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.

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.

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.

Impact of Telemedicine Versus In-Person Pediatric Outpatient Type 1 Diabetes Visits on Immediate Glycemic Control: Retrospective Chart Review.

BACKGROUND: Children and adolescents with type 1 diabetes require frequent outpatient evaluation to assess glucose trends, modify insulin doses, and screen for comorbidities. Continuous glucose monitoring (CGM) provides a detailed glycemic control assessment. Telemedicine has been increasingly used since the COVID-19 pandemic. OBJECTIVE: To investigate CGM profile parameter improvement immediately following pediatric outpatient diabetes visits and determine if visit modality impacted these metrics, completion of screening laboratory tests, or diabetic emergency occurrence. METHODS: A dual-center retrospective review of medical records assessed the CGM metrics time in range and glucose management indicator for pediatric outpatient diabetes visits during 2021. Baseline values were compared with those at 2 and 4 weeks post visit. Rates of completion of screening laboratory tests and diabetic emergencies following visits were determined. RESULTS: A total of 269 outpatient visits (41.2% telemedicine) were included. Mean time in range increased by 1.63% and 1.35% at 2 and 4 weeks post visit (P=.003 and .01, respectively). Mean glucose management indicator decreased by 0.07% and 0.06% at 2 and 4 weeks post visit (P=.003 and .02, respectively). These improvements in time in range and glucose management indicator were seen across both telemedicine visits and in-person visits without a significant difference. However, patients seen in person were 2.69 times more likely to complete screening laboratory tests (P=.03). Diabetic emergencies occurred too infrequently to analyze. CONCLUSIONS: Our findings demonstrate an immediate improvement in CGM metrics following outpatient visits, regardless of modality. While statistically significant, the magnitude of these changes was small; hence, multiple visits over time would be required to achieve clinically relevant improvement. However, completion of screening laboratory tests was found to be more likely after visits occurring in person. Therefore, we suggest a hybrid approach that allows patient convenience with telemedicine but also incorporates periodic in-person assessment.

Correlation between triglyceride-glucose index and diabetic kidney disease risk in adults with type 1 diabetes mellitus.

BACKGROUND: The triglyceride-glucose (TyG) index is identified as an alternative indicator of insulin resistance (IR) and is associated with macro- and micro-vascular diseases among patients with type 2 diabetes mellitus. The relationship between the TyG index and IR and its impact on diabetic kidney disease (DKD) remains unclear among adults with type 1 diabetes mellitus(T1DM). METHODS: This study comprised a cross-sectional analysis using data from the Guangdong T1DM Translational Medicine Study (GTT) and a longitudinal analysis using data from the type 1 diabetes (T1D) Exchange registry study. Correlation analysis was used to investigate the association between the TyG index and IR. Logistic regression and Cox proportional hazards regression were performed to explore the impact of the TyG index on DKD risk. RESULTS: The GTT Study included 836 adults (216 with DKD and 620 without DKD). A significant correlation existed between the TyG index and the estimated glucose disposal rate (r=-0.64, p < 0.01). The TyG index was a risk factor for DKD after confounder adjustment (OR = 1.34, 95% CI:1.03-1.74). The T1D Exchange registry study included 8,771 adults (2,050 with DKD and 6,721 without DKD). After adjusting confounding factors, the TyG index was identified as an independent risk factor for DKD at enrollment, with the highest risk of DKD incidence observed in the highest TyG tertile group (OR = 1.92, 95%CI:1.67-2.20). During a median follow-up of 44.58(21.84, 67.09) months, the risk of developing DKD was increased by 32% at every 1 SD increase of the TyG index over time among participants without DKD at enrollment. CONCLUSIONS: The TyG index could be used to assess IR and was identified as an independent risk factor of DKD among adults with T1DM.

Trends in endogenous insulin secretion capacity and anti-islet autoantibody titers in two childhood-onset slowly progressive insulin-dependent diabetes mellitus cases.

Slowly progressive insulin-dependent (type 1) diabetes mellitus (SPIDDM) is a subtype of type 1 diabetes. Although SPIDDM is not rare among Japanese children, there are few reports on endogenous insulin secretory capacity and anti-pancreatic islet autoantibodies in pediatric SPIDDM. We followed the trends in endogenous insulin secretory capacity and anti-pancreatic islet autoantibody titers in two pediatric SPIDDM cases over several years. Case 1 developed insulin deficiency eight months after diabetes diagnosis; as her insulinoma-associated antibody test result was positive, insulin therapy was initiated. Fourteen months after the diagnosis, she tested positive for glutamic acid decarboxylase autoantibodies (GADA) and was diagnosed with SPIDDM. Case 2 was mildly positive for GADA at the onset of diabetes, but became a high titer during the course of the disease. Fourteen months after the diagnosis of diabetes, he became mildly insulin deficient, and insulin therapy was initiated. However, his insulin secretory capacity was preserved for 60 mo after the onset. SPIDDM is generally indistinguishable from type 2 diabetes at diagnosis; therefore, repeated evaluation of the insulin secretory capacity and anti-islet autoantibodies facilitates early diagnosis and appropriate treatment, especially in nonobese children with type 2 diabetes.

Differential lipid signaling from CD4+ and CD8+ T cells contributes to type 1 diabetes development.

Introduction: We reported that Ca2+-independent phospholipase A2ß (iPLA2ß)-derived lipids (iDLs) contribute to type 1 diabetes (T1D) onset. As CD4+ and CD8+ T cells are critical in promoting ß-cell death, we tested the hypothesis that iDL signaling from these cells participates in T1D development. Methods: CD4+ and CD8+ T cells from wild-type non-obese diabetic (NOD) and NOD.iPLA2ß+/- (NOD.HET) mice were administered in different combinations to immunodeficient NOD.scid. Results: In mice receiving only NOD T cells, T1D onset was rapid (5 weeks), incidence 100% by 20 weeks, and islets absent. In contrast, onset was delayed 1 week and incidence reduced 40%-50% in mice receiving combinations that included NOD.HET T cells. Consistently, islets from these non-diabetic mice were devoid of infiltrate and contained insulin-positive ß-cells. Reduced iPLA2ß led to decreased production of proinflammatory lipids from CD4+ T cells including prostaglandins and dihydroxyeicosatrienoic acids (DHETs), products of soluble epoxide hydrolase (sEH), and inhibition of their signaling decreased (by 82%) IFNγ+CD4+ cells abundance. However, only DHETs production was reduced from CD8+ T cells and was accompanied by decreases in sEH and granzyme B. Discussion: These findings suggest that differential select iDL signaling in CD4+ and CD8+ T cells contributes to T1D development, and that therapeutics targeting such signaling might be considered to counter T1D.

The Effect of COVID-19 Lockdown Among Adolescents with Type 1 Diabetes: A Systematic Review and Meta-Analysis.

OBJECTIVE: The aim of this study was to assess how the lockdown of the COVID-19 pandemic had affected the glycaemic control of adolescents aged 10-19 with type 1 diabetes. METHODS: A comprehensive search of literature was performed in PubMed, Scopus, Web of Science, and ProQuest. Published articles up to September 2022 were included. The Glucose Monitoring Index (GMI) and HbA1c level were defined as outcome variables. Average glucose level was found to be a common variable in both HbA1c levels and GMI; therefore, HbA1c and GMI were converted to average glucose (mg/dL) using appropriate formulas. Studies reported the outcomes in two or three periods (pre-lockdown, lockdown, and post-lockdown) were included in the analysis. A paired wise meta-analysis was performed among the studies that reported all three periods. Homogeneity across studies was assessed using I2 statistic. RESULT: Fourteen studies were included in the study. The pooled average glucose during the lockdown decreased to 166.9 mg/dL (95% CI, 153.78, 180.02) from 205.793 mg/dL (95% CI, 188.412, 223.173) during the pre-lockdown period, then it increased to 204.23 mg/dL (95% CI, 186.17, 222.29) during the post-lockdown period. A paired wise meta-analysis indicated a reduction in average glucose levels. However, it was not statistically significant, possibly due to the small number of studies that reported data from all three periods. CONCLUSION: Although the descriptive analysis of our study showed that the lockdown had affected (decreased) the average glucose level among adolescents with type 1 diabetes, this was not statistically significant in the pooled analysis.

Progression to type 1 diabetes in the DPT-1 and TN07 clinical trials is critically associated with specific residues in HLA-DQA1-B1 heterodimers.

AIMS/HYPOTHESIS: The aim of this work was to explore molecular amino acids (AAs) and related structures of HLA-DQA1-DQB1 that underlie its contribution to the progression from stages 1 or 2 to stage 3 type 1 diabetes. METHODS: Using high-resolution DQA1 and DQB1 genotypes from 1216 participants in the Diabetes Prevention Trial-Type 1 and the Diabetes Prevention Trial, we applied hierarchically organised haplotype association analysis (HOH) to decipher which AAs contributed to the associations of DQ with disease and their structural properties. HOH relied on the Cox regression to quantify the association of DQ with time-to-onset of type 1 diabetes. RESULTS: By numerating all possible DQ heterodimers of α- and ß-chains, we showed that the heterodimerisation increases genetic diversity at the cellular level from 43 empirically observed haplotypes to 186 possible heterodimers. Heterodimerisation turned several neutral haplotypes (DQ2.2, DQ2.3 and DQ4.4) to risk haplotypes (DQ2.2/2.3-DQ4.4 and DQ4.4-DQ2.2). HOH uncovered eight AAs on the α-chain (-16α, -13α, -6α, α22, α23, α44, α72, α157) and six AAs on the ß-chain (-18ß, ß9, ß13, ß26, ß57, ß135) that contributed to the association of DQ with progression of type 1 diabetes. The specific AAs concerned the signal peptide (minus sign, possible linkage to expression levels), pockets 1, 4 and 9 in the antigen-binding groove of the α1ß1 domain, and the putative homodimerisation of the αß heterodimers. CONCLUSIONS/INTERPRETATION: These results unveil the contribution made by DQ to type 1 diabetes progression at individual residues and related protein structures, shedding light on its immunological mechanisms and providing new leads for developing treatment strategies. DATA AVAILABILITY: Clinical trial data and biospecimen samples are available through the National Institute of Diabetes and Digestive and Kidney Diseases Central Repository portal ( https://repository.niddk.nih.gov/studies ).

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.

PLAGL1 overexpression induces cytoplasmic DNA accumulation that triggers cGAS/STING activation.

Pancreatic ß-cell damage mediated by apoptosis is believed to be a main trigger of type 1 diabetes mellitus (T1DM), which is proposed as an organ-specific autoimmune disease mediated by T cells. Nonetheless, the fundamental origins of T1DM remain uncertain. Here, we illustrate that an increase in PLAGL1 expression induces ß-cell apoptosis, as evidenced by mitochondrial membrane impairment and nucleolar degradation. The gene expression levels from cDNA samples were determined using qRT-PCR method. Western blot and Co-immunoprecipitation were applied for protein expression and interactions, respectively. Flow cytometry and TUNEL assay were used to detect pancreatic ß cell apoptosis. Female NOD/LtJ mice with recent-onset T1DM has been used in in vivo studies. Glucose-stimulated insulin secretion (GSIS) and glucose tolerance test (GTT) method is used for islet function assessment. Haematoxylin and Eosin (H&E) and Immunohistochemistry (IHC) were performed to evalute histological improvement of islet beta. Subsequent cytoplasmic DNA accumulation triggers DNA senser, the cyclic guanosine monophosphate-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway. STING activation further stimulates downstream IRF3 and NF-kB pathways, thus boost type-I interferon signalling and NF-kB mediated inflammation. These findings elucidate a molecular mechanism linking PLAGL1 induced cell apoptosis to type-I interferon signalling and suggest a potential benefit for targeting cGAS/STING in T1DM treatment.

[The transition to the adult diabetes service: step-by-step support]. / La transition vers le service adultes de diabétologie : un accompagnement pas à pas.

The transition of young type 1 diabetic patients from pediatrics to adult diabetes services is a delicate stage, with the risk of a break in the care pathway. These adolescents are apprehensive about leaving the pediatric sector, and often experience the change as an abandonment. It is therefore vital to prepare them and support them during and after the transfer, in order to improve their experience.

[The contribution of social networks using the example of type 1 diabetes]. / Apport des réseaux sociaux à partir de l'exemple du diabète de type 1.

Type 1 diabetes has an impact not only on physical health, but also on social life, family life and psychological balance. Social networks play a decisive role, alongside associations, in helping patients to adopt the "other pace of life" implied by the disease. Beyond health, the skills needed to enable patients to achieve personal fulfillment are beyond the scope of healthcare professionals. Peer communities are an invaluable contribution to building this life with diabetes.

The protective effect of the intestinal microbiota in type-1 diabetes in NOD mice is limited to a time window in early life.

Introduction: The incidence of type-1 diabetes is on the rise, particularly in developed nations, and predominantly affects the youth. While genetic predisposition plays a substantial role, environmental factors, including alterations in the gut microbiota, are increasingly recognized as significant contributors to the disease. Methods: In this study, we utilized germ-free non-obese diabetic mice to explore the effects of microbiota colonization during early life on type-1 diabetes susceptibility. Results: Our findings reveal that microbiota introduction at birth, rather than at weaning, significantly reduces the risk of type-1 diabetes, indicating a crucial window for microbiota-mediated modulation of immune responses. This protective effect was independent of alterations in intestinal barrier function but correlated with testosterone levels in male mice. Additionally, early life colonization modulated T cell subset frequencies, particularly T helper cells and regulatory T cells, in the intestine, potentially shaping type-1 diabetes predisposition. Discussion: Our findings underscore the pivotal role of early-life microbial interactions in immune regulation and the development of autoimmune diseases.

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.

Abdominal Normothermic Regional Perfusion after Donation after Circulatory Death Improves Pancreatic Islet Isolation Yield.

Abdominal Normothermic Regional Perfusion (aNRP) is an in-situ normothermic oxygenated donor perfusion technique before procurement during controlled donation after circulatory death (cDCD) procedures and allows for organ quality evaluation. There are few data on the effect of aNRP on pancreatic islet isolation and subsequent transplantation outcomes. We aim to evaluate the impact of aNRP on cDCD pancreatic islet isolation and transplantation. A retrospective analysis was performed on pancreatic islet isolation outcomes from aNRP, cDCD, and Donation after Brain death (DBD) pancreases. Isolations were compared to previous donor age (60-75) matched isolations. Islet function was asses by a dynamic Glucose Stimulated Insulin Secretion (dGSIS). Donor baseline characteristics did not differ among groups. Isolations from aNRP pancreases (471,739 IEQ [655,435 - 244,851]) yielded more islets compared to cDCD (218,750 IEQ [375,951 - 112,364, p<0.01) and to DBD (206,522 IEQ [385,544 - 142,446, p=0.03) pancreases. dGSIS tests in seven aNRP islet preparations showed a mean stimulation index of 4.91, indicating good functionality. Bilirubin and alanine aminotransferase during aNRP correlated with islet yield (r2=0.685, p=0.002; r2=0.491, p=0.016 respectively). Islet isolation after aNRP in cDCD donors results in a high islet yield with viable functional islets. aNRP could increase the utilization of pancreases for islet transplantation.

Random C-Peptide and Islet Antibodies at Onset Predict ß Cell Function Trajectory and Insulin Dependence in Pediatric Diabetes.

CONTEXT: Identification of prognostic biomarkers in pediatric diabetes is important for precision medicine. OBJECTIVE: We assessed whether C-peptide and islet autoantibodies are useful to predict the natural history of children with new-onset diabetes. METHODS: We prospectively studied 72 children with new-onset diabetes (median follow-up: 8 months) by applying the Aß classification system ("A+": islet autoantibody positive, "ß+": random serum C-peptide≥1.3 ng/mL at diagnosis). Beta-cell function was assessed longitudinally with 2h post-prandial/stimulated urinary C-peptide-to-creatinine ratio (UCPCR) 3-12 weeks (V1) and 6-12 months after diagnosis (V2). We obtained a type 1 diabetes genetic risk score (T1D GRS2) for each participant, and compared characteristics at baseline, and clinical outcomes at V2. RESULTS: The cohort was 50% male. Racial distribution was 76.4% White, 20.8% Black and 2.8% Asian or other races. A total of 46.5% participants were Hispanic. Median age (Q1-Q3) was 12.4 (8.3-14.5) years. The Aß subgroup frequencies were 46 A+ß-(63.9%), 1 A-ß-(1.4%), 4 A+ß+(5.6%), and 21 A-ß+(29.2%). Baseline serum C-peptide correlated with UCPCR at both V1 (r=0.36, p=0.002) and V2 (r=0.47, p<0.001). There were significant subgroup differences in age, race, frequency of diabetic ketoacidosis and T1D GRS2 (p<0.01). At V2, the two ß- subgroups had lower UCPCR and higher HbA1c compared with the two ß+ subgroups (p<0.001 and p=0.02, respectively). Thirty-eight percent of A-ß+ but none of the other subgroups were insulin-independent at V2 (p<0.001). CONCLUSIONS: C-peptide and islet autoimmunity at diagnosis define distinct phenotypes and predict beta-cell function and insulin dependence 6-12 months later in racially/ethnically diverse children with new-onset diabetes.

A proposal for breakfast to improve the postprandial glucose response in children with type 1 diabetes - Preliminary results from a camp-based study.

This study aimed to evaluate post - prandial glucose response (PPGR) after a traditional Italian breakfast and an alternative meal in children with type 1 diabetes (T1D). Preliminary findings showed that by replacing a small portion ofcarbohydrates with fats helpsimprovingPPGR after breakfast in children with T1D.