Objective: To evaluate whether the efficacy and safety of finerenone varied by baseline hemoglobin A1c (HbA1c) levels, a proxy of glycemic control, and diabetes duration in people with type 1 diabetes and chronic kidney disease (CKD). Research Design and Methods: Adults with type 1 diabetes, urinary albumin-to-creatinine ratio (UACR) 200−<5000 mg/g and estimated glomerular filtration rate (eGFR) 25−<90 mL/min/1.73 m2 were randomized (1:1) to finerenone or placebo. UACR change from baseline over 6 months by baseline HbA1c and diabetes duration was analyzed. Results: Baseline HbA1c was available for 240/242 participants; mean (SD) HbA1c, diabetes duration, and eGFR were 7.6% (1.1; 60 [12] mmol/mol), 32.0 (14.2) years, and 58.9 (19.2) mL/min/1.73 m2, respectively. At 6 months, HbA1c (95% CI) remained unchanged (finerenone: +0.03% [–0.14, 0.20]; placebo: 0.00% [–0.12, 0.11]; between-group difference +0.04% [–0.17, 0.24]; P=0.74). Over 6 months, median UACR decreased from 574.6 to 373.5 mg/g with finerenone and from 506.4 to 475.6 mg/g with placebo, corresponding to a –25% placebo-corrected change (95% CI –35, –13; P=0.0001). Treatment effects were consistent across HbA1c tertiles (<7.1%, ≥7.1%−≤8.1%, and >8.1%), with placebo-corrected UACR changes (95% CI) of –17% (–40, 13), –18% (–39, 10), and –37% (–55, –13), respectively (P interaction=0.41). Effects were similarly consistent across diabetes duration tertiles (P interaction=0.70). Overall safety and incidence of hyperkalemia were similar across HbA1c tertiles. Conclusions: In adults with type 1 diabetes and CKD, finerenone reduced UACR and was well-tolerated irrespective of HbA1c levels or diabetes duration.

OBJECTIVE:To examine the associations between continuous glucose monitoring (CGM) metrics, including glucose management indicator (GMI) and overnight glucose levels, and pregnancy outcomes in women with type 1 diabetes. RESEARCH DESIGN AND METHODS:Secondary exploratory analysis of the CRISTAL trial including 95 pregnant women with type 1 diabetes using CGM. Associations were assessed using logistic regression and Spearman correlations, presented as odds ratios (95% confidence intervals [CIs]) adjusted for baseline HbA1c. GMI validity was assessed using scatter and Bland-Altman plots. RESULTS:Each 5% increase in overall pregnancy-specific time-in-range (TIRp) decreased the odds of gestational hypertension (odds ratio [OR] 0.63, 95% CI 0.41-0.97), birthweight >4.5 kg (OR 0.56, 95% CI 0.32-0.96), and neonatal hypoglycemia requiring hospital care (OR 0.09, 95% CI 0.01-0.57). Each 5% increase in overnight TIRp decreased the odds of gestational hypertension (OR 0.71, 95% CI 0.52-0.98) and neonatal hypoglycemia requiring hospital care (OR 0.15, 95% CI 0.03-0.79). Each 5% increase in overall time-above-range (TARp) increased the odds of birthweight >4.5 kg (OR 1.76, 95% CI 1.05-2.96), respiratory distress (OR 1.55, 95% CI 1.02-2.37), and neonatal hypoglycemia requiring hospital care (OR 5.10, 95% CI 1.14-22.78). Each 5% increase in TARp overnight increased the odds of hospital care for neonatal hypoglycemia (OR 2.55, 95% CI 1.15-5.66). Each 0.28 mmol/L increase in mean glucose and 0.5% increase in GMI were associated with increased respiratory distress (OR 1.54, 95% CI 1.07-2.23 and OR 6.15, 95% CI 1.33-28.40). Every 0.28 mmol/L increase in glycemic variability (SD) was associated with gestational hypertension (OR 1.69, 95% CI 1.02-2.80) and birthweight >4.5 kg (OR 2.31, 95% CI 1.20-4.43). Several combinations of CGM metrics (TIRp[-night], TARp[-night], SD, mean glucose) improved discriminative performance for pregnancy outcomes. GMI and HbA1c values were discordant. CONCLUSIONS:Specific combinations of CGM metrics, including overnight TIRp/TARp, may be informative for predicting pregnancy outcomes. GMI and HbA1c should not be considered interchangeable for glycemic control during pregnancy.

Background: Historically, type 1 diabetes (T1D) has been diagnosed following symptoms of overt hyperglycemia. However, the autoimmune processes driving the progression of the disease start years prior to the appearance of symptomatic disease. Early stages of T1D can be detected by screening individuals, including young children, for islet autoantibodies. Summary: The goal of this review is to discuss the benefits of early detection for individuals with presymptomatic T1D as well as discuss barriers that currently prevent a more widespread implementation of screening programs. Early detection of T1D can reduce the occurrence and severity of complications associated with clinical onset of T1D, including life-threatening diabetic ketoacidosis. It also facilitates the use of approved novel therapeutics that can delay the progression to clinical T1D and allows individuals to participate in clinical trials for other disease-modifying therapies in development. Despite these benefits, there are knowledge gaps that should be addressed before screening can be implemented optimally in practice. Key Messages: Diagnosis of presymptomatic stages of T1D offers several benefits to individuals and their caregivers. Given the multifaceted benefits screening can provide, this review offers expert perspective on the importance of adopting early-detection strategies to identify presymptomatic stages of T1D as part of clinical care.

AIMS:ONWARDS 10 assessed switching from daily basal insulins to once-weekly insulin icodec without a one-time additional dose at first injection. MATERIALS AND METHODS:In this treat-to-target, open-label, 26-week, phase 3b trial, adults with basal-insulin-treated type 2 diabetes (T2D) with glycated haemoglobin [HbA1c] 7.0%-10.0% were randomised to once-weekly icodec without an initial one-time additional dose or to once-daily insulin glargine U100. Primary endpoint was change in HbA1c from baseline to week 26 (non-inferiority margin: 0.3%-points); secondary endpoints included change in time in range (TIR; 70-180 mg/dL [3.9-10.0 mmol/L]) from baseline (weeks -4 to 0) to weeks 22-26, and number of combined clinically significant or severe hypoglycaemic episodes (weeks 0-31). RESULTS:Overall, 412 participants were randomised to icodec (n = 206) or glargine U100 (n = 206). At week 26, estimated mean HbA1c was 7.2% with icodec (baseline 8.1%) and 7.5% with glargine U100 (baseline 8.0%). Estimated treatment difference (ETD) for change in HbA1c was -0.2%-points (95% confidence interval [CI]: -0.4, -0.1), confirming non-inferiority of icodec versus glargine U100 (p < 0.0001). Self-measured blood glucose did not increase following icodec initiation. Change in TIR from baseline to weeks 22-26 was statistically significantly higher with icodec than with glargine U100 (estimated mean change: 18.0%-points vs. 12.1%-points; ETD: 5.9%-points [95% CI: 2.6, 9.2], p = 0.0005). Combined clinically significant or severe hypoglycaemia rate was numerically lower with icodec than with glargine U100 (0.45 vs. 0.59 episodes per patient-year of exposure). CONCLUSIONS:Omitting the one-time additional dose simplifies switching to icodec in adults with basal-insulin-treated T2D without compromising initial glycaemic control. TRIAL REGISTRATION:ClinicalTrials.gov identifier: NCT06340854.

Introduction and Objective: Type 1 diabetes in adults is frequently misclassified as type 2, delaying appropriate insulin treatment and leading to worse outcomes. We developed a probability-based tool that combines pre-laboratory clinical characteristics and laboratory results to estimate the likelihood of type 1 vs. type 2 diabetes among adults with new-onset diabetes across four geographic regions. Methods: We convened an expert panel to design a web-based tool using demographic, anthropometric, and laboratory data. We used the published University of Exeter type 1/type 2 diabetes clinical features model for Western Europe and estimated analogous region-specific logistic regression models for Northern Europe (Scania ANDIS), Eastern Europe (Ukraine Exomes), and South Asia (Mohan Clinics). Pre-laboratory type 1 diabetes probability was modelled using log(age at onset), log(BMI), male sex, and parental history. Likelihood ratios for islet autoantibodies (glutamic acid decarboxylase autoantibodies, insulinoma-associated protein-2 autoantibodies, zinc transporter 8 autoantibodies, insulin autoantibodies) were derived from a systematic review and regional datasets. Fasting C-peptide measured at or near diagnosis was modelled with gamma distributions for type 1 and type 2 diabetes to provide continuous likelihood ratios. Results: Across 139,518 adults with new-onset diabetes, the proportion with type 1 diabetes ranged from 2.8% in South Asia to 13.2% in Western Europe. We implemented demographic, anthropometric, and laboratory data in a prototype web-based calculator that generates a pre-laboratory probability and subsequently updates it with autoantibody and C-peptide results. Conclusion: This is the first region-adapted calculator for estimating the probability of type 1 vs. type 2 diabetes in adults with new-onset diabetes. With continued validation in new datasets, this tool has the potential to improve diagnostic accuracy in diabetes and enable earlier appropriate treatment for adults with new-onset diabetes. Disclosure L.K. Billings: Advisory Panel; Current; Novo Nordisk, Lilly, Sanofi, Amgen Inc., Bayer AG. S. Misra: Other - Speaker honorarium for a single presentation at a conferences; Ended; A. Menarini Diagnostics, Lilly Diabetes. Advisory Panel; Ended; Insulet Corporation. Other - Speaker honoararium for a single presentation at a conferences; Ended; Sanofi. M.A. Kohn: None. O. Asplund: None. E. Ahlqvist: Research Support; Current; AstraZeneca. Other - Honorarium for lecture; Ended; AstraZeneca. V. Mohan: None. T.K. Oleksyk: None. M.E. Al-Sofiani: Speaker's Bureau; Ended; Medtronic, Dexcom, Inc. Research Support; Current; Dexcom, Inc. Research Support; Ended; Medtronic. Speaker's Bureau; Ended; Insulet Corporation, Abbott Diabetes, Sanofi. J.M. Brix: Advisory Panel; Current; Abbott Diabetes, Boehringer Ingelheim International GmbH. Speaker's Bureau; Current; AstraZeneca. Speaker's Bureau; Ended; Dexcom, Inc. Speaker's Bureau; Current; Bayer AG. Advisory Panel; Current; Eli Lilly and Company, Merck Sharp & Dohme Corp. Speaker's Bureau; Ended; Medtronic. Advisory Panel; Current; Novo Nordisk. L. DiMeglio: Research Support; Ended; Dompé, Lilly. Stock/Shareholder; Ended; Lilly. Research Support; Current; MannKind Corporation. Research Support; Ended; Provention Bio, Inc. Research Support; Current; Sanofi. Research Support; Ended; Zealand Pharma A/S. Consultant; Current; Tandem Diabetes Care, Inc. Other - DSMB member; Current; Merck & Co., Inc., Lilly. K.L. Fantasia: Stock/Shareholder; Current; Eli Lilly and Company. D. Kerr: Stock/Shareholder; Current; Glooko, Inc. Research Support; Current; Abbott Diabetes. R. Ma: Research Support; Current; AstraZeneca. Speaker's Bureau; Ended; AstraZeneca. Research Support; Current; Boehringer Ingelheim International GmbH. Advisory Panel; Ended; Boehringer Ingelheim International GmbH. Research Support; Ended; Roche Diagnostics. Speaker's Bureau; Current; Roche Diagnostics. Speaker's Bureau; Ended; Eli Lilly and Company. Research Support; Ended; Novo Nordisk. Stock/Shareholder; Current; GemVCare Ltd. J.K. Mader: Research Support; Current; A. Menarini Diagnostics. Advisory Panel; Current; Abbott Diabetes. Speaker's Bureau; Current; Abbott Diabetes. Advisory Panel; Current; Becton, Dickinson and Company. Speaker's Bureau; Current; Becton, Dickinson and Company. Advisory Panel; Current; Insulet Corporation, Eli Lilly and Company. Speaker's Bureau; Current; Eli Lilly and Company. Advisory Panel; Current; Sanofi. Speaker's Bureau; Current; Sanofi. Advisory Panel; Current; Novo Nordisk A/S. Speaker's Bureau; Current; Novo Nordisk A/S. Advisory Panel; Current; Roche Diagnostics. Speaker's Bureau; Current; Roche Diagnostics. Advisory Panel; Current; Medtronic, Tandem Diabetes Care, Inc., Omnipod. Stock/Shareholder; Current; decide Clinical Software GmbH. Advisory Panel; Current; Dexcom, Inc. Speaker's Bureau; Current; Dexcom, Inc., Sinocare, Buzud. Advisory Panel; Current; Biomea Fusion, Pharmasens. Stock/Shareholder; Current; elyte Diagnostics. Other - CMO (unpaid); Current; elyte Diagnostics. Speaker's Bureau; Current; A. Menarini Diagnostics. Board Member; Current; OMNIA by AI APS. Advisory Panel; Current; Triple Jump. N. Mathioudakis: None. C. Mathieu: Advisory Panel; Current; Abbott Diagnostics, Dexcom, Inc. Board Member; Current; European Association for the Study of Diabetes. Advisory Panel; Current; Novo Nordisk, Eli Lilly and Company, Sanofi, Vertex Pharmaceuticals Incorporated, Medtronic. C. Mendez: None. Z. Quandt: Advisory Panel; Ended; Sanofi. M.J. Redondo: Advisory Panel; Current; Sanofi. Other - Data Safety Monitoring committee; Current; Lilly. E.D. Schleicher: None. V. Shah: Advisory Panel; Current; Abbott Diabetes, Dexcom, Inc. Advisory Panel; Ended; Medtronic. Advisory Panel; Current; Novo Nordisk, Eli Lilly and Company. Consultant; Current; Insulet Corporation, T1D Exchange. Advisory Panel; Current; Sanofi, Tandem Diabetes Care, Inc. Consultant; Ended; DreaMed Diabetes, Ltd. N. Thomas: Advisory Panel; Current; Sanofi. Other - Travel support; Ended; Sanofi. G. Umpierrez: Research Support; Current; Abbott, Dexcom, Inc., Bayer AG. Advisory Panel; Ended; Sanofi-Aventis U.S., Dexcom, Inc. Other - Education grant; Current; Lilly Diabetes, Abbott Diabetes. Advisory Panel; Current; Glycare, Glucotrack. Research Support; Current; Corcept Therapeutics. W. Wolfsberger: None. M. Shao: None. A.F. Scheideman: None. A.M. Zhou: None. A. Ayers: Consultant; Ended; Liom Health AG. D. Klonoff: Advisory Panel; Current; Afon Technology, Atropos Health, Embecta, Glooko, Inc., Glucotrack, Lifecare, Inc. Advisory Panel; Ended; Novo Nordisk. Advisory Panel; Current; Sanofi, Synchneuro, Thirdwayv Inc.

The ability to reduce the risk of developing diabetic ketoacidosis (DKA) remains a major care gap for people with diabetes, particularly those on intensive insulin therapy. The anticipated availability of continuous ketone monitoring (CKM) has the potential to reduce the risk of developing DKA, one of the most life-threatening acute complications of type 1 and type 2 diabetes. International clinical guidelines have established ketone thresholds for suspected and confirmed diagnoses of DKA, based on use of point-of-care testing, as part of a triad of markers with allied thresholds for hyperglycaemia and acidosis. The increasing occurrence of euglycemic DKA, with glucose concentrations below established diagnostic thresholds, makes the availability and use of CKM technology an important addition to the diabetes management toolkit. CKM data could alert the user when the risk of acute DKA is high on sick days in addition to signalling that individuals might be predicted to be at greater overall risk of future DKA on the basis of the distribution and degree of ketone measures in daily life. If widespread use of CKM devices is to be safe and effective in reducing the occurrence of DKA, it is important to establish clear ketone thresholds which notify CKM users when action on their part is required. In defining these thresholds and actions, it was important to ensure that the CKM user is not exposed to avoidable anxiety or suffers alarm fatigue, thus adding to the burden of living with diabetes. In the absence of substantial evidence that can identify appropriate ketone thresholds for CKM use, a panel of international experts in the management of DKA was convened with the aim of developing a number of objective, practical recommendations on how this novel diabetes technology could improve outcomes for individuals at risk of DKA, the results of which we report in this Personal View. These recommendations have been endorsed by the International Society for Pediatric and Adolescent Diabetes (ISPAD).

Doege-Potter syndrome (DPS) is a rare paraneoplastic disorder characterised by non-islet cell tumour hypoglycaemia (NICTH), resulting from ectopic secretion of insulin-like growth factor 2 (IGF-II) by solitary fibrous tumours (SFTs). We describe the case of an 85-year-old woman, presenting in October 2024, with a chronic subdural haematoma and profound intraoperative hypoglycaemia. Further investigation revealed a large pleural mass; the pathophysiological findings were consistent with DPS, and histopathology confirmed a malignant SFT. Hypoglycaemia resolved after complete tumour resection. The current case highlights the importance of considering NICTH in older patients with unexplained, treatment-resistant hypoglycaemia, especially when comorbidities (like subdural hematoma) mask the clinical picture. A focused narrative review accompanies this report, providing clinicians with practical insights into the spectrum of clinical presentations, diagnostic work-up, therapeutic modalities, and anaesthetic considerations in DPS. Early recognition is crucial to avoid serious complications. Complete surgical removal remains the cornerstone of effective management, while alternative therapies may be needed in inoperable cases.

In type 1 diabetes (T1D), preservation of β-cell function is correlated with improved long-term clinical outcomes, such as better glycemic control, fewer microvascular complications, and lower hypoglycemia risk. However, current interventions thus far are unable to stop the destruction of β-cells after clinical onset of T1D. Disease-modifying therapies must follow a long, complex regulatory path requiring clinical end points for full regulatory approval. To facilitate the development of new therapies, regulatory bodies should reinstate C-peptide, the most reliable and feasible measure of endogenous insulin secretion, as an end point for full, unconditional approval. T1D organizations and networks have accepted C-peptide as a primary efficacy end point for years, as did the U.S. Food and Drug Administration (FDA) from 2008 to 2023, followed by its failure to appear on the Surrogate Endpoint Table by the FDA, for unclear reasons. A C-peptide-based policy would substantially decrease the time for disease-modifying therapies to become available and increase investment in them, improving clinical outcomes and easing burden in those living with T1D.

Among the most impactful therapeutic advances in the management of diabetes over the past two decades has been the development of incretin-based therapies, specifically glucagon-like peptide-1 (GLP-1) receptor agonists (RAs) and in combination with glucose-dependent insulinotropic polypeptide (GIP) RAs. Since the introduction of exenatide in 2005, a growing number of these drugs has transformed the management of type 2 diabetes (T2D). Their pleiotropic effects include weight loss, reduced insulin resistance, improved glucose regulation, and reductions in known risk markers for diabetic kidney disease and cardiovascular disease. To date, these important noninsulin glucose-lowering therapies have only received regulatory approval for use in T2D, obesity, sleep apnea, and metabolic dysfunction-associated steatohepatitis with moderate-advanced fibrosis, supported by randomized controlled trials (RCTs) and real-world data that demonstrate efficacy and safety. Regulatory approval for use of weekly GLP-1 and GLP-1/GIP RAs in type 1 diabetes (T1D) has not yet been achieved, in part because of the limited number of inconsistent, small-scale, RCTs and real-world studies for glycemic impacts of these agents in T1D. Larger RCTs are ongoing or planned in participants with T1D. Potential safety risks include hypoglycemia and hyperglycemia-related ketosis in T1D after initiation of GLP-1/GIP RA drugs. While RCTs are ongoing to further investigate GLP-1 and GLP-1/GIP RA agents as adjunct therapy for people with T1D, access to these drugs is already possible, based on their use to treat overweight and obesity. However, without regulatory approval for the T1D indication, access and opportunities for people with T1D to engage with important education regarding the safety of GLP-1 and GLP-1/GIP RA therapy may be limited. This precludes support from diabetes health care professionals to optimize diabetes management of these agents alongside expected insulin dose changes. The purpose of this consensus report is to review the current literature and provide guidelines for diabetes clinicians and people with T1D to facilitate the safe use of GLP-1/GIP RAs in the management of T1D. This consensus statement has been endorsed by the following professional associations: Advanced Technologies & Treatments for Diabetes (ATTD), International Diabetes Federation-Europe, American Association of Clinical Endocrinologists (AACE), Breakthrough T1D, International Society for Pediatric and Adolescent Diabetes (ISPAD), Association of Diabetes Care and Education Specialists (ADCES).

BACKGROUND:Despite advancements in diabetes management technologies, restrictions on insulin-treated pilots persist, underscoring the need to evaluate the safety, efficacy and performance of these technologies in aviation settings. This systematic review aims to summarize the available evidence on the performance, safety and effectiveness of diabetes technologies in aviation settings. MATERIALS:Four bibliographic databases were searched, and eligible studies assessing diabetes technologies in-flight or simulated aviation conditions, focusing on glycaemic control and safety, were included. Due to high heterogeneity among the included studies, a qualitative synthesis of the evidence was performed. This systematic review was registered with PROSPERO (CRD42025634909). RESULTS:Out of 522 references, six human and in-vitro studies were included for final analysis. Human studies demonstrated the high accuracy of continuous glucose monitors (CGM) and good glycaemic control with insulin pump therapy. Automated insulin delivery (AID) systems demonstrated effective glycaemic control and safety under hypobaric conditions. However, hypoglycaemia during extended fasting was noted. In-vitro studies highlighted risks, such as excess insulin delivery during ascent and reduced delivery during descent, influenced by pressure changes. CGMs exhibited minor signal variability in hypobaric conditions. CONCLUSION:Diabetes technologies, particularly CGMs and AID systems, show promise in aviation environments. However, challenges such as insulin delivery variability, hypoglycaemia during fasting and the limited generalizability of hypobaric studies to real-flight conditions warrant further investigation. Future research should focus on larger, more diverse cohorts, real-world data, standardized protocols and a broader range of devices to further define the safety of their safety for aviation-specific diabetes management.

Introduction and Objective: The nonsteroidal mineralocorticoid receptor antagonist finerenone has been reported to improve UACR in people with T1D and CKD. This prespecified analysis evaluated whether safety and efficacy of finerenone varied by baseline HbA1c levels and diabetes duration. Methods: In total, 242 adults with T1D, CKD (eGFR ≥25 to <90 mL/min/1.73 m2; UACR ≥200 to <5000 mg/g), and on stable ACEi/ARB therapy were randomized 1:1 to receive finerenone (10 or 20 mg per day) or matching placebo. The primary outcome was the relative change in UACR from baseline over 6 months. Results: Baseline HbA1c (mean ± SD: 7.6 ± 1.1%) was available for 240 (99%) FINE-ONE participants. At 6 months, HbA1c was unchanged in both treatment arms (change from baseline [95% CI]: finerenone 0.03% [-0.14, 0.20]; placebo 0% [-0.12, 0.11]; between-group difference 0.04% [-0.17, 0.24]; p=0.74). Participants were stratified by HbA1c tertiles: 1 (HbA1c <7.1%), 2 (HbA1c ≥7.1 to ≤8.1%), and 3 (HbA1c >8.1%). Across the 6-month trial duration, median UACR decreased from 574.6 to 373.5 mg/g with finerenone and from 506.4 to 475.6 mg/g with placebo, corresponding to a 25% (95% CI 35, 13) UACR reduction (p=0.0001). There was no heterogeneity in the treatment effect of finerenone on UACR across HbA1c tertiles 1, 2, and 3 (geometric mean [95% CI]: -17% [-40, 13], -18% [-39, 10], and -37% [-55, -13], respectively; p interaction = 0.41). When analyzed by diabetes duration, the reduction in UACR with finerenone vs placebo was also consistent across tertiles (<25 years, ≥25 to ≤38 years, and >38 years; p interaction = 0.70). Hyperkalemia was the most common adverse event. Safety was comparable across tertiles of HbA1c and diabetes duration. Conclusion: In adults with T1D and CKD, finerenone reduced UACR compared with placebo irrespective of baseline HbA1c levels or diabetes duration, and it was well tolerated. Disclosure P. Rossing: Advisory Panel; Ended; Abbott Diagnostics. Advisory Panel; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, Novo Nordisk A/S, Eli Lilly and Company. Consultant; Current; Lexicon Pharmaceuticals, Inc., Roche Pharmaceuticals. Consultant; Ended; Amgen Inc. H. Heerspink: Consultant; Current; AstraZeneca, Alnylam Pharmaceuticals, Inc., Amgen Inc., Bayer AG, Boehringer Ingelheim International GmbH, Dimerix, Eli Lilly and Company, Novo Nordisk, Novartis AG, Roche Pharmaceuticals. A.J. Amor: Speaker's Bureau; Ended; Lilly. Research Support; Ended; Novo Nordisk. A.L. Birkenfeld: None. L. Caramori: Consultant; Current; Bayer AG. Research Support; Ended; Bayer AG, Eli Lilly and Company. Research Support; Current; Boehringer Ingelheim International GmbH. Consultant; Current; Novo Nordisk. Other - Content reviewer; Current; UpToDate. D. Cherney: Consultant; Current; Boehringer Ingelheim-Lilly, Merck, AstraZeneca, Sanofi, Mitsubishi-Tanabe, Abbvie, Janssen, AMGEN, Bayer, Prometic, BMS, Maze, Gilead, CSL-Behring, Otsuka, Novartis, Youngene, Lexicon, Inversago, GSK,. Research Support; Current; Boehringer Ingelheim-Lilly, Merck, Janssen, Sanofi, AstraZeneca, CSL-Behring, Lexicon, Novo-Nordisk, Bayer. H.M. Colhoun: Research Support; Current; Diabetes UK, IQVIA Inc., Sanofi, JDRF, Chief Scientist Office. Research Support; Ended; Medical Research Council (UKRI). Other - Personal payment for consultancy (ENDED);Research support (ongoing); Current; Sanofi. Other - Advisory board member (ongoing); Support for attendance at meetings /conferences and travel; Current; Novo Nordisk. Other - Advisory panel member (ongoing);Stockholder (up to January 2025- ENDED); Current; Bayer AG. Other - Stockholder (ongoing);Institutional payment for consultancy (ongoing); Current; Roche Pharmaceuticals. P. Henrick Groop: Other - Lecture Fees; Current; Astellas Pharma Inc., AstraZeneca, Bayer AG, Berlin-Chemie AG, Boehringer Ingelheim, Eli Lilly and Company, Elo Water, Medscape, MSD, Mundipharma, Nestlé, Novartis AG, Novo Nordisk, Sanofi. P. Fiorina: Board Member; Ended; A. Menarini Diagnostics, Novo Nordisk, AstraZeneca, Bristol-Myers Squibb Company. L. Ji: None. N. Jongs: Other - Travel Support; Current; AstraZeneca. C. Mathieu: Advisory Panel; Current; Abbott Diagnostics, Dexcom, Inc. Board Member; Current; European Association for the Study of Diabetes. Advisory Panel; Current; Novo Nordisk, Eli Lilly and Company, Sanofi, Vertex Pharmaceuticals Incorporated, Medtronic. U. Pagotto: Advisory Panel; Ended; Eli Lilly and Company. Speaker's Bureau; Ended; Eli Lilly and Company. Advisory Panel; Ended; Novo Nordisk. Speaker's Bureau; Ended; Novo Nordisk. Advisory Panel; Ended; Boehringer Ingelheim International GmbH. Speaker's Bureau; Ended; Rhythm Pharmaceuticals, Inc. Research Support; Current; Novo Nordisk. S. Rosas: Advisory Panel; Current; Bayer AG. Research Support; Ended; Bayer AG. Advisory Panel; Current; Novo Nordisk. Advisory Panel; Ended; Travere. E. Setola: Speaker's Bureau; Ended; Sanofi, Eli Lilly and Company. Advisory Panel; Ended; Novo Nordisk, Boehringer Ingelheim International GmbH. J. Skyler: Advisory Panel; Ended; AbbVie Inc. Consultant; Current; ADOCIA. Board Member; Current; Applied Therapeutics. Advisory Panel; Current; Avotres Inc., Bayer AG. Consultant; Current; Eli Lilly and Company. Advisory Panel; Current; Kriya Therapeutics. Consultant; Current; Novo Nordisk. Board Member; Current; SAB Biotherapeutics, Inc. Consultant; Current; Sanofi, Vertex Pharmaceuticals Incorporated. K. Tuttle: Consultant; Ended; Alnylam Pharmaceuticals, Inc. Consultant; Current; AstraZeneca, Bayer AG, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc., Novo Nordisk, Lilly, ProKidney. Consultant; Ended; Roche Diabetes Care. Research Support; Ended; Travere. R. Lawatscheck: Employee; Current; Bayer AG. M. Brinker: Employee; Current; Bayer AG. Other - pending patent for finerenone for treatment of patients with CKD and T1D; Current; Bayer AG. Stock/Shareholder; Current; Bayer AG. J. jRussell: Employee; Current; Bayer PLC. P. Schloemerk: Employee; Current; Bayer AG. J.B. McGill: Consultant; Current; Bayer AG. Advisory Panel; Current; MannKind Corporation. Advisory Panel; Ended; Novo Nordisk, Abbott Diagnostics. Consultant; Ended; Pfizer Inc. Research Support; Ended; Lexicon Pharmaceuticals, Inc. Research Support; Current; Novo Nordisk A/S, Lilly, Viking Therapeutics, Diamyd, Cour Pharmaceutical. Funding Funding Bayer. FINE-ONE Trial registration number: NCT05901831

Introduction and Objective: There is no validated and reliable survey to assess the psychosocial impact of paediatric screening for T1D on families. We aimed to develop and validate a novel self-administered measure assessing the psychosocial impact on daily functioning, understanding of the results and broader lived experience. Methods: Individual interviews with parents and healthcare professionals were conducted and analysed for the key themes, using a standardised topic guide. An iterative survey development process included multiple versions of the survey, followed by statistical validation against a number of psychosocial measures assessing emotional state, wellbeing and quality of life. Final survey items were refined via cognitive debriefing interviews for acceptability, ease of completion and comprehension. Results: Thirty adults, aged ≥18 years took part in 1:1 interviews. Interview duration was 60-90 minutes (mean 70 minutes). Sixty-six adults completed the statistical validation survey, age range 21-67 years, 71% female, 57% white, 76% married/co-habiting and 90% college/university degree or higher degree educated. Child’s age, where reported (n=31) was 3-30 years. Participants were located across Europe, India, Pakistan, Saudi Arabia, Rwanda, the USA and UK. Exploratory Factor Analyses (EFA) evaluated the factor structure of the initial 19-item measure. Items were removed due to low item-to-total correlations, low commonalities and >50% endorsed strongly agree. The final 12-item measure demonstrated reliability (Cronbach’s α=0.84). The two subscales reflected Positive Impact of screening (6 items, α=0.86, M=24.0±4.9, range=11-30) and Negative Impact of screening (6 items, α=0.85, M=20.7±4.9, range=6-30). Conclusion: This novel questionnaire is a valid, robust and reliable assessment of psychosocial factors associated with screening for T1D. Disclosure K. Barnard-Kelly: Research Support; Current; Abbott Diabetes, Dexcom, Inc. J. Shapiro: Research Support; Current; American Diabetes Association, Leona M. and Harry B. Helmsley Charitable Trust, Eli Lilly and Company. C. Woombs: None. E. Barnard: None. O. Boiko: None. J. Vercauteren: None. C. Mathieu: Advisory Panel; Current; Abbott Diagnostics, Dexcom, Inc. Board Member; Current; European Association for the Study of Diabetes. Advisory Panel; Current; Novo Nordisk, Eli Lilly and Company, Sanofi, Vertex Pharmaceuticals Incorporated, Medtronic. A. Omar Alsaleh: None. C. Nicholls: Employee; Current; Sanofi. A. Mahieu: Employee; Current; Sanofi. S. Greenfield: None. L.M. Quinn: None. R. Dias: Other - Speaker fee; Ended; Sandoz International GmbH. Advisory Panel; Ended; Sanofi. Other - speaker fee; Ended; Sanofi. P. Narendran: Speaker's Bureau; Current; Lilly. Other - Speaker and advisory board; Current; Sanofi. Funding This work is supported by the Innovative Health Initiative Joint Undertaking (IHI JU) under grant agreement No 101132379 (EDENT1FI). The JU receives support from the European Union’s Horizon Europe research and innovation programme, The Leona M. and Harry B. Helmsley Charitable Trust, Breakthrough T1D, EFPIA, COCIR, Vaccines Europe, EuropaBio and MedTech. Additional funding is provided to associated UK partners through the UK Research and Innovation (UKRI) Guarantee Fund.

Obesity and type-2 diabetes, two interconnected and increasingly prevalent metabolic disorders, are associated with poor bone quality, higher fracture risk, and impaired fracture repair. The causes are not yet resolved but appear to relate to the impaired glucose homeostasis, altered bone material properties and remodeling, and compromised skeletal vascularization. Each of these features is impacted by hypoxia-inducible factor (HIF) signaling, which led us to hypothesize that HIF pathway modulation might be an effective strategy to concomitantly improve energy metabolism and bone health in conditions of metabolic stress. Here, we evaluated whether pharmacological HIF activation using the HIF-prolyl-hydroxylase-domain enzyme (PHD) inhibitor FG-4592 (Roxadustat) could protect mice against the adverse skeletal and metabolic consequences of high-fat diet (HFD)-induced obesity. We found that systemic FG-4592 treatment effectively prevented HFD-triggered body weight gain, glucose intolerance, and peripheral fat accumulation, associated with globally increased energy expenditure. Concomitantly, FG-4592 administration prevented the skeletal vascular damage, marrow fat accumulation, and bone formation deficits that were caused by HFD. Moreover, the HIF-activating drug also improved glucose metabolism and bone regeneration in a model of compromised fracture repair associated with overnutrition. Specifically, short-term FG-4592 treatment during fracture recovery reduced the body weight and fat mass of obese mice, improved glucose tolerance, and enhanced the fracture bridging capacity, along with promoting callus vascularization. These findings demonstrate that systemic hypoxia signaling stimulation using PHD inhibitors alleviates both the metabolic and skeletal consequences of diet-induced obesity in mice, highlighting its potential as a dual-action therapeutic strategy for enhancing glucose homeostasis and bone health/regeneration in disorders of obesity and metabolic dysfunction.

Introduction Women with postpartum pre-diabetes following gestational diabetes mellitus (GDM) are at particularly high risk of developing type 2 diabetes mellitus (T2DM). While the implementation of effective lifestyle interventions in the early postpartum period is often difficult and has in general limited efficacy to prevent T2DM after GDM, effective preventive strategies, including medical therapies, are needed in this population. The ‘semaglutide for the treatment of pre-diabetes in women with prior gestational diabetes (SERENA) study’ aims to evaluate the efficacy, safety and cost-effectiveness of semaglutide in preventing progression to T2DM during the early postpartum period.Methods and analysis SERENA is a Belgian multicentre, double-blind randomised controlled trial conducted in 13 hospitals. A total of 252 women with a recent history of GDM and postpartum pre-diabetes will be randomised in a 1:1 ratio to receive once-weekly subcutaneous injections of semaglutide 1 mg or placebo in addition to standardised lifestyle intervention. Randomisation is stratified by body mass index at early postpartum assessment (<25, 25–29.9 and ≥30 kg/m²). Participants will be treated for up to 160 weeks (3 years), with a total follow-up period of up to 184 weeks (3 years and 6 months). Study visits are scheduled every 6 months and include blood sampling, clinical examinations and completion of self-administered questionnaires. The primary outcome is the development of T2DM based on the American Diabetes Association criteria. Secondary outcomes include need for diabetes rescue therapy, regression to normoglycaemia, weight loss, insulin sensitivity, beta-cell function, cardiometabolic risk profile, patient-reported outcomes and cost-effectiveness.Ethics and dissemination The study was approved by the Federal Agency for Medicines and Health Products and the relevant Ethics Committees (2022–502082-22-00) (S66967). Recruitment started in September 2023. Study results will be disseminated through peer-reviewed publications and presentations at scientific conferences. Individual participant data will be made available on reasonable request after study completion, database lock, unblinding and publication of the primary results, subject to applicable ethical, legal and data protection requirements.Trial registration number NCT05569772.

OBJECTIVE:To evaluate the association between fear and perceived frequency of hypoglycemia and continuous glucose monitoring (CGM) metrics in adults with type 1 diabetes using diabetes technology over 12 months. RESEARCH DESIGN AND METHODS:This retrospective explorative analysis evaluated correlations between hypoglycemia fear, perceived hypoglycemia frequency, and CGM metrics in 1,370 adults with type 1 diabetes using real-time CGM (Comparing Continuous With Flash Glucose Monitoring in Adults With Type 1 Diabetes [ALERTT1] study, n = 254) or hybrid closed-loop (The Impact of Hybrid Closed-Loop Insulin Delivery in Type 1 Diabetes on Glycemic Control and PROMs [INRANGE] studies, n = 1,116) for 12 months. Hypoglycemia fear was assessed with the Hypoglycemia Fear Survey II worry (HFS-worry) and behavior (HFS-behavior) subscales and perceived hypoglycemia frequency with the hypoglycemia subscale of the Diabetes Treatment Satisfaction Questionnaire-status (DTSQs-hypo). Data are reported as mean ± SD. RESULTS:At baseline (before the start of technology), mean age was 41.0 ± 13.7 years, 55.9% were women, diabetes duration was 21.6 ± 12.7 years, HbA1c was 7.6 ± 1.0% (59.0 ± 10.8 mmol/mol), and time in 3.9-10.0 mmol/L was 61.1 ± 15.5%. Over 12 months, time <3.9/<3.0 mmol/L decreased from 3.4 ± 3.5%/0.8 ± 1.4% to 2.3 ± 2.2%/0.5 ± 0.7%, while HFS-worry (21.0 ± 12.9 to 16.8 ± 12.1) and DTSQs-hypo (3.3 ± 1.5 to 2.7 ± 1.4) also decreased. HFS-worry, HFS-behavior, and DTSQs-hypo showed no clear correlations with time in hypoglycemia or other CGM metrics at baseline, at 12 months, or over 12-month change. CONCLUSIONS:In adults using diabetes technology over 12 months, fear and perceived frequency of hypoglycemia showed no clear correlations with CGM metrics, suggesting both are influenced by more than glycemic profiles alone.

Background Although international guidelines provide recommendations for screening and monitoring of early-stage type 1 diabetes (T1D), navigating the care pathway can still be difficult for individuals, caregivers, and healthcare professionals (HCPs). These challenges are exacerbated by variations in healthcare systems, gaps in communication, and limited psychosocial support.Aims This manuscript aims to bridge the gap between theory and clinical practice and present practical, stage-specific recommendations for early-stage T1D care in pediatric and adult populations.Materials and Methods This article was informed by a structured literature review, qualitative interviews with HCPs in the UK, Germany, France, Italy, and Spain, and multidisciplinary expert input from the CARE-T1D working group. The group comprised six pediatric and six adult endocrinologists, and two psychologists from the EU, UK, and US.Results, Discussion and Conclusion Here we present proposed care pathways for pediatric and adult early-stage T1D, integrating recommendations for clear communication, care coordination, and psychosocial support throughout. This manuscript is intended to support the standardization of early-stage T1D detection and monitoring, thereby contributing to improved outcomes, including reducing the incidence of diabetic ketoacidosis (DKA) and hospitalization at stage 3 T1D diagnosis.