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![Schematic of the configuration of closed-loop insulin delivery. A CGM transmits information about interstitial glucose concentrations to an algorithm hosted on a smartphone or insulin pump that translates information from the glucose sensor and computes the amount of insulin to deliver. An insulin pump delivers a rapid-acting insulin analogue subcutaneously. Insulin delivery is modulated in real time by the control algorithm. Communication between system components is wireless. CSII, continuous subcutaneous insulin infusion. Figure adapted from [36]. This figure is available as part of a downloadable slideset](publication/349096677/figure/fig1/AS:988441084956672@1612674127373/Schematic-of-the-configuration-of-closed-loop-insulin-delivery-A-CGM-transmits.png)
Schematic of the configuration of closed-loop insulin delivery. A CGM transmits information about interstitial glucose concentrations to an algorithm hosted on a smartphone or insulin pump that translates information from the glucose sensor and computes the amount of insulin to deliver. An insulin pump delivers a rapid-acting insulin analogue subcutaneously. Insulin delivery is modulated in real time by the control algorithm. Communication between system components is wireless. CSII, continuous subcutaneous insulin infusion. Figure adapted from [36]. This figure is available as part of a downloadable slideset
Source publication
Advances in diabetes technologies have enabled the development of automated closed-loop insulin delivery systems. Several hybrid closed-loop systems have been commercialised, reflecting rapid transition of this evolving technology from research into clinical practice, where it is gradually transforming the management of type 1 diabetes in children...
Similar publications
Purpose of Review: This review aims to address the actual state of the most advanced diabetes devices, as follows: continuous subcutaneous insulin infusions (CSII), continuous glucose monitoring systems (CGM), hybrid-closed loop (HCL) systems, and "Do-it-yourself" Artificial Pancreas Systems (DIYAPS) in children, adolescents, and young adults. This...
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,...
Citations
... mean glucose and CV were also improved more with the AID system than the SAP. Despite advances in insulin pump technology [5,17,18], many individuals still do not use insulin pumps [4,10]. An important factor contributing to patient reluctance to use pumps is discomfort with the tube of the insulin infusion set that delivers insulin from a pump to subcutaneous tissue [19]. ...
Aims/hypothesis
This study compares the efficacy and safety of a tubeless, on-body automated insulin delivery (AID) system with that of a tubeless, on-body sensor-augmented pump (SAP).
Methods
This multicentre, parallel-group, RCT was conducted at 13 tertiary medical centres in South Korea. Adults aged 19–69 years with type 1 diabetes who had HbA1c levels of <85.8 mmol/mol (<10.0%) were eligible. The participants were assigned at a 1:1 ratio to receive a tubeless, on-body AID system (intervention group) or a tubeless, on-body SAP (control group) for 12 weeks. Stratified block randomisation was conducted by an independent statistician. Blinding was not possible due to the nature of the intervention. The primary outcome was the percentage of time in range (TIR), blood glucose between 3.9 and 10.0 mmol/l, as measured by continuous glucose monitoring. ANCOVAs were conducted with baseline values and study centres as covariates.
Results
A total of 104 participants underwent randomisation, with 53 in the intervention group and 51 in the control group. The mean (±SD) age of the participants was 40±11 years. The mean (±SD) TIR increased from 62.1±17.1% at baseline to 71.5±10.7% over the 12 week trial period in the intervention group and from 64.7±17.0% to 66.9±15.0% in the control group (difference between the adjusted means: 6.5% [95% CI 3.6%, 9.4%], p<0.001). Time below range, time above range, CV and mean glucose levels were also significantly better in the intervention group compared with the control group. HbA1c decreased from 50.9±9.9 mmol/mol (6.8±0.9%) at baseline to 45.9±7.4 mmol/mol (6.4±0.7%) after 12 weeks in the intervention group and from 48.7±9.1 mmol/mol (6.6±0.8%) to 45.7±7.5 mmol/mol (6.3±0.7%) in the control group (difference between the adjusted means: −0.7 mmol/mol [95% CI −2.0, 0.8 mmol/mol] (−0.1% [95% CI −0.2%, 0.1%]), p=0.366). No diabetic ketoacidosis or severe hypoglycaemia events occurred in either group.
Conclusions/interpretation
The use of a tubeless, on-body AID system was safe and associated with superior glycaemic profiles, including TIR, time below range, time above range and CV, than the use of a tubeless, on-body SAP.
Trial registration
Clinical Research Information Service (CRIS) KCT0008398
Funding
The study was funded by a grant from the Korea Medical Device Development Fund supported by the Ministry of Science and ICT; the Ministry of Trade, Industry and Energy; the Ministry of Health and Welfare; and the Ministry of Food and Drug Safety (grant number: RS-2020-KD000056).
Graphical Abstract
... Also, the small number of trials included may not provide a meaningful interpretation of the publication bias and funnel plot. Third, the studies used different pump models and algorithms within the HCL group, lacking representativeness of the open-source automated insulin delivery system (42,43). Fourth, crossover studies were excluded due to concerns regarding potential bias in the trial design. ...
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 glucose level 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.
Keywords
Closed-loop; glucose control; diabetes technology; type 1 diabetes, meta-analysis
... 22 However, it should be recognized that, while glucose control with exercise can be significantly enhanced using AID, all commercially available devices in this class remain limited by the pharmacokinetics of subcutaneously delivered rapid-acting insulin and therefore are hybrid systems requiring manual meal-time insulin dosing. 23,24 Most importantly, there is a delayed offset in the glucose lowering action of insulin already delivered, which is more significantly prolonged in comparison with its relatively rapid-acting onset. 25,26 In addition, evidence suggests that the so named ''ultra-rapid'' acting insulin formulations currently available provide no clinically significant glycemic advantage. ...
The physical and psychological benefits of exercise are particularly pertinent to people with type 1 diabetes (T1D). The variability in subcutaneous insulin absorption and the delay in offset and onset in glucose lowering action impose limitations, given the rapidly varying insulin requirements with exercise. Simultaneously, there are challenges to glucose monitoring. Consequently, those with T1D are less likely to exercise because of concerns regarding glucose instability. While glucose control with exercise can be enhanced using automated insulin delivery (AID), all commercially available AID systems remain limited by the pharmacokinetics of subcutaneous insulin delivery. Although glycemic responses may vary with exercises of differing intensities and durations, the principles providing the foundation for guidelines include minimization of insulin on board before exercise commencement, judicious and timely carbohydrate supplementation, and when possible, a reduction in insulin delivered in anticipation of planned exercise. There is an increasing body of evidence in support of superior glucose control with AID over manual insulin dosing in people in T1D who wish to exercise. The MiniMed™ 780G AID system varies basal insulin delivery with superimposed automated correction boluses. It incorporates a temporary (elevated glucose) target of 8.3 mmol/L (150 mg/dL) and when it is functioning, the autocorrection boluses are stopped. As the device has recently become commercially available, there are limited data assessing glucose control with the MiniMed™ 780G under exercise conditions. Importantly, when exercise was planned and implemented within consensus guidelines, %time in range and %time below range targets were met. A practical approach to exercising with the device is provided with illustrative case studies. While there are limitations to spontaneity imposed on any AID device due to the pharmacokinetics associated with the subcutaneous delivery of current insulin formulations, the MiniMed™ 780G system provides people with T1D an excellent option for exercising safely if the appropriate strategies are implemented.
... However, as with all current HCL systems, the MiniMedÔ 780G system is not fully automated and requires users to enter the estimated amount of carbohydrate consumed for meal announcement. 14 Given the lack of complete automation, there has recently been heightened interest in simplifying the approach to meal announcement in people using HCL systems and understanding the abilities and limits of HCL systems regarding unannounced snacks and meals. The use of simplified systems for physicians, paramedical personnel, and/or patients for carbohydrate counting to assist in with self-adjustment of insulin dose was introduced many years ago. ...
Background and Aims: Carbohydrate counting is a well-established tool for self-management of type 1 diabetes (T1D) and can improve glycemic control and potentially reduce long-term complication risk. However, it can also be burdensome, error-prone, and complicated for the patient. A randomized controlled trial was conducted to investigate glycemic control with carbohydrate counting ("flex") versus simplified meal announcement ("fix") in adolescents with T1D using the MiniMed™ 780G system. The present study reports follow-up data to 12 months. Methods: Adolescents with T1D were randomly assigned 1:1 to use the MiniMed™ 780G system alongside the flex versus fix approaches. Participants were followed for 12 months with outcomes recorded at 3, 6, 9, and 12 months. The primary endpoint was the difference in time-in-range (TIR), and secondary endpoints included glycated hemoglobin (HbA1c) and other glucose and insulin metrics. Results: At 12 months, TIR (proportion of time with sensor glucose 70-180 mg/dL) was significantly lower in the fix versus flex group (72.9% vs. 80.1%, respectively; P = 0.001). There was no significant difference in HbA1c between the fix (6.8% ± 0.5%) and flex groups (6.5% ± 0.5%) at 12 months (P = 0.092), and mean HbA1c was below 7% at all time points in both arms. Conclusions: Glycemic control with simplified meal announcement was maintained over 12 months. On average, the international consensus targets were met in both arms for all time points. The simplified approach represents a viable alternative to carbohydrate counting, particularly in people who find the latter burdensome; however, carbohydrate counting resulted in superior TIR. This study is registered with ClinicalTrials.gov, number NCT05069727.
... Outside of pregnancy, use of HCL is associated with improved glycemic outcomes (both HbA 1c and CGM metrics) as well as improved patient-reported outcomes (27,28). Randomized controlled trials consistently demonstrate lower HbA 1c and higher percentage of time in range and quality of life benefits in children, young people, and adults with T1D (27,(29)(30)(31). ...
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.
... [2][3][4][5][6][7] Automated insulin delivery (AID) systems, which combine an insulin pump, continuous glucose monitor (CGM), and a dosing algorithm to automatically adjust insulin delivery, have been shown to be safe and effective for people with T1D in clinical trials. [8][9][10][11][12][13][14] Beyond their performance in a controlled study environment, several AID systems have demonstrated successful use in a real-world setting, [15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] with glycemic outcomes from large-scale clinical trial and real-world studies across systems compiled in a recent review article. 24 Further, two recent real-world studies demonstrated improvements in time in range (TIR, 70-180 mg/dL) and time spent in hypoglycemia (<70 mg/dL) for both children and adults with T1D initiating different AID systems in a clinic setting. ...
Background: The Omnipod® 5 Automated Insulin Delivery System was associated with favorable glycemic outcomes for people with type 1 diabetes (T1D) in two pivotal clinical trials. Real-world evidence is needed to explore effectiveness in nonstudy conditions. Methods: A retrospective analysis of the United States Omnipod 5 System users (aged ≥2 years) with T1D and sufficient data (≥90 days of data; ≥75% of days with ≥220 continuous glucose monitor readings/day) available in Insulet Corporation's device and person-reported datasets as of July 2023 was performed. Target glucose setting usage (i.e., 110-150 mg/dL in 10 mg/dL increments) was summarized and glycemic outcomes were examined. Subgroup analyses of those using the lowest average glucose target (110 mg/dL) and stratification by baseline characteristics (e.g., age, prior therapy, health insurance coverage) were conducted. Results: In total, 69,902 users were included. Multiple and higher glucose targets were more commonly used in younger age groups. Median percentage of time in range (TIR; 70-180 mg/dL) was 68.8%, 61.3%, and 53.6% for users with average glucose targets of 110, 120, and 130-150 mg/dL, respectively, with minimal time <70 mg/dL (all median <1.13%). Among those with an average glucose target of 110 mg/dL (n = 37,640), median TIR was 65.0% in children and adolescents (2-17 years) and 69.9% in adults (≥18 years). Subgroup analyses of users transitioning from Omnipod DASH or multiple daily injections and of Medicaid/Medicare users demonstrated favorable glycemic outcomes among these groups. Conclusion: These glycemic outcomes from a large and diverse sample of nearly 70,000 children and adults demonstrate effective use of the Omnipod 5 System under real-world conditions.
... Automated insulin delivery (AID) systems have greatly enhanced glycemic control in patients with type 1 diabetes (T1D), concurrently reducing the risk of hypoglycemia. [1][2][3] To date, ''advanced hybrid closed loop'' (AHCL) systems are at the forefront of this technological progression for T1D treatment. 4,5 These systems, integrating an insulin pump with a continuous glucose monitoring (CGM) system, automatically adjust basal insulin infusion based on real-time glucose monitoring, and also manage corrective bolus administration. ...
Automated insulin delivery (AID) systems have improved glycaemic control in individuals with type 1 diabetes (T1D). The "advanced hybrid closed-loop" (AHCL) stands out as the most recent development in AID systems for T1D management. In a real-world clinical environment, we retrospectively evaluated the AHCL Minimed™ 780G system's effectiveness to achieve and sustain glycaemic control over a 12 month period in 22 adult T1D subjects. Within just 14 days of activating the automatic mode, the AHCL Minimed™ 780G system showed rapid improvements in glycaemic control, which persisted for 12 months. These findings underscore the effectiveness of AHCL systems in achieving and preserving optimal glycaemic control in adults with T1D over a very long follow-up.
... The three essential elements of a closed-loop system used as medical devices are the implanted biosensor, controller, and operating mechanism. There are many emerging examples of closed-loop control systems in the healthcare industry that can improve or replace existing physiological functions [20][21][22][23][24][25]. Implanted biosensors can monitor various physiological conditions, such as circulating drug concentration or bio-marker levels. ...
Biosignal monitoring using wearable and implantable devices (WIMDs) is driving the advent of highly personalized medicine. However, such devices may suffer from the same faulty behavior as any electronic system and may furthermore be targeted by malicious actors seeking to do harm. Closed-loop medical control systems, which monitor biosignals for data acquisition, contain and interact with many other components, any of which may be maliciously targeted or suffer a naturally occurring fault. Any measure aiming to improve the security and reliability of these systems must also consider the interplay between each component. In this paper, we explore the vulnerability of closed-loop medical control systems considering both individual system components and the system as a whole and utilize a predictive model based on a nonlinear autoregressive neural network (NARNN) to detect and correct faulty behavior in real time. We present a case study using a human bladder pressure dataset from nine subjects undergoing acute urodynamics testing. Signals are corrupted to simulate faulty sensor readings or malicious attacks and then processed using a custom bladder event detection algorithm designed for use in a closed-loop neuromodulation system. Using the proposed technique, 100% of faulty measurements were detected and corrected, so the control algorithm induced no additional false positives. We present the circuit-level implementation of the NARNN suitable for on-chip machine learning (ML)/artificial intelligence (AI) applications. We synthesized and generated the layout of the NARNN architecture in SAED 32 nm technology. The implementation requires an area of \(0.022~mm^2\) and a total power consumption of 0.31 mW, which is suitable for WIMDs.
... The glucose target can be manually raised between 80 -200 mg/dL (4.4 -11.1 mmol/L) for exercise. It also offers a "Boost mode", when more insulin is needed, and an "Ease-off mode", when less insulin is required, which can both be useful during and post-exercise [73][74][75] . Unfortunately, however, no specific exercise studies on CamAPS are currently available. ...
Physical activity and exercise have many beneficial effects on general and type 1 diabetes (T1D) specific health and are recommended for individuals with T1D. Despite these health benefits, many people with T1D still avoid exercise since glycemic management during physical activity poses substantial glycemic and psychological challenges – which hold particularly true for unannounced exercise when using an AID system. Automated insulin delivery (AID) systems have demonstrated their efficacy in improving overall glycemia and in managing announced exercise in numerous studies. They are proven to increase time in range (70-180 mg/dL) and can especially counteract nocturnal hypoglycemia, even when evening exercise was performed. AID-systems consist of a pump administering insulin as well as a CGM sensor (plus transmitter), both communicating with a control algorithm integrated into a device (insulin pump, mobile phone/smart watch). Nevertheless, without manual pre-exercise adaptions, these systems still face a significant challenge around physical activity. Automatically adapting to the rapidly changing insulin requirements during unannounced exercise and physical activity is still the Achilles' heel of current AID systems. There is an urgent need for improving current AID-systems to safely and automatically maintain glucose management without causing derailments – so that going forward, exercise announcements will not be necessary in the future. Therefore, this narrative literature review aimed to discuss technological strategies to how current AID-systems can be improved in the future and become more proficient in overcoming the hurdle of unannounced exercise. For this purpose, the current state-of-the-art therapy recommendations for AID and exercise as well as novel research approaches are presented along with potential future solutions - in order to rectify their deficiencies in the endeavor to achieve fully automated AID-systems even around unannounced exercise.
... Clinical trials affirm their effectiveness and safety for T1DM outpatient management [94]. Compared to sensor-augmented pumps, CLSs enhance glucose control, reflected by an average 11% increase in TiR, reduce hyperglycemia and hypoglycemia, and improve glycated hemoglobin levels according to a recent randomized controlled trial [95][96][97][98]. ...
Achieving optimal glucose control in individuals with type 1 diabetes (T1DM) continues to pose a significant challenge. While continuous insulin infusion systems have shown promise as an alternative to conventional insulin therapy, there remains a crucial need for greater awareness regarding the necessary adaptations for various special circumstances. Nutritional choices play an essential role in the efficacy of diabetes management and overall health status for patients with T1DM. Factors such as effective carbohydrate counting, assessment of the macronutrient composition of meals, and comprehending the concept of the glycemic index of foods are paramount in making informed pre-meal adjustments when utilizing insulin pumps. Furthermore, the ability to handle such situations as physical exercise, illness, pregnancy, and lactation by making appropriate adjustments in nutrition and pump settings should be cultivated within the patient–practitioner relationship. This review aims to provide healthcare practitioners with practical guidance on optimizing care for individuals living with T1DM. It includes recommendations on carbohydrate counting, managing mixed meals and the glycemic index, addressing exercise-related challenges, coping with illness, and managing nutritional needs during pregnancy and lactation. Additionally, considerations relating to closed-loop systems with regard to nutrition are addressed. By implementing these strategies, healthcare providers can better equip themselves to support individuals with T1DM in achieving improved diabetes management and enhanced quality of life.
