Trial of Hybrid Closed-Loop Control in Young Children with Type 1 Diabetes.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Psychosocial outcomes with the Omnipod® 5 Automated Insulin Delivery System in caregivers of very young children with type 1 diabetes.

AIM: Automated insulin delivery (AID) systems have demonstrated improved glycaemic outcomes in people with type 1 diabetes (T1D), yet limited data exist on these systems in very young children and their impact on caregivers. We evaluated psychosocial outcomes following use of the tubeless Omnipod® 5 AID System in caregivers of very young children. MATERIALS AND METHODS: This 3-month single-arm, multicentre, pivotal clinical trial enrolled 80 children aged 2.0-5.9 years with T1D to use the Omnipod 5 AID System. Caregivers completed questionnaires assessing psychosocial outcomes-diabetes distress (Problem Areas in Diabetes), hypoglycaemia confidence (Hypoglycemia Confidence Scale), well-being (World Health Organization 5 Well-Being Index), sleep quality (Pittsburgh Sleep Quality Index), insulin delivery satisfaction (Insulin Delivery Satisfaction Survey) and system usability (System Usability Scale) at baseline with standard therapy and after 3 months of AID use. RESULTS: Following 3 months of Omnipod 5 use, caregivers experienced significant improvements across all measures, including diabetes-related psychosocial outcomes (Problem Areas in Diabetes; p < 0.0001, Hypoglycemia Confidence Scale; p < 0.01), well-being (World Health Organization 5 Well-Being Index; p < 0.0001) and perceived system usability (System Usability Scale; p < 0.0001). Significant improvements were seen in the Pittsburgh Sleep Quality Index total score and the overall sleep quality, sleep duration and efficiency subscales (all p < 0.05). Insulin Delivery Satisfaction Survey scores improved on all subscales (greater satisfaction, reduced burden and reduced inconvenience; all p < 0.0001). CONCLUSIONS: Caregivers face unique challenges when managing T1D in very young children. While glycaemic metrics have unquestioned importance, these results evaluating psychosocial outcomes reveal additional meaningful benefits and suggest that the Omnipod 5 AID System alleviates some of the burdens caregivers face with diabetes management.

Frequency and Causes of Nocturnal Alarms in Youth and Young Adults With Type 1 Diabetes Using a First-Generation Hybrid Closed-Loop System.

Background: Meeting glycemic recommendations is challenging for youth with type 1 diabetes. Diabetes technology, including continuous glucose monitoring (CGM) and hybrid closed-loop (HCL) automated insulin delivery systems, significantly increase achievement of glycemic targets; however, many youth struggle to sustain use of early HCL systems. Nocturnal alarm fatigue contributes to disrupted sleep and device discontinuation. Methods: We examined the frequency and causes of nocturnal (10:00 p.m. to 6:00 a.m.) alarms in pediatric patients (N = 76, median age 14.5 years [interquartile range 11.8-17.0 years, range 7-24 years]) starting on a first-generation HCL system in a prospective observational study. Device data were analyzed with linear mixed-effects models to examine change across time at 3-month intervals for 12 months. Results: At baseline (HCL system in nonautomated mode), participants averaged 3.3 ± 0.6 alarms per night. In the 2 weeks after starting HCL (automated) mode, alarm frequency significantly increased to 5.4 ± 0.5 times per night (P <0.001). Alarm frequency decreased through the remainder of the observational period; however, CGM sensor and HCL system use also declined. The types of alarms were evenly distributed among sensor maintenance, sensor threshold, pump, and HCL-specific alarms. Conclusion: These data show that HCL system nocturnal alarms are frequent and may be barriers to sleep quality and device use. Further research is needed to assess the impact of diabetes technology on sleep and to determine method to improve sleep quality with technology use.

A Randomized Trial of Closed-Loop Control in Children with Type 1 Diabetes.

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.).

Situational Awareness and Proactive Engagement Predict Higher Time in Range in Adolescents and Young Adults Using Hybrid Closed-Loop.

Background: Adolescents and young adults with type 1 diabetes have high HbA1c levels and often struggle with self-management behaviors and attention to diabetes care. Hybrid closed-loop systems (HCL) like the t:slim X2 with Control-IQ technology (Control-IQ) can help improve glycemic control. The purpose of this study is to assess adolescents' situational awareness of their glucose control and engagement with the Control-IQ system to determine significant factors in daily glycemic control. Methods: Adolescents (15-25 years) using Control-IQ participated in a 2-week prospective study, gathering detailed information about Control-IQ system engagements (boluses, alerts, and so on) and asking the participants' age and gender about their awareness of glucose levels 2-3 times/day without checking. Mixed models assessed which behaviors and awareness items correlated with time in range (TIR, 70-180 mg/dl, 3.9-10.0 mmol/L). Results: Eighteen adolescents/young adults (mean age 18 ± 1.86 years and 86% White non-Hispanic) completed the study. Situational awareness of glucose levels did not correlate with time since the last glucose check (p = 0.8). In multivariable modeling, lower TIR was predicted on days when adolescents underestimated their glucose levels (r = -0.22), received more CGM alerts (r = -0.31), and had more pump engagements (r = -0.27). A higher TIR was predicted when adolescents responded to CGM alerts (r = 0.20) and entered carbohydrates into the bolus calculator (r = 0.49). Conclusion: Situational awareness is an independent predictor of TIR and may provide insight into patterns of attention and focus that could positively influence glycemic outcomes in adolescents. Proactive engagements predict better TIR, whereas reactive engagement predicted lower TIR. Future interventions could be designed to train users to develop awareness and expertise in effective diabetes self-management.

Hyperglycemia and Other Glycemic Measures Throughout Therapy for Pediatric Acute Lymphoblastic Leukemia and Lymphoma.

Transient hyperglycemia during induction chemotherapy is associated with increased morbidity and mortality in patients with acute lymphoblastic leukemia (ALL). Treatment with glucocorticoids, asparaginase, and stress are the proposed causal factors. Although these risks are not exclusive to induction, glycemic control throughout the remainder of ALL/lymphoma (ALL/ALLy) therapy has not been described. Furthermore, prior research has been limited to transient hyperglycemia. This study aimed to characterize glycemic control throughout ALL/ALLy and to evaluate risk factors and outcomes associated with increased mean glucose and glucose coefficient of variation (glucose CV) during induction chemotherapy. The records for 220 pediatric/young adult patients, age 1 to 26 years, who underwent treatment for ALL/ALLy from 2010 to 2014 at Children's Hospital Colorado were retrospectively reviewed. Measures of glycemic control were calculated for each cycle. For the cycle with the highest mean glucose, induction (n=208), multivariable models were performed to identify potential risk factors and consequences of increased glucose. Highest mean glucose by cycle were induction 116 mg/dL, pretreatment 108 mg/dL, delayed intensification 96 mg/dL, and maintenance 93 mg/dL; these cycles also had the most glycemic variability. During induction, patients with Down syndrome, or who were ≥12 years and overweight/obese, had higher mean glucoses; age and overweight/obese status were each associated with increased glucose CV. In multivariable analysis, neither induction mean glucose nor glucose CV were associated with increased hazard of infection, relapse, or death.

Increasing Use of Diabetes Devices: What Do Health Care Professionals Need?

Despite evidence of improved diabetes outcomes with diabetes technology such as continuous glucose monitoring (CGM) systems, insulin pumps, and hybrid closed-loop (HCL) insulin delivery systems, these devices are underutilized in clinical practice for the management of insulin-requiring diabetes. This low uptake may be the result of health care providers' (HCPs') lack of confidence or time to prescribe and manage devices for people with diabetes. We administered a survey to HCPs in primary care, pediatric endocrinology, and adult endocrinology practices in the United States. Responding HCPs expressed a need for device-related insurance coverage tools and online data platforms with integration to electronic health record systems to improve diabetes technology uptake in these practice settings across the United States.

Noninvasive Glucose Sensing In Vivo.

Blood glucose monitoring is an essential aspect of disease management for individuals with diabetes. Unfortunately, traditional methods require collecting a blood sample and thus are invasive and inconvenient. Recent developments in minimally invasive continuous glucose monitors have provided a more convenient alternative for people with diabetes to track their glucose levels 24/7. Despite this progress, many challenges remain to establish a noninvasive monitoring technique that works accurately and reliably in the wild. This review encompasses the current advancements in noninvasive glucose sensing technology in vivo, delves into the common challenges faced by these systems, and offers an insightful outlook on existing and future solutions.

Effect of Tight Glycemic Control on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial.

Importance: Near normalization of glucose levels instituted immediately after diagnosis of type 1 diabetes has been postulated to preserve pancreatic beta cell function by reducing glucotoxicity. Previous studies have been hampered by an inability to achieve tight glycemic goals. Objective: To determine the effectiveness of intensive diabetes management to achieve near normalization of glucose levels on preservation of pancreatic beta cell function in youth with newly diagnosed type 1 diabetes. Design, Setting, and Participants: This randomized, double-blind, clinical trial was conducted at 6 centers in the US (randomizations from July 20, 2020, to October 13, 2021; follow-up completed September 15, 2022) and included youths with newly diagnosed type 1 diabetes aged 7 to 17 years. Interventions: Random assignment to intensive diabetes management, which included use of an automated insulin delivery system (n = 61), or standard care, which included use of a continuous glucose monitor (n = 52), as part of a factorial design in which participants weighing 30 kg or more also were assigned to receive either oral verapamil or placebo. Main Outcomes and Measures: The primary outcome was mixed-meal tolerance test-stimulated C-peptide area under the curve (a measure of pancreatic beta cell function) 52 weeks from diagnosis. Results: Among 113 participants (mean [SD] age, 11.8 [2.8] years; 49 females [43%]; mean [SD] time from diagnosis to randomization, 24 [5] days), 108 (96%) completed the trial. The mean C-peptide area under the curve decreased from 0.57 pmol/mL at baseline to 0.45 pmol/mL at 52 weeks in the intensive management group, and from 0.60 to 0.50 pmol/mL in the standard care group (treatment group difference, -0.01 [95% CI, -0.11 to 0.10]; P = .89). The mean time in the target range of 70 to 180 mg/dL, measured with continuous glucose monitoring, at 52 weeks was 78% in the intensive management group vs 64% in the standard care group (adjusted difference, 16% [95% CI, 10% to 22%]). One severe hypoglycemia event and 1 diabetic ketoacidosis event occurred in each group. Conclusions and Relevance: In youths with newly diagnosed type 1 diabetes, intensive diabetes management, which included automated insulin delivery, achieved excellent glucose control but did not affect the decline in pancreatic C-peptide secretion at 52 weeks. Trial Registration: ClinicalTrials.gov Identifier: NCT04233034.

Effect of Verapamil on Pancreatic Beta Cell Function in Newly Diagnosed Pediatric Type 1 Diabetes: A Randomized Clinical Trial.

Importance: In preclinical studies, thioredoxin-interacting protein overexpression induces pancreatic beta cell apoptosis and is involved in glucotoxicity-induced beta cell death. Calcium channel blockers reduce these effects and may be beneficial to beta cell preservation in type 1 diabetes. Objective: To determine the effect of verapamil on pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes. Design, Setting, and Participants: This double-blind, randomized clinical trial including children and adolescents aged 7 to 17 years with newly diagnosed type 1 diabetes who weighed 30 kg or greater was conducted at 6 centers in the US (randomized participants between July 20, 2020, and October 13, 2021) and follow-up was completed on September 15, 2022. Interventions: Participants were randomly assigned 1:1 to once-daily oral verapamil (n = 47) or placebo (n = 41) as part of a factorial design in which participants also were assigned to receive either intensive diabetes management or standard diabetes care. Main Outcomes and Measures: The primary outcome was area under the curve values for C-peptide level (a measure of pancreatic beta cell function) stimulated by a mixed-meal tolerance test at 52 weeks from diagnosis of type 1 diabetes. Results: Among 88 participants (mean age, 12.7 [SD, 2.4] years; 36 were female [41%]; and the mean time from diagnosis to randomization was 24 [SD, 4] days), 83 (94%) completed the trial. In the verapamil group, the mean C-peptide area under the curve was 0.66 pmol/mL at baseline and 0.65 pmol/mL at 52 weeks compared with 0.60 pmol/mL at baseline and 0.44 pmol/mL at 52 weeks in the placebo group (adjusted between-group difference, 0.14 pmol/mL [95% CI, 0.01 to 0.27 pmol/mL]; P = .04). This equates to a 30% higher C-peptide level at 52 weeks with verapamil. The percentage of participants with a 52-week peak C-peptide level of 0.2 pmol/mL or greater was 95% (41 of 43 participants) in the verapamil group vs 71% (27 of 38 participants) in the placebo group. At 52 weeks, hemoglobin A1c was 6.6% in the verapamil group vs 6.9% in the placebo group (adjusted between-group difference, -0.3% [95% CI, -1.0% to 0.4%]). Eight participants (17%) in the verapamil group and 8 participants (20%) in the placebo group had a nonserious adverse event considered to be related to treatment. Conclusions and Relevance: In children and adolescents with newly diagnosed type 1 diabetes, verapamil partially preserved stimulated C-peptide secretion at 52 weeks from diagnosis compared with placebo. Further studies are needed to determine the longitudinal durability of C-peptide improvement and the optimal length of therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT04233034.

Six-Month Randomized, Multicenter Trial of Closed-Loop Control in Type 1 Diabetes.

BACKGROUND: Closed-loop systems that automate insulin delivery may improve glycemic outcomes in patients with type 1 diabetes. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.).

Glycemic outcomes of children 2-6 years of age with type 1 diabetes during the pediatric MiniMed™ 670G system trial.

BACKGROUND: Highly variable insulin sensitivity, susceptibility to hypoglycemia and inability to effectively communicate hypoglycemic symptoms pose significant challenges for young children with type 1 diabetes (T1D). Herein, outcomes during clinical MiniMed™ 670G system use were evaluated in children aged 2-6 years with T1D. METHODS: Participants (N = 46, aged 4.6 ± 1.4 years) at seven investigational centers used the MiniMed™ 670G system in Manual Mode during a two-week run-in period followed by Auto Mode during a three-month study phase. Safety events, mean A1C, sensor glucose (SG), and percentage of time spent in (TIR, 70-180 mg/dl), below (TBR, <70 mg/dl) and above (TAR, >180 mg/dl) range were assessed for the run-in and study phase and compared using a paired t-test or Wilcoxon signed-rank test. RESULTS: From run-in to end of study (median 87.1% time in auto mode), mean A1C and SG changed from 8.0 ± 0.9% to 7.5 ± 0.6% (p < 0.001) and from 173 ± 24 to 161 ± 16 mg/dl (p < 0.001), respectively. Overall TIR increased from 55.7 ± 13.4% to 63.8 ± 9.4% (p < 0.001), while TBR and TAR decreased from 3.3 ± 2.5% to 3.2 ± 1.6% (p = 0.996) and 41.0 ± 14.7% to 33.0 ± 9.9% (p < 0.001), respectively. Overnight TBR remained unchanged and TAR was further improved 12:00 am-6:00 am. Throughout the study phase, there were no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA) and no serious adverse device-related events. CONCLUSIONS: At-home MiniMed™ 670G Auto Mode use by young children safely improved glycemic outcomes compared to two-week open-loop Manual Mode use. The improvements are similar to those observed in older children, adolescents and adults with T1D using the same system for the same duration of time.

Continuous Glucose Monitor, Insulin Pump, and Automated Insulin Delivery Therapies for Type 1 Diabetes: An Update on Potential for Cardiovascular Benefits.

PURPOSE OF REVIEW: The incidence of type 1 diabetes (T1D) is rising in all age groups. T1D is associated with chronic microvascular and macrovascular complications but improving glycemic trends can delay the onset and slow the progression of these complications. Utilization of technological devices for diabetes management, such as continuous glucose monitors (CGM) and insulin pumps, is increasing, and these devices are associated with improvements in glycemic trends. Thus, device use may be associated with long-term prevention of T1D complications, yet few studies have investigated the direct impacts of devices on chronic complications in T1D. This review will describe common diabetes devices and combination systems, as well as review relationships between device use and cardiovascular outcomes in T1D. RECENT FINDINGS: Findings from existing cohort and national registry studies suggest that pump use may aid in improving cardiovascular risk factors such as hypertension and dyslipidemia. Furthermore, pump users have been shown to have lower arterial stiffness and better measures of myocardial function. In registry and case-control longitudinal data, pump use has been associated with fewer cardiovascular events and reduction of cardiovascular disease (CVD) and all-cause mortality. CVD is the leading cause of morbidity and mortality in T1D. Consistent use of diabetes devices may protect against the development and progression of macrovascular complications such as CVD through improvement in glycemic trends. Existing literature is limited, but findings suggest that pump use may reduce acute cardiovascular risk factors as well as chronic cardiovascular complications and overall mortality in T1D.

Clinical Implementation of the Omnipod 5 Automated Insulin Delivery System: Key Considerations for Training and Onboarding People With Diabetes.

Automated insulin delivery (AID) systems, which connect an insulin pump, continuous glucose monitoring system, and software algorithm to automate insulin delivery based on real-time glycemic data, hold promise for improving outcomes and reducing therapeutic burden for people with diabetes. This article reviews the features of the Omnipod 5 Automated Insulin Delivery System and how it compares to other AID systems available on or currently under review for the U.S. market. It also provides practical guidance for clinicians on how to effectively train and onboard people with diabetes on the Omnipod 5 System, including how to personalize therapy and optimize glycemia. Many people with diabetes receive their diabetes care in primary care settings rather than in a diabetes specialty clinic. Therefore, it is important that primary care providers have access to resources to support the adoption of AID technologies such as the Omnipod 5 System.

Real-world performance of hybrid closed loop in youth, young adults, adults and older adults with type 1 diabetes: Identifying a clinical target for hybrid closed-loop use.

AIM: To describe real-world hybrid closed loop (HCL) use and glycaemic outcomes across the lifespan and identify a clinical threshold for HCL use associated with meeting the internationally recommended target of 70% sensor glucose time in range (TIR; 70-180 mg/dL). MATERIALS AND METHODS: Mixed models examined MiniMed 670G HCL use and glycaemic outcomes in 276 people with type 1 diabetes from four age groups: youth (aged <18 years), young adults (18-25 years), adults (26-49 years) and older adults (≥50 years) for 1 year. ROC analysis identified the minimum percentage HCL use associated with meeting the TIR goal of 70%. RESULTS: HCL use at month 1 was 70.7% ± 2.9% for youth, 71.0% ± 3.8% for young adults, 78.9% ± 2.1% for adults and 84.7% ± 3.8% in older adults. HCL use declined significantly at 12 months to 49.3% ± 3.2% in youth (P < .001) and 55.7% ± 4.3% in young adults (P = .002). HCL use was sustained at 12 months in adults (76.4% ± 2.2%, P = .36) and older adults (80.4% ± 3.9%, P = .36). HCL use of 70.6% was associated with 70% TIR (sensitivity 58.3%, specificity 85%, AUC 0.77). Older age, 80% or higher continuous glucose monitor use and four or more blood glucose checks per day were associated with attaining the HCL-use threshold. CONCLUSIONS: HCL use of 70% or higher may be a useful target for clinicians to use to assist people with diabetes in attaining glycaemic goals. Youth may struggle with HCL use more than adults and require clinical intervention to help sustain HCL use across time.

Initiating hybrid closed loop: A program evaluation of an educator-led Control-IQ follow-up at a large pediatric clinic.

BACKGROUND: Control-IQ (Tandem Diabetes) is a hybrid closed-loop (HCL) system that users self-initiate after completing online training. Best practices for clinical follow-up are not known. Our quality improvement objective was to evaluate the usefulness of an educator-led follow-up program for new HCL users in a type 1 diabetes pediatric clinic. METHODS: We implemented an ''HCLCheck-in'' program, first determining when users started HCL, then having diabetes educators contact them for a follow-up call 2-weeks after start. Educators used a Clinical Tool to inform insulin dose and behavior recommendations, and used four benchmarks to determine need for further follow-up: ≥71% HCL use, ≥71% CGM use, ≥60% Time-in-Range (TIR, 70-180 mg/dL), <5% below 70 mg/dL. Family and educator satisfaction were surveyed. RESULTS: One-hundred-twenty-three youth [mean age 13.6 ± 3.7 y, 53.7% female, mean HbA1c 7.6 ± 1.4% (60 mmol/mol)] completed an HCLCheck-in call a median (IQR) of 18(15, 21) days post-HCL start. 74 users (60%) surpassed benchmarks with 94% HCL use and 71% TIR. Of the 49 who did not, 16 completed a second call, and improved median TIR 12.5% (p = 0.03). HCL users reported high satisfaction with the program overall [median 10 (9, 10) out of 10]. Educators spent a median of 45 (32,70) minutes per user and rated satisfaction with the program as 8 (7,9.5) and the Tool as 9 (9, 10). CONCLUSION: Our HCLCheck-in program received high satisfaction ratings and resulted in improved TIR for those initially not meeting benchmarks, suggesting users may benefit from early follow-up. Similar programs may be beneficial for other new technologies.

Six months of hybrid closed loop in the real-world: An evaluation of children and young adults using the 670G system.

OBJECTIVE: To describe glycemic and psychosocial outcomes in youth with type 1 diabetes using a hybrid closed loop (HCL) system. SUBJECTS: Youth with type 1 diabetes (2-25 years) starting the 670G HCL system for their diabetes care were enrolled in an observational study. METHODS: Prospective data collection occurred during routine clinical care and included glycemic variables (sensor time in range [70-180 mg/dL], HbA1c), and psychosocial variables (Hypoglycemia Fear Survey [HFS]; Problem Areas in Diabetes [PAID]). Mixed models were used to analyze change across time. RESULTS: Ninety-two youth (mean age 15.7 ± 3.6 years, 50% female, HbA1c 8.8% ± 1.8%) started HCL for their diabetes care. Youth used Auto Mode 65.5% ± 3.0% of the time at month 1, which decreased to 51.2% ± 3.4% at month 6 (P = .001). Sensor time in range increased from 50.7% ± 1.8% at baseline to 56.9% ± 2.1% at 6 months (P = .007). HbA1c decreased from 8.7% ± 0.2% at baseline to 8.4% ± 0.2% after 6 months of use (P ≤ .0001), with the greatest HbA1c decline in participants with high baseline HbA1c. Increased percent time in auto mode was associated with lower HbA1c (P = .02). Thirty percent of youth discontinued HCL in the first 6 months of use. There were no changes in the HFS or PAID scores across time. CONCLUSIONS: HCL use is associated with improved glycemic control and no change in psychosocial outcomes in this clinical sample. The decline in HCL use across time suggests that youth experience barriers in sustaining use of HCL. Further research is needed to understand reasons for HCL discontinuation and determine intervention strategies.

Real world hybrid closed-loop discontinuation: Predictors and perceptions of youth discontinuing the 670G system in the first 6 months.

OBJECTIVE: To describe predictors of hybrid closed loop (HCL) discontinuation and perceived barriers to use in youth with type 1 diabetes. SUBJECTS: Youth with type 1 diabetes (eligible age 2-25 y; recruited age 8-25 y) who initiated the Minimed 670G HCL system were followed prospectively for 6 mo in an observational study. RESEARCH DESIGN AND METHODS: Demographic, glycemic (time-in-range, HbA1c), and psychosocial variables [Hypoglycemia Fear Survey (HFS); Problem Areas in Diabetes (PAID)] were collected for all participants. Participants who discontinued HCL (<10% HCL use at clinical visit) completed a questionnaire on perceived barriers to HCL use. RESULTS: Ninety-two youth (15.7 ± 3.6 y, HbA1c 8.8 ± 1.3%, 50% female) initiated HCL, and 28 (30%) discontinued HCL, with the majority (64%) discontinuing between 3 and 6 mo after HCL start. Baseline HbA1c predicted discontinuation (P = .026) with the odds of discontinuing 2.7 times higher (95% CI: 1.123, 6.283) for each 1% increase in baseline HbA1c. Youth who discontinued HCL rated difficulty with calibrations, number of alarms, and too much time needed to make the system work as the most problematic aspects of HCL. Qualitatively derived themes included technological difficulties (error alerts, not working correctly), too much work (calibrations, fingersticks), alarms, disappointment in glycemic control, and expense (cited by parents). CONCLUSIONS: Youth with higher HbA1c are at greater risk for discontinuing HCL than youth with lower HbA1c, and should be the target of new interventions to support device use. The primary reasons for discontinuing HCL relate to the workload required to use HCL.

Glycemic variability is associated with poor outcomes in pediatric hematopoietic stem cell transplant patients.

BACKGROUND: Among pediatric hematopoietic stem cell transplant (HSCT) recipients, abnormal glycemic control is shown to be associated with increased risk of transplant-related mortality, death from any cause, risk of infection, increased hospitalized, and intensive care days. Independent effects of higher glycemic variability, a component of glycemic control, have not been described. This study aimed to characterize risk factors for, and consequences of, higher glycemic variability in HSCT patients. PROCEDURE: Medical records for a cohort of 344 patients, age 0-30 years, who underwent first HSCT from 2007 to 2016 at Children's Hospital Colorado were retrospectively reviewed. Glucose coefficients of variation (CV) were analyzed for HSCT days -14 to 0 and 0-30, and patients were assessed for potential risk factors and outcomes. RESULTS: Roughly one-third of patients had pre-HSCT and day 0-30 glucose CV above the reported healthy adult range. Independent of HSCT type, doubling of pre-HSCT glucose CV was associated with a 4.91-fold (95% confidence interval [CI], 1.40-17.24) increased hazard of infection, as well as increased risk for intensive care hospitalization for allogenic HSCT patients. Multivariable analysis demonstrated that allogeneic HSCT patients had a 1.40- and 1.38-fold (95% CI, 0.98-1.99 and 1.00-1.91) increased hazard of death for every doubling of pre-HSCT and day 0-30 glucose CV, respectively. CONCLUSIONS: Just as with higher mean glucose, higher glycemic variability in the pediatric HSCT population is independently associated with significantly increased morbidity. Additional research is required to evaluate the utility of glucose control to mitigate these relationships and improve HSCT outcomes.

Closed loop control in adolescents and children during winter sports: Use of the Tandem Control-IQ AP system.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.