Closed-loop Insulin Delivery System Research Articles

Time With Rapid Change of Glucose.

A variety of metrics are used to describe glycemic variation, some of which may be difficult to comprehend or require complex strategies for smoothing of the glucose curve. We aimed to describe a new metric named time with rapid change of glucose (TRC), which is presented as percentage of time, similar to time above range (TAR), time in range (TIR), and time below range (TBR). We downloaded glucose data for 90 days from 159 persons with type 1 diabetes using the Abbott Freestyle Libre version 1. We defined TRC as the proportion of time (%) with an absolute rate of change of glucose > 1.5 mmol/L/15 minutes (1.8mg/dL/min) corresponding to a minimum rate of change for glucose in the 3.9-10.0 mmol/L (70-180 mg/dL) range within 1 hour. TRC is related to the other glucose variability metrics: CV within day (CVw) and mean amplitude of glycemic excursion (MAGE). The more than 1.27 million glucose rates were t-location scale distributed with SD 0.91 mmol/L/15 min (1.1 mg/dL/15 min). The median TRC was 6.9% (IQR 4.5%-9.5%). The proportion of TRC with positive slope was 3.9% (2.6%-5.3%) and significantly higher than the proportion with negative slope 2.8% (1.5%-4.4%) P < .001. TRC correlated with CVw and MAGE (Spearman's correlation coefficient .56 and .65, respectively, P < .001). TRC is proposed as an easily perceived metric to compare the performance of hybrid or fully automated closed-loop insulin delivery systems to obtain glucose homeostasis.

Navigating the Digital Landscape of Diabetes Care: Current State of the Art and Future Directions

Diabetes mellitus remains a global health challenge, requiring innovative solutions for effective disease management. This paper offers a thorough analysis of diabetes technologies, highlighting their various roles in diabetes care. Through a thorough review of the literature and analysis of emerging trends, we explore the multifaceted impact of technology on diabetes care. We investigate the key role of continuous glucose monitoring systems, insulin pumps and smart insulin pens in achieving optimal glycaemic control. The paper also evaluates the integration of artificial intelligence and machine learning algorithms in predictive modelling for early detection of glucose fluctuations, ultimately preventing diabetes-related complications. Additionally, studies the potential of telemedicine and mobile applications in enhancing patient engagement and self-management. Moreover, the review covers advancements in closed-loop insulin delivery systems, offering insights into their clinical effectiveness and potential to revolutionize diabetes care. Ethical and privacy considerations related to the use of patient data in these technologies are discussed, emphasizing the importance of striking a balance between technological innovation and patient security. This paper's evidence synthesis underscores the increasing influence of diabetes technologies on patient outcomes, quality of life, and healthcare systems. It underscores the need for multidisciplinary collaboration between healthcare professionals, researchers and technology developers to ensure the seamless integration and accessibility of these tools to patients living with diabetes. This study serves as a valuable resource for clinicians, researchers, and policymakers, providing a comprehensive view of evolving diabetes technologies and their potential in the field.

Closed-loop insulin delivery systems in patients with pancreatitis or pancreatectomy-induced diabetes: A case series

Pancreatic diabetes is associated with glycemic variability, poor metabolic control, and reduced quality of life. Though hybrid closed-loop (HCL) insulin delivery systems were not originally developed for these types of diabetes, they could address the therapeutic challenge. We aimed to evaluate long-term metabolic control in ten adult patients (mean ± SD age: 59 ± 12) treated with HCL insulin delivery systems for pancreatitis or pancreatectomy-induced diabetes. After a median of 346 days (range 64 - 631) with HCL insulin delivery, continuous glucose monitoring showed 59±19 % time-in-range [70–180 mg/dl] (versus 49±24 % before HCL insulin delivery, P = 0. 049) and 0.8 ± 1.0 % time-below-range [< 70 mg/dl] (versus 2.2 ± 2.6 %, P = 0.142), with the coefficient of glucose variability at 35.4 ± 7.6 (versus 37.8 ± 7.1, P = 0.047). HbA1c decreased from 8.5 ± 1.7 % to 7.7 ± 1.3 % [69±18 to 60±14 mmol/mol] (P = 0.076). No patient experienced an acute adverse metabolic event.

Efficacy of the hybrid closedloop insulin delivery system in children and adolescents with type 1 diabetes: a meta-analysis with trial sequential analysis.

The aim of this study was to assess the efficacy and safety of hybrid closed-loop (HCL) systems for insulin delivery in children and adolescents with type 1 diabetes (T1D). We searched Embase, PubMed, and Cochrane Library for randomized controlled trials (RCTs) published until March 2023 comparing the HCL therapy with control therapies for children and adolescents with T1D. We computed weighted mean differences (WMDs) for continuous outcomes and risk ratios (RRs) with 95% confidence intervals (CIs) for binary endpoints. Four RCTs and 501 patients were included, of whom 323 were randomized to HCL therapy. Compared with control therapies, HCL significantly improved the period during which glucose level was 70-180 mg/dL (WMD 10.89%, 95% CI 8.22-13.56%) and the number of participants with glycated hemoglobin (HbA1c) level < 7% (RR 2.61, 95% CI 1.29-5.28). Also, HCL significantly reduced the time during which glucoselevel was > 180 mg/dL (WMD-10.46%, 95% CI-13.99 to-6.93%) and the mean levels of glucose (WMD-16.67 mg/dL, 95% CI-22.25 to-11.09 mg/dL) and HbA1c (WMD-0.50%, 95% CI-0.68 to-0.31). There were no significant differences between therapies regarding time during which glucose level was < 70 mg/dL or <54 mg/dL or number of episodes of ketoacidosis, hyperglycemia, and hypoglycemia. In this meta-analysis, HCL compared with control therapies was associated with improved time in range and HbA1c control in children and adolescents with T1D and a similar profile of side effects. These findings support the efficacy of HCL in the treatment of T1D in this population.

Evaluation of hybrid closed-loop insulin delivery system in type 1 diabetes in real-world clinical practice: One-year observational study.

In 2016, the Food and Drug Administration approved the first hybrid closed-loop (HCL) insulin delivery system for adults with type 1 diabetes (T1D). There is limited information on the impact of using HCL systems on patient-reported outcomes (PROs) in patients with T1D in real-world clinical practice. In this independent study, we evaluated glycemic parameters and PROs over one year of continuous use of Medtronic's 670G HCL in real-world clinical practice. To assess the effects of hybrid closed loop system on glycemic control and quality of life in adults with T1D. We evaluated 71 patients with T1D (mean age: 45.5 ± 12.1 years; 59% females; body weight: 83.8 ± 18.7 kg, body mass index: 28.7 ± 5.6 kg/m2, A1C: 7.6% ± 0.8%) who were treated with HCL at Joslin Clinic from 2017 to 2019. We measured A1C and percent of glucose time-in-range (%TIR) at baseline and 12 months. We measured percent time in auto mode (%TiAM) for the last two weeks preceding the final visit and assessed PROs through several validated quality-of-life surveys related to general health and diabetes management. At 12 mo, A1C decreased by 0.3% ± 0.1% (P = 0.001) and %TIR increased by 8.1% ± 2.5% (P = 0.002). The average %TiAM was only 64.3% ± 32.8% and was not associated with A1C, %TIR or PROs. PROs, provided at baseline and at the end of the study, showed that the physical functioning submodule of 36Item Short-Form Health Survey increased significantly by 22.9% (P < 0.001). Hypoglycemia fear survey/worry scale decreased significantly by 24.9% (P < 0.000); Problem Areas In Diabetes reduced significantly by -17.2% (P = 0.002). The emotional burden submodules of dietary diversity score reduced significantly by -44.7% (P = 0.001). Furthermore, analysis of Clarke questionnaire showed no increase in awareness of hypoglycemic episodes. WHO-5 showed no improvements in subject's wellbeing among participants after starting the 670G HCL system. Finally, analysis of Pittsburgh Sleep Quality Index showed no difference in sleep quality, sleep latency, or duration of sleep from baseline to 12 mo. The use of HCL in real-world clinical practice for one year was associated with significant improvements in A1C, %TIR, physical functioning, hypoglycemia fear, emotional distress, and emotional burden related to diabetes management. However, these changes were not associated with time in auto mode.

A Diabetes Pregnancy Technology Roadmap: The 2023 Norbert Freinkel Award Lecture.

Norbert Freinkel emphasized the need for "more aggressive therapy with exogenous insulin" during type 1 diabetes (T1D) pregnancy. Recent advances in diabetes technology, continuous glucose monitoring (CGM), and hybrid closed-loop (HCL) insulin delivery systems allow us to revisit Freinkel's observations from a contemporary perspective. The Continuous Glucose Monitoring in Women With Type 1 Diabetes in Pregnancy Trial (CONCEPTT) led to international recommendations that CGM be offered to all pregnant women with T1D to help them meet their pregnancy glucose targets and improve neonatal outcomes. However, despite CGM use, only 35% of trial participants reached the pregnancy glucose targets by 35 weeks' gestation, which is too late for optimal obstetric and neonatal outcomes. The constant vigilance to CGM data and insulin dose adjustment, with perpetual worry about the impact of hyperglycemia on the developing fetal structures, leave many pregnant women feeling overwhelmed. HCL systems that can adapt to marked gestational changes in insulin sensitivity and pharmacokinetics may help to bridge the gap between the nonpregnant time in range glycemic targets (70-180 mg/dL) and the substantially more stringent pregnancy-specific targets (TIRp) (63-140 mg/dL) required for optimal obstetric and neonatal outcomes. Use of HCL (CamAPS FX system) was associated with a 10.5% higher TIRp, 10.2% less hyperglycemia, and 12.3% higher overnight TIRp. Clinical benefits were accompanied by 3.7 kg (8 lb) less gestational weight gain and consistently achieved across a representative patient population of insulin pump or injection users, across trial sites, and across maternal HbA1c categories. Working collaboratively, women, HCL technology, and health care teams achieved improved glycemia with less worry, less work, and more positive pregnancy experiences.

Quickest detection of bias injection attacks on the glucose sensor in the artificial pancreas under meal disturbances

Modern glucose sensors deployed in closed-loop insulin delivery systems, so-called artificial pancreas use wireless communication channels. While this allows a flexible system design, it also introduces vulnerability to cyberattacks. Timely detection and mitigation of attacks are imperative for device safety. However, large unknown meal disturbances are a crucial challenge in determining whether the sensor has been compromised or the sensor glucose trajectories are normal. We address this issue from a control-theoretic security perspective. In particular, a time-varying Kalman filter is employed to handle the sporadic meal intakes. The filter prediction error is then statistically evaluated to detect anomalies if present. We compare two state-of-the-art online anomaly detection algorithms, namely the χ2 and CUSUM tests. We establish a robust optimal detection rule for unknown bias injections. Even if the optimality holds only for the restrictive case of constant bias injections, we show that the proposed model-based anomaly detection scheme is also effective for generic non-stealthy sensor deception attacks through numerical simulations.

Closed-Loop Insulin Delivery Systems for People with Type 1 Diabetes and Chronic Very Poor Metabolic Control: It Works and Is Safe!

To evaluate the percentage of patients with type 1 diabetes (T1D) and very poor metabolic control who would agree to be treated with a hybrid closed-loop (HCL) insulin delivery system, and to assess metabolic improvement and safety. In a single center, we identified all patients aged >18 years with hemoglobin A1c (HbA1c) >11% (97 mmol/mol) before HCL treatment. We collected metabolic control and safety data up to 1 year post-HCL in those who accepted HCL after it was proposed to them. We identified 65 patients eligible for the study, 32 (50%) already used, or accepted to start using HCL. Patients were aged 18-49 years; mean(±standard deviation) baseline HbA1c was 12.5(±1.8)% (113 ± 20 mmol/mol). After 1 year, 25 patients (78%) were still using HCL and their mean HbA1c decreased to 9.4(±1.9)% (79 mmol/mol) (P < 0.001). The rate of acute metabolic events was similar during the year of follow-up to the rate in the 3 years before HCL initiation. HCL systems should be considered in patients with T1D and very poor metabolic control. ClinicalTrials registration no. NCT05282264.

Hybrid closed-loop insulin delivery system and postprandial glycemia

Hybrid closed-loop insulin delivery system and postprandial glycemia

Safety and performance of a hybrid closed-loop insulin delivery system with carbohydrate suggestion in adults with type 1 diabetes prone to hypoglycemia

AimsTo evaluate the safety and performance of a hybrid closed-loop (HCL) system with automatic carbohydrate suggestion in adults with type 1 diabetes (T1D) prone to hypoglycemia. MethodsA 32-hour in-hospital pilot study, including a night period, 4 meals and 2 vigorous unannounced 45-minute aerobic sessions, was conducted in 11 adults with T1D prone to hypoglycemia. The primary outcome was the percentage of time in range 70–180 mg/dL (TIR). Main secondary outcomes were time below range < 70 mg/dL (TBR < 70) and < 54 (TBR < 54). Data are presented as median (10th-90th percentile ranges). ResultsThe participants, 6 (54.5%) men, were 24 (22–48) years old, and had 22 (9–32) years of T1D duration. All of them regularly used an insulin pump and a continuous glucose monitoring system. The median TIR was 78.7% (75.6–91.2): 92.7% (68.2–100.0) during exercise and recovery period, 79.3% (34.9–100.0) during postprandial period, and 95.4% (66.4–100.0) during overnight period. The TBR < 70 and TBR < 54 were 0.0% (0.0–6.6) and 0.0% (0.0–1.2), respectively. A total of 4 (3–9) 15-g carbohydrate suggestions were administered per person. No severe acute complications occurred during the study. ConclusionsThe HCL system with automatic carbohydrate suggestion performed well and was safe in this population during challenging conditions in a hospital setting.

Real-World Glycemic Improvements with Hybrid Closed Loop Pumps in Youth with Type 1 Diabetes

Objective. The use of hybrid closed-loop insulin delivery systems, specifically the t:slim X2 insulin pump with Control IQ (CIQ), has demonstrated improvement in glycemic control in clinical trials and real-world settings. We sought to describe changes in glycemic control with use of CIQ in minority and nonminority youth. Research Design and Methods. This was a retrospective study of youth with type 1 diabetes (T1D) using CIQ over a 12-month period. Medical record data, pump data, and hemoglobin A1c (HbA1c) were collected from the visit prior to starting CIQ and at each clinic visit up to 12 months after starting CIQ. Continuous glucose monitor (CGM) data and HbA1c trajectory over time were compared to baseline and between minority and nonminority youth. Results. The study included 136 patients of whom 21 were minority youth (non-Hispanic Black and Hispanic), 50% were male, with median age of 13.3y, and median diabetes duration of 4.9y. After starting CIQ, baseline median HbA1c for the nonminority group decreased from 7.8% to 7.1% ( p &lt; 0.001 ), baseline median HbA1c for minority youth decreased from 9.8% to 7.8% ( p = 0.03 ), and the percentage of patients meeting target HbA1c &lt;7% increased from 26% to 45%. Both nonminority and minority youth had a significant increase in time in range and decrease of average CGM glucose ( p &lt; 0.05 ). Conclusions. HbA1c levels decreased in both minority and nonminority youth within 12 months of starting CIQ, and more patients reached the HbA1c target of less than 7%. Disparities in HbA1c between minority and nonminority youth remained and additional studies are warranted to improve this.

A Closed Loop Stimuli-Responsive Concanavalin A-Loaded Chitosan-Pluronic Hydrogel for Glucose-Responsive Delivery of Short-Acting Insulin Prototyped in RIN-5F Pancreatic Cells.

The optimal treatment of diabetes (in particular, type 1 diabetes-T1D) remains a challenge. Closed-loop systems (implants/inserts) provide significant advantages for glucose responsivity and providing real-time sustained release of rapid-acting insulin. Concanavalin A (ConA), a glucose affinity agent, has been used to design closed-loop insulin delivery systems but not without significant risk of leakage of ConA from the matrices and poor mechanical strength of the hydrogels impacting longevity and control of insulin release. Therefore, this work focused on employing a thermoresponsive co-forming matrix between Pluronic F-127 (PL) and structurally robust chitosan (CHT) via EDC/NHS coupling (i.e., covalent linkage of -NH2 from CHT and ConA to the -COOH of PL). The system was characterized for its chemical structure stability and integrity (FTIR, XRD and TGA), injectability, rheological parameters and hydrogel morphology (Texture Analysis, Elastosens TM Bio2 and SEM). The prepared hydrogels demonstrated shear-thinning for injectability with a maximum force of 4.9 ± 8.3 N in a 26G needle with sol-gel transitioning from 25 to 38 °C. The apparent yield stress value of the hydrogel was determined to be 67.47 Pa. The insulin loading efficiency within the hydrogel matrix was calculated to be 46.8%. Insulin release studies revealed glucose responsiveness in simulated glycemic media (4 and 10 mg/mL) over 7 days (97%) (305 nm via fluorescence spectrophotometry). The MTT studies were performed over 72 h on RIN-5F pancreatic cells with viability results >80%. Results revealed that the thermoresponsive hydrogel is a promising alternative to current closed-loop insulin delivery systems.

Monitoring Statistical Properties of Kalman Filter Residuals in an Artificial Pancreas to Detect Overnight Pump Malfunctions Causing Insulin Suspension

Continuous Subcutaneous Insulin Infusion (CSII) pumps are essential components in a closed-loop insulin delivery system (the so-called artificial pancreas), a recent therapeutic option for type 1 diabetes management. The efficacy of glucose regulation obtained by such a system might be severely compromised if the pump fails, possibly putting the patient’s safety at risk. Therefore, reliable and timely detection of these malfunctions is of critical practical importance. For this reason, in this study we present a novel algorithm specifically designed to detect overnight pump malfunctions resulting in insulin suspension. This algorithm adopts a real-time model-based approach and builds upon our team’s previous work, which relied solely on the magnitude of prediction residuals. In contrast, our current contribution extends the fault detection strategy by incorporating a comprehensive analysis of various statistical properties associated with the residuals. These properties encompass not only the magnitude but also the sample mean, median, variance, power, and other statistics related to the whiteness of the residuals. The considered linear black-box patients’ models have been individualized by estimating the model parameters on seven days of each patient’s data. Subsequently, the model is used in a Kalman filter to generate the predicted glucose levels with their confidence intervals. The effectiveness of the new strategy is compared to the previously proposed approach on an in-silico dataset generated by the UVa/Padova Type 1 Diabetes simulator, which has been accepted by the US Food and Drug Administration as a substitute for animal testing prior to human clinical trials with an artificial pancreas. The best performing detection strategy is based on the sign-sum test and achieves a recall of 91.3%, while generating less than 1 false alarm every 10 days. This improves the performance of our previous contribution that exhibits a comparable number of false alarms, but an overall lower recall metric, equal to 82.7%. The proposed algorithm is designed to complement other dedicated modules within the system, aiming to detect malfunctions related to glucose sensors (such as missed samples and pressure-induced sensitivity losses) as well as human errors (including missed meal announcements). A robustness analysis has been conducted to examine the performance of the algorithm in the presence of these additional anomalies. The results of these analyses demonstrated that the proposed algorithm maintains its sensitivity to pump malfunctions while exhibiting only a marginal increase in false alarms.

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

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. 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. 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]). 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.

COMPARATIVE EFFECTIVENESS AND SAFETY OF METHODS OF INSULIN DELIVERY AND GLUCOSE MONITORING FOR DIABETES MELLITUS: A SYSTEMATIC REVIEW

Introduction: Achieving glycemic control remains difficult for patients with type 1 diabetes. We compared the efficacy of day-and-night hybrid closed-loop insulin delivery to sensor-augmented pump therapy in individuals 6 years and older with suboptimally controlled type 1 diabetes.&#x0D; The aim: This article compared effectiveness and safety of methods of insulin delivery and glucose monitoring for diabetes mellitus.&#x0D; Methods: By comparing itself to the standards set by the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) 2020, this study was able to show that it met all of the requirements. So, the experts were able to make sure that the study was as up-to-date as it was possible to be. For this search approach, publications that came out between 2013 and 2023 were taken into account. Several different online reference sources, like Pubmed and SagePub, were used to do this. It was decided not to take into account review pieces, works that had already been published, or works that were only half done.&#x0D; Result: In the PubMed database, the results of our search brought up 166 articles, whereas the results of our search on SagePub brought up 143 articles. The results of the search conducted for the last year of 2013 yielded a total 116 articles for PubMed and 89 articles for SagePub. In the end, we compiled a total of 23 papers, 15 of which came from PubMed and eight of which came from SagePub. We included six research that met the criteria.&#x0D; Conclusion: The use of a hybrid closed-loop insulin delivery system in free-living conditions for a period of twelve weeks led to clinically relevant improvements in glycaemic control while simultaneously reducing the risk of hypoglycemia in suboptimally controlled type 1 diabetes in adults, adolescents, and children aged six years and older.

Auto adaptation of closed-loop insulin delivery system using continuous reward functions and incremental discretization

Several closed or hybrid loop controllers for Blood Glucose (BG) regulation, which are also known as Artificial Pancreas (AP) Systems or Automated Insulin Delivery systems (AIDs), are in development worldwide. Most AIDs are designed and evaluated for short-term performance, with a particular emphasis on the post-meal period. However, if controllers are not adapted properly to account for variations in physiology that affect Insulin Sensitivity (IS), the AIDs may perform inadequately. In this work, the performance of two Reinforcement Learning (RL) agents trained under both piecewise and continuous reward functions is evaluated in-silico for long-term adaptation of a Fully Automated Insulin Delivery (fAID) system. An automatic adaptive discretization scheme that expands the state space as needed is also implemented to avoid disproportionate state space exploration. The proposed agents are evaluated for long-term adaptation of the Automatic Regulation of Glucose (ARG) algorithm, considering variations in IS. Results show that both RL agents have improved performance compared to a rule-based decision-making approach and the baseline controller for the majority of the adult population. Moreover, the use of a continuous shaped reward function proves to enhance the performance of the agents further than a piecewise one.

914-P: Veteran Experiences with Hybrid Closed-Loop (HCL) Insulin Delivery Systems in Type 1 Diabetes (T1D)

While HCL systems are increasingly recommended, data regarding veteran experiences are limited. We performed semi-structured interviews to characterize veteran experiences with HCL systems at the VA Ann Arbor Healthcare System. We used qualitative description methodology to elicit participant experiences with HCL and identify factors that could improve practice. Semi-structured interviews were conducted with veterans with T1D using an HCL device for at least 6 months. The interview guide was developed based on a modified Theory of Planned Behavior, examining the domains of attitudes/knowledge, network support, and perceived behavioral control. Inductive thematic analysis of interview transcripts was performed to understand factors that contribute to the overall HCL experience. Nine HCL users (mean age 68 years, mean A1c 7.4%, mean diabetes duration 30 years, 78% Medtronic HCL users, 22% Tandem HCL users) were interviewed. Participants reported that HCL systems ease self-management burden, increase lifestyle flexibility, and enhance the perception of safety. However, challenges in alarm fatigue exist. Participants were satisfied with their outpatient multidisciplinary network support but noted significant gaps in inpatient support for HCL use. Lastly, participants reported an improved sense of confidence in diabetes management using HCL systems. Key facilitators for successful HCL use were a desire to stay healthy for their spouse and to avoid long-term diabetes complications. Our findings confirm that HCL systems improve self-management and enhance safety in veterans as well, similar with prior reports in non-veterans with T1D. Veterans felt supported in using these systems as outpatients though challenges remain for HCL systems in the inpatient setting. Future studies should focus on improving network support for inpatient use of these devices. Disclosure S.Azzawi: None. M.Dejonckheere: None. H.Thompson: None. K.Hurren: None. V.A.Leone: None. R.Busui: Board Member; American Diabetes Association, Consultant; Averitas Pharma, Inc., Lexicon Pharmaceuticals, Inc., Nevro Corp., Novo Nordisk, Roche Diagnostics, Procter &amp; Gamble, Research Support; Novo Nordisk, Medtronic, National Institutes of Health. G.Piatt: None. J.M.Lee: Advisory Panel; GoodRx, Consultant; Tandem Diabetes Care, Inc. K.R.Mizokami-stout: None. Funding National Institute of Diabetes and Digestive and Kidney Diseases (P30DK020572-43S1)

Electro-responsive silk fibroin microneedles for controlled release of insulin

To date, very limited work has been done on convenient and active control of insulin release. Herein, we report an electro-responsive insulin delivery system based on thiolated silk fibroin. The disulfide cross-linking points in TSF were reduced and broken to form sulfhydryl groups under electrification, which led to the increase of microneedle swelling degree and promoted insulin release. After power failure, the sulfhydryl group is oxidised to form disulfide bond crosslinking point again, resulting in the reduction of microneedle swelling degree and thus the reduction of release rate. The insulin loaded in the electro-responsive insulin delivery system showed good reversible electroresponsive release performance. The addition of graphene reduced the microneedle resistance and increased the drug release rate under current conditions. In vivo studies on type 1 diabetic mice show that electro-responsive insulin delivery system effectively controls the blood glucose before and after feeding by switching on and off the power supply, and this blood glucose control can be maintained within the safe range (100–200 mg/dL) for a long time (11h). Such electrically responsive delivery microneedles show potential for integration with glucose signal monitoring and are expected to build closed-loop insulin delivery systems.

Clinician Experiences With Hybrid Closed Loop Insulin Delivery Systems in Veterans With Type 1 Diabetes: Qualitative Study.

Hybrid closed loop (HCL) insulin pumps adjust insulin delivery based on input from a continuous glucose monitor. Several systems are FDA approved and associated with improved time in range, reduction in hemoglobin A1c, and decreased incidence of hypoglycemia. Major diabetes guidelines differ in their strength of recommendations regarding the use of HCL systems. Overall, limited information about the factors that influence HCL pump clinical decision-making is available, especially among endocrinology clinicians. The study objective is to describe the knowledge and attitudes, network support, and self-efficacy regarding HCL insulin delivery systems among endocrinology clinicians in one Veterans Affairs (VA) Healthcare System in the Midwest. Following a descriptive approach, this qualitative study used semistructured interviews and inductive thematic analysis. All endocrinologists, endocrinology fellows, and nurses in the endocrinology and metabolism department at one VA Healthcare System in the Midwest were invited to participate in one-on-one phone interviews. Thematic analysis explored clinician perspectives on HCL insulin pump systems. Participants (n=11) had experience within VA and university health care system endocrinology clinics. From their experiences, 4 themes were identified involving the evaluation and assessment of insulin pump candidates, prescribing challenges, clinical benefits of HCL pumps, and overall clinician confidence. Findings suggest that clinicians believe HCL systems have significant glycemic benefits but are not appropriate for all patients, especially those with cognitive impairment. HCL pump initiation is a multi-step process requiring an interdisciplinary team of health care clinicians to ensure patient and pump success. Furthermore, HCL systems improve clinician confidence in overall diabetes management.

Closed-loop insulin delivery in pregnant women with type 1 diabetes (CRISTAL): a multicentre randomized controlled trial – study protocol

BackgroundDespite increasing use of continuous glucose monitoring (CGM) and continuous subcutaneous insulin infusion (CSII, insulin pumps) in type 1 diabetes (T1D) in pregnancy, achieving recommended pregnancy glycaemic targets (3.5–7.8 mmol/L or 63–140 mg/dL) remains challenging. Consequently, the risk of adverse pregnancy outcomes remains high. Outside pregnancy, hybrid closed-loop (HCL) insulin delivery systems have led to a paradigm shift in the management of T1D, with 12% higher time in glucose target range (TIR) compared to conventional CSII. However, most commercially available HCL systems are currently not approved for use in pregnancy. This study aims to evaluate the efficacy, safety and cost-effectiveness of the MiniMed™ 780G HCL system (Medtronic) in T1D in pregnancy.MethodsIn this international, open-label, randomized controlled trial (RCT), we will compare the MiniMed™ 780G HCL system to standard of care (SoC) in T1D in pregnancy. Women aged 18–45 years with T1D diagnosis of at least one year, HbA1c ≤ 86 mmol/mol (≤ 10%), and confirmed singleton pregnancy up to 11 weeks 6 days will be eligible. After providing written informed consent, all participants will wear a similar CGM system (Guardian™ 3 or Guardian™ 4 CGM) during a 10-day run-in phase. After the run-in phase, participants will be randomised 1:1 to 780G HCL (intervention) or SoC [control, continuation of current T1D treatment with multiple daily injections (MDI) or CSII and any type of CGM] stratified according to centre, baseline HbA1c (< 53 vs. ≥ 53 mmol/mol or < 7 vs. ≥ 7%), and method of insulin delivery (MDI or CSII). The primary outcome will be the time spent within the pregnancy glucose target range, as measured by the CGM at four time points in pregnancy: 14–17, 20–23, 26–29, and 33–36 weeks. Prespecified secondary outcomes will be overnight TIR, time below range (TBR: <3.5 mmol/L or < 63 mg/dL), and overnight TBR. Other outcomes will be exploratory. The planned sample size is 92 participants. The study will end after postpartum discharge from hospital. Analyses will be performed according to intention-to-treat as well as per protocol.DiscussionThis large RCT will evaluate a widely used commercially available HCL system in T1D in pregnancy. Recruitment began in January 2021 and was completed in October 2022. Study completion is expected in May 2023.Trial registrationClinicalTrials.gov: NCT04520971. Registration date: August 20, 2020. https://clinicaltrials.gov/ct2/show/NCT04520971