Impact of Missed and Late Meal Boluses on Glycemic Outcomes in Automated Insulin Delivery-Treated Children and Adolescents with Type 1 Diabetes: A Two-Center, Population-Based, Cohort Study.

OBJECTIVE: To evaluate the impact of missed or late meal boluses (MLBs) on glycemic outcomes in children and adolescents with type 1 diabetes using automated insulin delivery (AID) systems. RESEARCH DESIGN AND METHODS: AID-treated (Tandem Control-IQ or Medtronic MiniMed 780G) children and adolescents (aged 6-21 years) from Stanford Medical Center and Steno Diabetes Center Copenhagen with ≥10 days of data were included in this two-center, binational, population-based, retrospective, 1-month cohort study. The primary outcome was the association between number of algorithm-detected MLBs and time in target glucose range (TIR; 70-180 mg/dL). RESULTS: The study included 189 children and adolescents (48% females with a mean ± SD age of 13 ± 4 years). Overall, the mean number of MLBs per day in the cohort was 2.2 ± 0.9. For each additional MLB per day, TIR decreased by 9.7%-points (95% CI 11.3; 8.1), and compared to the quartile with fewest MLBs (Q1), the quartile with most (Q4) had 22.9% less TIR (95% CI 27.2; 18.6). The age-, sex-, and treatment modality-adjusted probability of achieving a TIR of >70% in Q4 was 1.4% compared to 74.8% in Q1 (p<0.001). CONCLUSIONS: MLBs significantly impacted glycemic outcomes in AID-treated children and adolescents. The results emphasize the importance of maintaining a focus on bolus behavior to achieve higher TIR, and supports the need for further research in technological or behavioral support tools to handle missed and late meal boluses.

Cost-Effectiveness of Closed-Loop Automated Insulin Delivery Using the Cambridge Hybrid Algorithm in Children and Adolescents with Type 1 Diabetes: Results from a Multicenter 6-Month Randomized Trial.

BACKGROUND/OBJECTIVE: The main objective of this study is to evaluate the incremental cost-effectiveness (ICER) of the Cambridge hybrid closed-loop automated insulin delivery (AID) algorithm versus usual care for children and adolescents with type 1 diabetes (T1D). METHODS: This multicenter, binational, parallel-controlled trial randomized 133 insulin pump using participants aged 6 to 18 years to either AID (n = 65) or usual care (n = 68) for 6 months. Both within-trial and lifetime cost-effectiveness were analyzed. Analysis focused on the treatment subgroup (n = 21) who received the much more reliable CamAPS FX hardware iteration and their contemporaneous control group (n = 24). Lifetime complications and costs were simulated via an updated Sheffield T1D policy model. RESULTS: Within-trial, both groups had indistinguishable and statistically unchanged health-related quality of life, and statistically similar hypoglycemia, severe hypoglycemia, and diabetic ketoacidosis (DKA) event rates. Total health care utilization was higher in the treatment group. Both the overall treatment group and CamAPS FX subgroup exhibited improved HbA1C (-0.32%, 95% CI: -0.59 to -0.04; P = .02, and -1.05%, 95% CI: -1.43 to -0.67; P < .001, respectively). Modeling projected increased expected lifespan of 5.36 years and discounted quality-adjusted life years (QALYs) of 1.16 (U.K. tariffs) and 1.52 (U.S. tariffs) in the CamAPS FX subgroup. Estimated ICERs for the subgroup were £19 324/QALY (United Kingdom) and -$3917/QALY (United States). For subgroup patients already using continuous glucose monitors (CGM), ICERs were £10 096/QALY (United Kingdom) and -$33 616/QALY (United States). Probabilistic sensitivity analysis generated mean ICERs of £19 342/QALY (95% CI: £15 903/QALY to £22 929/QALY) (United Kingdom) and -$28 283/QALY (95% CI: -$59 607/QALY to $1858/QALY) (United States). CONCLUSIONS: For children and adolescents with T1D on insulin pump therapy, AID using the Cambridge algorithm appears cost-effective below a £20 000/QALY threshold (United Kingdom) and cost saving (United States).

Decreasing the Burden of Carbohydrate Counting and Meal Announcement with Automated Insulin Delivery, Meal Recognition, and Autocorrection Doses: A Case Study.

The use of automated insulin delivery (AID) has led to a decrease in the burden of diabetes, allowing for better sleep, decreased anxiety about hypoglycemia, and automatic corrections doses, and meal recognition algorithms have provided "forgiveness" for imprecise carbohydrate (CHO) entries and missed or late meal boluses. We provide a case report and review of the current literature assessing the effect of AID on the burden of meal bolus. The case also demonstrates how sensor and pump data provide insight into insulin bolus behavior, and access to integrated cloud-based data has allowed for virtual patient visits. Glucose sensor metrics provides time in range and time below range, and the sensor-derived glucose management indicator provides an assessment of the long-term risk of complications when a laboratory glycated hemoglobin is not available.

Glycemic Outcomes Persist for up to 2 Years in Very Young Children with the Omnipod® 5 Automated Insulin Delivery System.

Background: To evaluate the long-term safety and effectiveness of the Omnipod® 5 Automated Insulin Delivery (AID) System in very young children with type 1 diabetes with up to 2 years of use. Methods: Following a 13-week single-arm, multicenter, pivotal trial that took place after 14 days of standard therapy data collection, participating children (2-5.9 years of age at study enrollment) were provided the option to continue use of the AID system in an extension phase. HbA1c was measured every 3 months, up to 15 months of total use, and continuous glucose monitor metrics were collected through the completion of the extension study (for up to 2 years). Results: Participants (N = 80) completed 18.2 [17.4, 23.4] (median [interquartile range]) total months of AID, inclusive of the 3-month pivotal trial. During the pivotal trial, HbA1c decreased from 7.4% ± 1.0% (57 ± 10.9 mmol/mol) to 6.9% ± 0.7% (52 ± 7.7 mmol/mol, P < 0.0001) and was maintained at 7.0% ± 0.7% (53 ± 7.7 mmol/mol) after 15 months total use (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 57.2% ± 15.3% during standard therapy to 68.1% ± 9.0% during the pivotal trial (P < 0.0001) and was maintained at 67.2% ± 9.3% during the extension phase (P < 0.0001 from standard therapy). Participants spent a median 97.1% of time in Automated Mode during the extension phase, with one episode of severe hypoglycemia and one episode of diabetic ketoacidosis. Conclusion: This evaluation of the Omnipod 5 AID System indicates that long-term use can safely maintain improvements in glycemic outcomes with up to 2 years of use in very young children with type 1 diabetes. Clinical Trials Registration Number: NCT04476472.

Patient reported outcomes (PROs) and user experiences of young children with type 1 diabetes using t:slim X2 insulin pump with control-IQ technology.

OBJECTIVE: Examine patient-reported outcomes (PROs) after the use of t:slim X2 insulin pump with Control-IQ technology (CIQ) in young children with type 1 diabetes. METHODS: Children with type 1 diabetes, ages 2 to < 6 years (n = 102), were randomly assigned 2:1 to either CIQ or standard care (SC) with pump or multiple daily injections (MDI) plus continuous glucose monitoring (CGM) for 13 weeks. Both groups were offered to use CIQ for an additional 13 weeks after the randomized control trial's (RCT) completion. Guardians completed PRO questionnaires at baseline, 13-, and 26-weeks examining hypoglycemia concerns, quality of life, parenting stress, and sleep. At 26 weeks, 28 families participated in user-experience interviews. Repeated measures analyses compared PRO scores between systems used. RESULT: Comparing CIQ vs SC, responses on all 5 PRO surveys favored the CIQ group, showing that CIQ was superior to SC at 26 weeks (p values < 0.05). User-experience interviews indicated significant benefits in optimized glycemic control overall and nighttime control (28 of 28 families endorsed). All but 2/28 families noted substantial reduction in management burden resulting in less mental burden and all but 4 stated that they wanted their children to continue using CIQ. CONCLUSIONS: Families utilizing CIQ experienced glycemic benefits coupled with substantial benefits in PROs, documented in surveys and interviews. Families utilizing CIQ had reduced hypoglycemia concerns and parenting stress, and improved quality of life and sleep. These findings demonstrate the benefit of CIQ in young children with type 1 diabetes that goes beyond documented glycemic benefit.

Diabetic Ketoacidosis at Diagnosis in Youth with Type 1 Diabetes Is Associated with a Higher Hemoglobin A1c Even with Intensive Insulin Management.

Introduction: Diabetic ketoacidosis (DKA) at diagnosis is associated with short- and long-term complications. We assessed the relationship between DKA status and hemoglobin A1c (A1c) levels in the first year following type 1 diabetes (T1D) diagnosis. Research Design and Methods: The Pilot Teamwork, Targets, Technology, and Tight Control (4T) study offered continuous glucose monitoring to youth with T1D within 1 month of diagnosis. A1c levels were compared between historical (n = 271) and Pilot 4T (n = 135) cohorts stratified by DKA status at diagnosis (DKA: historical = 94, 4T = 67 versus without DKA: historical = 177, 4T = 68). A1c was evaluated using locally estimated scatter plot smoothing. Change in A1c from 4 to 12 months postdiagnosis was evaluated using a linear mixed model. Results: Median age was 9.7 (interquartile range [IQR]: 6.6, 12.7) versus 9.7 (IQR: 6.8, 12.7) years, 49% versus 47% female, 44% versus 39% non-Hispanic White in historical versus Pilot 4T. In historical and 4T cohorts, DKA at diagnosis demonstrated higher A1c at 6 (0.5% [95% confidence interval (CI): 0.21-0.79; P < 0.01] and 0.38% [95% CI: 0.02-0.74; P = 0.04], respectively), and 12 months (0.62% [95% CI: -0.06 to 1.29; P = 0.07] and 0.39% [95% CI: -0.32 to 1.10; P = 0.29], respectively). The highest % time in range (TIR; 70-180 mg/dL) was seen between weeks 15-20 (69%) versus 25-30 (75%) postdiagnosis for youth with versus without DKA in Pilot 4T, respectively. Conclusions: Pilot 4T improved A1c outcomes versus the historical cohort, but those with DKA at diagnosis had persistently elevated A1c throughout the study and intensive diabetes management did not mitigate this difference. DKA prevention at diagnosis may translate into better glycemic outcomes in the first-year postdiagnosis. Clinical Trial Registration: clinicaltrials.gov: NCT04336969.

The Minimally-Invasive Oral Glucose Minimal Model: Estimation of Gastric Retention, Glucose Rate of Appearance, and Insulin Sensitivity From Type 1 Diabetes Data Collected in Real-Life Conditions.

OBJECTIVE: Modeling the effect of meal composition on glucose excursion would help in designing decision support systems (DSS) for type 1 diabetes (T1D) management. In fact, macronutrients differently affect post-prandial gastric retention (GR), rate of appearance (R[Formula: see text]), and insulin sensitivity (S[Formula: see text]). Such variables can be estimated, in inpatient settings, from plasma glucose (G) and insulin (I) data using the Oral glucose Minimal Model (OMM) coupled with a physiological model of glucose transit through the gastrointestinal tract (reference OMM, R-OMM). Here, we present a model able to estimate those quantities in daily-life conditions, using minimally-invasive (MI) technologies, and validate it against the R-OMM. METHODS: Forty-seven individuals with T1D (weight =78±13 kg, age =42±10 yr) underwent three 23-hour visits, during which G and I were frequently sampled while wearing continuous glucose monitoring (CGM) and insulin pump (IP). Using a Bayesian Maximum A Posteriori estimator, R-OMM was identified from plasma G and I measurements, and MI-OMM was identified from CGM and IP data. RESULTS: The MI-OMM fitted the CGM data well and provided precise parameter estimates. GR and R[Formula: see text] model parameters were not significantly different using the MI-OMM and R-OMM (p 0.05) and the correlation between the two S[Formula: see text] was satisfactory ( ρ =0.77). CONCLUSION: The MI-OMM is usable to estimate GR, R[Formula: see text], and S[Formula: see text] from data collected in real-life conditions with minimally-invasive technologies. SIGNIFICANCE: Applying MI-OMM to datasets where meal compositions are available will allow modeling the effect of each macronutrient on GR, R[Formula: see text], and S[Formula: see text]. DSS could finally exploit this information to improve diabetes management.

Two Years with a Tubeless Automated Insulin Delivery System: A Single-Arm Multicenter Trial in Children, Adolescents, and Adults with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery (AID) System was shown to be safe and effective following 3 months of use in people with type 1 diabetes (T1D); however, data on the durability of these results are limited. This study evaluated the long-term safety and effectiveness of Omnipod 5 use in people with T1D during up to 2 years of use. Materials and Methods: After a 3-month single-arm, multicenter, pivotal trial in children (6-13.9 years) and adolescents/adults (14-70 years), participants could continue system use in an extension phase. HbA1c was measured every 3 months for up to 15 months; continuous glucose monitor metrics were collected for up to 2 years. Results: Participants (N = 224) completed median (interquartile range) 22.3 (21.7, 22.7) months of AID. HbA1c was reduced in the pivotal trial from 7.7% ± 0.9% in children and 7.2% ± 0.9% in adolescents/adults to 7.0% ± 0.6% and 6.8% ± 0.7%, respectively, (P < 0.0001), and was maintained at 7.2% ± 0.7% and 6.9% ± 0.6% after 15 months (P < 0.0001 from baseline). Time in target range (70-180 mg/dL) increased from 52.4% ± 15.6% in children and 63.6% ± 16.5% in adolescents/adults at baseline to 67.9% ± 8.0% and 73.8% ± 10.8%, respectively, during the pivotal trial (P < 0.0001) and was maintained at 65.9% ± 8.9% and 72.9% ± 11.3% during the extension (P < 0.0001 from baseline). One episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia occurred during the extension. Children and adolescents/adults spent median 96.1% and 96.3% of time in Automated Mode, respectively. Conclusion: Our study supports that long-term use of the Omnipod 5 AID System can safely maintain improvements in glycemic outcomes for up to 2 years of use in people with T1D. Clinical Trials Registration Number: NCT04196140.

Safety and Glycemic Outcomes During the MiniMedTM Advanced Hybrid Closed-Loop System Pivotal Trial in Children and Adolescents with Type 1 Diabetes.

Background: During MiniMed™ advanced hybrid closed-loop (AHCL) use by adolescents and adults in the pivotal trial, glycated hemoglobin (A1C) was significantly reduced, time spent in range (TIR) was significantly increased, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA). The present study investigated the same primary safety and effectiveness endpoints during AHCL use by a younger cohort with type 1 diabetes (T1D). Methods: An intention-to-treat population (N = 160, aged 7-17 years) with T1D was enrolled in a single-arm study at 13 investigational centers. There was a run-in period (∼25 days) using HCL or sensor-augmented pump with/without predictive low-glucose management, followed by a 3-month study period with AHCL activated at two glucose targets (GTs; 100 and 120 mg/dL) for ∼45 days each. The mean ± standard deviation values of A1C, TIR, mean sensor glucose (SG), coefficient of variation (CV) of SG, time at SG ranges, and insulin delivered between run-in and study were analyzed (Wilcoxon signed-rank test or t-test). Results: Compared with baseline, AHCL use was associated with reduced A1C from 7.9 ± 0.9% (N = 160) to 7.4 ± 0.7% (N = 136) (P < 0.001) and overall TIR increased from the run-in 59.4 ± 11.8% to 70.3 ± 6.5% by end of study (P < 0.001), without change in CV, time spent below range (TBR) <70 mg/dL, or TBR <54 mg/dL. Relative to longer active insulin time (AIT) settings (N = 52), an AIT of 2 h (N = 19) with the 100 mg/dL GT increased mean TIR to 73.4%, reduced TBR <70 mg/dL from 3.5% to 2.2%, and reduced time spent above range (TAR) >180 mg/dL from 28.7% to 24.4%. During AHCL use, there was no severe hypoglycemia or DKA. Conclusions: In children and adolescents with T1D, MiniMed AHCL system use was safe, A1C was lower, and TIR was increased. The lowest GT and shortest AIT were associated with the highest TIR and lowest TBR and TAR, all of which met consensus-recommended glycemic targets. ClinicalTrials.gov ID: NCT03959423.

Glycemic Outcomes During Early Use of the MiniMed™ 780G Advanced Hybrid Closed-Loop System with Guardian™ 4 Sensor.

Background: Safety and significant improvement in overall glycated hemoglobin (A1C) and percentage of time spent in (TIR), below (TBR), and above (TAR) glucose range were demonstrated in the pivotal trial of adolescents and adults using the MiniMed™ advanced hybrid closed-loop (AHCL) system with the adjunctive, calibration-required Guardian™ Sensor 3. The present study evaluated early outcomes of continued access study (CAS) participants who transitioned from the pivotal trial investigational system to the approved MiniMed™ 780G system with the non-adjunctive, calibration-free Guardian™ 4 Sensor (MM780G+G4S). Study data were presented alongside those of real-world MM780G+G4S users from Europe, the Middle East, and Africa. Methods: The CAS participants (N = 109, aged 7-17 years and N = 67, aged >17 years) used the MM780G+G4S for 3 months and data of real-world MM780G+G4S system users (N = 10,204 aged ≤15 years and N = 26,099 aged >15 years) were uploaded from September 22, 2021 to December 02, 2022. At least 10 days of real-world continuous glucose monitoring (CGM) data were required for analyses. Glycemic metrics, delivered insulin and system use/interactions underwent descriptive analyses. Results: Time in AHCL and CGM use were >90% for all groups. AHCL exits averaged 0.1/day and there were few blood glucose measurements (BGMs) (0.8/day-1.0/day). Adults in both cohorts met most consensus recommendations for glycemic targets. Pediatric groups met recommendations for %TIR and %TBR, although not those for mean glucose variability and %TAR, possibly due to low use of recommended glucose target (100 mg/dL) and active insulin time (2 h) settings (28.4% in the CAS cohort and 9.4% in the real-world cohort). The CAS pediatric and adult A1C were 7.2% ± 0.7% and 6.8% ± 0.7%, respectively, and there were no serious adverse events. Conclusions: Early clinical use of the MM780G+G4S was safe and involved minimal BGMs and AHCL exits. Consistent with real-world pediatric and adult use, outcomes were associated with achievement of recommended glycemic targets. Clinical Trial Registration number: NCT03959423.

Practical Aspects and Exercise Safety Benefits of Automated Insulin Delivery Systems in Type 1 Diabetes.

Regular exercise is essential to overall cardiovascular health and well-being in people with type 1 diabetes, but exercise can also lead to increased glycemic disturbances. Automated insulin delivery (AID) technology has been shown to modestly improve glycemic time in range (TIR) in adults with type 1 diabetes and significantly improve TIR in youth with type 1 diabetes. Available AID systems still require some user-initiated changes to the settings and, in some cases, significant pre-planning for exercise. Many exercise recommendations for type 1 diabetes were developed initially for people using multiple daily insulin injections or insulin pump therapy. This article highlights recommendations and practical strategies for using AID around exercise in type 1 diabetes.

A Meta-Analysis of Randomized Trial Outcomes for the t:slim X2 Insulin Pump with Control-IQ Technology in Youth and Adults from Age 2 to 72.

Objective: To evaluate the effect of hybrid-closed loop Control-IQ technology (Control-IQ) in randomized controlled trials (RCTs) in subgroups based on baseline characteristics such as race/ethnicity, socioeconomic status (SES), prestudy insulin delivery modality (pump or multiple daily injections), and baseline glycemic control. Methods: Data were pooled and analyzed from 3 RCTs comparing Control-IQ to a Control group using continuous glucose monitoring in 369 participants with type 1 diabetes (T1D) from age 2 to 72 years old. Results: Time in range 70-180 mg/dL (TIR) in the Control-IQ group (n = 256) increased from 57% ± 17% at baseline to 70% ± 11% during follow-up, and in the Control group (n = 113) was 56% ± 15% and 57% ± 14%, respectively (adjusted treatment group difference = 11.5%, 95% confidence interval +9.7% to +13.2%, P < 0.001), an increase of 2.8 h/day on average. Significant reductions in mean glucose, hyperglycemia metrics, hypoglycemic metrics, and HbA1c were also observed. A statistically similar beneficial treatment effect on time in range 70-180 mg/dL was observed across the full age range irrespective of race-ethnicity, household income, prestudy continuous glucose monitor use, or prestudy insulin delivery method. Participants with the highest baseline HbA1c levels showed the greatest improvements in TIR and HbA1c. Conclusion: This pooled analysis of Control-IQ RCTs demonstrates the beneficial effect of Control-IQ in T1D across a broad spectrum of participant characteristics, including racial-ethnic minority, lower SES, lack of prestudy insulin pump experience, and high HbA1c levels. The greatest benefit was observed in participants with the worst baseline glycemic control in whom the auto-bolus feature of the Control-IQ algorithm appears to have substantial impact. Since no subgroups were identified that did not benefit from Control-IQ, hybrid-closed loop technology should be strongly considered for all youth and adults with T1D. Clinical Trials Registry: clinicaltrials.gov; NCT03563313, NCT03844789, and NCT04796779.

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.).

Continuous glucose monitoring and metrics for clinical trials: an international consensus statement.

Randomised controlled trials and other prospective clinical studies for novel medical interventions in people with diabetes have traditionally reported HbA1c as the measure of average blood glucose levels for the 3 months preceding the HbA1c test date. The use of this measure highlights the long-established correlation between HbA1c and relative risk of diabetes complications; the change in the measure, before and after the therapeutic intervention, is used by regulators for the approval of medications for diabetes. However, with the increasing use of continuous glucose monitoring (CGM) in clinical practice, prospective clinical studies are also increasingly using CGM devices to collect data and evaluate glucose profiles among study participants, complementing HbA1c findings, and further assess the effects of therapeutic interventions on HbA1c. Data is collected by CGM devices at 1-5 min intervals, which obtains data on glycaemic excursions and periods of asymptomatic hypoglycaemia or hyperglycaemia (ie, details of glycaemic control that are not provided by HbA1c concentrations alone that are measured continuously and can be analysed in daily, weekly, or monthly timeframes). These CGM-derived metrics are the subject of standardised, internationally agreed reporting formats and should, therefore, be considered for use in all clinical studies in diabetes. The purpose of this consensus statement is to recommend the ways CGM data might be used in prospective clinical studies, either as a specified study endpoint or as supportive complementary glucose metrics, to provide clinical information that can be considered by investigators, regulators, companies, clinicians, and individuals with diabetes who are stakeholders in trial outcomes. In this consensus statement, we provide recommendations on how to optimise CGM-derived glucose data collection in clinical studies, including the specific glucose metrics and specific glucose metrics that should be evaluated. These recommendations have been endorsed by the American Association of Clinical Endocrinologists, the American Diabetes Association, the Association of Diabetes Care and Education Specialists, DiabetesIndia, the European Association for the Study of Diabetes, the International Society for Pediatric and Adolescent Diabetes, the Japanese Diabetes Society, and the Juvenile Diabetes Research Foundation. A standardised approach to CGM data collection and reporting in clinical trials will encourage the use of these metrics and enhance the interpretability of CGM data, which could provide useful information other than HbA1c for informing therapeutic and treatment decisions, particularly related to hypoglycaemia, postprandial hyperglycaemia, and glucose variability.

Improved Glycemia with Hybrid Closed-Loop Versus Continuous Subcutaneous Insulin Infusion Therapy: Results from a Randomized Controlled Trial.

Objective: To evaluate safety and effectiveness of MiniMed™ 670G hybrid closed loop (HCL) in comparison with continuous subcutaneous insulin infusion (CSII) therapy for 6 months in persons with type 1 diabetes (T1D). Methods: Adults (aged 18-80 years), adolescents, and children (aged 2-17 years) with T1D who were using CSII therapy were enrolled and randomized (1:1) to 6 months of HCL intervention (n = 151, mean age of 39.9 ± 19.8 years) or CSII without continuous glucose monitoring (n = 151, 35.7 ± 18.4 years). Primary effectiveness endpoints included change in A1C for Group 1 (baseline A1C >8.0%), from baseline to the end of study, and difference in the end of study percentage of time spent below 70 mg/dL (%TBR <70 mg/dL) for Group 2 (baseline A1C ≤8.0%), to show superiority of HCL intervention versus control. Secondary effectiveness endpoints were change in A1C and %TBR <70 mg/dL for Group 2 and Group 1, respectively, to show noninferiority of HCL intervention versus control. Primary safety endpoints were rates of severe hypoglycemia and diabetic ketoacidosis (DKA). Results: Change in A1C and difference in %TBR <70 mg/dL for the overall group were significantly improved, in favor of HCL intervention. In addition, a significant mean (95% confidence interval) change in A1C was observed for both Group 1 (-0.8% [-1.1% to -0.4%], P < 0.0001) and Group 2 (-0.3% [-0.5% to -0.1%], P < 0.0001), in favor of HCL intervention. The same was observed for difference in %TBR <70 mg/dL for Group 1 (-2.2% [-3.6% to -0.9%]) and Group 2 (-4.9% [-6.3% to -3.6%]) (P < 0.0001 for both). There was one DKA event during run-in and six severe hypoglycemic events: two during run-in and four during study (HCL: n = 0 and CSII: n = 4 [6.08 per 100 patient-years]). Conclusions: This RCT demonstrates that the MiniMed 670G HCL safely and significantly improved A1C and %TBR <70 mg/dL compared with CSII control in persons with T1D, irrespective of baseline A1C level.

Consensus Recommendations for the Use of Automated Insulin Delivery Technologies in Clinical Practice.

The significant and growing global prevalence of diabetes continues to challenge people with diabetes (PwD), healthcare providers, and payers. While maintaining near-normal glucose levels has been shown to prevent or delay the progression of the long-term complications of diabetes, a significant proportion of PwD are not attaining their glycemic goals. During the past 6 years, we have seen tremendous advances in automated insulin delivery (AID) technologies. Numerous randomized controlled trials and real-world studies have shown that the use of AID systems is safe and effective in helping PwD achieve their long-term glycemic goals while reducing hypoglycemia risk. Thus, AID systems have recently become an integral part of diabetes management. However, recommendations for using AID systems in clinical settings have been lacking. Such guided recommendations are critical for AID success and acceptance. All clinicians working with PwD need to become familiar with the available systems in order to eliminate disparities in diabetes quality of care. This report provides much-needed guidance for clinicians who are interested in utilizing AIDs and presents a comprehensive listing of the evidence payers should consider when determining eligibility criteria for AID insurance coverage.

Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial.

Objective: To evaluate the insulin-only configuration of the iLet® bionic pancreas (BP) in youth 6-17 years old with type 1 diabetes (T1D). Research Design and Methods: In this multicenter, randomized, controlled trial, 165 youth with T1D (6-17 years old; baseline HbA1c 5.8%-12.2%; 35% using multiple daily injections, 36% using an insulin pump without automation, 4% using an insulin pump with low glucose suspend, and 25% using a hybrid closed-loop system before the study) were randomly assigned 2:1 to use BP (n = 112) with insulin aspart or insulin lispro (BP group) or to a control group (n = 53) using their personal standard care insulin delivery (SC group) plus real-time continuous glucose monitoring (CGM). The primary outcome was HbA1c at 13 weeks. Results: Mean HbA1c decreased from 8.1% ± 1.2% at baseline to 7.5% ± 0.7% at 13 weeks with BP versus 7.8% ± 1.1% at both baseline and 13 weeks with SC (adjusted difference = -0.5%, 95% CI -0.7% to -0.2%, P < 0.001). Participants with baseline HbA1c ≥9.0% (n = 34) decreased mean HbA1c from 9.7% ± 0.8% to 7.9% ± 0.6% after 13 weeks with BP compared with 9.7% ± 0.5% to 9.8% ± 0.8% with SC. Over 13 weeks, mean time in range (TIR) 70-180 mg/dL increased by 10% (2.4 h per day) and mean CGM glucose was reduced by 15 mg/dL with BP compared with SC (P < 0.001). Analyses of time >180 mg/dL, time >250 mg/dL, and standard deviation of CGM glucose favored BP (P < 0.001). Time <54 mg/dL was low at baseline (median 0.2%) and not significantly different between groups over 13 weeks (P = 0.24). A severe hypoglycemia event occurred in 3 (2.7%) participants in the BP group and in 1 (1.9%) in the SC group. Conclusions: In youth 6-17 years old with T1D, use of insulin-only configuration of BP improved HbA1c, TIR, and hyperglycemic metrics without increasing CGM-measured hypoglycemia compared with standard of care. Improvement in glycemic metrics was most pronounced in participants with high baseline HbA1c levels. Clinical Trial Registry: clinicaltrials.gov; NCT04200313.

Lived experience of CamAPS FX closed loop system in youth with type 1 diabetes and their parents.

AIM: To examine changes in the lived experience of type 1 diabetes after use of hybrid closed loop (CL), including the CamAPS FX CL system. MATERIALS AND METHODS: The primary study was conducted as an open-label, single-period, randomized, parallel design contrasting CL versus insulin pump (with or without continuous glucose monitoring). Participants were asked to complete patient-reported outcomes before starting CL and 3 and 6 months later. Surveys assessed diabetes distress, hypoglycaemia concerns and quality of life. Qualitative focus group data were collected at the completion of the study. RESULTS: In this sample of 98 youth (age range 6-18, mean age 12.7 ± 2.8 years) and their parents, CL use was not associated with psychosocial benefits overall. However, the subgroup (n = 12) using the CamAPS FX system showed modest improvements in quality of life and parent distress, reinforced by both survey (p < .05) and focus group responses. There were no negative effects of CL use reported by study participants. CONCLUSIONS: Closed loop use via the CamAPS FX system was associated with modest improvements in aspects of the lived experience of managing type 1 diabetes in youth and their families. Further refinements of the system may optimize the user experience.