Real-world outcomes of Omnipod DASH system use in people with type 1 diabetes: Evidence from the Association of British Clinical Diabetologists (ABCD) study.

AIMS: To evaluate real-world outcomes in people with Type 1 Diabetes (PwT1D) initiated on Omnipod DASH® Insulin Management System. METHODS: Anonymized clinical data were submitted to a secure web-based tool within the National Health Service network. Hemoglobin A1c (HbA1c), sensor-derived glucometrics, total daily dose of insulin (TDD), and patient-reported outcome changes between baseline and follow-up were assessed. Individuals were classified to "new-to-pump" (switched from multiple daily injections) and "established-on-pump" (switched from a tethered insulin pump) groups. RESULTS: 276 individuals from 11 centers [66.7 % female; 92 % White British; median age 41 years (IQR 20-50); diabetes duration 20 years (IQR 11-31); 49.3 % within "new-to-pump" group] were included. Baseline HbA1c was 8.0 ± 1.3 % (64 ± 14 mmol/mol). At follow-up [3 years (IQR 1.5-3.2)], HbA1c reduced by 0.3 % [(3 mmol/mol); p = 0.002] across the total population, 0.4 % [(5 mmol/mol); p = 0.001] in those "new-to-pump" and remained unchanged in those "established-on-pump". TDD decreased in the "new-to-pump" cohort (baseline:44.9 ± 21.0units vs follow-up:38.1 ± 15.4units, p = 0.002). Of those asked, 141/143 (98.6 %) stated Omnipod DASH had a positive impact on quality of life. CONCLUSIONS: Omnipod DASH was associated with improvements in HbA1c in PwT1D "new-to-pump" and maintained previous HbA1c levels in those "established-on-pump". User satisfaction in all groups and TDD reduction in those "new-to-pump" were reported.

Following in Banting's footsteps or straying from the path? Observations from contemporary diabetes innovation.

While advancements in the treatment of diabetes continue to rapidly evolve, many of the newer technologies have financial barriers to care, opposing the egalitarian ethos of Banting who sold his patent on insulin for a nominal cost to allow it to be made widely available. Inequity in access to new therapies drives disparity in diabetes burden with potential for these gaps to widen in the future. The 2023 International Conference on Advanced Technologies and Treatments of Diabetes (ATTD) presented ground-breaking and current research in diabetes technology. Oral presentations of the ATTD conference 2023 were analyzed to describe what percentage of speakers discussed equity in their talks. Overall, less than a quarter of presenters discussed equity, though there was regional variation. To ensure that diabetes technologies reduce disparity and improve outcomes, we encourage future speakers at diabetes (technology) conferences to consider equity of diabetes care and incorporate this into their presentations.

Mesenchymal stromal cell secretory molecules improve the functional survival of human islets.

AIMS: Human islet transplantation as a therapy for type 1 diabetes is compromised by the loss of functional beta cells in the immediate post-transplantation period. Mesenchymal stromal cells (MSCs) and MSC-derived secretory peptides improve the outcomes of islet transplantation in rodent models of diabetes. Here, we utilized a mouse model for human islet transplantation and assessed the effects of a cocktail of MSC-secreted peptides (screened by MSC-secretome for human islet GPCRs) on the functional survival of human islets. METHODS: Human islets from nine donors (Age: 36-57; BMI: 20-35) were treated with a cocktail of human recombinant annexin A1 (ANXA1), stromal cell-derived factor-1 (SDF-1/CXCL12) and complement component C3 (C3a). Glucose-stimulated insulin secretion (GSIS) was assessed in static incubation, and cytokine-induced apoptosis was assessed by measuring caspase 3/7 activity. mRNA expression levels were determined by qPCR. Human islet function in vivo was assessed using a novel model for human islet transplantation into a T1D mouse model. Human islet function in vivo was assessed using islet transplantation under the kidney capsule of immunodeficient mice prior to STZ destruction of endogenous mouse beta cells to model T1DM. RESULTS: Pretreatment with a cocktail of MSC-secreted peptides increased GSIS in vitro and protected against cytokine-induced apoptosis in human islets isolated from nine donors. Animals transplanted with either treated or untreated human islets remained normoglycaemic for up to 28 days after STZ-administration to ablate the endogenous mouse beta cells, whereas non-transplanted animals showed significantly increased blood glucose immediately after STZ administration. Removal of the human islet graft by nephrectomy resulted in rapid increases in blood glucose to similar levels as the non-transplanted controls. Pretreating human islets with the MSC-derived cocktail significantly improved glucose tolerance in graft recipients, consistent with enhanced functional survival of the treated islets in vivo. CONCLUSION: Pretreating human islets before transplantation with a defined cocktail of MSC-derived molecules could be employed to improve the quality of human islets for transplantation therapy for type 1 diabetes.

Presentation of new onset type 1 diabetes with diabetic ketoacidosis and hyperosmolar hyperglycaemia after a single dose of nivolumab and ipilimumab.

Summary: A Caucasian man in his 60s with recent diagnosis of metastatic renal cell carcinoma presented to the emergency department with a 5-day history of severe polyuria, polydipsia and fatigue and 1-day history of confusion, abdominal pain, nausea and vomiting. Investigations revealed an overlap of diabetic ketoacidosis (DKA) and hyperosmolar hyperglycaemic state (HHS). He had received the first dose of immunotherapy with nivolumab and ipilimumab 3 weeks prior to this attendance. New-onset type 1 diabetes (T1DM) was confirmed based on the clinical features at presentation, seropositivity for glutamic acid decarboxylase antibodies and significant insulin deficiency. He is currently on a multiple daily injections of insulin and uses intermittent-scanned glucose monitoring. Given the irreversible impact on beta-cell function and clinical response with insulin resulting in improved diabetes control, immunotherapy was resumed for his metastatic cancer with good radiological response. Although rare, new-onset T1DM can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes. Learning points: Although rare, new onset of T1DM after immunotherapy can present with DKA and HSS overlap after a single dose of nivolumab/ipilimumab in individuals without pre-existing history of diabetes and normal glycaemic parameters. Due to the irreversible destruction of beta-cells, treatment with steroids is not indicated in contrast to other settings such as immunotherapy-induced hypophysitis. Presence of low c-peptide levels post-acute presentation is indicative of an irreversible impact on beta-cell function and supports resuming immunotherapy given the significant benefits on cancer prognosis. Clinicians must maintain a high index of suspicion in regards to diagnosis and management of new-onset type 1 diabetes and advice patients on reporting symptoms suggestive of diabetes and/or diabetes-related hyperglycaemic emergencies.

Hybrid Closed-Loop Therapy in Adults With Type 1 Diabetes and Above-Target HbA1c: A Real-world Observational Study.

OBJECTIVE: We explored longitudinal changes associated with switching to hybrid closed-loop (HCL) insulin delivery systems in adults with type 1 diabetes and elevated HbA1c levels despite the use of intermittently scanned continuous glucose monitoring (isCGM) and insulin pump therapy. RESEARCH DESIGN AND METHODS: We undertook a pragmatic, preplanned observational study of participants included in the National Health Service England closed-loop pilot. Adults using isCGM and insulin pump across 31 diabetes centers in England with an HbA1c ≥8.5% who were willing to commence HCL therapy were included. Outcomes included change in HbA1c, sensor glucometrics, diabetes distress score, Gold score (hypoglycemia awareness), acute event rates, and user opinion of HCL. RESULTS: In total, 570 HCL users were included (median age 40 [IQR 29-50] years, 67% female, and 85% White). Mean baseline HbA1c was 9.4 ± 0.9% (78.9 ± 9.1 mmol/mol) with a median follow-up of 5.1 (IQR 3.9-6.6) months. Of 520 users continuing HCL at follow-up, mean adjusted HbA1c reduced by 1.7% (95% CI 1.5, 1.8; P < 0.0001) (18.1 mmol/mol [95% CI 16.6, 19.6]; P < 0.0001). Time in range (70-180 mg/dL) increased from 34.2 to 61.9% (P < 0.001). Individuals with HbA1c of ≤58 mmol/mol rose from 0 to 39.4% (P < 0.0001), and those achieving ≥70% glucose time in range and <4% time below range increased from 0.8 to 28.2% (P < 0.0001). Almost all participants rated HCL therapy as having a positive impact on quality of life (94.7% [540 of 570]). CONCLUSIONS: Use of HCL is associated with improvements in HbA1c, time in range, hypoglycemia, and diabetes-related distress and quality of life in people with type 1 diabetes in the real world.

A Systematic Review of Commercial Hybrid Closed-Loop Automated Insulin Delivery Systems.

INTRODUCTION: Several different forms of automated insulin delivery systems (AID systems) have recently been developed and are now licensed for type 1 diabetes (T1D). We undertook a systematic review of reported trials and real-world studies for commercial hybrid closed-loop (HCL) systems. METHODS: Pivotal, phase III and real-world studies using commercial HCL systems that are currently approved for use in type 1 diabetes were reviewed with a devised protocol using the Medline database. RESULTS: Fifty-nine studies were included in the systematic review (19 for 670G; 8 for 780G; 11 for Control-IQ; 14 for CamAPS FX; 4 for Diabeloop; and 3 for Omnipod 5). Twenty were real-world studies, and 39 were trials or sub-analyses. Twenty-three studies, including 17 additional studies, related to psychosocial outcomes and were analysed separately. CONCLUSIONS: These studies highlighted that HCL systems improve time In range (TIR) and arouse minimal concerns around severe hypoglycaemia. HCL systems are an effective and safe option for improving diabetes care. Real-world comparisons between systems and their effects on psychological outcomes require further study.

The First Regulatory Clearance of an Open-Source Automated Insulin Delivery Algorithm.

Open-source Automated Insulin Dosing (OS-AID) algorithms are made publicly accessible so that every facet of their operation can be understood. Currently, commercial AID algorithms are kept proprietary trade secrets, despite the role they take in making life and death decisions for people living with type 1 diabetes. Loop was the second OS-AID algorithm, developed initially by Nate Racklyeft and Pete Schwamb. In 2018, the nonprofit organization Tidepool (Palo Alto, CA) announced the launch of the "Tidepool Loop" initiative with the aim to generate real-world evidence and obtain regulatory clearance. By the end of 2020, the U.S. Food and Drug Administration received Tidepool's application for an interoperable automated glycemic controller based on Loop. After 2 years, the FDA approved the Tidepool Loop on January 23, 2023.

UK's Association of British Clinical Diabetologist's Diabetes Technology Network (ABCD-DTN): Best practice guide for hybrid closed-loop therapy.

This best practice guide is written with the aim of providing an overview of current hybrid closed-loop (HCL) systems in use within the United Kingdom's (UK) National Health Service (NHS) and to provide education and advice for their management on both an individual and clinical service level. The environment of diabetes technology, and particularly HCL systems, is rapidly evolving. The past decade has seen unprecedented advances in the development of HCL systems. These systems improve glycaemic outcomes and reduce the burden of treatment for people with type 1 diabetes (pwT1D). It is anticipated that access to these systems will increase in England as a result of updates in National Institute of Health and Care Excellence (NICE) guidance providing broader support for the use of real-time continuous glucose monitoring (CGM) for pwT1D. NICE is currently undertaking multiple-technology appraisal into HCL systems. Based on experience from centres involved in supporting advanced technologies as well as from the recent NHS England HCL pilot, this guide is intended to provide healthcare professionals with UK expert consensus on the best practice for initiation, optimisation and ongoing management of HCL therapy.

Management of adults with diabetes on dialysis: Summary of recommendations of the Joint British Diabetes Societies guidelines 2022.

Diabetes is the commonest cause of end-stage kidney disease in many parts of the world, and many people on dialysis programmes live with diabetes. Such people are vulnerable to complications from their diabetes, and their care may be fragmented due to the many specialists involved. This updated guidance from the Joint British Diabetes Societies aims to review and update the 2016 guidance, with particular emphasis on glycaemic monitoring in the light of recent advances in this area. In addition, the guidance covers clinical issues related to the management of diabetes in people on peritoneal dialysis, along with acute complications such as hypoglycaemia and ketoacidosis, and chronic complications such as foot and eye disease.

Practical Guidance on Open Source and Commercial Automated Insulin Delivery Systems: A Guide for Healthcare Professionals Supporting People with Insulin-Requiring Diabetes.

As increasing numbers of people with insulin-managed diabetes use automated insulin delivery (AID) systems or seek such technologies, healthcare providers are faced with a steep learning curve. Healthcare providers need to understand how to support these technologies to help inform shared decision making, discussing available options, implementing them in the clinical setting, and guiding users in special situations. At the same time, there is a growing diversity of commercial and open source automated insulin delivery systems that are evolving at a rapid pace. This practical guide seeks to provide a conversational framework for healthcare providers to first understand and then jointly assess AID system options with users and caregivers. Using this framework will help HCPs in learning how to evaluate potential new commercial or open source AID systems, while also providing a guide for conversations to help HCPs to assess the readiness and understanding of users for AID systems. The choice of an AID system is not as simple as whether the system is open source or commercially developed, and indeed there are multiple criteria to assess when choosing an AID system. Most importantly, the choices and preferences of the person living with diabetes should be at the center of any decision around the ideal automated insulin delivery system or any other diabetes technology. This framework highlights issues with AID use that may lead to burnout or perceived failures or may otherwise cause users to abandon the use of AID. It discusses the troubleshooting of basic AID system operation and discusses more advanced topics regarding how to maximize the time spent on AID systems, including how to optimize settings and behaviors for the best possible outcomes with AID technology for people with insulin-requiring diabetes. This practical approach article demonstrates how healthcare providers will benefit from assessing and better understanding all available AID system options to enable them to best support each individual.

Automated insulin delivery (AID) systems are a useful tool for people with insulin-requiring diabetes. AID systems include an insulin pump, continuous glucose monitor (CGM), and an algorithm embedded within the pump or a separate mobile device that can determine and automatically adjust insulin delivery in response to glucose levels. There are now a number of AID systems available, some which are made and distributed by commercial manufacturers and some that are available open source. Both open source and commercially developed automated insulin delivery systems have been proven to be safe and effective. Open source and commercially developed automated insulin delivery systems have also been proven to improve the quality of life of people with insulin-requiring diabetes. The choice of an AID system is not merely whether the system is open source or commercially developed. There are multiple criteria to assess when choosing an AID system: pump, CGM, smartphone connectivity and algorithm capabilities, flexibility of the system overall, and interoperability with connected platforms for real-time data access. Most importantly, the choices and preferences of the person living with diabetes should be at the center of any decision around the ideal automated insulin delivery system or any other diabetes technology. Healthcare providers will benefit from assessing and better understanding all available AID system options to enable them to best support each individual. This practical guide seeks to provide a conversational framework for healthcare providers to first understand and then jointly assess AID system options with users and caregivers.

Symptoms of Anxiety and Depression Are Independently Associated With Impaired Awareness of Hypoglycemia in Type 1 Diabetes.

OBJECTIVE: We tested the hypothesis that impaired awareness of hypoglycemia (IAH) is independently associated with symptoms of anxiety and depression in type 1 diabetes. RESEARCH DESIGN AND METHODS: In this cross-sectional observational study in 950 adults with type 1 diabetes, associations were examined using multiple regression models, adjusting for sociodemographic and clinical characteristics. RESULTS: Prevalence for probable anxiety, depression, and IAH were 9.4%, 9.8%, and 22.6%, respectively. When included in separate regression models, both depression and anxiety were independently associated with an increased odds of IAH and robust to adjustment (odds ratio 3.64 [95% CI 2.19-6.04] and 2.46 [1.46-4.14], respectively). Further analysis demonstrated a dose-response relationship between increased severity of probable mental disorder and increased odds of having IAH (P < 0.001). CONCLUSIONS: The robust independent relationship between probable anxiety and depression with IAH demonstrates the need for routine psychological assessment and management of people with type 1 diabetes and IAH.

African Caribbean Ethnicity Is an Independent Predictor of Significant Decline in Kidney Function in People With Type 1 Diabetes.

OBJECTIVE: The aim of the study was to identify the demographic and clinical features in an urban cohort of people with type 1 diabetes who developed a ≥50% decline in estimated glomerular filtration rate (eGFR). RESEARCH DESIGN AND METHODS: We evaluated 5,261 people with type 1 diabetes (51% female, 13.4% African Caribbean) with baseline eGFR >45 mL/min/1.73 m2 between 2004 and 2018. The primary end point was an eGFR decline of ≥50% from baseline with a final eGFR <30 mL/min/1.73 m2. eGFR was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. RESULTS: Of the cohort, 263 (5%) reached the primary end point. These individuals were more likely to be of African Caribbean ethnicity, be older, have a longer duration of diabetes, have higher systolic blood pressure and HbA1c, have more prevalent retinopathy, and have higher albuminuria (all P < 0.05). In multivariable Cox regression models, African Caribbean ethnicity emerged as a significant risk factor for the primary end point (hazard ratio 1.57, 95% CI 1.19, 2.08) compared with other ethnicities and independent of established risk factors (P < 0.01). The incidence rate for the primary end point in African Caribbean people was double that in non-African Caribbean people (16 vs. 7.7 per 1000 patient-years, P < 0.001). A similar significant independent impact of African Caribbean ethnicity for secondary end points (≥40% and ≥30% fall in eGFR) was observed. CONCLUSIONS: We report a novel observation that African Caribbean ethnicity increased the risk of kidney function loss in people with type 1 diabetes, an effect that was independent of traditional risk factors. Further studies are needed to examine the associated pathophysiology that may explain this observation.

Home Use of Mini-Dose Glucagon As a Novel Treatment for Hypoglycemia Following Repeated, Prolonged Fasts in Type 1 Diabetes During Ramadan.

OBJECTIVE: We determined the efficacy of self-administered subcutaneous mini-dose glucagon (MDG) to treat fasting-induced hypoglycemia in type 1 diabetes (T1D). RESEARCH DESIGN AND METHODS: This was a 4-week randomized, controlled crossover trial of 2-week MDG or 2-week oral glucose tablets (OG, control) involving 17 adults with T1D during Ramadan. RESULTS: Compared with OG, MDG demonstrated a significant higher change in blood glucose from baseline to 30 min (Δt30, P < 0.001) and 1 h (Δt60, P = 0.02). The efficacy of MDG was preserved following ≥8 h fasting with significantly higher Δt30 in MDG (P = 0.01). Over the entire 2 weeks, MDG period had increased time in 70-180 mg/dL (P = 0.009) and less time <70 mg/dL (P = 0.04). MDG use resulted in higher completion of fasts compared with OG (P < 0.001). CONCLUSIONS: MDG administration is an effective alternative to OG for prevention and treatment of fasting-induced hypoglycemia, offering improved glycemic control and promoting successful completion of prolonged fasts.

Association of British Clinical Diabetologists, Diabetes Technology Network UK and Association of Children's Diabetes Clinicians Survey of UK Healthcare Professional Attitudes Towards Open-Source Automated Insulin Delivery Systems.

INTRODUCTION: Automated insulin delivery (AID) systems can enable improved glycaemic outcomes with reduced mental burden. Open-source AID (OS-AID) systems overcome some of the developmental and access barriers enabling a wider use of these systems. Limited data are available on healthcare professional (HCP) opinions and current practice regarding these systems. The aim of this survey was to gain insight into HCP perceptions and practices around OS-AID. METHODS: This survey was developed collaboratively with OS-AID users and distributed to adult and children's teams, using an online survey tool. Results were received between February and April 2019. Responses were assessed using simple descriptive statistics with analyses stratified by respondent characteristics. RESULTS: 317 responses were obtained from a range of HCPs in both adult and paediatric services. Key results include: HCP perception of OS-AID as "risky in the wrong hands" (43%); 91% felt uncomfortable initiating discussions around OS-AID because of lack of regulation (67%) and/or their own lack of knowledge (63%). Half of HCPs (47%) reported that they would choose OS-AID if they themselves had type 1 diabetes. CONCLUSIONS: HCPs are generally supportive of OS-AID users but many feel uncomfortable with the technicalities of the systems given the lack of approval. Knowledge around the use of these systems was limited. Re-assessment of HCP perceptions should be performed in the future given the evolving landscape of diabetes technology, recent consensus statements and emerging ethical and legal perspectives.

Open-source automated insulin delivery systems are an increasingly encountered diabetes technology. These involve a small glucose sensor and an insulin delivery device called an insulin pump. These two devices interact to allow adjustment of insulin delivery to maintain glucose levels in a desirable range. The computer codes which drive these systems are developed by people with diabetes or their families rather than by device companies; as such, they have not been through formal approval processes and therefore there is limited formal evidence concerning whether they are safe or beneficial to use. Users report high satisfaction with these devices and improvements in their diabetes management. This survey was performed to assess the opinions of UK healthcare professionals and their usual practice. Key results include: UK healthcare professionals would not routinely recommend the use of these devices and there was concern about the medicolegal implications of use. However, UK healthcare professionals were generally supportive of those who chose to use the devices. Interestingly, almost half of the healthcare professionals would use the systems if they had diabetes.

Real-world evidence on clinical outcomes of people with type 1 diabetes using open-source and commercial automated insulin dosing systems: A systematic review.

AIMS: Several commercial and open-source automated insulin dosing (AID) systems have recently been developed and are now used by an increasing number of people with diabetes (PwD). This systematic review explored the current status of real-world evidence on the latest available AID systems in helping to understand their safety and effectiveness. METHODS: A systematic review of real-world studies on the effect of commercial and open-source AID system use on clinical outcomes was conducted employing a devised protocol (PROSPERO ID 257354). RESULTS: Of 441 initially identified studies, 21 published 2018-2021 were included: 12 for Medtronic 670G; one for Tandem Control-IQ; one for Diabeloop DBLG1; two for AndroidAPS; one for OpenAPS; one for Loop; three comparing various types of AID systems. These studies found that several types of AID systems improve Time-in-Range and haemoglobin A1c (HbA1c ) with minimal concerns around severe hypoglycaemia. These improvements were observed in open-source and commercially developed AID systems alike. CONCLUSIONS: Commercially developed and open-source AID systems represent effective and safe treatment options for PwD of several age groups and genders. Alongside evidence from randomized clinical trials, real-world studies on AID systems and their effects on glycaemic outcomes are a helpful method for evaluating their safety and effectiveness.

Open-source automated insulin delivery: international consensus statement and practical guidance for health-care professionals.

Open-source automated insulin delivery systems, commonly referred to as do-it-yourself automated insulin delivery systems, are examples of user-driven innovations that were co-created and supported by an online community who were directly affected by diabetes. Their uptake continues to increase globally, with current estimates suggesting several thousand active users worldwide. Real-world user-driven evidence is growing and provides insights into safety and effectiveness of these systems. The aim of this consensus statement is two-fold. Firstly, it provides a review of the current evidence, description of the technologies, and discusses the ethics and legal considerations for these systems from an international perspective. Secondly, it provides a much-needed international health-care consensus supporting the implementation of open-source systems in clinical settings, with detailed clinical guidance. This consensus also provides important recommendations for key stakeholders that are involved in diabetes technologies, including developers, regulators, and industry, and provides medico-legal and ethical support for patient-driven, open-source innovations.