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.

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.

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.

Current provision and HCP experiences of remote care delivery and diabetes technology training for people with type 1 diabetes in the UK during the COVID-19 pandemic.

BACKGROUND: The COVID-19 pandemic has led to the rapid implementation of remote care delivery in type 1 diabetes. We studied current modes of care delivery, healthcare professional experiences and impact on insulin pump training in type 1 diabetes care in the United Kingdom (UK). METHODS: The UK Diabetes Technology Network designed a 48-question survey aimed at healthcare professionals providing care in type 1 diabetes. RESULTS: One hundred and forty-three healthcare professionals (48% diabetes physicians, 52% diabetes educators and 88% working in adult services) from approximately 75 UK centres (52% university hospitals, 46% general and community hospitals), responded to the survey. Telephone consultations were the main modality of care delivery. There was a higher reported time taken for video consultations versus telephone (p < 0.001). Common barriers to remote consultations were patient familiarity with technology (72%) and access to patient device data (67%). We assessed the impact on insulin pump training. A reduction in total new pump starts (73%) and renewals (61%) was highlighted. Common barriers included patient digital literacy (61%), limited healthcare professional experience (46%) and time required per patient (44%). When grouped according to size of insulin pump service, pump starts and renewals in larger services were less impacted by the pandemic compared to smaller services. CONCLUSION: This survey highlights UK healthcare professional experiences of remote care delivery. While supportive of virtual care models, a number of factors highlighted, especially patient digital literacy, need to be addressed to improve virtual care delivery and device training.

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.

A real-world study of user characteristics, safety and efficacy of open-source closed-loop systems and Medtronic 670G.

We report a real-world evaluation of the first commercially approved automated insulin delivery (AID) system, MiniMed 670G (670G), and open source-automated insulin delivery (OS-AID) systems. This was undertaken as a retrospective observational study in adults with type 1 diabetes using AID systems for 6 months or longer in a publicly funded health service using clinically validated data. Sixty-eight adults (38 670G, 30 OS-AID systems) were included. OS-AID system users were younger, had a shorter diabetes duration and a higher education status. OS-AID systems displayed a significantly better change in HbA1c (median -0.9% [-0.4%, -1.1%] vs. -0.1% [IQR -0.7%, 0.2%], P = .004) and time in range 3.9-10 mmol/L (mean 78.5%, SD ± 12.0% vs. 68.2% ± 14.7%, P = .024) compared with 670G. Both systems showed minimal hypoglycaemia, with OS-AID systems revealing significantly improved secondary outcomes of mean glucose and percentage of time more than 10 mmol/L, with a higher percentage of time of less than 3 mmol/L. OS-AID system users displayed improved glycaemic outcomes with no clinical safety concerns compared with 670G, although higher weight-adjusted insulin dose and weight gain were noted. The study highlights key differences in OS-AID system user characteristics that are important for interpreting real-world findings from recent OS-AID system studies.

Fasting with adrenal insufficiency: Practical guidance for healthcare professionals managing patients on steroids during Ramadan.

There are limited recommendations for fasting in many chronic diseases such as adrenal insufficiency (AI). Research in such situations highlights potential for complications and need for education for patients with AI undertaking fasting during Ramadan. This article aimed to provide up-to-date guidance for healthcare professionals to educate, discuss and manage patients with AI who are considering fasting in Ramadan and is religiously compatible. Latest guidance on this topic and the evidence base for steroid dosing are reviewed and discussed. Risk stratification for patients with AI and optimal strategies for management, including steroid dosing, are detailed. Our review highlights that patients with AI wishing to fast should undergo a thorough risk assessment ideally several months before Ramadan. 'High risk' and 'Very high risk' patients should be encouraged to explore alternative options to fasting discussed below. Prior to the commencement of Ramadan, all patients must receive up-to-date education on sick day rules, instructions on when to terminate their fast or abstain from fasting, carry steroid warning information and must have a valid intramuscular (IM) hydrocortisone pack and know how to administer this. Switching patients with AI desiring to fast from multiple daily hydrocortisone replacement to prednisolone 5 mg once daily at dawn (during Suhoor or Sehri) is recommended and discussed. Patients on fludrocortisone for AI should be advised to take their total dose at dawn. We provide practically relevant case-based scenarios to help with the application of this guidance. Future efforts need to focus on healthcare professional awareness and further research in this setting.

Hypothalamic arcuate nucleus glucokinase regulates insulin secretion and glucose homeostasis.

AIMS: To investigate the role of arcuate glucokinase (GK) in the regulation of glucose homeostasis. MATERIALS AND METHODS: A recombinant adeno-associated virus expressing either GK or an antisense GK construct was used to alter GK activity specifically in the hypothalamic arcuate nucleus (arc). GK activity in this nucleus was also increased by stereotactic injection of the GK activator, compound A. The effect of altered arc GK activity on glucose homeostasis was subsequently investigated using glucose and insulin tolerance tests. RESULTS: Increased GK activity specifically within the arc increased insulin secretion and improved glucose tolerance in rats during oral glucose tolerance tests. Decreased GK activity in this nucleus reduced insulin secretion and increased glucose levels during the same tests. Insulin sensitivity was not affected in either case. The effect of arc GK was maintained in a model of type 2 diabetes. CONCLUSIONS: These results demonstrate a role for arc GK in systemic glucose homeostasis.

Insights into the role of neuronal glucokinase.

Glucokinase is a key component of the neuronal glucose-sensing mechanism and is expressed in brain regions that control a range of homeostatic processes. In this review, we detail recently identified roles for neuronal glucokinase in glucose homeostasis and counterregulatory responses to hypoglycemia and in regulating appetite. We describe clinical implications from these advances in our knowledge, especially for developing novel treatments for diabetes and obesity. Further research required to extend our knowledge and help our efforts to tackle the diabetes and obesity epidemics is suggested.

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.

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.

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.

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.

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.

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.

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.

Use of automated insulin delivery systems in people with type 1 diabetes fasting during Ramadan: An observational study.

Fasting among people with type 1 diabetes imposes the risk of metabolic decompensation. Automated insulin dosing systems can allow better glycemic control without safety concerns. The utility in prolonged and repetitive fasting has not been studied. In this observational study, validated glycemic data were reviewed and analyzed from people with type 1 diabetes who observed fasting during Ramadan in 2019 and 2020 using automated insulin dosing systems. Six profiles met the inclusion criteria. The average age was 33.7 ± 4.8 years, diabetes duration was 23.5 ± 7.9 years, body mass index 23.6 ± 1.9 kg/m2 and glycated hemoglobin was 6.3 ± 0.2% (45 ± 5 mmol/mol). The average glucose during Ramadan was 7.0 ± 0.5 mmol/L (126 ± 9 mg/dL), coefficient of variation 28.5%, percentage of time in range 3.9-10 mmol/L (70-180 mg/dL) 88.8 ± 7.3% and percentage time <3.9 mmol/L (<70.0 mg/dL) 2.5 ± 1.3%. The number of fasting days was 27.3 ± 3.3, and the number of days where fasting was broken due diabetes was 1 ± 1.5/participant. No significant differences in glycemic outcomes were noted between Ramadan and non-Ramadan periods. In this first clinically validated study, automated insulin dosing systems showed a safe and effective management strategy to support prolonged and consecutive fasting in people with type 1 diabetes.

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.