, Hashimoto's thyroiditis, Graves' disease, and advanced primary biliary cholangitis-are refractory to these drugs. This article suggests that the refractoriness of certain autoimmune diseases is due to near-total loss of secreting cells coupled with the extremely low regenerative capacity of the affected tissues. The near-complete destruction of cells responsible for secreting insulin, thyroid hormones, or biliary HCO3 - diminishes the protective effects of immunosuppressants against further damage. The slow regeneration rate of these cells hinders tissue recovery, even after drug-induced immune suppression, thus preventing remission. Although the liver can fully regenerate after injury, severe primary biliary cholangitis may impair this ability, preventing liver recovery. Consequently, these four autoimmune diseases are resistant to immunosuppressive drugs and corticosteroids. In contrast, early stages of type 1 diabetes and early primary biliary cholangitis, where damage to secreting cells is partial, may benefit from immunosuppressant treatment. In contrast to these four diseases, chronic degenerative autoimmune conditions like multiple sclerosis may respond positively to corticosteroid use despite the limited regenerative potential of the affected tissue (the central nervous system). The opposite is true for acute autoimmune conditions like Guillain-Barré syndrome.

Küttner's Tumor and Autoimmune Pancreatitis as Metachronous Manifestations of IgG4-Related Disease.

Immunoglobulin G4-related disease (IgG4-RD) is a multiorgan, fibro-inflammatory condition that presents with painless organ swelling, lymphoplasmacytic infiltration, and obliterative phlebitis, often showing a favorable response to corticosteroid therapy. The most affected organs include the pancreas, kidneys, retroperitoneum, lacrimal glands, and salivary glands. Diagnosis relies on serological, imaging, and histopathological findings, with glucocorticoids as the primary treatment. Despite its reversible nature and good prognosis in many cases, long-term complications such as organ dysfunction or malignancy can still occur. International collaborative efforts have enhanced the understanding, diagnosis, and management of IgG4-RD, emphasizing the importance of comprehensive diagnostic criteria and appropriate therapeutic strategies. Herein, we present an interesting case of a geriatric male who was referred to our clinic because of concern for pancreatic cancer. We diagnosed the patient with autoimmune pancreatitis, a manifestation of IgG4-RD. The patient experienced a dramatic response to steroid therapy and is currently on maintenance therapy.

Effect of exercise training on clinical and physiological variables in adults with myotonic dystrophy type 1: A systematic review protocol.

Myotonic dystrophy Type 1 (DM1) is a neuromuscular disease characterized by multisystemic involvement including a progressive loss of muscle mass and strength. Further investigation on the effect of exercise in adults with DM1 is needed to incorporate impactful recent findings to better understand the utility of exercise as an intervention. This review aims to summarize and appraise the literature on the effects of aerobic and strength training on clinical and physiological variables in adults with DM1. Six online databases (PubMed, Scopus, Web of Science, CINAHL, EMBASE, and CENTRAL) will be searched using appropriate search terms. Two reviewers will independently screen the relevant studies and extract the data from the selected articles. The methodological quality of the studies included will be assessed using the Joanna Briggs Critical Appraisal checklist. A meta-analysis will be performed if appropriate. This systematic review and meta-analysis will summarize, synthesize, and appraise evidence on the effect of aerobic and strength training on clinical and physiological variables in adults with DM1. The findings of this review will help in clinical decision-making and guide future researchers working with this patient population.

Acupuncture improves spatial learning and memory impairment caused by herpes simplex virus type-1 in rats through the p38 MAPK/CREB pathway.

BACKGROUND: Acupuncture can improve herpes simplex encephalitis (HSE), but the underlying mechanism is not clear. Therefore, we evaluated the cognitive function and apoptosis in hippocampus caused by herpes simplex virus type-1 (HSV-1) in rats after acupuncture and described the molecular mechanism. METHODS: Sprague-Dawley rats were induced into HSE models by HSV-1 infection. After 3 days, they received acupuncture at the acupoints of Xuanzhong (GB39), Baihui (GV20), Shenmen (HT7), Shenting (GV24), and Sanyinjiao (SP6), and/or intraperitoneal injection of the p38 MAPK inhibitor SB203580. Morris water maze test was performed on rats. The hippocampus of rats was obtained, and the expression of apoptosis-related genes in the tissues was detected by qRT-PCR. In addition, apoptosis-related proteins and proteins related to the p38 MAPK/CREB pathway in the tissues was detected by western blot. RESULTS: After HSV-1 induction, the rat's escape latency was increased, the time spent on the platform in the target quadrant and the number of platform crossings significantly decreased. In addition, there was an increase in apoptosis in the hippocampus, accompanied by elevated levels of p-p38 and decreased levels of p-CREB. However, these effects could be improved by acupuncture treatment. Interestingly, SB203580 plays a similar role to acupuncture, and acupuncture could further enhance the impacts of SB203580 on cognitive function and apoptosis in hippocampus in HSE rats. CONCLUSION: Acupuncture improves spatial learning and memory impairment caused by HSV-1 in rats. The functional mechanism of acupuncture may be through the p38 MAPK/CREB pathway.

The role of islet autoantigen-specific T cells in the onset and treatment of type 1 diabetes mellitus.

Type 1 diabetes mellitus (T1DM), a complex chronic disease with an intricate etiology and pathogenesis, involves the recognition of self-antigens by pancreatic islet autoantigen-specific T cells and plays crucial roles in both early- and late-stage destruction of beta cells, thus impacting disease progression. Antigen-specific T cells regulate and execute immune responses by recognizing particular antigens, playing broad roles in the treatment of various diseases. Immunotherapy targeting antigen-specific T cells holds promising potential as a targeted treatment approach. This review outlines the pathogenesis of diabetes, emphasizing the pivotal role of pancreatic islet autoantigen-specific T cells in the progression and treatment of T1DM. Exploring this avenue in research holds promise for identifying novel therapeutic targets for effectively managing diabetes.

Whole Exome Sequencing in Children With Type 1 Diabetes Before Age 6 Years Reveals Insights Into Disease Heterogeneity.

Aims: This study is aimed at comparing whole exome sequencing (WES) data with the clinical presentation in children with type 1 diabetes onset ≤ 5 years of age (EOT1D). Methods: WES was performed in 99 unrelated children with EOT1D with subsequent analysis to identify potentially deleterious rare variants in MODY genes. High-resolution HLA class II haplotyping, SNP genotyping, and T1D-genetic risk score (T1D-GRS) were also evaluated. Results: Eight of the ninety-nine EOT1D participants carried a potentially deleterious rare variant in a MODY gene. Rare variants affected five genes: GCK (n = 1), HNF1B (n = 2), HNF4A (n = 1), PDX1 (n = 2), and RFX6 (n = 2). At diagnosis, these children had a mean age of 3.0 years, a mean HbA1c of 10.5%, a detectable C-peptide in 5/8, and a positive islet autoantibody in 6/7. Children with MODY variants tend to exhibit a lower number of pancreatic autoantibodies and a lower fasting C-peptide compared to EOT1D without MODY rare variants. They also carried at least one high-risk DR3-DQ2 or DR4-DQ8 haplotype and exhibited a T1D-GRS similar to the other individuals in the EOT1D cohort, but higher than healthy controls. Conclusions: WES found potentially deleterious rare variants in MODY genes in 8.1% of EOT1D, occurring in the context of a T1D genetic background. Such genetic variants may contribute to disease precipitation by a ß-cell dysfunction mechanism. This supports the concept of different endotypes of T1D, and WES at T1D onset may be a prerequisite for the implementation of precision therapies in children with autoimmune diabetes.

New peripherally-restricted CB1 receptor antagonists, PMG-505-010 and -013 ameliorate obesity-associated NAFLD and fibrosis.

The endocannabinoid system plays a crucial role in metabolic regulation, prompting the investigation of cannabinoid type 1 receptor (CB1R) antagonists for obesity and its complications like non-alcoholic fatty liver disease (NAFLD). Concerns over psychiatric side effects led to the development of peripheral CB1R antagonists that circumvent the blood-brain barrier (BBB). In this study, we synthesized PMG-505-010 and PMG-505-013 as peripherally restricted CB1 receptor antagonists by modifying rimonabant to minimize BBB penetration. Physicochemical analysis confirmed their reduced lipophilicity and increased polarity compared to rimonabant, indicating limited brain exposure. Molecular docking studies revealed similar binding modes to rimonabant at CB1R, characterized by robust hydrophobic interactions. Functionally, they acted as CB1R antagonists and inverse agonists, effectively reversing CP55,940-induced cAMP inhibition. In a murine model of obesity-related NAFLD, PMG-505-010 and -013 improved metabolic profiles, including fasting blood glucose levels and dyslipidemia. They also ameliorated hepatic injury, steatosis, and inflammation, evidenced by reduced liver enzymes, lipid peroxidation, hepatic lipid levels, and inflammatory cytokine levels. Notably, these compounds inhibited hepatic fibrosis by reducing extracellular matrix (ECM) deposition and altering fibrosis-related gene and protein expressions. In conclusion, PMG-505-010 and PMG-505-013 hold promise for treating obesity-related liver diseases, including NAFLD and fibrosis, through selective peripheral CB1R targeting, potentially avoiding CNS-related side effects seen with earlier CB1R antagonists.

A successful combined spinal-epidural anesthesia for cesarean section in a patient with neurofibromatosis type 1-associated dural ectasia.

BACKGROUND: Dural ectasia is a common manifestation of neurofibromatosis type 1. Although there have been reports of unsuccessful spinal anesthesia due to dual ectasia in Marfan syndrome, reports describing similar unsuccessful spinal anesthesia in neurofibromatosis type 1 are lacking. CASE PRESENTATION: A parturient with neurofibromatosis type 1 was scheduled for a repeat cesarean section. During a previous cesarean section, she had experienced a failed spinal anesthesia, which resulted in a conversion to general anesthesia. Preoperative lumbar magnetic resonance imaging revealed dural ectasia, which was speculated to be the cause of the previous spinal anesthesia failure. Therefore, combined spinal-epidural anesthesia was implemented. Because the block level of spinal anesthesia was insufficient as predicted, supplemental administration of epidural anesthesia successfully provided adequate analgesia for the surgery. CONCLUSIONS: Combined spinal-epidural anesthesia can be useful for the management of cesarean sections in patients with neurofibromatosis type 1-associated dural ectasia.

Parents' and children's experiences of participating in a randomized controlled clinical trial: AIDIT-QS.

Participation in a paediatric, complex randomized controlled trial (RCT) might add to the family burden when a child is diagnosed with a severe disease. Although important, there are only a limited number of papers describing this aspect of research from the family point of view. This study explored parents' and children's experiences of participation in a research study shortly after the child had been diagnosed with type 1 diabetes. Sixteen parents (nine mothers, seven fathers) and nine children were interviewed by an independent researcher about their inducement, the decision-making process within the family which led to their participation, and their experience of having done so. The result showed that the parents wanted to contribute to improve treatment for children with diabetes in general but also specifically for their own child. Older children were more involved in the decision making than the younger children. Study information needs to be communicated clearly and effectively since decision-making based on information of a clinical trial directly after the child's diabetes onset proved difficult. Being randomized to the intervention group in this specific study was considered somewhat burdensome. However, parental participants in both intervention and control group claimed that they would recommend participation in research studies to other parents in a similar situation, and so did the children. There was no difference between the mothers' and fathers' experiences.

Parents' expectations: A predominant driving force for the parents was the expectation that the study outcome could lead to something good for both their own child and other children with type 1 diabetes.Children's perspective on participation: Older children appreciated being involved in the decision-making process and valued their role in potentially helping others with diabetes. However, younger children were less involved and often relied on their parents for decision-making.Personal benefits: Both children and parents considered it important to gain something for themselves; by participating, they could benefit from more advanced technology and more rigorous follow-ups.Importance of control group: It was important for the families' motivation for completing the study that the researchers conveyed that the control group was as important for the outcome of the study as the intervention group.Future treatments: The parents felt that participation in the clinical trial could eventually lead to new treatments that could help their own child.Perceived safety: The fact that the clinical trial was considered well-planned and safe and implied no risk for the child made it easier to agree to participation.Effective communication: Since the onset of diabetes is emotionally stressful, and diabetes treatment itself is demanding, effective communication about the content of such a clinical trial is necessary, otherwise families may not understand what they are agreeing to.Burden on the intervention group: This clinical trial was somewhat burdensome for the intervention group to participate in; nevertheless, all of the families remained committed to their reasons for participating and completed the study.

Different diseases, different needs: Patient preferences for gene therapy in lysosomal storage disorders, a probabilistic threshold technique survey.

BACKGROUND: Gene therapy is currently in development for several monogenetic diseases including lysosomal storage disorders. Limited evidence is available on patient preferences for gene therapy in this population. In this study, we compare gene therapy-related risk tolerance between people affected by three lysosomal storage diseases currently faced with different therapeutic options and prognoses. METHODS: A survey including the probabilistic threshold technique was developed in which respondents were asked to choose between gene therapy and the current standard of care. The attributes included to establish participants' risk tolerance were previously identified in focus groups of affected people or their representatives, namely: risk of mild side effects, severe side effects, the need for additional medication, and the likelihood of long-term effectiveness. The survey was distributed among people receiving outpatient care for type 1 Gaucher disease (good prognosis with current treatment options), Fabry disease (varying prognosis with current treatment options, XY-genotype on average more severely affected than XX), and parents representing people with severe forms of mucopolysaccharidosis type III A/B (poor prognosis, no disease-specific therapy available). RESULTS: A total of 85 surveys were completed (15 Gaucher disease respondents, 62 Fabry disease respondents (17 self-identifying male), eight parents of ten people with mucopolysaccharidosis type III). Disease groups with higher disease severity trended towards higher risk tolerance: Gaucher disease respondents were most cautious and predominantly preferred the current standard of care as opposed to MPS III representatives who were more risk tolerant. Respondents with Fabry disease were most heterogeneous in their risk tolerance, with male participants being more risk tolerant than female participants. Long-term effectiveness was the attribute in which respondents tolerated the least risk. CONCLUSIONS: People affected by a lysosomal storage disease associated with a poorer prognosis and less effective current treatment options trended towards more risk tolerance when choosing between gene therapy and the current standard of care. This study shows the importance of involvement of patient preferences before and during the development process of new treatment modalities such as gene therapy for rare diseases, to ensure that innovative therapies align with the wishes and needs of people affected by these diseases.

Bacteriological characteristics and changes of Streptococcus pneumoniae serotype 35B after vaccine implementation in Japan.

Streptococcus pneumoniae serotype 35B, a non-vaccine type, is a major contributor to the increase in pneumococcal infection post-vaccination. We aimed to understand the mechanism of its spread by characterizing 35B. The serotype, type 1 pilus (T1P) positivity, and antimicrobial susceptibility of 319 isolates in 2018-2022 were analysed and compared with those of isolates in 2014-2017 to find the changes. 35B accounted for 40 (12.5%) isolates. T1P positivity was notably higher in 35B (87.5%) than in the other serotypes. To confirm the role of T1P, an adhesion factor, we compared adherence to A549 cells between T1P-positive 35B isolates and their T1P-deficient mutants, showing contribution of T1P to adherence. Penicillin-non-susceptible rate of 35B was 87.5%, and meropenem-resistant 35B rate was 35.0%, which increased from 14.5% of 2014-2017 (p = 0.009). Multilocus sequence typing was performed in 35B strains. Prevalence of clonal complex 558, harbouring T1P and exhibiting multidrug non-susceptibility, suggested the advantages of 35B in attachment and survival in the host. The emergence of ST156 isolates, T1P-positive and non-susceptible to ß-lactams, has raised concern about expansion in Japan. The increase of serotype 35B in pneumococcal diseases might have occurred due to its predominant colonizing ability after the elimination of the vaccine-serotypes.

Prediction of Incident Diabetic Retinopathy in Adults With Type 1 Diabetes Using Machine Learning Approach: An Exploratory Study.

BACKGROUND: Early detection and intervention are crucial for preventing vision-threatening diabetic retinopathy (DR) in adults with type 1 diabetes (T1D). This exploratory study uses machine learning on continuous glucose monitoring (CGM) data to identify factors influencing DR and predict high-risk individuals for timely intervention. METHODS: Between June 2018 and March 2022, adults with T1D with incident DR or no retinopathy (control) were identified. The CGM data were collected retrospectively for up to seven years before the date of defining incident DR or no retinopathy. A mixture of three machine learning algorithms was trained and evaluated in two different scenarios, using different glycemic features extracted from CGM traces (scenario 1), and the two principal components (two PCs; exposure to hyperglycemia and hypoglycemia risk) of those features (scenario 2). Classifiers were evaluated through 10-fold cross-validation using the receiver operating characteristic area under the curve (AUC-ROC) to select the best classification model. RESULTS: The CGM data of 30 adults with incident DR (mean±SD age of 21.2±9.4 years, glycated hemoglobin [HbA1c] of 8.6%±1.0%, and body mass index [BMI] of 24.5±4.8 kg/m2) and 30 adults without DR (age of 41.8±14.7 years, HbA1c of 7.0%±0.9%, and BMI of 26.2±3.6 kg/m2) were included in this analysis. In scenario 2, classifiers outperformed scenario 1, resulting in an average AUC-ROC increase to 0.92 for two of three models, indicating that the two PCs captured vital classification data, representing the most discriminative aspects and enhancing model performance. CONCLUSION: Machine learning approaches using CGM data may have potential to aid in identifying adults with T1D at risk of DR.

Twelve-Month Real-World Use of an Advanced Hybrid Closed-Loop System Versus Previous Therapy in a Dutch Center For Specialized Type 1 Diabetes Care.

BACKGROUND: Complexity of glucose regulation in persons with type 1 diabetes (PWDs) necessitates increased automation of insulin delivery (AID). This study aimed to analyze real-world data over 12 months from PWDs who started using the MiniMed 780G (MM780G) advanced hybrid closed-loop (aHCL) AID system at the Diabeter clinic, focusing on glucometrics and clinical outcomes. METHODS: Persons with type 1 diabetes switching to the MM780G system were included. Clinical data (e.g. HbA1c, previous modality) was collected from Diabeter's electronic health records and glucometrics (time in range [TIR], time in tight range [TITR], time above range [TAR], time below range [TBR], glucose management indicator [GMI]) from CareLink Personal for a 12-month post-initiation period of the MM780G system. Outcomes were age-stratified, and the MM780G system was compared with previous use of older systems (MM640G and MM670G). Longitudinal changes in glucometrics were also evaluated. RESULTS: A total of 481 PWDs were included, with 219 having prior pump/sensor system data and 334 having monthly longitudinal data. After MM780G initiation, HbA1c decreased from 7.6 to 7.1% (P < .0001) and the percentage of PWDs with HbA1c <7% increased from 30% to 50%. Glucose management indicator and TIR remained stable with mean GMI of 6.9% and TIR >70% over 12 months. Age-stratified analysis showed consistent improvements of glycemic control across all age groups, with older participants achieving better outcomes. Participants using recommended system settings achieved better glycemic outcomes, reaching TIR up to 77% and TTIR up to 55%. CONCLUSIONS: Use of MM780G system results in significant and sustained glycemic improvements, consistent across age groups and irrespective of previous treatment modalities.

Psychological distress in Aotearoa New Zealand adults with type 1 diabetes.

The psychological burden of type 1 diabetes (T1D) can negatively impact health outcomes. This study evaluates the prevalence of low mood (WHO-5), disordered eating (DEPS-R), diabetes distress (PAID) and fear of hypoglycaemia (HFS-II), in a sample of 250 New Zealand adults (8.4% Maori/91.6% non-Maori; 43.6% female/56.4% male) with T1D using validated tools. Maori and female patients indicated low mood, with lower median WHO-5 scores than non-Maori (p = 0.027) and males (p = 0.002). Maori were more likely to score in the clinical range on the WHO-5, DEPS-R, PAID and HFS-II (all p < 0.05). HbA1c was correlated with emotional well-being (rs = -0.189), diabetes distress (rs = 0.223) and disordered eating (rs = 0.389; all p < 0.001) whilst DEPS-R correlated with age (rs = -0.232) and BMI (rs = 0.343; both p ≤ 0.001). Thus, diabetes-related psychological distress is common in New Zealand adults with T1D, particularly for Maori, females and those with elevated HbA1c levels.