Recent, rapid changes in the treatment of type 1 diabetes have allowed for commercialization of an "artificial pancreas" that is better described as a closed-loop controller of insulin delivery. This ...review presents the current state of closed-loop control systems and expected future developments with a discussion of the human factor issues in allowing automation of glucose control. The goal of these systems is to minimize or prevent both short-term and long-term complications from diabetes and to decrease the daily burden of managing diabetes. The closed-loop systems are generally very effective and safe at night, have allowed for improved sleep, and have decreased the burden of diabetes management overnight. However, there are still significant barriers to achieving excellent daytime glucose control while simultaneously decreasing the burden of daytime diabetes management. These systems use a subcutaneous continuous glucose sensor, an algorithm that accounts for the current glucose and rate of change of the glucose, and the amount of insulin that has already been delivered to safely deliver insulin to control hyperglycemia, while minimizing the risk of hypoglycemia. The future challenge will be to allow for full closed-loop control with minimal burden on the patient during the day, alleviating meal announcements, carbohydrate counting, alerts, and maintenance. The human factors involved with interfacing with a closed-loop system and allowing the system to take control of diabetes management are significant. It is important to find a balance between enthusiasm and realistic expectations and experiences with the closed-loop system.
Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes.
In this 6-month randomized, multicenter trial, patients with type 1 diabetes were ...assigned in a 2:1 ratio to receive treatment with a closed-loop system (closed-loop group) or a sensor-augmented pump (control group). The primary outcome was the percentage of time that the blood glucose level was within the target range of 70 to 180 mg per deciliter (3.9 to 10.0 mmol per liter), as measured by continuous glucose monitoring.
A total of 168 patients underwent randomization; 112 were assigned to the closed-loop group, and 56 were assigned to the control group. The age range of the patients was 14 to 71 years, and the glycated hemoglobin level ranged from 5.4 to 10.6%. All 168 patients completed the trial. The mean (±SD) percentage of time that the glucose level was within the target range increased in the closed-loop group from 61±17% at baseline to 71±12% during the 6 months and remained unchanged at 59±14% in the control group (mean adjusted difference, 11 percentage points; 95% confidence interval CI, 9 to 14; P<0.001). The results with regard to the main secondary outcomes (percentage of time that the glucose level was >180 mg per deciliter, mean glucose level, glycated hemoglobin level, and percentage of time that the glucose level was <70 mg per deciliter or <54 mg per deciliter 3.0 mmol per liter) all met the prespecified hierarchical criterion for significance, favoring the closed-loop system. The mean difference (closed loop minus control) in the percentage of time that the blood glucose level was lower than 70 mg per deciliter was -0.88 percentage points (95% CI, -1.19 to -0.57; P<0.001). The mean adjusted difference in glycated hemoglobin level after 6 months was -0.33 percentage points (95% CI, -0.53 to -0.13; P = 0.001). In the closed-loop group, the median percentage of time that the system was in closed-loop mode was 90% over 6 months. No serious hypoglycemic events occurred in either group; one episode of diabetic ketoacidosis occurred in the closed-loop group.
In this 6-month trial involving patients with type 1 diabetes, the use of a closed-loop system was associated with a greater percentage of time spent in a target glycemic range than the use of a sensor-augmented insulin pump. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; iDCL ClinicalTrials.gov number, NCT03563313.).
A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes.
In a 16-week, multicenter, randomized, open-label, ...parallel-group trial, we assigned, in a 3:1 ratio, children 6 to 13 years of age who had type 1 diabetes to receive treatment with the use of either a closed-loop system of insulin delivery (closed-loop group) or a sensor-augmented insulin pump (control group). The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring.
A total of 101 children underwent randomization (78 to the closed-loop group and 23 to the control group); the glycated hemoglobin levels at baseline ranged from 5.7 to 10.1%. The mean (±SD) percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter increased from 53±17% at baseline to 67±10% (the mean over 16 weeks of treatment) in the closed-loop group and from 51±16% to 55±13% in the control group (mean adjusted difference, 11 percentage points equivalent to 2.6 hours per day; 95% confidence interval, 7 to 14; P<0.001). In both groups, the median percentage of time that the glucose level was below 70 mg per deciliter was low (1.6% in the closed-loop group and 1.8% in the control group). In the closed-loop group, the median percentage of time that the system was in the closed-loop mode was 93% (interquartile range, 91 to 95). No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either group.
In this 16-week trial involving children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with the use of a closed-loop system than with the use of a sensor-augmented insulin pump. (Funded by Tandem Diabetes Care and the National Institute of Diabetes and Digestive and Kidney Diseases; ClinicalTrials.gov number, NCT03844789.).
Closed-loop control systems of insulin delivery may improve glycemic outcomes in young children with type 1 diabetes. The efficacy and safety of initiating a closed-loop system virtually are unclear.
...In this 13-week, multicenter trial, we randomly assigned, in a 2:1 ratio, children who were at least 2 years of age but younger than 6 years of age who had type 1 diabetes to receive treatment with a closed-loop system of insulin delivery or standard care that included either an insulin pump or multiple daily injections of insulin plus a continuous glucose monitor. The primary outcome was the percentage of time that the glucose level was in the target range of 70 to 180 mg per deciliter, as measured by continuous glucose monitoring. Secondary outcomes included the percentage of time that the glucose level was above 250 mg per deciliter or below 70 mg per deciliter, the mean glucose level, the glycated hemoglobin level, and safety outcomes.
A total of 102 children underwent randomization (68 to the closed-loop group and 34 to the standard-care group); the glycated hemoglobin levels at baseline ranged from 5.2 to 11.5%. Initiation of the closed-loop system was virtual in 55 patients (81%). The mean (±SD) percentage of time that the glucose level was within the target range increased from 56.7±18.0% at baseline to 69.3±11.1% during the 13-week follow-up period in the closed-loop group and from 54.9±14.7% to 55.9±12.6% in the standard-care group (mean adjusted difference, 12.4 percentage points equivalent to approximately 3 hours per day; 95% confidence interval, 9.5 to 15.3; P<0.001). We observed similar treatment effects (favoring the closed-loop system) on the percentage of time that the glucose level was above 250 mg per deciliter, on the mean glucose level, and on the glycated hemoglobin level, with no significant between-group difference in the percentage of time that the glucose level was below 70 mg per deciliter. There were two cases of severe hypoglycemia in the closed-loop group and one case in the standard-care group. One case of diabetic ketoacidosis occurred in the closed-loop group.
In this trial involving young children with type 1 diabetes, the glucose level was in the target range for a greater percentage of time with a closed-loop system than with standard care. (Funded by the National Institute of Diabetes and Digestive and Kidney Diseases; PEDAP ClinicalTrials.gov number, NCT04796779.).
Summary Background The safety and effectiveness of a continuous, day-and-night automated glycaemic control system using insulin and glucagon has not been shown in a free-living, home-use setting. We ...aimed to assess whether bihormonal bionic pancreas initialised only with body mass can safely reduce mean glycaemia and hypoglycaemia in adults with type 1 diabetes who were living at home and participating in their normal daily routines without restrictions on diet or physical activity. Methods We did a random-order crossover study in volunteers at least 18 years old who had type 1 diabetes and lived within a 30 min drive of four sites in the USA. Participants were randomly assigned (1:1) in blocks of two using sequentially numbered sealed envelopes to glycaemic regulation with a bihormonal bionic pancreas or usual care (conventional or sensor-augmented insulin pump therapy) first, followed by the opposite intervention. Both study periods were 11 days in length, during which time participants continued all normal activities, including athletics and driving. The bionic pancreas was initialised with only the participant's body mass. Autonomously adaptive dosing algorithms used data from a continuous glucose monitor to control subcutaneous delivery of insulin and glucagon. The coprimary outcomes were the mean glucose concentration and time with continuous glucose monitoring (CGM) glucose concentration less than 3·3 mmol/L, analysed over days 2–11 in participants who completed both periods of the study. This trial is registered with ClinicalTrials.gov , number NCT02092220. Findings We randomly assigned 43 participants between May 6, 2014, and July 3, 2015, 39 of whom completed the study: 20 who were assigned to bionic pancreas first and 19 who were assigned to the comparator first. The mean CGM glucose concentration was 7·8 mmol/L (SD 0·6) in the bionic pancreas period versus 9·0 mmol/L (1·6) in the comparator period (difference 1·1 mmol/L, 95% CI 0·7–1·6; p<0·0001), and the mean time with CGM glucose concentration less than 3·3 mmol/L was 0·6% (0·6) in the bionic pancreas period versus 1·9% (1·7) in the comparator period (difference 1·3%, 95% CI 0·8–1·8; p<0·0001). The mean nausea score on the Visual Analogue Scale (score 0–10) was greater during the bionic pancreas period (0·52 SD 0·83) than in the comparator period (0·05 0·17; difference 0·47, 95% CI 0·21–0·73; p=0·0024). Body mass and laboratory parameters did not differ between periods. There were no serious or unexpected adverse events in the bionic pancreas period of the study. Interpretation Relative to conventional and sensor-augmented insulin pump therapy, the bihormonal bionic pancreas, initialised only with participant weight, was able to achieve superior glycaemic regulation without the need for carbohydrate counting. Larger and longer studies are needed to establish the long-term benefits and risks of automated glycaemic management with a bihormonal bionic pancreas. Funding National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.
Hybrid closed-loop (HCL) artificial pancreas (AP) systems are now moving from research settings to widespread clinical use. In this study, the inControl algorithm developed by TypeZero Technologies ...was embedded to a commercial Tandem t:slim X2 insulin pump, now called Control-IQ, paired with a Dexcom G6 continuous glucose monitor and tested for superiority against sensor augmented pump (SAP) therapy. Both groups were physician-monitored throughout the clinical trial.
In a randomized controlled trial, 24 school-aged children (6-12 years) with type 1 diabetes (T1D) participated in a 3-day home-use trial at two sites: Stanford University and the Barbara Davis Center (50% girls, 9.6 ± 1.9 years of age, 4.5 ± 1.9 years of T1D, baseline hemoglobin A1c 7.35% ± 0.68%). Study subjects were randomized 1:1 at each site to either HCL AP therapy with the Control-IQ system or SAP therapy with remote monitoring.
The primary outcome, time in target range 70-180 mg/dL, using Control-IQ significantly improved (71.0% ± 6.6% vs. 52.8% ± 13.5%; P = 0.001) and mean sensor glucose (153.6 ± 13.5 vs. 180.2 ± 23.1 mg/dL; P = 0.003) without increasing hypoglycemia time <70 mg/dL (1.7% 1.3%-2.1% vs. 0.9% 0.3%-2.7%; not significant). The HCL system was active for 94.4% of the study period. Subjects reported that use of the system was associated with less time thinking about diabetes, decreased worry about blood sugars, and decreased burden in managing diabetes.
The use of the Tandem t:slim X2 with Control-IQ HCL AP system significantly improved time in range and mean glycemic control without increasing hypoglycemia in school-aged children with T1D during remote monitored home use.
Type 1 diabetes (T1D) is the most frequent form of diabetes in pediatric age, affecting more than 1.5 million people younger than age 20 years worldwide. Early and intensive control of diabetes ...provides continued protection against both microvascular and macrovascular complications, enhances growth, and ensures normal pubertal development. In the absence of definitive reversal therapy for this disease, achieving and maintaining the recommended glycemic targets is crucial. In the last 30 years, enormous progress has been made using technology to better treat T1D. In spite of this progress, the majority of children, adolescents and young adults do not reach the recommended targets for glycemic control and assume a considerable burden each day. The development of promising new therapeutic advances, such as more physiologic insulin analogues, pioneering diabetes technology including continuous glucose monitoring and closed loop systems as well as new adjuvant drugs, anticipate a new paradigm in T1D management over the next few years. This review presents insights into current management of T1D in youths.
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•Achieving and maintaining the recommended glycemic targets for type 1 diabetes is crucial to avoid complications.•Most youths do not reach the recommended targets for glycemic control.•The development of new advances in therapies will offer new treatment opportunities.•New insulin analogues, diabetes technology and adjuvant drugs showed promising results in improving glycemic control.
Background:
The accuracy of point-of-care blood glucose (BG) meters is important for the detection of dysglycemia, calculation of insulin doses, and the calibration of continuous glucose monitors. ...The objective of this study was to compare the accuracy of commercially available glucose meters in a challenging laboratory study using samples with a wide range of reference BG and hemoglobin values.
Methods:
Fresh, discarded blood samples from a hospital STAT laboratory were either used without modification, spiked with a glucose solution, or incubated at 37°C to produce 347 samples with an even distribution across reference BG levels from 20 to 440 mg/dl and hemoglobin values from 9 to 16 g/dl. We measured the BG of each sample with 17 different commercially available glucose meters and the reference method (YSI 2300) at the same time. We determined the mean absolute relative difference (MARD) for each glucose meter, overall and stratified by reference BG and by hemoglobin level.
Results:
The accuracy of different meters widely, exhibiting a range of MARDs from 5.6% to 20.8%. Accuracy was lower in the hypoglycemic range, but was not consistently lower in samples with anemic blood hemoglobin levels.
Conclusions:
The accuracy of commercially available glucose meters varies widely. Although the sample mix in this study was much more challenging than those that would be collected under most use conditions, some meters were robust to these challenges and exhibited high accuracy in this setting. These data on relative accuracy and robustness to challenging samples may be useful in informing the choice of a glucose meter.
Artificial pancreas (AP) systems have been shown to improve glycemic control throughout the day and night in adults, adolescents, and children. However, AP testing remains limited during intense and ...prolonged exercise in adolescents and children. We present the performance of the Tandem Control-IQ AP system in adolescents and children during a winter ski camp study, where high altitude, low temperature, prolonged intense activity, and stress challenged glycemic control.
In a randomized controlled trial, 24 adolescents (ages 13-18 years) and 24 school-aged children (6-12 years) with Type 1 diabetes (T1D) participated in a 48 hours ski camp (∼5 hours skiing/day) at three sites: Wintergreen, VA; Kirkwood, and Breckenridge, CO. Study participants were randomized 1:1 at each site. The control group used remote monitored sensor-augmented pump (RM-SAP), and the experimental group used the t: slim X2 with Control-IQ Technology AP system. All subjects were remotely monitored 24 hours per day by study staff.
The Control-IQ system improved percent time within range (70-180 mg/dL) over the entire camp duration: 66.4 ± 16.4 vs 53.9 ± 24.8%; P = .01 in both children and adolescents. The AP system was associated with a significantly lower average glucose based on continuous glucose monitor data: 161 ± 29.9 vs 176.8 ± 36.5 mg/dL; P = .023. There were no differences between groups for hypoglycemia exposure or carbohydrate interventions. There were no adverse events.
The use of the Control-IQ AP improved glycemic control and safely reduced exposure to hyperglycemia relative to RM-SAP in pediatric patients with T1D during prolonged intensive winter sport activities.
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