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.
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
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
Closed Loop Control in Adolescents and Children During Winter Sports: Use of the Tandem Control-IQ AP System.
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
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 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
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 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
Biopsychosocial Aspects of Weight Management in Type 1 Diabetes: a Review and Next Steps.
Current diabetes reports
2017; 17 (8): 58
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
Comparative Accuracy of 17 Point-of-Care Glucose Meters.
Journal of diabetes science and technology
2017; 11 (3): 558–66
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
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
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
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