Health-Related Quality of Life and Treatment Satisfaction in Parents and Children with Type 1 Diabetes Using Closed-Loop Control.
Diabetes technology & therapeutics
Extended Use of the Control-IQ Closed-Loop Control System in Children With Type 1 Diabetes.
INTRODUCTION: Hybrid closed-loop systems increase time-in-range and reduce glycemic variability. Person-reported outcomes (PROs) are essential to assess the utility of new devices and their impact on quality of life. This manuscript focuses on the PROs for pediatric participants (ages 6-13 yrs) with type 1 diabetes (T1D) and their parents during a trial using the Tandem Control-IQ system, which was shown to increase time-in-range and improve other glycemic metrics.METHODS: One-hundred-one children 6 to 13 years old with T1D were randomly assigned to closed-loop control (CLC) or sensor augmented pump (SAP) in a 16-week randomized clinical trial with extension to 28 weeks during which the SAP group crossed over to CLC. Health-related quality of life and treatment satisfaction measures were obtained from children and their parents at baseline, 16 weeks, and 28 weeks.RESULTS: Neither the children in the CLC group nor their parents had statistically significant changes in PRO outcomes compared with the SAP group at the end of the 16-week RCT and the 28-week extension. Parents in the CLC group reported non-significant improvements in some PRO scores when compared with the SAP group at 16 weeks, which were sustained at 28 weeks. Sleep scores for parents improved from "poor sleep quality" to "adequate sleep quality" between baseline and 16 weeks, however, the change in scores was not statistically different between groups.CONCLUSIONS: Children with T1D who used the Control-IQ system did not experience increased burden compared with those using SAP based on person-reported outcomes from the children and their parents.
View details for DOI 10.1089/dia.2020.0532
View details for PubMedID 33404325
Safety and Performance of the Tandem t:slim X2 with Control-IQ Automated Insulin Delivery System in Toddlers and Preschoolers.
Diabetes technology & therapeutics
OBJECTIVE: To further evaluate the safety and efficacy of the Control-IQ closed-loop control (CLC) system in children with type 1 diabetes.RESEARCH DESIGN AND METHODS: After a 16-week randomized clinical trial (RCT) comparing CLC with sensor-augmented pump (SAP) therapy in 101 children age 6-13 years old with type 1 diabetes, 22 participants in the SAP group initiated use of the CLC system (referred to as SAP-CLC cohort), and 78 participants in the CLC group continued use of CLC (CLC-CLC cohort) for 12 weeks.RESULTS: In the SAP-CLC cohort, mean percentage of time in range 70-180 mg/dL (TIR) increased from 55 ± 13% using SAP during the RCT to 65 ± 10% using CLC (P < 0.001), with 36% of the cohort achieving TIR >70% plus time <54 mg/dL <1% compared with 14% when using SAP (P = 0.03). Substantial improvement in TIR was seen after the 1st day of CLC. Time <70 mg/dL decreased from 1.80 to 1.34% (P < 0.001). In the CLC-CLC cohort, mean TIR increased from 53 ± 17% prerandomization to 67 ± 10% during the RCT and remained reasonably stable at 66 ± 10% through the 12 weeks post-RCT. No episodes of diabetic ketoacidosis or severe hypoglycemia occurred in either cohort.CONCLUSIONS: This further evaluation of the Control-IQ CLC system supports the findings of the preceding RCT that use of a closed-loop system can safely improve glycemic control in children 6-13 years old with type 1 diabetes from the 1st day of use and demonstrates that these improvements can be sustained through 28 weeks of use.
View details for DOI 10.2337/dc20-1729
View details for PubMedID 33355258
Clinical Management and Pump Parameter Adjustment of the Control-IQ Closed-loop Control System: Results from a 6-month Multicenter Randomized Clinical Trial.
Diabetes technology & therapeutics
BACKGROUND: Glycemic control is particularly challenging for toddlers and preschoolers with type 1 diabetes (T1D), and data on the use of closed-loop systems in this age range is limited.MATERIALS AND METHODS: We studied use of a modified investigational version of the Tandem t:slim X2 Control-IQ system in children aged 2 to 5 years during 48 hours in a supervised outpatient hotel (SH) setting followed by 3 days of home use to examine the safety of this system in young children. Meals and snacks were not restricted and boluses were estimated per parents' usual routine. At least 30 minutes of daily exercise was required during the SH phase. All participants were remotely monitored by study staff while on closed-loop in addition to monitoring by at least one parent throughout the study.RESULTS: Twelve participants diagnosed with T1D for at least three months with mean age 4.7±1.0 years (range 2.0-5.8 years) and HbA1c of 7.3±0.8% were enrolled at three sites. With use of Control-IQ, the percentage of participants meeting our prespecified goals of less than 6% time below 70 mg/dL and less than 40% time above 180 mg/dL increased from 33% to 83%. Control-IQ use significantly improved percent time in range (70-180 mg/dL) compared to baseline (71.3±12.5 vs. 63.7±15.1, p=0.016). All participants completed the study with no adverse events.CONCLUSIONS: In this brief pilot study, use of the modified Control-IQ system was safe in 2-5 year-old children with T1D and improved glycemic control.
View details for DOI 10.1089/dia.2020.0507
View details for PubMedID 33226837
A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes.
The New England journal of medicine
2020; 383 (9): 836?45
BACKGROUND: Data are limited on the need for and benefits of pump setting optimization with automated insulin delivery. We examined clinical management of a closed-loop control (CLC) system and its relationship to glycemic outcomes.MATERIALS AND METHODS: We analyzed personal parameter adjustments in 168 participants in a 6-month multicenter trial of CLC with Control-IQ vs sensor-augmented pump therapy (SAP). Preset parameters (BR=basal rates, CF=correction factors, CR=carbohydrate ratios) were optimized at randomization, 2 and 13 weeks, for safety issues, participant concerns, or initiation by participants' usual diabetes care team. Time-in-range (TIR 70-180mg/dL) was compared in the week preceding and following parameter changes.RESULTS: In 607 encounters for parameter changes, there were fewer adjustments for CLC than SAP (3.4 vs. 4.1/participant). Adjustments involved BR (CLC 69%, SAP 80%), CR (CLC 68%, SAP 50%), CF (CLC 44%, SAP 41%), and overnight parameters (CLC 62%, SAP 75%). TIR preceding and following adjustments was CLC 71.2% and 71.3% and SAP 61.0% and 62.9%. The highest baseline HbA1c CLC subgroup had the largest TIR improvement (51.2% v 57.7%). When a CR was made more aggressive in the CLC group, postprandial time above 180mg/dL was 43.1% preceding and 36.0% following the change. The median postprandial time <70mg/dL before making CR less aggressive was 1.8%, and following the change was 0.7%.CONCLUSION: No difference in TIR was detected with parameter changes overall but they may have an effect in higher HbA1c1c subgroups or following user-directed boluses suggesting changes may matter more in suboptimal control or during discrete periods of the day.
View details for DOI 10.1089/dia.2020.0472
View details for PubMedID 33155824
Randomized Controlled Trial of Mobile Closed-Loop Control.
BACKGROUND: A closed-loop system of insulin delivery (also called an artificial pancreas) may improve glycemic outcomes in children with type 1 diabetes.METHODS: 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.RESULTS: 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.CONCLUSIONS: 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.).
View details for DOI 10.1056/NEJMoa2004736
View details for PubMedID 32846062
Closed-Loop Insulin Therapy Improves Glycemic Control in Adolescents and Young Adults: Outcomes from the International Diabetes Closed-Loop (iDCL) Trial.
Diabetes technology & therapeutics
OBJECTIVE: Assess the efficacy of inControl AP: a mobile closed-loop control (CLC) system.RESEARCH DESIGN AND METHODS: This protocol, NCT02985866, is a 3-month parallel group, multicenter, randomized unblinded trial designed to compare mobile CLC with sensor augmented pump (SAP) therapy. Eligibility criteria were type 1 diabetes for at least 1 year, use of insulin pumps for at least 6 months, age ?14 years, and baseline HbA1c <10.5% (91 mmol/mol). The study was designed to assess two coprimary outcomes: superiority of CLC over SAP in continuous glucose monitor (CGM)-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L.RESULTS: Between November 2017 and May 2018, 127 participants were randomly assigned 1:1 to CLC (n = 65) versus SAP (n = 62); 125 participants completed the study. CGM time below 3.9 mmol/L was 5.0% at baseline and 2.4% during follow-up in the CLC group vs. 4.7% and 4.0%, respectively, in the SAP group (mean difference -1.7% [95% CI -2.4, -1.0%]; P < 0.0001 for superiority). CGM time above 10 mmol/L was 40% at baseline and 34% during follow-up in the CLC group vs. 43% and 39%, respectively, in the SAP group (mean difference -3.0% [95% CI -6.1, +0.1%]; P < 0.0001 for noninferiority). One severe hypoglycemic event occurred in the CLC group, which was unrelated to the study device.CONCLUSIONS: In meeting its coprimary end points, superiority of CLC over SAP in CGM-measured time below 3.9 mmol/L and noninferiority in CGM-measured time above 10 mmol/L, the study has demonstrated that mobile CLC is feasible and could offer certain usability advantages over embedded systems, provided the connectivity between system components is stable.
View details for DOI 10.2337/dc19-1310
View details for PubMedID 31937608
Glycemic Outcomes of Use of CLC Versus PLGS in Type 1 Diabetes: A Randomized Controlled Trial.
2020; 43 (8): 1822?28
To assess the efficacy and safety of closed-loop control (CLC) insulin delivery system in adolescents and young adults with type 1 diabetes.Pre-specified sub-analysis of outcomes in adolescents and young adults 14-24 years old with type 1 diabetes in a previously published 6-month multicenter randomized trial. Participants were randomly assigned 2:1 to CLC (Tandem Control-IQ) or sensor augmented pump (SAP, various pumps+Dexcom G6 CGM) and followed for six months.Mean age of the 63 participants was 17 years, median type 1 diabetes duration was 7 years, and mean baseline HbA1c was 8.1%. All 63 completed the trial. Time in Range (TIR) increased by 13% with CLC versus decreasing by 1% with SAP (adjusted treatment group difference = +13% [+3.1 hours/day]; 95% CI 9% to 16%, P<0.001), which largely reflected a reduction in time >180 mg/dL (adjusted difference -12% [-2.9 hours/day], P<0.001). Time <70 mg/dL decreased by 1.6% with CLC versus 0.3% with SAP (adjusted difference -0.7% [-10 min/day], 95% CI -1.0% to -0.2%, P=0.002). CLC use averaged 89% of the time over 6 months. The mean adjusted difference in HbA1c after 6 months was 0.30% in CLC vs. SAP (95% CI -0.67 to +0.08, P=0.13). There was one DKA episode in the CLC group.CLC use over 6 months was substantial and associated with improved TIR and reduced hypoglycemia in adolescents and young adults with type 1 diabetes. Thus, CLC has the potential to improve glycemic outcomes in this challenging age group.
View details for DOI 10.1089/dia.2020.0572
View details for PubMedID 33216667
First outpatient evaluation of a tubeless automated insulin delivery system with customizable glucose targets in children and adults with type 1 diabetes.
Diabetes technology & therapeutics
Limited information is available about glycemic outcomes with a closed-loop control (CLC) system compared with a predictive low-glucose suspend (PLGS) system.After 6 months of use of a CLC system in a randomized trial, 109 participants with type 1 diabetes (age range, 14-72 years; mean HbA1c, 7.1% [54 mmol/mol]) were randomly assigned to CLC (N = 54, Control-IQ) or PLGS (N = 55, Basal-IQ) groups for 3 months. The primary outcome was continuous glucose monitor (CGM)-measured time in range (TIR) for 70-180 mg/dL. Baseline CGM metrics were computed from the last 3 months of the preceding study.All 109 participants completed the study. Mean ± SD TIR was 71.1 ± 11.2% at baseline and 67.6 ± 12.6% using intention-to-treat analysis (69.1 ± 12.2% using per-protocol analysis excluding periods of study-wide suspension of device use) over 13 weeks on CLC vs. 70.0 ± 13.6% and 60.4 ± 17.1% on PLGS (difference = 5.9%; 95% CI 3.6%, 8.3%; P < 0.001). Time >180 mg/dL was lower in the CLC group than PLGS group (difference = -6.0%; 95% CI -8.4%, -3.7%; P < 0.001) while time <54 mg/dL was similar (0.04%; 95% CI -0.05%, 0.13%; P = 0.41). HbA1c after 13 weeks was lower on CLC than PLGS (7.2% [55 mmol/mol] vs. 7.5% [56 mmol/mol], difference -0.34% [-3.7 mmol/mol]; 95% CI -0.57% [-6.2 mmol/mol], -0.11% [1.2 mmol/mol]; P = 0.0035).Following 6 months of CLC, switching to PLGS reduced TIR and increased HbA1c toward their pre-CLC values, while hypoglycemia remained similarly reduced with both CLC and PLGS.
View details for DOI 10.2337/dc20-0124
View details for PubMedID 32471910
Fast-Acting Insulin Aspart Use with the MiniMed? 670G System.
Diabetes technology & therapeutics
The objective of this study was to assess the safety and effectiveness of the first commercial configuration of a tubeless automated insulin delivery system, Omnipod® 5, in children (6-13.9 years) and adults (14-70 years) with type 1 diabetes in an outpatient setting.This was a single-arm, multicenter, prospective clinical study. Data were collected over a 14-day standard therapy (ST) phase followed by a 14-day hybrid closed-loop (HCL) phase, where participants (n=36) spent 72 hours at each of three pre-specified glucose targets (130, 140 and 150mg/dL, nine days total) then five days with free choice of glucose targets (110-150mg/dL) using the Omnipod 5. Remote safety monitoring alerts were enabled during the HCL phase. Primary endpoints were difference in time in range (TIR) (70-180mg/dL) between ST and HCL phases and proportion of participants reporting serious device-related adverse events.Mean TIR was significantly higher among children in the free-choice period overall (64.9 ± 12.2%, p<0.01) and when using a 110mg/dL target (71.2 ± 10.2%, p<0.01), a 130mg/dL target (61.5 ± 7.7%, p<0.01), and a 140mg/dL target (64.8 ± 11.6%, p<0.01), and among adults using a 130mg/dL target (75.1 ± 11.6%, p<0.05), compared to the ST phase (children: 51.0 ± 13.3% and adults: 65.6 ± 15.7%). There were no serious device-related adverse events reported during the HCL phase, nor were there episodes of severe hypoglycemia or diabetic ketoacidosis.The Omnipod 5 System was safe and effective when used at glucose targets from 110 to 150mg/dL for 14 days at home in children and adults with type 1 diabetes.
View details for DOI 10.1089/dia.2020.0546
View details for PubMedID 33325779
Safety and Performance of the Omnipod Hybrid Closed-Loop System in Adults, Adolescents, and Children with Type 1 Diabetes Over 5 Days Under Free-Living Conditions.
Diabetes technology & therapeutics
BACKGROUND This study assessed the efficacy and safety of ultra-rapid insulin Fiasp® in the hybrid closed-loop MiniMed? 670G system. METHODS This was a pilot randomized, double-blinded, cross-over study among established MiniMed? 670G users comparing percent time in range (TIR) and hypoglycemia for Novolog® and Fiasp®. Following two weeks optimization with their home insulin, participants were randomized to receive Novolog® or Fiasp® for two weeks, followed by the other insulin for the next two weeks. Data from the second week of blinded insulin use was analyzed to allow one week for 670G adaptation. During the second week, individuals were asked to eat the same breakfast for three days to assess differences in meal pharmacodynamics. RESULTS Nineteen adults were recruited with mean age of 40±18 years, diabetes duration of 27±12 years and median HbA1c of 7.1 (6.9,7.5)%, using 0.72 (0.4,1.2) units/kg/day. For Novolog® and Fiasp® respectively the %TIR (70-180mg/dL) was 75.3±9.5 and 78.4 ±9.3; %time <70mg/dL was 3.1±2.1 and 2.3±2.0; %time >180mg/dL was 21.6±9.0 and 19.3±8.9; mean glucose was 147±12 and 146±12mg/dL; coefficient of variation was 28.6±4.5% and 26.8±4.4%; %time in Auto Mode 86.4±9.2 and 84.4±9.2. All comparisons were non-significant for insulin type. Total daily dose (Novolog® 48.8±28.4 vs. Fiasp® 52.4±31.7 units; p=0.01) and daily basal (Novolog® 17.6 (15.5,33.8) vs. Fiasp® 19.1 (15.3,38.5) units; p=0.07) correlated with TIR and %time >180mg/dL. For insulin delivery in Auto Mode there was no statistical difference in total daily dose or daily basal between arms. Paired analysis for matched breakfast meals revealed no significant differences in time to maximum glucose, peak glucose or glucose excursion. CONCLUSIONS In this pilot study the use of either Novolog® or Fiasp® in a commercially available MiniMed? 670G system operating in Auto Mode resulted in clinically similar glycemic outcomes, with a slight increase in daily insulin requirements using Fiasp®.
View details for DOI 10.1089/dia.2020.0083
View details for PubMedID 32520594
Closed loop control in adolescents and children during winter sports: Use of the Tandem Control-IQ AP system
2019; 20 (6): 759?68
Realizing a Closed-Loop (Artificial Pancreas) System for the Treatment of Type 1 Diabetes.
BACKGROUND: The objective of this study was to assess the safety and performance of the Omnipod personalized model predictive control (MPC) algorithm in adults, adolescents, and children aged ?6 years with type 1 diabetes (T1D) under free-living conditions using an investigational device.METHODS: A 96-h hybrid closed-loop (HCL) study was conducted in a supervised hotel/rental home setting following a 7-day outpatient standard therapy (ST) phase. Eligible participants were aged 6-65 y with A1C <10.0% using CSII or MDI. Meals during HCL were unrestricted, with boluses administered per usual routine. There was daily physical activity. The primary endpoints were percentage of time with sensor glucose <70 mg/dL and ?250 mg/dL.RESULTS: Participants were 11 adults, 10 adolescents, and 15 children aged (mean±SD) 28.8±7.9 y, 14.3±1.3 y, and 9.9±1.0 y, respectively. Percentage time ?250 mg/dL during HCL was 4.5±4.2%, 3.5±5.0%, and 8.6±8.8% per respective age group, a 1.6-, 3.4-, and 2.0-fold reduction compared to ST (p=0.1, p=0.02, and p=0.03). Percentage time <70 mg/dL during HCL was 1.9±1.3%, 2.5±2.0%, and 2.2±1.9%, a statistically significant decrease in adults when compared to ST (p=0.005, p=0.3, and p=0.3). Percentage time 70-180 mg/dL increased during HCL compared to ST, reaching significance for adolescents and children: HCL 73.7±7.5% vs. ST 68.0±15.6% for adults (p=0.08), HCL 79.0±12.6% vs. ST 60.6±13.4% for adolescents (p=0.01), and HCL 69.2±13.5% vs. ST 54.9±12.9% for children (p=0.003).CONCLUSIONS: The Omnipod personalized MPC algorithm was safe and performed well over 5 days and 4 nights of use by a cohort of participants ranging from youth aged ?6 years to adults with T1D under supervised free-living conditions with challenges including daily physical activity and unrestricted meals.
View details for DOI 10.1089/dia.2019.0286
View details for PubMedID 31596130
A Review of Continuous Glucose Monitoring Data Interpretation in the Age of Automated Insulin Delivery.
Journal of diabetes science and technology
Recent, rapid changes in the treatment of type 1 diabetes have allowed for commercialization of an "artificial pancreas" which 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 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 utilize 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 which has already been delivered in order 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 closed loop.
View details for DOI 10.1210/er.2018-00174
View details for PubMedID 31276160
Successful At-Home Use of the Tandem Control-IQ Artificial Pancreas System in Young Children During a Randomized Controlled Trial
DIABETES TECHNOLOGY & THERAPEUTICS
2019; 21 (4): 159?69
Successful At-Home Use of the Tandem Control-IQ Artificial Pancreas System in Young Children During a Randomized Controlled Trial.
Diabetes technology & therapeutics
Using a continuous glucose monitor (CGM) improves glycemic control in patients with type 1 diabetes. The ambulatory glucose profile (AGP) has been recommended as a standard method for reporting CGM data. However, in recently developed automated insulin delivery (AID) systems, a standard format for reporting data has not yet been developed. Instead, reports are specific to each system being used. Currently, the only FDA approved AID system is a hybrid closed-loop insulin pump. In these systems, the patient is still required to announce a meal, respond to alerts, and keep the system in automated insulin delivery. The integrated pump and sensor information provides insights into how the system is performing, and how to make changes to tunable parameters, such as carbohydrate to insulin ratios. The reports also offer a window into human behavior related to performing diabetes tasks, responding to alarms, reasons for exiting HCL, and how glycemic goals are being met. This article reviews the pump and CGM data provided by several of the current closed-loop systems with a focus on systems that are currently approved in the United States (MiniMed 670G, Tandem Basal:IQ) and those used by patients using do-it-yourself systems. A step-wise approach to reviewing the nuances of these systems is provided. The comparison may reinforce the importance of the continued need for streamlining a standard report for providers to be able to interpret the CGM data of these systems.
View details for DOI 10.1177/1932296819851790
View details for PubMedID 31130007
Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes.
The New England journal of medicine
OBJECTIVE: 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.RESEARCH DESIGN AND METHODS: 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.RESULTS: The primary outcome, time in target range 70-180mg/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±23.1mg/dL; P=0.003) without increasing hypoglycemia time <70mg/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.CONCLUSIONS: 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.
View details for PubMedID 30888835
Feasibility Studies of an Insulin-Only Bionic Pancreas in a Home-Use Setting.
Journal of diabetes science and technology
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.).
View details for DOI 10.1056/NEJMoa1907863
View details for PubMedID 31618560
Closed Loop Control in Adolescents and Children During Winter Sports: Use of the Tandem Control-IQ AP System.
We tested the safety and performance of the "insulin-only" configuration of the bionic pancreas (BP) closed-loop blood-glucose control system in a home-use setting to assess glycemic outcomes using different static and dynamic glucose set-points.This is an open-label non-randomized study with three consecutive intervention periods. Participants had consecutive weeks of usual care followed by the insulin-only BP with (1) an individualized static set-point of 115 or 130 mg/dL and (2) a dynamic set-point that automatically varied within 110 to 130 mg/dL, depending on hypoglycemic risk. Human factors (HF) testing was conducted using validated surveys. The last five days of each study arm were used for data analysis.Thirteen participants were enrolled with a mean age of 28 years, mean A1c of 7.2%, and mean daily insulin dose of 0.6 U/kg (0.4-1.0 U/kg). The usual care arm had an average glucose of 145 ± 20 mg/dL, which increased in the static set-point arm (159 ± 8 mg/dL, P = .004) but not in the dynamic set-point arm (154 ± 10 mg/dL, P = ns). There was no significant difference in time spent in range (70-180 mg/dL) among the three study arms. There was less time <70 mg/dL with both the static (1.8% ± 1.4%, P = .009) and dynamic set-point (2.7±1.5, P = .051) arms compared to the usual-care arm (5.5% ± 4.2%). HF testing demonstrated preliminary user satisfaction and no increased risk of diabetes burden or distress.The insulin-only configuration of the BP using either static or dynamic set-points and initialized only with body weight performed similarly to other published insulin-only systems.
View details for DOI 10.1177/1932296819872225
View details for PubMedID 31470740
Predictive Low-Glucose Suspend Reduces Hypoglycemia in Adults, Adolescents, and Children With Type 1 Diabetes in an At-Home Randomized Crossover Study: Results of the PROLOG Trial
2018; 41 (10): 2155?61
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 hr ski camp (?5 h skiing/day) at three sites: Wintergreen, VA; Kirkwood, CA 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 ± 16.4vs 53.9 ± 24.8%; P = 0.01 in both children and adolescents. The AP system was associated with a significantly lower average glucose based on CGM data: 161 ± 29.9 vs 176.8 ± 36.5 mg/dL; P = 0.023. 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 type 1 diabetes during prolonged intensive winter sport activities. This article is protected by copyright. All rights reserved.
View details for PubMedID 31099946
Predictive hyperglycemia and hypoglycemia minimization: In-home double-blind randomized controlled evaluation in children and young adolescents
2018; 19 (3): 420?28
This study evaluated a new insulin delivery system designed to reduce insulin delivery when trends in continuous glucose monitoring (CGM) glucose concentrations predict future hypoglycemia.Individuals with type 1 diabetes (n = 103, age 6-72 years, mean HbA1c 7.3% [56 mmol/mol]) participated in a 6-week randomized crossover trial to evaluate the efficacy and safety of a Tandem Diabetes Care t:slim X2 pump with Basal-IQ integrated with a Dexcom G5 sensor and a predictive low-glucose suspend algorithm (PLGS) compared with sensor-augmented pump (SAP) therapy. The primary outcome was CGM-measured time <70 mg/dL.Both study periods were completed by 99% of participants; median CGM usage exceeded 90% in both arms. Median time <70 mg/dL was reduced from 3.6% at baseline to 2.6% during the 3-week period in the PLGS arm compared with 3.2% in the SAP arm (difference [PLGS - SAP] = -0.8%, 95% CI -1.1 to -0.5, P < 0.001). The corresponding mean values were 4.4%, 3.1%, and 4.5%, respectively, represent-ing a 31% reduction in the time <70 mg/dL with PLGS. There was no increase in mean glucose concentration (159 vs. 159 mg/dL, P = 0.40) or percentage of time spent >180 mg/dL (32% vs. 33%, P = 0.12). One severe hypoglycemic event occurred in the SAP arm and none in the PLGS arm. Mean pump suspension time was 104 min/day.The Tandem Diabetes Care Basal-IQ PLGS system significantly reduced hypoglycemia without rebound hyperglycemia, indicating that the system can benefit adults and youth with type 1 diabetes in improving glycemic control.
View details for PubMedID 30089663
Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial
2017; 389 (10067): 369-380
The primary objective of this trial was to evaluate the feasibility, safety, and efficacy of a predictive hyperglycemia and hypoglycemia minimization (PHHM) system vs predictive low glucose suspension (PLGS) alone in optimizing overnight glucose control in children 6 to 14 years old.Twenty-eight participants 6 to 14 years old with T1D duration ?1?year with daily insulin therapy ?12 months and on insulin pump therapy for ?6?months were randomized per night into PHHM mode or PLGS-only mode for 42 nights. The primary outcome was percentage of time in sensor-measured range 70 to 180?mg/dL in the overnight period.The addition of automated insulin delivery with PHHM increased time in target range (70-180?mg/dL) from 66?±?11% during PLGS nights to 76?±?9% during PHHM nights (P<.001), without increasing hypoglycemia as measured by time below various thresholds. Average morning blood glucose improved from 176?±?28?mg/dL following PLGS nights to 154?±?19?mg/dL following PHHM nights (P<.001).The PHHM system was effective in optimizing overnight glycemic control, significantly increasing time in range, lowering mean glucose, and decreasing glycemic variability compared to PLGS alone in children 6 to 14 years old.
View details for PubMedID 29159870
In-Home Closed Loop Control for Artificial Pancreas: Patient and Provider Perspective
DIABETES TECHNOLOGY & THERAPEUTICS
2017; 19 (1): 4?6
Comparative Accuracy of 17 Point-of-Care Glucose Meters.
Journal of diabetes science and technology
2017; 11 (3): 558?66
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.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.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.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.National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and National Center for Advancing Translational Sciences.
View details for DOI 10.1016/S0140-6736(16)32567-3
View details for PubMedID 28007348
Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps.
Current diabetes reports
2017; 17 (8): 58
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.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.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.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.
View details for DOI 10.1177/1932296816672237
View details for PubMedID 27697848
View details for PubMedCentralID PMC5505415
Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial.
The lancet. Diabetes & endocrinology
2016; 4 (3): 233?43
This review aims to summarize the type 1 diabetes (T1D) and weight literature with an emphasis on barriers associated with weight management, the unique T1D-specific factors that impact weight loss success, maladaptive and adaptive strategies for weight loss, and interventions to promote weight loss.Weight gain is associated with intensive insulin therapy. Overweight and obese weight status in individuals with T1D is higher than the general population and prevalence is rising. A variety of demographic (e.g., female sex), clinical (e.g., greater insulin needs), environmental (e.g., skipping meals), and psychosocial (e.g., depression, stress) factors are associated with overweight/obese weight status in T1D. Fear of hypoglycemia is a significant barrier to engagement in physical activity. Studies evaluating adaptive weight loss strategies in people with T1D are limited. There is a growing literature highlighting the prevalence and seriousness of overweight and obesity among both youth and adults with T1D. There is an urgent need to develop evidence-based weight management guidelines and interventions that address the unique concerns of individuals with T1D and that concurrently address glycemic control.
View details for PubMedID 28660565
Bone Density in Adolescents and Young Adults with Autism Spectrum Disorders.
Journal of autism and developmental disorders
2016; 46 (11): 3387?91
The safety and efficacy of continuous, multiday, automated glycaemic management has not been tested in outpatient studies of preadolescent children with type 1 diabetes. We aimed to compare the safety and efficacy of a bihormonal bionic pancreas versus conventional insulin pump therapy in this population of patients in an outpatient setting.In this randomised, open-label, crossover study, we enrolled preadolescent children (aged 6-11 years) with type 1 diabetes (diagnosed for ?1 year) who were on insulin pump therapy, from two diabetes camps in the USA. With the use of sealed envelopes, participants were randomly assigned in blocks of two to either 5 days with the bionic pancreas or conventional insulin pump therapy (control) as the first intervention, followed by a 3 day washout period and then 5 days with the other intervention. Study allocation was not masked. The autonomously adaptive algorithm of the bionic pancreas received data from a continuous glucose monitoring (CGM) device to control subcutaneous delivery of insulin and glucagon. Conventional insulin pump therapy was administered by the camp physicians and other clinical staff in accordance with their established protocols; participants also wore a CGM device during the control period. The coprimary outcomes, analysed by intention to treat, were mean CGM-measured glucose concentration and the proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L, on days 2-5. This study is registered with ClinicalTrials.gov, number NCT02105324.Between July 20, and Aug 19, 2014, 19 children with a mean age of 9·8 years (SD 1·6) participated in and completed the study. The bionic pancreas period was associated with a lower mean CGM-measured glucose concentration on days 2-5 than was the control period (7·6 mmol/L [SD 0·6] vs 9·3 mmol/L [1·7]; p=0·00037) and a lower proportion of time with a CGM-measured glucose concentration below 3·3 mmol/L on days 2-5 (1·2% [SD 1·1] vs 2·8% [1·2]; p<0·0001). The median number of carbohydrate interventions given per participant for hypoglycaemia on days 1-5 (ie, glucose <3·9 mmol/L) was lower during the bionic pancreas period than during the control period (three [range 0-8] vs five [0-14]; p=0·037). No episodes of severe hypoglycaemia were recorded. Medium-to-large concentrations of ketones (range 0·6-3·6 mmol/dL) were reported on seven occasions in five participants during the control period and on no occasion during the bionic pancreas period (p=0·063).The improved mean glycaemia and reduced hypoglycaemia with the bionic pancreas relative to insulin pump therapy in preadolescent children with type 1 diabetes in a diabetes camp setting is a promising finding. Studies of a longer duration during which children use the bionic pancreas during their normal routines at home and school should be done to investigate the potential for use of the bionic pancreas in real-world settings.The Leona M and Harry B Helmsley Charitable Trust and the US National Institute of Diabetes and Digestive and Kidney Diseases.
View details for DOI 10.1016/S2213-8587(15)00489-1
View details for PubMedID 26850709
View details for PubMedCentralID PMC4799495
Patients with autism spectrum disorder (ASD) are at increased risk for fracture, and peri-pubertal boys with ASD have lower bone mineral density (BMD) than controls. Data are lacking regarding BMD in older adolescents with ASD. We compared BMD using dual-energy X-ray absorptiometry in 9 adolescents/young adults with ASD against 9 typically developing matched controls. Patients with ASD and controls were excluded if they had other underlying conditions that may affect bone. Compared to controls, patients with ASD had (i) lower femoral neck and hip BMD Z-scores, and (ii) lower spine, femoral neck and hip height adjusted BMD Z-scores even after controlling for BMI. Understanding the underlying pathophysiology will be key to developing therapies to improve BMD and reduce fracture risk.
View details for DOI 10.1007/s10803-016-2871-9
View details for PubMedID 27491424
View details for PubMedCentralID PMC5074906