Accuracy of a Real-Time Continuous Glucose Monitor in Pediatric Diabetic Ketoacidosis Admissions.

Objective: Continuous glucose monitoring (CGM) devices are integral in the outpatient care of people with type 1 diabetes, although they lack inpatient labeling. Food and Drug Administration began allowing inpatient use during the coronavirus disease 2019 (COVID-19) pandemic, with some accuracy data now available, primarily from adult hospitals. Pediatric inpatient data remain limited, particularly during diabetic ketoacidosis (DKA) admissions and for patients receiving intravenous (IV) insulin. Design and Methods: This retrospective chart review compared point-of-care glucose values to personal Dexcom G6 sensor data during pediatric hospitalizations. Accuracy was assessed using mean absolute relative difference (MARD), Clarke Error Grids, and the percentage of values within 15/20/30% if glucose value >100 mg/dL and 15/20/30 mg/dL if glucose value ≤100 mg/dL. Results: Matched paired glucose values (N = 612) from 36 patients (median age 14 years, 58.3% non-Hispanic White, 47.2% male) and 42 inpatient encounters were included in this subanalysis of DKA admissions. The MARDs for DKA and non-DKA admissions (N = 503) were 11.8% and 11.7%, with 97.6% and 98.6% of pairs falling within A and B zones of the Clarke Error Grid, respectively. Severe DKA admissions (pH <7.15 and/or bicarbonate <5 mmol/L) had a MARD of 8.9% compared to 14.3% for nonsevere DKA admissions. The MARD during administration of IV insulin (N = 266) was 13.4%. Conclusions: CGM accuracy is similar between DKA and non-DKA admissions and is maintained in severe DKA and during IV insulin administration, suggesting potential usability in pediatric hospitalizations. Further study on the feasibility of implementation of CGM in the hospital is needed.

Real-World Evidence of Omnipod® 5 Automated Insulin Delivery System Use in 69,902 People with Type 1 Diabetes.

Background: The Omnipod® 5 Automated Insulin Delivery System was associated with favorable glycemic outcomes for people with type 1 diabetes (T1D) in two pivotal clinical trials. Real-world evidence is needed to explore effectiveness in nonstudy conditions. Methods: A retrospective analysis of the United States Omnipod 5 System users (aged ≥2 years) with T1D and sufficient data (≥90 days of data; ≥75% of days with ≥220 continuous glucose monitor readings/day) available in Insulet Corporation's device and person-reported datasets as of July 2023 was performed. Target glucose setting usage (i.e., 110-150 mg/dL in 10 mg/dL increments) was summarized and glycemic outcomes were examined. Subgroup analyses of those using the lowest average glucose target (110 mg/dL) and stratification by baseline characteristics (e.g., age, prior therapy, health insurance coverage) were conducted. Results: In total, 69,902 users were included. Multiple and higher glucose targets were more commonly used in younger age groups. Median percentage of time in range (TIR; 70-180 mg/dL) was 68.8%, 61.3%, and 53.6% for users with average glucose targets of 110, 120, and 130-150 mg/dL, respectively, with minimal time <70 mg/dL (all median <1.13%). Among those with an average glucose target of 110 mg/dL (n = 37,640), median TIR was 65.0% in children and adolescents (2-17 years) and 69.9% in adults (≥18 years). Subgroup analyses of users transitioning from Omnipod DASH or multiple daily injections and of Medicaid/Medicare users demonstrated favorable glycemic outcomes among these groups. Conclusion: These glycemic outcomes from a large and diverse sample of nearly 70,000 children and adults demonstrate effective use of the Omnipod 5 System under real-world conditions.

Reducing Diabetes Burden in Medtronic's Automated Insulin Delivery Systems.

Background: The MiniMed™ 780G advanced hybrid closed-loop system (MM780G) builds on the basal automation and low-glucose protection features of the MiniMed™ 670G and 770G systems. While previous publications have focused on glycemic control improvements with MM780G, burden reduction has not been fully described. Methods: Data from two 3-month pivotal trials for the MM670G with Guardian™ Sensor 3 (GS3) (104 adults; 125 children) and MM780G with Guardian™ 4 Sensor (G4S) (67 adults;109 children) were compared. Real-world data (RWD) from United States users (N = 3851) transitioning from MM770G+GS3 to MM780G+G4S were also analyzed. Analyses included a new metric for diabetes management burden (i.e., pentagon composite metric), glycemic outcomes and system burden (e.g., closed-loop exits and fingersticks per day). Results: Diabetes burden metric (-22.8% and -28.5%), time in range (+3.1% [*P = 0.035] and +6.4% [P < 0.001]) and time below range (-1.8% [*P < 0.001] and -0.7% [*P < 0.001]) significantly improved, compared to MM670G for adult and pediatric participants, respectively. The pediatric mean sensor glucose (SG) reduced by -8.6 mg/dL (*P < 0.001), while the adults' saw no change. Closed-loop use significantly increased for both cohorts (+17.1% [*P < 0.001] and +20.5% [*P < 0.001]). Closed-loop exits were significantly reduced to about 1 per week (-0.5 [*P < 0.001] and -0.7 [*P < 0.001]); fingerstick tests were also reduced (-6.2 [*P < 0.001] and -6.9 [*P < 0.001]). Similar outcomes were observed from U.S. RWD. Conclusions: MiniMed™ 780G with G4S use was associated with significant reduction in diabetes management burden with fewer closed-loop exits, fingersticks and other interactions, and improvements in glycemic control when compared to the MiniMed™ 670G with GS3.

Accuracy of a Continuous Glucose Monitor During Pediatric Type 1 Diabetes Inpatient Admissions.

Objective: Continuous glucose monitors (CGMs) used for type 1 diabetes management are associated with lower hemoglobin A1c. CGMs are not approved for inpatient use, when close glucose monitoring and intensive insulin management are essential for optimal health. Accuracy data from adult hospitalizations have been published, but pediatric data are limited. Design and Methods: This retrospective review of Dexcom G6 data from youth with type 1 diabetes during hospitalization assessed CGMs and matched (within 5 min) point-of-care (POC) and laboratory glucose values. Glucose values >400 and <40 mg/dL were excluded due to sensor reporting capabilities. Standard methods for CGM accuracy were used including mean absolute relative difference (MARD), Clarke Error Grids, and percentage of CGM values within 15%/20%/30% if glucose value is >100 mg/dL and 15/20/30 mg/dL if value is ≤100 mg/dL. Results: A total of 1120 POC and 288 laboratory-matched pairs were collected from 83 unique patients (median age 12.0 years, 68.7% non-Hispanic white, 54.2% male) during 100 admissions. For POC values, overall, MARD was 11.8%, that on the medical floor was 13.5%, and that in the intensive care unit was 7.9%. The MARD for all laboratory values was 6.5%. In total, 98% of matched pairs were within Clarke Error Grid A and B zones. Conclusions: Findings from our pediatric population were similar to accuracy reported in hospitalized adults, indicating the potential role for CGM use during pediatric hospitalizations. Additional research is needed to assess accuracy under various conditions, including medication use, as well as development of safe hospital protocols for successful CGM implementation for routine inpatient care.

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.

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.

Time in Range Is Associated with Incident Diabetic Retinopathy in Adults with Type 1 Diabetes: A Longitudinal Study.

Abstract Objective: To evaluate the association between continuous glucose monitoring (CGM)-based time in various ranges and the subsequent development of diabetic retinopathy (incident DR) in adults with type 1 diabetes. Methods: Between June 2018 and March 2022, adults with type 1 diabetes with incident DR or no retinopathy (control) were identified. CGM data were collected retrospectively for up to 7 years before the date of eye examination defining incident DR or control. Associations between incident DR and CGM metrics were evaluated using logistic regression models. Results: This analysis included 71 adults with incident DR (mean age 27 years, 52% females, and mean diabetes duration 15 years) and 92 adults without DR (mean age 38 years, 48% females, and mean diabetes duration 20 years). Adjusting for age, diabetes duration, and CGM type, each 0.5% increase in glycated hemoglobin (HbA1c), 10 mg/dL increase in mean glucose, 5% decrease in time in target range 70-180 mg/dL (TIR), 5% decrease in time in tight target range 70-140 mg/dL (TITR), and 5% increase in time above 180 mg/dL (TAR) were associated with 24%, 22%, 18%, 28%, and 20% increase in odds of incident DR, respectively. Spearman correlations of TIR, TITR, TAR, and mean glucose with each other were all ≥0.97. Conclusion: Similar to HbA1c, TIR, TITR, TAR, and mean glucose were associated with increased risk for incident DR in adults with type 1 diabetes. These CGM metrics are highly correlated indicating that they provide similar information on glycemic control and diabetic retinopathy risk.

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.

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.

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.

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.

Coverage for Continuous Glucose Monitoring for Individuals with Type 2 Diabetes Treated with Nonintensive Therapies: An Evidence-Based Approach to Policymaking.

Numerous studies have demonstrated the clinical benefits of continuous glucose monitoring (CGM) in individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) who are treated with intensive insulin regimens. Based on this evidence, CGM is now a standard of care for individuals within these diabetes populations and widely covered by commercial and public insurers. Moreover, recent clinical guidelines from the American Diabetes Association and American Association of Clinical Endocrinology now endorse CGM use in individuals treated with nonintensive insulin regimens. However, despite increasing evidence supporting CGM use for individuals treated with less-intensive insulin therapy or noninsulin medications, insurance coverage is limited or nonexistent. This narrative review reports key findings from recent randomized, observational, and retrospective studies investigating use of CGM in T2D individuals treated with basal insulin only and/or noninsulin therapies and presents an evidence-based rationale for expanding access to CGM within this population.

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.

Increased Technology Use Associated With Lower A1C in a Large Pediatric Clinical Population.

OBJECTIVE: While continuous glucose monitors (CGMs), insulin pumps, and hybrid closed-loop (HCL) systems each improve glycemic control in type 1 diabetes, it is unclear how the use of these technologies impacts real-world pediatric care. RESEARCH DESIGN AND METHODS: We found 1,455 patients aged <22 years, with type 1 diabetes duration >3 months, and who had data from a single center in between both 2016-2017 (n = 2,827) and 2020-2021 (n = 2,731). Patients were grouped by multiple daily injections or insulin pump, with or without an HCL system, and using a blood glucose monitor or CGM. Glycemic control was compared using linear mixed-effects models adjusting for age, diabetes duration, and race/ethnicity. RESULTS: CGM use increased from 32.9 to 75.3%, and HCL use increased from 0.3 to 27.9%. Overall A1C decreased from 8.9 to 8.6% (P < 0.0001). CONCLUSIONS: Adoption of CGM and HCL was associated with decreased A1C, suggesting promotion of these technologies may yield glycemic benefits.

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.).

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.

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.