Closed-loop Insulin Delivery System Research Articles

The SMHP™ position statement on therapeutic carbohydrate reduction for type 1 diabetes

This article presents the position of the Society of Metabolic Health Practitioners (SMHP) regarding therapeutic carbohydrate reduction (TCR) nutrition interventions for type 1 diabetes mellitus (T1DM). A modified Delphi methodology was used to arrive at a consensus consisting of several focus groups, multiple rounds, and an anonymous survey. The field of endocrinology has seen many new advances for the treatment of T1DM including hybrid closed-loop insulin delivery systems and continuous glucose monitors for better glycaemic control, monoclonal antibodies to delay the onset of disease and increased access to paediatric endocrinologists, among many other noteworthy achievements. Despite these advancements, standard of care approaches to T1DM result in higher than acceptable morbidity and mortality, with a high prevalence of microvascular and macrovascular complications. Insulin resistance in type 1 diabetes is an independent risk factor for adverse outcomes even in well controlled type 1 diabetes. In 2021, only 21% of adults with T1DM in the United States achieved the American Diabetes Association’s (ADA’s) target haemoglobin A1C goal of 7.0%, while data in the paediatric and adolescent population have demonstrated worse glycaemic control. Supported by observational and interventional evidence, the SMHP advocates for the reevaluation of the prevailing nutritional therapy for T1DM with more broad consideration for TCR. The SMHP recommends open access and clinical support for TCR nutrition interventions for individuals with T1DM of all ages and calls upon the medical community to help foster more attention and research on TCR for T1DM.

The Feasibility of an Experimental Hypobaric Simulation to Evaluate the Safety of Closed-Loop Insulin Delivery Systems in Flight-Related Atmospheric Pressure Changes.

Hybrid closed-loop (HCL) systems remain underexplored within aviation, and as atmospheric pressure changes can independently affect insulin pumps and continuous glucose monitoring readings, this preliminary study assessed the feasibility of HCL safety evaluation, in both fasting and post-prandial states, by using hypobaric chamber to simulate flights. Participants with type 1 diabetes and on HCL were studied: Medtronic Guardian 4-Medtronic 780G-SmartGuard (n = 4), Dexcom G6-Omnipod DASH-Android APS (n = 1), and Dexcom G6-Ypsomed Pump-CamAPS (n = 1). Flight cabin pressures of 550 mmHg and 750 mmHg were simulated in a hypobaric chamber. Seven-hundred-50 glucose measurements were taken, with glucose levels demonstrating a stable decline to 4 mmol/L during fasting. To maintain a tight fasting and post-prandial glucose range across the different pressure settings, the HCL administered insulin as expected. While not demonstrating any apparent issues, repeating flight simulation protocol with other systems, examining longer flights, and undertaking larger, powered randomised controlled trials can confirm their safety in aviation.

Innovations in Drug Delivery: From Microtechnology to Targeted Therapeutics

Drug delivery systems are developed to maximize drug efficacy and minimize side effects. As drug delivery technologies improve, the drug becomes safer and more comfortable for patients to use. The study on advanced drug delivery systems aims to increase patient compliance, decrease adverse effects, and improve treatment efficacy. Furthermore, the goal of these systems is to deliver drugs to particular body tissues or cells in a targeted manner, which should enhance treatment outcomes. During the last seven decades, extraordinary progress has been made in drug delivery technologies, such as systems for long-term delivery for months and years, localized delivery, and targeted delivery. In this review, we explain the general principles of several advanced drug delivery systems, their introduction objective, components, mechanism, functioning principle, and application. The implantable polymeric drug delivery system, cardiac pacemaker, prefilled dual chamber device, closed-loop insulin delivery system, hepatic infusion pumps, MEMS devices, inhaled insulin devices, and hydrogel-forming microneedles are among the medical devices that are being discussed in this article as being at the forefront of technological innovation in medicine. For a variety of medical diseases, these devices provide minimally invasive procedures, real-time monitoring, and more accurate drug delivery. The scope of medical treatment and monitoring procedures is changing due to the integration of cutting-edge materials and technology. By increasing convenience, decreasing adverse effects, and increasing efficacy, these cutting-edge solutions directly help patients. Furthermore, the adoption of advanced drug delivery systems has demonstrated promising results in enhancing patient compliance and treatment outcomes. By increasing the bioavailability and pharmacokinetics of pharmaceuticals, these systems have the potential to transform the fields of drug delivery and personalized medicine. However, the field also faces challenges in overcoming physicochemical barriers and biological unknowns. Challenges facing the advanced drug delivery systems industry include complicated formulation requirements, regulatory obstacles, and the need for new technologies to enhance patient outcomes and therapeutic efficacy. Strict intellectual property rules and competition from generic drug manufacturers can also directly hinder the expansion and financial success of businesses in this field. To progress, the field should focus on translatable research ideas, develop realistic goals, and most importantly, diversify technologies. This emphasis on diversity will inspire new ideas and approaches, leading to the development of more effective, patient-friendly drug delivery systems.

Women’s and Partners’ Experiences With a Closed-loop Insulin Delivery System to Manage Type 1 Diabetes in the Postpartum Period

ObjectivesClosed-loop insulin delivery has the potential to offer women with type 1 diabetes a break from intense diabetes self-care efforts postpartum. Our aim in this study was to explore the views and opinions of hybrid closed-loop users and their partners in the first 24 weeks postpartum. MethodsThis qualitative study was embedded in a controlled study of women with type 1 diabetes randomized to closed-loop insulin delivery (MiniMed™ 670G or 770G) or sensor-augmented pump use for 1 to 11 weeks 6 days postpartum, with all on closed-loop delivery from 12 to 24 weeks postpartum. Semistructured interviews were conducted with 16 study participants and their partners at 12 and 24 weeks postpartum. Thematic analyses were used to examine participants’ and partners’ experiences. ResultsParticipants’ positive perceptions of closed-loop use related to reduced hypoglycemia, in contrast to previous experiences with nonautomated insulin delivery. These perceptions were balanced against frustrations with the system, allowing blood glucose levels to be higher than desired. Closed-loop use did not influence infant feeding choice, but infant feeding and care impacted participants’ diabetes management. Partners expressed uncertainty about the closed loop taking away control from participants who were highly skilled with diabetes self-management. ConclusionsParticipants reported that closed-loop insulin delivery resulted in less time spent in hypoglycemia when compared with the previously used nonautomated delivery. Yet, participants desired a greater understanding of the workings of the closed-loop algorithm. Our study provides potential users with realistic expectations about the experience with the MiniMed 670G or 770G closed-loop system in the postpartum period.

Patient Satisfaction and Clinical Experience With the Tandem t:slim X2 With Control-IQ Technology Advanced Hybrid Closed-Loop Insulin Delivery System.

The purpose of this study was to assess patient satisfaction and clinical experience with the t:slim X2 with Control-IQ Technology automated insulin delivery system. This descriptive study used a retrospective electronic health record review of all individuals trained on the Control-IQ system between December 2019 and April 2022 in one adult endocrinology practice. A total of 99 patients using the Control-IQ system for at least 3 months completed the glucose monitoring satisfaction survey (GMSS). The primary outcome was overall satisfaction with the system as measured by the GMSS. Secondary outcomes included changes in A1C from baseline at 3, 6, and 12 months; the association between GMSS scores and A1C levels; and the use of the system's sleep activity feature to achieve lower A1C levels. The overall satisfaction score for patients using the system was 4.0 ± 0.6 (possible score range 1-5). A1C decreased by 0.6% 3 months, 0.7% at 6 months, and 0.8% at 12 months. Participants with A1C levels ≤7% did not experience greater satisfaction compared to those with higher A1C levels. Participants using the Control-IQ system reported a high rate of overall satisfaction and experienced significant reductions from baseline A1C at 3, 6, and 12 months.

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.