Our aim in this study was to present a summary of recent evidence describing the clinical and economic impact of continuous glucose monitoring (CGM) in the care of people living with type 2 diabetes mellitus (T2DM). Outcomes associated with CGM use in T2DM were searched using PubMed and Google Scholar, with specific inclusion and exclusion criteria to select evidence. Preference was given to randomized controlled trials, real-world observational studies, and meta-analyses. Guidelines, consensus statements, and systematic reviews were also considered. An overall favourable trend was seen for people living with T2DM who used CGM in addition to their regular therapies. When compared with traditional self-monitoring of blood glucose, CGM was found to improve glycemic outcomes as evidenced by significant differences in change from baseline for glycated hemoglobin, time in range, time above range, time below range, and glycemic variability. Patient satisfaction reflected favoured use of CGM, with an overall cost-efficiency improvement as well. The Canadian health care system could benefit from CGM use through decreased hospitalizations and related costs. Integration of CGM to enhance treatment for Canadians living with T2DM as a component of comprehensive care should be recognized. Structural barriers, including provincial inequalities in coverage for devices and access to care, currently pose a barrier for much this population.

Introduction and Objective: Type 1 diabetes (T1D) requires constant self-management and carries substantial psychological and lifestyle burdens. Cell-based therapies such as islet transplantation (ITx) may reduce reliance on exogenous insulin and meaningfully alter lived experience. Objectives: To explore perceptions of freedom, flexibility and risk among ITx recipients and health-care providers (HCPs). Secondly, to increase awareness of ITx benefits and challenges for individuals with T1D, HCPs, and policymakers. Methods: Using focused ethnography, semi-structured interviews were conducted with adult ITx recipients, family members, and transplant-HCPs. Thematic analysis was used to systematically identify and interpret patterns across participant narratives. Results: Identified themes reflected increased autonomy, quality of life, and re-engagement in restricted activities. Participants described freedom from constant T1D vigilance, leading to greater daily flexibility, psychological relief, and renewed social and professional participation. Additionally, HCP-patient relationships were central to care trajectories, with trust, advocacy, and shared decision-making shaping T1D care, transplantation experiences, and sustained outcomes. Conclusion: ITx offers both biomedical and psychosocial benefits for people living with T1D. Findings underscore the importance of patient-reported outcomes (PROs) that capture daily experiences, psychosocial well-being, and relational aspects of care. Developing novel tools for measuring perceived freedom, flexibility, quality of life, and care relationships beyond glycemic metrics will be essential to fully assess the impact of emerging cell treatments and possible curative therapies. Disclosure R. Lucciantonio: Speaker's Bureau; Current; Abbott Diabetes, Dexcom, Inc. Advisory Panel; Ended; Diabetes Canada, Novo Nordisk Canada Inc. Speaker's Bureau; Current; Tandem Diabetes Care, Inc. Consultant; Current; Medtronic, Insulet Corporation. Research Support; Ended; Vertex Pharmaceuticals Incorporated. R. Crossman: None. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. Funding Canadian Institute of Health Research (524598)

Introduction and Objective: Automated insulin delivery (AID) improves glycemic outcomes in type 1 diabetes (T1D), raising questions about the added value of preserving endogenous β-cell function. We examined whether residual β-cell function adds benefit in new-onset T1D using AID. Methods: Patient-level CGM data were analyzed from individuals with new-onset, stage 3 T1D enrolled in randomized trials of hybrid closed-loop AID (CLVR n=88; CLOUD n=97). CGM data required ≥3 days of wear. CGM metrics were compared using linear mixed-effects models with treatment, log-transformed C-peptide AUC, and their interaction, and study as fixed effects, and participant-level random intercepts. For visualization, participants were stratified by C-peptide and compared with non-diabetic controls (n=153) and adults with established T1D (n=25). Results: Residual C-peptide was strongly associated with improved CGM metrics, including time in range, time in tight range, and time above range (all p < 0.001). The incremental benefit of AID was greatest at low C-peptide and diminished with increasing C-peptide (interaction p = 0.021). Conclusion: While AID improves glycemic control, it does not eliminate the biological advantage of endogenous insulin secretion; residual β-cell function provides additional benefit beyond technology alone. CGM captures biologically meaningful differences, supporting CGM-based endpoints for trials evaluating β-cell-preserving therapies. Disclosure A. Lam: Advisory Panel; Ended; Vertex Pharmaceuticals Incorporated. T. Bakhtiyarli: None. A.L. Carr: None. C.K. Boughton: Consultant; Current; CamDiab Ltd. Research Support; Current; Abbott Diabetes, Dexcom, Inc., Ypsomed AG. R. Hovorka: Board Member; Current; CamDiab Ltd. Consultant; Current; Abbott Diabetes. Research Support; Current; Abbott Diabetes, Dexcom, Inc., Ypsomed AG, Novo Nordisk Foundation. Other - Speaker bureau; Ended; Novo Nordisk, Eli Lilly and Company. P. Taylor: None. C.M. Dayan: Consultant; Current; Sanofi, SAB Biotherapeutics, Inc., Immunocore, Ltd. Consultant; Ended; Vertex Pharmaceuticals Incorporated. Consultant; Current; Quell. Advisory Panel; Current; Amarna, ArgenX, Amgen Inc. J.A. Hedrick: None. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG.

Introduction and Objective: Several disease-modifying immunotherapies in new onset type 1 diabetes (T1D) have demonstrated preservation of C-peptide, but associated effects on glycemic control have been variable across studies. Using continuous glucose monitoring (CGM), we examined how preserved C-peptide influences different aspects of glycemia. Methods: We pooled participant level data from six disease modifying intervention trials in new onset T1D (n=495). C-peptide levels were grouped into four ordered categories (<0.2, ≥0.2-0.5, ≥0.5-0.8, and ≥0.8). Associations between C-peptide and CGM outcomes were assessed using linear mixed-effects models with fixed effects for C-peptide level and study and a random effect for participant. Significance was evaluated using likelihood ratio tests and tests for linear trend. Results: From the lowest to highest C-peptide groups, there was a significant increase in time in range (3.9-10.0 mmol/L: from 58.5% to 80.5%; p<0.001) and time in tight range (3.9-7.8 mmol/L: from 40.1% to 62.4%; p<0.001), while HbA1c decreased, but only modestly (7.4% to 6.9%; p<0.001). Additionally, across increasing C-peptide levels there were decreases in coefficient of variation (39% to 32%), time spent at 10.0-13.9 mmol/L (21% to 11 %), and >13.9 mmol/L (14.8% to 2.7%); p<0.001 for all. Hypoglycemia exposure was low across C-peptide groups, with time spent between 3.0 and 3.9 mmol/L ranging from 3.7-4.1% and time <3.0 mmol/L from 1.2-2.0% and showed no consistent association with C-peptide level. Conclusion: Preserved beta-cell function in new-onset T1D is associated with clear differences in CGM metrics, including higher time in range, lower glycemic variability, and reduced hyperglycemia, but only modestly lower HbA1c and no difference in hypoglycemia. These findings also show that CGM captures glycemic differences that are not apparent using HbA1c alone, supporting its complementary role in evaluating metabolic outcomes in disease modifying immunotherapy trials. Disclosure A. Lam: Advisory Panel; Ended; Vertex Pharmaceuticals Incorporated. T. Bakhtiyarli: None. A.L. Carr: None. C.K. Boughton: Consultant; Current; CamDiab Ltd. Research Support; Current; Abbott Diabetes, Dexcom, Inc., Ypsomed AG. U. Hannelius: Employee; Current; Diamyd Medical. R. Hovorka: Board Member; Current; CamDiab Ltd. Consultant; Current; Abbott Diabetes. Research Support; Current; Abbott Diabetes, Dexcom, Inc., Ypsomed AG, Novo Nordisk Foundation. Other - Speaker bureau; Ended; Novo Nordisk, Eli Lilly and Company. A.L. Lindqvist: Employee; Current; Diamyd Medical AB. J. Ludvigsson: Research Support; Current; Diamyd Medical. Consultant; Current; Diamyd Medical. P. Taylor: None. C.M. Dayan: Consultant; Current; Sanofi, SAB Biotherapeutics, Inc., Immunocore, Ltd. Consultant; Ended; Vertex Pharmaceuticals Incorporated. Consultant; Current; Quell. Advisory Panel; Current; Amarna, ArgenX, Amgen Inc. J.A. Hedrick: None. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG.

Abatacept, a cytotoxic T lymphocyte–associated protein 4 immunoglobulin that inhibits T-cell costimulation, was evaluated for 12 months in stage 1 type 1 diabetes (T1D) to delay disease progression. Despite modest preservation of area under the curve C-peptide at 12 months, the primary end point was not met. We adopted the oral minimal model (OMM) to assess β-cell function over 48 months and explored how baseline insulin secretion (ϕtotal) modified treatment response. Using the OMM, ϕtotal was computed from oral glucose tolerance tests conducted at baseline and every 6 months. Participants were stratified into high- and low-secretor groups depending on baseline ϕtotal ≥33rd or <33rd centile, respectively. A sensitivity analysis was performed to validate threshold choice. Among 203 participants (abatacept n = 96; 107 placebo n = 107), 39% receiving abatacept and 47% receiving placebo experienced progression to stage 2 or 3 within 96 months. High secretors receiving abatacept gained 15.8 progression-free months (95% CI 4.85, 26.68; P = 0.005) and had a 54% lower hazard of progression versus those receiving placebo (hazard ratio [HR] 0.46; 95% CI 0.25, 0.84; P = 0.012). Treatment effect differed significantly by secretor status (interaction HR 2.92; 95% CI 1.23, 6.96; P = 0.015). A subgroup of responders to 12 months of abatacept was identified by ϕtotal, providing the first evidence that an immune intervention in stage 1 T1D may delay disease progression. ARTICLE HIGHLIGHTS:We sought to investigate whether baseline insulin secretion (ϕtotal), quantified using the oral minimal model assessing β-cell function, could identify a subgroup of responders to abatacept (a cytotoxic T lymphocyte-associated protein 4 immunoglobulin that inhibits T-cell costimulation) among those with stage 1 type 1 diabetes (T1D). Abatacept preserved ϕtotal during and up to 1 year after treatment cessation; high baseline secretors treated with abatacept gained ∼16 months of progression-free survival and had a 54% lower hazard of progression versus those receiving placebo, whereas no benefit was observed in low secretors. This is the first evidence of an immune intervention delaying disease progression in those with stage 1 T1D. Continued treatment may result in a greater delay in progression.

Introduction and Objective: Despite substantial metabolic benefit, islet transplantation (ITx) shows variable graft durability, with ~30% of recipients not sustaining function over time. We used mixed effects regression within a causal directed acyclic graph (DAG) framework to describe baseline determinants of 1 year graft function. Methods: We evaluated data from 415 ITx recipients from the Collaborative Islet Transplant Registry. A DAG represented relationships between baseline variables, initial ITx decisions and 1 year graft function. A total of 237 baseline variables were grouped into categories: immunosuppressant regimen (IR), era, immune status (IS), center, metabolic status (MS) and donor characteristics (DON). Mixed-effects models estimated each baseline association with 1 year graft function, defined as C-peptide normalized to fasting glucose, adjusted for cumulative islet equivalents (IEQs). Variables were ranked by effect size and summarized per category among those p< 0.05. Results: Categories most strongly associated with 1 year graft function were ERA (mean rank=2, range 2-2]), CENTER (13.5, 6-21), IR (14.8, 1-28), IS (21.7, 3-46), DON (45.5, 8-95), and MET (56.6, 7-103). IEQs rank was low (216). The DAG (Fig) specifies baseline effects on 1 year graft function. Conclusion: This DAG-based framework provides a foundation for future machine learning analysis, identifying key baseline determinants of ITx outcome, including era, centre, IR and IS. Disclosure A.L. Carr: None. N. Mehta: None. L. Wilson: Research Support; Current; Eli Lilly and Company, Rezolute Bio, Dexcom, Inc. S. Forbes: None. R. Dodier: None. C. Mosquera-Lopez: Employee; Current; Insulet Corporation. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. P.G. Jacobs: Research Support; Current; Dexcom, Inc., Eli Lilly and Company. Advisory Panel; Current; Sequel Medtech. Consultant; Current; Roche Diabetes Care. Research Support; Current; SFC Fluidics. Consultant; Current; 4YouAndMe. Funding Breakthrough T1D 3-SRA-2025-1715-S-B

AIMS:This study explores the experiences of diabetes distress among young adults, aged 18-29 years, living with type 1 diabetes (T1D), focusing on how these experiences are shaped by healthcare encounters and self-management practices. METHODS:Using an interpretive descriptive design, 19 participants were interviewed as part of a co-design trial aimed at developing a mental health intervention for young adults with T1D. RESULTS:Two main themes were identified: 1) the perceived overemphasis on glycemic metrics by healthcare professionals, which often overshadowed the broader emotional and social dimensions of living with T1D, and 2) the conceptualization of distress as an "everyday" reality rather than an acute or episodic phenomenon. Participants reported feeling reduced to "a set of data points" during clinical encounters, contributing to feelings of inadequacy and exacerbating mental health challenges and worsening diabetes self-management. CONCLUSIONS:The findings highlight the need for healthcare professionals to adopt a more holistic, strengths-based approach to care, which recognizes the complex interplay between physical and mental health and supports the overall wellbeing of young adults with T1D. The study calls for a re-evaluation of current care practices, emphasizing the importance of integrating emotional support into routine diabetes care to enhance quality of life.

Introduction and Objective: Severe hypoglycemic events (SHEs) and impaired awareness of hypoglycemia (IAH) remain major challenges for some people with type 1 diabetes (T1D), despite using continuous glucose monitoring (CGM) and insulin pumps. This study describes health status and productivity outcomes among adults with T1D using CGM and insulin pumps with recurrent SHEs and IAH. Methods: This ongoing 12-month prospective online survey enrolled adults with T1D using CGM and insulin pumps who reported recurrent SHEs (≥2 in the past year) and IAH (Clarke score ≥4). Participants were recruited through patient advocacy groups from Canada, Germany, France, Italy, UK and US. Participants reported diabetes-related complications and completed the EuroQoL Visual Analogue Scale (EQ-VAS), Diabetes Productivity Measure (DPM), and Work Productivity and Activity Impairment (WPAI) questionnaires. Baseline results are compared against US T1D and general population norms for contextualization. Results: Participants (N=137) had a mean age of 49.6 years (range: 20-75), 71.5% were female, 65.0% were from US, 59.1% worked for pay, and mean T1D duration was 34 years (range: 5-72). Health status (EQ-VAS score: 68.5, SD:19.8) was 15% lower compared to US general population norm (80.4). Diabetes-specific work and life productivity (DPM scores: 66.9 and 52.5) were 20% and 23% lower compared to US adults with diabetes (83.3 and 68.5), respectively. Generic work productivity showed 2.2 times greater work productivity loss compared to US general population norm (WPAI scores: 37% vs 17%). Conclusion: Despite using CGM and insulin pumps, adults with T1D and recurrent SHEs and IAH reported substantial burden, including sub-optimal health and productivity, highlighting continuing unmet needs. Disclosure A. Boateng-Kuffour: Employee; Current; Vertex Pharmaceuticals Incorporated. Q. Zhang: Employee; Current; Veloxis Pharmaceuticals, Inc. A. Albanese-O'Neill: Consultant; Current; Sanofi. Advisory Panel; Current; Roche Pharmaceuticals, Vertex Pharmaceuticals Incorporated. Research Support; Current; Abbott Diabetes. A. Bubeck: None. L. Green: Other - Sponsorship to my organization; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated, Sanofi. B. Hauck: None. S. Heller: Consultant; Current; Novo Nordisk. Other - DSMC chair and member; Current; Eli Lilly and Company. Advisory Panel; Current; Zucara Therapeutics, Vertex Pharmaceuticals Incorporated. W. Polonsky: Consultant; Current; Vertex Pharmaceuticals Incorporated, Dexcom, Inc., Abbott Diabetes. Research Support; Current; Abbott Diabetes, Dexcom, Inc. Consultant; Current; Lilly Diabetes, MannKind Corporation. Research Support; Current; Lilly Diabetes. Consultant; Current; Sanofi, Insulet Corporation. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. J. Speight: Advisory Panel; Current; Vertex Pharmaceuticals Incorporated. Other - AU$10k Sponsorship for PSAD 2026 conference, Geelong, Australia; Current; Sanofi. S. Tutton: Advisory Panel; Ended; Vertex Pharmaceuticals Incorporated. Other - Patient Advisory Group Participation in the T1D Multi-National PRO study; Current; Vertex Pharmaceuticals Incorporated. R. Ziegler: Advisory Panel; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Sanofi. Speaker's Bureau; Current; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Current; Roche Diabetes Care. N. Ainsworth: Consultant; Current; Vertex Pharmaceuticals Incorporated. C. Abbott: Employee; Current; Vertex Pharmaceuticals. A. Martin: Consultant; Current; Vertex Pharmaceuticals Incorporated. N. Li: Employee; Current; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. B.L. Barber: None.

Introduction and Objective: Quantifying β-cell function in preclinical T1D is essential for understanding progression and intervention design. The Oral Minimal Model (OMM) applied to OGTTs provides a mechanistic estimate of β-cell responsiveness (ɸtotal). We derive stage-specific ɸtotal trajectories, compared to AUC C-peptide, aligned to 4 years before Stage 1 (S1) and Stage 2 (S2) transition, to better characterise β-cell decline. Methods: ɸtotal and AUC C-peptide were derived from 2597 OGTTs in 867 TrialNet Pathway to Prevention/TEDDY participants with a transition event. Generalized Additive Mixed Models adjusted for sex, age, BMI, and participant level random effects modelled trajectories. 2 year progression probability was evaluated using all S1 observations (7152 OGTTs; N=2583). Results: ɸtotal was higher in S1 than S2 (-32.2%, p < 0.001), with clearer stage contrast than AUC C-peptide (-2.9% p=0.03). Over the last 4 years of S1, ɸtotal had steady exponential decline (~4.8%/yr, p<0.001), undetectable until the final year with AUC C-peptide (Fig 1). In S2, decline was more variable with both measures until the final year of accelerated deterioration. In S1, ɸtotal ≥ 3.8 had 89% negative predictive value for non-progression within 2 years. Conclusion: ɸtotal captures early functional deterioration in S1 T1D compared to AUC C-peptide and provides robust rule-out information for near-term progression, supporting greater sensitivity and statistical power for monitoring and trial design in early-stage T1D. Disclosure A. Carr: None. S. Perazzolo: None. J.A. Hedrick: None. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. H.M. Ismail: None. T. Moran: Other - Data Safety Monitoring Board Member; Ended; Novo Nordisk. Advisory Panel; Ended; Abbott Diabetes. Research Support; Current; Abbott Diabetes. C.M. Dayan: Consultant; Current; Sanofi, SAB Biotherapeutics, Inc., Immunocore, Ltd. Consultant; Ended; Vertex Pharmaceuticals Incorporated. Consultant; Current; Quell. Advisory Panel; Current; Amarna, ArgenX, Amgen Inc. A. Galderisi: Advisory Panel; Current; Sanofi. Advisory Panel; Ended; Novo Nordisk. Advisory Panel; Current; vTv Therapeutics. Funding Breakthrough T1D (3-SRA-2022-1186-S-B, 3-SRA-2023-1422-S-B, 3-SRA-2023-1422-S-B). The Type 1 Diabetes TrialNet Study Group is a clinical trials network currently funded by the National Institutes of Health (NIH) through the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), the National Institute of Allergy and Infectious Diseases (NIAID), and the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), through the cooperative agreements U01 DK060782, U01 DK060916, U01 DK060987, U01 DK061010, U01 DK061016, U01 DK061029, U01 DK061030, U01 DK061034, U01 DK061035, U01 DK061036, U01 DK061037, U01 DK061040, U01 DK061041, U01 DK061042, U01 DK061055, U01 DK061058, U01 DK084565, U01 DK085453, U01 DK085461, U01 DK085463, U01 DK085465, UC4 DK085466, U01 DK085476, U01 DK085499, U01 DK085504, U01 DK085505, U01 DK085509, U01 DK097835, U01 DK103153, U01 DK103180, U01 DK103266, U01 DK103282, U01 DK106984, U01 DK106993, U01 DK106994, U01 DK107013, U01 DK107014, and a contract HHSN267200800019C; the National Center for Research Resources, through Clinical Translational Science Awards UL1 RR024131, UL1 RR024139, UL1 RR024153, UL1 RR024975, UL1 RR024982, UL1 RR025744, UL1 RR025761, UL1 RR025780, UL1 RR029890, UL1 RR031986, UL1 TR001872, and General Clinical Research Center Award M01 RR00400.

Introduction and Objective: The health and psychosocial impacts of recurrent severe hypoglycemic events (SHEs) and impaired awareness of hypoglycemia (IAH) in adults with type 1 diabetes (T1D) who use continuous glucose monitors (CGM) and insulin pumps remain poorly understood. This study describes the health and psychosocial burden of adults with T1D using CGM and insulin pumps with recurrent SHEs and IAH. Methods: This ongoing 12-month prospective online survey enrolled adults with T1D using CGM and insulin pumps with recurrent SHEs (≥2 SHEs in the past year) and IAH (Clarke score ≥4). Participants were recruited through patient advocacy groups from Canada, Germany, France, Italy, UK, and US. Participants reported diabetes-related complications and completed the Hypoglycemia Fear Survey-II (HFS-II) and the 17-item Diabetes Distress Scale (DDS-17). Baseline results are presented and compared against US T1D and general population norms for contextualization. Results: Participants (N=137) had a mean age of 49.6 years (range: 20-75), 71.5% were female, 65.0% were from the US, and mean T1D duration was 34 years (range: 5-72). Participants reported a mean of 5.7 SHEs (SD: 8.0) in the past year. The most frequently reported diabetes-related complications included mental health problems (79.6%), vision problems (58.4%), heart and circulation problems (50.4%), and nerve complications (46.7%). Participants reported high psychosocial burden: fear of hypoglycemia score (mean HFS-II total score 58.0, SD: 24.9) was 32% higher compared to the US T1D population norm (44.1). Diabetes distress was substantial (mean DDS-17 total score: 2.67, SD: 1.10), with 64.2% indicating moderate-to-high diabetes distress (DDS-17 score≥2), which warrants clinical support. Conclusion: Despite using CGM and insulin pumps, adults living with T1D and recurrent SHEs and IAH reported substantial health and psychosocial burden, highlighting continuing unmet needs. Disclosure A. Boateng-Kuffour: Employee; Current; Vertex Pharmaceuticals Incorporated. Q. Zhang: Employee; Current; Veloxis Pharmaceuticals, Inc. A. Albanese-O'Neill: Consultant; Current; Sanofi. Advisory Panel; Current; Roche Pharmaceuticals, Vertex Pharmaceuticals Incorporated. Research Support; Current; Abbott Diabetes. A. Bubeck: None. L. Green: Other - Sponsorship to my organization; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated, Sanofi. B. Hauck: None. S. Heller: Consultant; Current; Novo Nordisk. Other - DSMC chair and member; Current; Eli Lilly and Company. Advisory Panel; Current; Zucara Therapeutics, Vertex Pharmaceuticals Incorporated. W. Polonsky: Consultant; Current; Vertex Pharmaceuticals Incorporated, Dexcom, Inc., Abbott Diabetes. Research Support; Current; Abbott Diabetes, Dexcom, Inc. Consultant; Current; Lilly Diabetes, MannKind Corporation. Research Support; Current; Lilly Diabetes. Consultant; Current; Sanofi, Insulet Corporation. P. Senior: Consultant; Ended; Abbott. Consultant; Current; Dexcom, Inc. Consultant; Ended; GlaxoSmithKline plc. Research Support; Current; Eli Lilly and Company. Consultant; Current; Novo Nordisk, Sana Biotechnology Inc., Sanofi, Vertex Pharmaceuticals Incorporated. Consultant; Ended; Ypsomed AG. J. Speight: Advisory Panel; Current; Vertex Pharmaceuticals Incorporated. Other - AU$10k Sponsorship for PSAD 2026 conference, Geelong, Australia; Current; Sanofi. S. Tutton: Advisory Panel; Ended; Vertex Pharmaceuticals Incorporated. Other - Patient Advisory Group Participation in the T1D Multi-National PRO study; Current; Vertex Pharmaceuticals Incorporated. R. Ziegler: Advisory Panel; Current; Abbott Diabetes, Vertex Pharmaceuticals Incorporated. Speaker's Bureau; Current; Novo Nordisk. Advisory Panel; Current; Sanofi. Speaker's Bureau; Current; Sanofi-Aventis Deutschland GmbH. Advisory Panel; Current; Roche Diabetes Care. N. Ainsworth: Consultant; Current; Vertex Pharmaceuticals Incorporated. C. Abbott: Employee; Current; Vertex Pharmaceuticals. A. Martin: Consultant; Current; Vertex Pharmaceuticals Incorporated. N. Li: Employee; Current; Vertex Pharmaceuticals Incorporated. Stock/Shareholder; Current; Vertex Pharmaceuticals Incorporated. B.L. Barber: None.

Language profoundly shapes how diabetes is perceived, experienced and managed, with the potential to perpetuate stigma or promote dignity and respect. This expert review, conducted by an international, multidisciplinary team, traces the evolution of the global diabetes #LanguageMatters movement and synthesises evidence on the effects of language on diabetes management, health and wellbeing, alongside community-preferred terminology. We identified 32 language position statements/guidance documents published in more than 19 countries. Most are applicable to all diabetes types, diverse audiences and address verbal communication; many also consider non-verbal, paraverbal and, to a lesser extent, visual communication. Beyond recommendations of terms to use or avoid, these statements articulate overarching principles grounded in person-centred, strengths-based, empathic and non-judgemental communication. Evidence of uptake is emerging, including incorporation into clinical standards and research presentation guidance, alongside gradual shifts in language use within some research and media contexts. However, implementation remains uneven, and stigmatising language persists across healthcare, research, policy and public discourse. Despite growing momentum, empirical evidence on community preferences and robust evaluation of adoption and impact remain limited. Language practices are also evolving alongside new technologies, screening approaches and therapeutics, creating additional challenges and opportunities. We identify key gaps in evidence, guidance and implementation mechanisms, and highlight persistent and emerging forms of hidden stigma within systems and structures. We propose a constructive agenda centred on community partnership and system-level implementation. Treating language as foundational to person-centred, equitable and compassionate diabetes care is essential to ending diabetes stigma and discrimination across all settings.

Aim:Type 1 diabetes (T1D) is a complex, chronic condition that requires active and intensive daily self-management, often necessitating specialized and integrated care. Individuals with T1D are at a heightened risk of experiencing diabetes distress (DD) and other mental health challenges, which, when unaddressed, can impair diabetes self-management and diminish quality of life. These challenges are particularly pronounced for young adults with T1D, who must navigate the typical developmental transitions of early adulthood while managing changes in their diabetes care, self-management, and support systems. However, physical and mental healthcare remain fragmented. While previous studies have explored interventions to address DD, many have faced limitations in scalability. This study aims to evaluate the feasibility and acceptability of the co-designed technology-enabled collaborative care model (TECC-T1D3) tailored to young adults with T1D and DD. Methods:A randomized controlled trial in young adults aged 18-29 years living with T1D in Ontario, Canada (n = 60), to assess the feasibility and acceptability of the co-designed TECC-T1D3 intervention. Secondary objectives include evaluating the preliminary effectiveness of the program in reducing DD, enhancing self-efficacy, improving quality of life, and exploring the impact of the intervention on connectedness to care and community. Results:This paper presents the trial protocol of the TECC-T1D3 study. Recruitment began in December 2024, and the trial was registered on clinicaltrials.gov (NCT06804694). Conclusion:The TECC-T1D3 study will determine whether a TECC model is feasible and acceptable for young adults with T1D and DD.

CLINICAL IMPACT RATINGS:GIM/FP/GP: [Formula: see text] Endocrinology: [Formula: see text].

Islet transplantation (ITx) is advancing rapidly, with clinical trials of stem cell derived islets demonstrating short-term insulin independence. However, long-term insulin independence may still require multiple infusions. We examined the effects of sequential ITx on portal venous pressure and factors influencing acute pressure changes across 693 intraportal ITx procedures in 298 adults (44% M); who received up to 5 procedures, at the University of Alberta Hospital over 24 years. We assessed acute portal pressure changes per infusion, using linear mixed-effects models to compare sequential pre-infusion pressures to baseline and assess relationships between pressure changes and packed cell volume (PCV), purity, islet dose (IE/kg) and estimated total liver volume (eTLV). Portal pressure transiently increased, similarly, after each infusion by an overall median 2.0 mmHg (IQR 1.0,4.0). PCV exhibited the strongest relationship with change in pressure, with1mmHg increase per 1 mL of PCV, when adjusted for other parameters (Coefficient = 1.0 [95%CI 0.81,1.21];p < 0.0001). Conversely, higher purity and larger eTLV were associated with smaller increases in pressure. A significant interaction term indicated that the effect that PCV has on pressure change may be moderated at higher purities. Our work provides insights from deceased-donor intraportal ITx that can inform the design of future clinical protocols for ITx.

INTRODUCTION:User experience design aims to create products and services that are accessible, usable, and enjoyable. The Reshape T1D study aims to apply these principles to understand how individuals living with T1D interact with and experience healthcare to inform T1D clinical quality improvement. METHODS:Using a community-based participatory research design, we involved four patients and four clinicians as co-researchers throughout the research. A questionnaire and virtual semi-structured interview were applied across a purposeful sample of 41 adults living with T1D across Alberta, Canada, between September 2021 and May 2022. Audio recordings were transcribed verbatim and de-identified before coding. Thematic analysis was conducted on coded participant discourse through multiple coders. RESULTS:Participants indicated the need for a centralized hub that provides consistent, reliable, and up-to-date T1D education and resources and an emphasis on access to mental health resources within T1D care settings. Providing greater flexibility for appointment types (ie. in-person, virtual, etc.) and after-hours access contributed to better self-management and prevented emergency room visits. Participants desired a choice as to who comprises their T1D care team and for teams to address patient needs specific to their reality. We identified that medical trauma had long-term impacts on perceptions of healthcare and contributed to a reluctance to seek future care. Women expressed challenges in discussing reproductive health with their clinicians. Diabetes online communities provide an adjunct to clinical care through peer support. Cost and access to the latest technology are ongoing barriers for many participants, especially concerning publicly funded programmes that use advanced insulin pump therapy, continuous glucose monitoring, and automated insulin delivery systems. A quality improvement framework emerged through data analysis, and findings were synthesized into actionable recommendations for ongoing clinical quality improvement. CONCLUSION:Our findings highlight how important health system user suggestions are for more equitable, accessible, and empathetic healthcare for individuals living with T1D. Further work is needed to explore health system user experiences with clinicians and healthcare administrators to effectively carry out T1D clinical quality improvement.

Abatacept, a CTLA-4 immunoglobulin that inhibits T cell costimulation, was evaluated for 12 months in Stage 1 type 1 diabetes to delay disease progression. Despite modest preservation of AUC C-peptide at 12 months, the primary endpoint was not met. Herein, we adopt the oral minimal model (OMM) to assess beta cell function over 48 months and explore how baseline insulin secretion (Phitot) modifies treatment response. Phitot was computed using the OMM from the oral glucose tolerance test at baseline and every 6 months. Participants were stratified into high- or low-secretors depending on baseline Phitot 33rd or <33rd centile, respectively. A sensitivity analysis was performed to validate threshold choice. Among 203 participants (96 abatacept and 107 placebo), 39% on abatacept and 47% on placebo progressed to Stage 2 or 3 within 96 months. High-secretors on abatacept gained 15.8 progression-free months ([95%CI 4.85, 26.68] p=0.005) and had 54% lower hazard of progression vs placebo (HR 0.46 [95%CI 0.25, 0.84] p=0.012). Treatment effect differed significantly by secretor status (interaction HR 2.92[95%CI 1.23, 6.96] p=0.015). Phitot identifies a responder subgroup to 12-months of abatacept, with delayed disease progression, providing the first evidence that an immune intervention in Stage 1 may delay disease progression.