Technology advances in diabetes pregnancy: right technology, right person, right time.

This review outlines some of the extraordinary recent advances in diabetes technology, which are transforming the management of type 1 diabetes before, during and after pregnancy. It highlights recent improvements associated with use of continuous glucose monitoring (CGM) but acknowledges that neither CGM nor insulin pump therapy are adequate for achieving the pregnancy glucose targets. Furthermore, even hybrid closed-loop (HCL) systems that are clinically effective outside of pregnancy may not confer additional benefits throughout pregnancy. To date, there is only one HCL system, the CamAPS FX, with a strong evidence base for use during pregnancy, suggesting that the pregnancy benefits are HCL system specific. This is in stark contrast to HCL system use outside of pregnancy, where benefits are HCL category specific. The CamAPS FX HCL system has a rapidly adaptive algorithm and lower glucose targets with benefits across all maternal glucose categories, meaning that it is applicable for all women with type 1 diabetes, before and during pregnancy. For women of reproductive years living with type 2 diabetes, the relative merits of using non-insulin pharmacotherapies vs diabetes technology (dipeptidyl peptidase-4 inhibitors, glucagon-like peptide-1 receptor agonists and sodium-glucose cotransporter 2 inhibitors) are unknown. Despite the urgent unmet need and potential benefits, studies of pharmacotherapy and technology use are extremely limited in pregnant women with type 2 diabetes.

Technology in the management of diabetes in hospitalised adults.

Suboptimal glycaemic management in hospitals has been associated with adverse clinical outcomes and increased financial costs to healthcare systems. Despite the availability of guidelines for inpatient glycaemic management, implementation remains challenging because of the increasing workload of clinical staff and rising prevalence of diabetes. The development of novel and innovative technologies that support the clinical workflow and address the unmet need for effective and safe inpatient diabetes care delivery is still needed. There is robust evidence that the use of diabetes technology such as continuous glucose monitoring and closed-loop insulin delivery can improve glycaemic management in outpatient settings; however, relatively little is known of its potential benefits and application in inpatient diabetes management. Emerging data from clinical studies show that diabetes technologies such as integrated clinical decision support systems can potentially mediate safer and more efficient inpatient diabetes care, while continuous glucose sensors and closed-loop systems show early promise in improving inpatient glycaemic management. This review aims to provide an overview of current evidence related to diabetes technology use in non-critical care adult inpatient settings. We highlight existing barriers that may hinder or delay implementation, as well as strategies and opportunities to facilitate the clinical readiness of inpatient diabetes technology in the future.

An automatic deep reinforcement learning bolus calculator for automated insulin delivery systems.

In hybrid automatic insulin delivery (HAID) systems, meal disturbance is compensated by feedforward control, which requires the announcement of the meal by the patient with type 1 diabetes (DM1) to achieve the desired glycemic control performance. The calculation of insulin bolus in the HAID system is based on the amount of carbohydrates (CHO) in the meal and patient-specific parameters, i.e. carbohydrate-to-insulin ratio (CR) and insulin sensitivity-related correction factor (CF). The estimation of CHO in a meal is prone to errors and is burdensome for patients. This study proposes a fully automatic insulin delivery (FAID) system that eliminates patient intervention by compensating for unannounced meals. This study exploits the deep reinforcement learning (DRL) algorithm to calculate insulin bolus for unannounced meals without utilizing the information on CHO content. The DRL bolus calculator is integrated with a closed-loop controller and a meal detector (both previously developed by our group) to implement the FAID system. An adult cohort of 68 virtual patients based on the modified UVa/Padova simulator was used for in-silico trials. The percentage of the overall duration spent in the target range of 70-180 mg/dL was 71.2 % and 76.2 % , < 70 mg/dL was 0.9 % and 0.1 % , and > 180 mg/dL was 26.7 % and 21.1 % , respectively, for the FAID system and HAID system utilizing a standard bolus calculator (SBC) including CHO misestimation. The proposed algorithm can be exploited to realize FAID systems in the future.

Injectable Gelled Multiple Emulsion for Glucose-Responsive Insulin Delivery.

A glucose-responsive insulin delivery system that sustains blood glucose equilibrium for an extended duration can address the low therapeutic window of insulin in diabetes treatment. Herein, insulin is loaded in a water-in-oil-in-water (W1/O/W2) gelled multiple emulsion using poly (4-vinylphenylboronic acid) (PVPBA) homopolymer as an effective emulsifier. The gelled multiple emulsion exhibits a high encapsulation efficiency (99%), enhanced stability and remarkable shear-thinning behavior, making it easy to inject. Under hyperglycemic conditions, the gelled emulsion system instantly binds to glucose molecules and reduces the hydrogen bonds of the PVPBA homopolymer, resulting in insulin release. In a streptozotocin-induced type 1 diabetic mouse model, a single subcutaneous injection of the gelled emulsion rapidly responds to high blood glucose concentration (BGC) and release insulin in a glucose dependent manner, thus prolonging the antihyperglycemic effect compared with free insulin.

Advances in diabetes technology to improve the lives of people with cystic fibrosis.

People with cystic fibrosis (CF) are at risk for dysglycaemia caused by progressive beta cell dysfunction and destruction due to pancreatic exocrine disease and fibrosis. CF-related diabetes (CFRD) is a unique form of diabetes that has distinctive features from both type 1 and type 2 diabetes. Recent advances in diabetes technology may be of particular benefit in this population given the complex, multi-system organ involvement and challenging health issues that people with CFRD often face. This review summarises how diabetes technologies, such as continuous glucose monitors (CGMs) and insulin delivery devices: (1) have improved our understanding of CFRD, including how hyperglycaemia affects clinical outcomes in people with CF; (2) may be helpful in the screening and diagnosis of CFRD; and (3) offer promise for improving the management of CFRD and easing the burden that this diagnosis can add to an already medically complicated patient population.

Use of diabetes technology in children.

Children with type 1 diabetes and their caregivers face numerous challenges navigating the unpredictability of this complex disease. Although the burden of managing diabetes remains significant, new technology has eased some of the load and allowed children with type 1 diabetes to achieve tighter glycaemic management without fear of excess hypoglycaemia. Continuous glucose monitor use alone improves outcomes and is considered standard of care for paediatric type 1 diabetes management. Similarly, automated insulin delivery (AID) systems have proven to be safe and effective for children as young as 2 years of age. AID use improves not only blood glucose levels but also quality of life for children with type 1 diabetes and their caregivers and should be strongly considered for all youth with type 1 diabetes if available and affordable. Here, we review key data on the use of diabetes technology in the paediatric population and discuss management issues unique to children and adolescents.

The use of technology in type 2 diabetes and prediabetes: a narrative review.

The increasing incidence of type 2 diabetes, which represents 90% of diabetes cases globally, is a major public health concern. Improved glucose management reduces the risk of vascular complications and mortality; however, only a small proportion of the type 2 diabetes population have blood glucose levels within the recommended treatment targets. In recent years, diabetes technologies have revolutionised the care of people with type 1 diabetes, and it is becoming increasingly evident that people with type 2 diabetes can also benefit from these advances. In this review, we describe the current knowledge regarding the role of technologies for people living with type 2 diabetes and the evidence supporting their use in clinical practice. We conclude that continuous glucose monitoring systems deliver glycaemic benefits for individuals with type 2 diabetes, whether treated with insulin or non-insulin therapy; further data are required to evaluate the role of these systems in those with prediabetes (defined as impaired glucose tolerance and/or impaired fasting glucose and/or HbA1c levels between 39 mmol/mol [5.7%] and 47 mmol/mol [6.4%]). The use of insulin pumps seems to be safe and effective in people with type 2 diabetes, especially in those with an HbA1c significantly above target. Initial results from studies exploring the impact of closed-loop systems in type 2 diabetes are promising. We discuss directions for future research to fully understand the potential benefits of integrating evidence-based technology into care for people living with type 2 diabetes and prediabetes.

Safety and Psychological Outcomes of Tandem t:Slim X2 Insulin Pump with Control-IQ Technology in Children, Adolescents, and Young Adults with Type 1 Diabetes: A Systematic Review.

The Tandem t:slim X2 insulin pump is a second-generation automated insulin delivery system with Control-IQ technology. It consists of an X2 insulin pump, an integrated Dexcom sensor, and an embedded 'Control-IQ' algorithm, which predicts glucose levels 30 min in the future, adapting the programmed basal insulin rates to get glucose levels between 112.5 and 160 mg/dl (8.9 mmol/l). The system delivers automatic correction boluses of insulin when glucose levels are predicted to rise > 180 mg/dl (10 mmol/l). It has been commercially available since 2016. We reviewed the current evidence about the psychological, safety, and exercise-related outcomes of this device in children, adolescents, and young adults living with type 1 diabetes. We screened 552 papers, but only 21 manuscripts were included in this review. Fear of hypoglycemia is significantly reduced in young people with diabetes and their parents. Interestingly, diabetes-related distress is decreased; thus, the system is well accepted by the users. The sleeping quality of subjects living with diabetes and their caregivers is improved to a lesser extent as well. Despite the small number of data, this system is associated with a low rate of exercise-related hypoglycemia. Finally, evidence from the literature shows that this system is safe and effective in improving psychological personal outcomes. Even if further steps toward the fully closed loop are still mandatory, this second-generation automated insulin delivery system reduces the burden of diabetes. It properly addresses most psychological issues in children, adolescents, and young adults with type 1 diabetes mellitus; thus, it appears to be well accepted.

Neuro-fuzzy model for predicting insulin delivery from crosslinked agar-carbomer hydrogels.

This study focuses on the innovation of an inhaled sustained release form of insulin and the development of a neuro-fuzzy model specifically tailored to predict insulin release kinetics from polycondensed agar-carbomer hydrogels. These were synthesized by blending agar and carbomer, incorporating propylene glycol and glycerol, and then cross-linking by polycondensation. The structure and morphology of the hydrogel were analyzed via Fourier Transform Infrared Spectroscopy, Scanning Electron Microscopy and Proton Nuclear Magnetic Resonance Spectroscopy. The neuro-fuzzy model, a combination of artificial neural networks and fuzzy logic, employs inputs such as concentrations of crosslinking agents, polycondensation time, and release time, with the output being the rate of insulin release. The model demonstrated a strong correlation with experimental data, highlighting its effectiveness and precision in predicting insulin delivery from hydrogel compositions and temporal parameters. This emphasizes the importance of intelligent modelling for forecasting the kinetic release of therapeutic agents from novel drug delivery systems.

The Dilemma of Insulin Delivery into the Brain: A Comprehensive Review.

Insulin is a peptide hormone that is essential for regulating body homeostasis. Furthermore, it is involved in various neurological functions such as memory, behaviors, and cognition. The ubiquitous distribution of insulin receptors on various brain cells, such as neurons, microglia, astrocytes, and oligodendrocytes, and their differential localization across various brain regions, including the hippocampus, hypothalamus, and olfactory bulb, collectively underscore the crucial involvement of insulin in the modulation of cerebral functions. Along with ageing, in some pathological conditions such as diabetes and brain insulin resistance, the need for exogenous insulin is felt to compensate for insulin deficiency. In these cases, the biggest obstacle to the delivery of insulin to the brain is the blood-brain barrier (a physical barrier consisting of endothelial cells with tight junctions), which prevents the direct entry of most substances possessing high molecular weight, like insulin, into the brain. Therefore, different delivery methods have been proposed by researchers for insulin delivery that directly or indirectly cause the transfer of insulin to the brain. Some of these methods lack high efficiency and cause many side effects for the patient. In this regard, many new technologies have come to the aid of researchers and have introduced more effective delivery strategies, including the use of nanocarriers. Despite the promising outcomes demonstrated in the experimental models, the utilization of these techniques in human studies remains at a nascent stage and necessitates further comprehensive investigation. This review article aims to examine the diverse methods of insulin administration to the brain by gathering extensive information on insulin and its obstacles to brain delivery.

Protocol for a prospective, multicenter, parallel-group, open-label randomized controlled trial comparing standard care with Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control: the CO-PILOT trial.

Purpose: Advanced hybrid closed loop (AHCL) systems have the potential to improve glycemia and reduce burden for people with type 1 diabetes (T1D). Children and youth, who are at particular risk for out-of-target glycemia, may have the most to gain from AHCL. However, no randomized controlled trial (RCT) specifically targeting this age group with very high HbA1c has previously been attempted. Therefore, the CO-PILOT trial (Closed lOoP In chiLdren and yOuth with Type 1 diabetes and high-risk glycemic control) aims to evaluate the efficacy and safety of AHCL in this group. Methods: A prospective, multicenter, parallel-group, open-label RCT, comparing MiniMed™ 780G AHCL to standard care (multiple daily injections or continuous subcutaneous insulin infusion). Eighty participants aged 7-25 years with T1D, a current HbA1c ≥ 8.5% (69 mmol/mol), and naïve to automated insulin delivery will be randomly allocated to AHCL or control (standard care) for 13 weeks. The primary outcome is change in HbA1c between baseline and 13 weeks. Secondary outcomes include standard continuous glucose monitor glycemic metrics, psychosocial factors, sleep, platform performance, safety, and user experience. This RCT will be followed by a continuation phase where the control arm crosses over to AHCL and all participants use AHCL for a further 39 weeks to assess longer term outcomes. Conclusion: This study will evaluate the efficacy and safety of AHCL in this population and has the potential to demonstrate that AHCL is the gold standard for children and youth with T1D experiencing out-of-target glucose control and considerable diabetes burden. Trial registration: This trial was prospectively registered with the Australian New Zealand Clinical Trials Registry on 14 November 2022 (ACTRN12622001454763) and the World Health Organization International Clinical Trials Registry Platform (Universal Trial Number U1111-1284-8452). Supplementary Information: The online version contains supplementary material available at 10.1007/s40200-024-01397-4.

Review Article - Diabetes Technology in the Hospital: An Update.

PURPOSE OF REVIEW: There have been many developments in diabetes technology in recent years, with continuous glucose monitoring (CGM), insulin pump therapy (CSII) and automated insulin delivery (AID) becoming progressively accepted in outpatient diabetes care. However, the use of such advanced diabetes technology in the inpatient setting is still limited for several reasons, including logistical challenges and staff training needs. On the other hand, hospital settings with altered diet and stress-induced hyperglycemia often pose challenges to tight glycemic control using conventional treatment tools. Integrating smarter glucose monitoring and insulin delivery devices into the increasingly technical hospital environment could reduce diabetes-related morbidity and mortality. This narrative review describes the most recent literature on the use of diabetes technology in the hospital and suggests avenues for further research. RECENT FINDINGS: Advanced diabetes technology has the potential to improve glycemic control in hospitalized people with and without diabetes, and could add particular value in certain conditions, such as nutrition therapy or perioperative management. Taken together, CGM allows for more accurate and patient-friendly follow-up and ad hoc titration of therapy. AID may also provide benefits, including improved glycemic control and reduced nursing workload. Before advanced diabetes technology can be used on a large scale in the hospital, further research is needed on efficacy, accuracy and safety, while implementation factors such as cost and staff training must also be overcome.

Real-world data on the Minimed 780G advanced hybrid closed-loop system use during type 1 diabetes pregnancy: One centre observational study.

Aim The efficacy of hybrid closed-loop systems (HCLs) in managing glycemic control in pregnant women with type 1 diabetes remains inadequately characterized. We evaluated the use of the Medtronic Minimed 780G HCLs. METHODS: The retrospective observational study analyzed the glycemic and perinatal outcomes of pregnant women using the HCLs, followed at our tertiary centre. Independent t-tests were employed to compare data among trimesters based on pre-pregnancy HbA1c. The associations between glycemic parameters and perinatal outcomes were explored using Spearman rho. RESULTS: Among the 21 women (age: 33.5 ± 4.2 years, diabetes duration: 21.2 ± 7.6 years, pre-pregnancy HbA1c 7.0 ± 1.1 % (52.9 ± 11.9 mmol/mol)) time in range (pTIR, 63-140 mg/dl; 3.5-7.8 mmol/l) increased progressively throughout pregnancy (trimesters: first: 64.0 ± 9.0 %; second:71.3 ± 11.8 %; third: 75.7 ± 8.1 %). Simultaneously, mean sensor glucose decreased (trimesters: first: 130 ± 10.4 mg/dl (7.2 ± 0.6 mmol/l); second: 120.9 ± 13.4 mg/dl (6.7 ± 0.7 mmol/l); third: 117.3 ± 9.1 mg/dl (6.5 ± 0.5 mmol/l)). Although a majority of women achieved the target pTIR until the third trimester, this did not consistently prevent the delivery of a large-for-gestational-age baby. Notably, one ketoacidosis event occurred, and there were no reported instances of severe hypoglycemia. CONCLUSION: Use of the Minimed 780G HCLs enabled the attainment of recommended pregnancy glycemic targets for most women with type 1 diabetes in a real-world setting.

Recommendations for recognizing, risk stratifying, treating, and managing children and adolescents with hypoglycemia.

There has been continuous progress in diabetes management over the last few decades, not least due to the widespread dissemination of continuous glucose monitoring (CGM) and automated insulin delivery systems. These technological advances have radically changed the daily lives of people living with diabetes, improving the quality of life of both children and their families. Despite this, hypoglycemia remains the primary side-effect of insulin therapy. Based on a systematic review of the available scientific evidence, this paper aims to provide evidence-based recommendations for recognizing, risk stratifying, treating, and managing patients with hypoglycemia. The objective of these recommendations is to unify the behavior of pediatric diabetologists with respect to the timely recognition and prevention of hypoglycemic episodes and the correct treatment of hypoglycemia, especially in patients using CGM or advanced hybrid closed-loop systems. All authors have long experience in the specialty and are members of the Italian Society of Pediatric Endocrinology and Diabetology. The goal of treating hypoglycemia is to raise blood glucose above 70 mg/dL (3.9 mmol/L) and to prevent further decreases. Oral glucose at a dose of 0.3 g/kg (0.1 g/kg for children using "smart pumps" or hybrid closed loop systems in automated mode) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L), although any form of carbohydrate (e.g., sucrose, which consists of glucose and fructose, or honey, sugary soft drinks, or fruit juice) containing glucose may be used. Using automatic insulin delivery systems, the oral glucose dose can be decreased to 0.1 g/kg. Practical flow charts are included to aid clinical decision-making. Although representing the official position of the Italian Society of Pediatric Endocrinology and Diabetology (ISPED), these guidelines are applicable to the global audience and are especially pertinent in the era of CGM and other advanced technologies.

Engineered nanoparticles in non-invasive insulin delivery for precision therapeutics of diabetes.

Diabetes mellitus is a chronic disease leading to the death of millions a year across the world. Insulin is required for Type 1, Type 2, and gestational diabetic patients, however, there are various modes of insulin delivery out of which oral delivery is noninvasive and convenient. Moreover, factors like insulin degradation and poor intestinal absorption play a crucial role in its bioavailability and effectiveness. This review discusses various types of engineered nanoparticles used in-vitro, in-vivo, and ex-vivo insulin delivery along with their administration routes and physicochemical properties. Injectable insulin formulations, currently in use have certain limitations, leading to invasiveness, low patient compliance, causing inflammation, and side effects. Based on these drawbacks, this review emphasizes more on the non-invasive route, particularly oral delivery. The article is important because it focuses on how engineered nanoparticles can overcome the limitations of free therapeutics (drugs alone), navigate the barriers, and accomplish precision therapeutics in diabetes. In future, more drugs could be delivered with a similar strategy to cure various diseases and resolve challenges in drug delivery. This review significantly describes the role of various engineered nanoparticles in improving the bioavailability of insulin by protecting it from various barriers during non-invasive routes of delivery.

Preparation and Characterization of Chitosan Nanofiber: Kinetic Studies and Enhancement of Insulin Delivery System.

Insulin-loaded nanofibers were prepared using chitosan as a natural polymer. The loaded insulin with polyethylene oxide was used for preparing monolayer batch S1. Nanofiber S1 was coated by seven layers of film on both sides to form batch S2 as a sandwich containing Layer A (CS, PEG and PEO) and Layer B (PEG and PEO) using electrospinning apparatus. SEM, TEM and FT-IR techniques were used to confirm the drug loading within the composite nanofibers. The in vitro activity that provided a sustained and controlled release of the drug from the nanofiber batch was studied at different pH values spectrophotometrically using a dialysis method. In batches S1 and S2, the release of insulin from nanofiber proceeds via burst release necessary to produce the desired therapeutic activity, followed by slow step. The rate and the percentage release of insulin in batch S2 are found to be higher at all pH values.

Real-world glycaemic outcomes of automated insulin delivery in type 1 diabetes: A meta-analysis.

AIM: To evaluate the real-world effectiveness of automated insulin delivery (AID) systems in patients with type 1 diabetes (T1D). MATERIALS AND METHODS: PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov were searched for studies published up until 2 March 2024. We included pragmatic randomized controlled trials (RCTs), cohort studies, and before-after studies that compared AID systems with conventional insulin therapy in real-world settings and reported continuous glucose monitoring outcomes. Percent time in range (TIR; 3.9-10 mmol/L), time below range (TBR; <3.9 mmol/L), time above range (TAR; >10 mmol/L), and glycated haemoglobin (HbA1c) level were extracted. Data were summarized as mean differences (MDs) with 95% confidence interval. RESULTS: A total of 23 before-after studies (101 704 participants) were included in the meta-analysis. AID systems were associated with an increased percentage of TIR (11.61%, 10.47 to 12.76; p < 0.001). The favourable effect of AID systems was consistently observed when used continuously for 6 (11.76%) or 12 months (11.33%), and in both children (12.16%) and adults (11.04%). AID systems also showed favourable effects on TBR (-0.53%, -0.63 to -0.42), TAR (-9.65%, -10.63 to -8.67) and HbA1c level (-0.42%, -0.47 to -0.37) when compared with previous treatments. CONCLUSIONS: Similar improvements in glycaemic parameters were observed in real-world settings in RCTs using AID systems in T1D. AID systems benefit both children and adults by increasing TIR for both short- and long-term interventions.

A Biomineralized Bifunctional Patient-Friendly Nanosystem for Sustained Glucose Monitoring and Control in Diabetes.

Regular blood glucose monitoring and control is necessary for people with type 1 or advanced type 2 diabetes, yet diagnosing and treating patients with diabetes in an accurate, sustained and patient-friendly manner remains limited. Here, a glucose-responsive bifunctional nanosystem (PGOxMns) is constructed via one-pot biomineralisation of manganese dioxide with glucose oxidase and ε-poly-L-lysine. Under hyperglycaemic conditions, the cascade reactions that occur when glucose interacts with PGOxMns can trigger the production of Mn(II), which enhances the magnetic resonance imaging signal. Simultaneously, manganese dioxide catalyses the decomposition of toxic hydrogen peroxide into oxygen, which also maintains glucose oxidase (GOx) activity. In an in vivo model of diabetes, PGOxMns is used to monitor glucose levels (0-20 mm) and allowed identification of diabetic mice via T1-weighted MRI. Furthermore, PGOxMns is found to have a high insulin-loading capacity (83.6%), likely due to its positive charge. A single subcutaneous injection of insulin-loaded nanosystem (Ins-PGOxMns) into diabetic mice resulted in a rapid and efficient response to a glucose challenge and prolonged blood glucose level control (< 200 mg dL-1) for up to 50 h. Overall, this proof-of-concept study demonstrates the feasibility of using biomineralised nanosystems to develop patient-friendly strategies for glucose monitoring and control.

Effects of subcutaneous vs. oral nanoparticle-mediated insulin delivery on hemostasis disorders in type 1 diabetes: A rat model study.

Complications associated with Type 1 diabetes (T1D) have complex origins that revolve around chronic hyperglycemia; these complications involve hemostasis disorders, coagulopathies, and vascular damage. Our study aims to develop innovative approaches to minimize these complications and to compare the outcomes of the new approach with those of traditional methods. To achieve our objective, we designed novel nanoparticles comprising covalent organic frameworks (nCOF) loaded with insulin, termed nCOF/Insulin, and compared it to subcutaneous insulin to elucidate the influence of insulin delivery methods on various parameters, including bleeding time, coagulation factors, platelet counts, cortisol plasma levels, lipid profiles, and oxidative stress parameters. Traditional subcutaneous insulin injections exacerbated hemostasis disorder and vascular injuries in streptozotocin (STZ)-induced diabetic rats through increasing plasma triglycerides and lipid peroxidation. Conversely, oral delivery of nCOF/Insulin ameliorated hemostatic disorders and restored the endothelial oxidant/antioxidant balance by reducing lipid peroxidation and enhancing the lipid profile. Our study pioneers the understanding of how STZ-induced diabetes disrupts bleeding time, induces a hypercoagulable state, and causes vascular damage through lipid peroxidation. Additionally, it provides the first evidence for the involvement of subcutaneous insulin treatment in exacerbating vascular and hemostasis disorders in type 1 diabetes (T1D). Introducing an innovative oral insulin delivery via the nCOF approach represents a potential paradigm shift in diabetes management and patient care and promises to improve treatment strategies for type 1 Diabetes.

The role of automated insulin delivery technology in diabetes.

The role of automated insulin delivery systems in diabetes is expanding. Hybrid closed-loop systems are being used in routine clinical practice for treating people with type 1 diabetes. Encouragingly, real-world data reflects the performance and usability observed in clinical trials. We review the commercially available hybrid closed-loop systems, their distinctive features and the associated real-world data. We also consider emerging indications for closed-loop systems, including the treatment of type 2 diabetes where variability of day-to-day insulin requirements is high, and other challenging applications for this technology. We discuss issues around access and implementation of closed-loop technology, and consider the limitations of present closed-loop systems, as well as innovative approaches that are being evaluated to improve their performance.