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Meghan E Pauley, Cari Berget, Laurel H Messer, Gregory P Forlenza Barbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, Aurora, CO, USACorrespondence: Gregory P ForlenzaBarbara Davis Center for Childhood Diabetes, University of Colorado Anschutz Medical Campus, 1775 Aurora CT, MS A140, Aurora, CO, 80045, USATel +1 303-724-2323Fax +1 303-724-6779Email gregory.forlenza@cuanschutz.eduAbstract: Diabetes-related technology has undergone great advancement in recent years. These technological devices are more commonly utilized in the type 1 diabetes population, which requires insulin as the primary treatment modality. Available devices include insulin pumps, continuous glucose monitors, and hybrid systems referred to as automated insulin delivery systems or hybrid closed-loop systems, which combine those two devices along with software algorithms to achieve advanced therapeutic capabilities, including automatic modulation of insulin delivery based on sensor-derived glucose levels to minimize abnormal glucose trends. Use of diabetes technology is associated with significant positive health and psychosocial outcomes, yet utilization rates are generally lacking across both adult and pediatric type 1 diabetes populations in the United States and other countries. There are consistent themes in existing barriers to technology uptake reported by individuals with type 1 diabetes or parents of children with type 1 diabetes, including physical burdens associated with wearing the devices, concerns in navigating the technology and the devices’ abilities to meet user expectations, high cost, inadequate resources within the healthcare team to support device use, disparities in technology access, and psychosocial barriers. It is important to understand the common barriers to uptake of not only the automated insulin delivery systems but also their component devices (insulin pumps and continuous glucose monitors) to fully support individuals in utilizing these devices and optimizing health benefits. The purpose of this article is to summarize the current automated insulin delivery devices that are available for use in management of type 1 diabetes, review common barriers to uptake of those systems and their component devices, and provide expert opinion on existing and future solutions to identified barriers.Keywords: type 1 diabetes, artificial pancreas, insulin pump, continuous glucose monitor, hybrid closed loop

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.

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.

Numerous studies have demonstrated the clinical value of continuous glucose monitoring (CGM) in type 1 diabetes (T1D) and type 2 diabetes (T2D) populations. However, the eligibility criteria for CGM coverage required by the Centers for Medicare & Medicaid Services (CMS) ignore the conclusive evidence that supports CGM use in various diabetes populations that are currently deemed ineligible. In an earlier article, we discussed the limitations and inconsistencies of the agency's CGM eligibility criteria relative to current scientific evidence and proposed practice solutions to address this issue and improve the safety and care of Medicare beneficiaries with diabetes. Although Medicaid is administered through CMS, there is no consistent Medicaid policy for CGM coverage in the United States. This article presents a rationale for modifying and standardizing Medicaid CGM coverage eligibility across the United States., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: R.J.G. is supported by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) of the National Institutes of Health (NIH) under award numbers 2P30DK1110246 and K23DK123384-3. R.J.G. received research support to Emory University for investigator-initiated studies from Novo Nordisk, Dexcom, and Eli-Lilly and consulting fees from Sanofi, Eli-Lilly, Boehringer, Pfizer, and Weight Watchers, outside of this work. G.A. has received research support to Northwestern University from Astra Zeneca, Dexcom, Eli-Lilly, Emmes, Fractyl Health, Insulet, Novo Nordisk, and WellDoc. G.A. has received consulting fees from Eli-Lilly, Dexcom, and Insulet outside of this work. C.G.P. has received consulting fees from Abbott Diabetes Care, CeQur, Dexcom, LifeScan, Mannkind, Roche Diabetes Care, and ProventionBio. D.A.B. has no disclosures associated with this manuscript. A.L.C. has received research support from UnitedHealthcare, Abbott, Dexcom, Eli-Lilly, Insulet, Medtronic, Novo Nordisk, and Sanofi, and is a consultant for Medtronic and Insulet, with all financial support going to his institution. In addition, ALC has a patent, Treatment of Hypoglycemia Unawareness with Intranasal Insulin, pending to HealthPartners Institute. EC is a scientific advisor for Eli-Lilly, Novo Nordisk, Adocia, and Arecor. G.P.F. received research support from Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly, and has served as a consultant, speaker, and advisory board member for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. D.F.K. institution has received research support from NIH, Helmsley Foundation, Novo Nordisk, Abbott Diabetes, and Dexcom. D.F.K. has received consulting fees from Novo Nordisk, Abbott Diabetes, Mannkind, CeQur, Sanofi, Medical Module, ProventionBio, and Pendulum. D.F.K. is the speaker for Dexcom, Novo Nordisk, Sanofi-Aventis, Xeris, and CeQur. D.F.K. has stock options not redeemed in Pendulum. C.J.L. has received research support by the NIDDK and Helmsley Foundation and industry support paid to the Icahn School of Medicine at Mount Sinai from Abbott Diabetes, Dexcom, Insulet, Novo Nordisk, Senseonics, and Tandem. C.J.L. has received consulting fees from Eli-Lilly, and Dexcom outside of this work. J.B.M. has received research support from the NIH, Helmsley Foundation, JDRF, Novo Nordisk, and Beta Bionics. J.B.M. has received consulting fees from Bayer, Boehringer Ingelheim and Lilly, Mannkind, Novo Nordisk, and Thermo Fisher outside of this work. G.E.U. is partly supported by research grants from the National Institutes of Health (NIH/NATS UL 3UL1TR002378-05S2) from the Clinical and Translational Science Award program, and from National Institutes of Health and National Center for Research Resources (NIH/NIDDK 2P30DK111024-06). G.E.U. has received research support (to Emory University) from Astra Zeneca, Bayer, Abbott, and Dexcom.

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.

Objectives: To report the safety and side effects associated with taking verapamil for beta-cell preservation in children with newly-diagnosed T1D., Research Design and Methods: Eighty-eight participants aged 8.5 to 17.9 years weighing ≥ 30 kg were randomly assigned to verapamil (N = 47) or placebo (N = 41) within 31 days of T1D diagnosis and followed for 12 months from diagnosis, main CLVer study. Drug dosing was weight-based with incremental increases to full dosage. Side effect monitoring included serial measurements of pulse, blood pressure, liver enzymes, and electrocardiograms (ECGs). At study end, participants were enrolled in an observational extension study (CLVerEx), which is ongoing. No study drug is provided during the extension, but participants may use verapamil if prescribed by their diabetes care team., Results: Overall rates of adverse events were low and comparable between verapamil and placebo groups. There was no difference in the frequency of liver function abnormalities. Three CLVer participants reduced or discontinued medication due to asymptomatic ECG changes. One CLVerEx participant (18 years old), treated with placebo during CLVer, who had not had a monitoring ECG, experienced complete AV block with a severe hypotensive episode 6 weeks after reaching his maximum verapamil dose following an inadvertent double dose on the day of the event., Conclusions: The use of verapamil in youth newly-diagnosed with T1D appears generally safe and well tolerated with appropriate monitoring. We strongly recommend monitoring for potential side effects including an ECG at screening and an additional ECG once full dosage is reached.ClinicalTrials.gov number: NCT04233034., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Ekhlaspour receives salary support from NIH and research support from JDRF. She reports receiving consulting fees from Medtronic, Tandem Diabetes Care and Ypsomed; receiving speaking fees from Insulet; and receiving research support from Medtronic, MannKind and Abbot through her institution. Her prior institution has received research support from Medtronic, Tandem Diabetes Care, Insulet, Dexcom and Beta Bionics. Dr. Buckingham reports receiving grants, personal fees, and/or nonfinancial support from Medtronic, Tandem Diabetes Care, Insulet, NovoNordisk, and Lilly and reports his institution has received research funding from Medtronic, Tandem Diabetes Care, Beta Bionics, and Insulet. Dr. Bauza reports no disclosures. Dr. Clements reports receiving personal fees from Glooko Inc and nonfinancial support from Dexcom and Abbott Diabetes Care. Dr. Forlenza reports serving as a consultant, speaker or advisory board member for Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics and reports his institution has received funding on his behalf for research grants from Medtronic, Dexcom, Abbott, Tandem Diabetes Care, Insulet, Lilly, and Beta Bionics. Dr. Neyman reports no disclosures. Dr. Norlander reports no disclosures. Dr. Schamberger reports no disclosures. Dr. Sherr reported receiving speaking honoraria from Lilly, Insulet, Medtronic, and Zealand Pharma; serving on advisory boards for Bigfoot Biomedical, Cecelia Health, Insulet, Medtronic Diabetes, JDRF (formally the Juvenile Diabetes Research Foundation) T1D Fund, StartUp Health T1D Moonshot, and Vertex Pharmaceuticals; receiving consultant fees from Insulet and Medtronic; and reported that her institution has received research grant support from Medtronic and Insulet. Mr. Bailey reports no disclosures. Dr. Beck reports his institution has received funding on his behalf as follows: grant funding and study supplies from Tandem Diabetes Care, Beta Bionics, and Dexcom; grant funding from Bigfoot Biomedical; study supplies from Medtronic, Ascencia, and Roche; consulting fees and study supplies from Lilly and NovoNordisk; and consulting fees from Insulet and Zucara Therapeutics. Dr. Kollman reports receiving grants from Dexcom and Tandem Diabetes Care. Ms. Beasley reports no disclosures. Dr. Cobry reports no disclosures. Dr. DiMeglio reports receiving consulting or advisory fees from Abata Therapeutics, MannKind, Provention Bio, and Zealand Pharma and study supplies from Dexcom. Dr. Paprocki reports no disclosures. Dr. Van Name reports receiving research support from ProventionBio. Dr. Moran reports serving on advisory boards from Dompé Farmaceutici SpA, ProventionBio, and Abata Therapeutics; serving on a data and safety monitoring board for NovoNordisk; and reported that her institution has received grant funding on her behalf from Abbott Diabetes, ProventionBio, Intrexon (now Precigen), and Caladrius Biosciences and study supplies from NovoNordisk, Medtronic, and Abbott Diabetes., (© 2024 The Authors.)

In the last decade, technology developed by people with diabetes and their loved ones has added to the options for diabetes management. One such example is that of automated insulin delivery (AID) algorithms, which were created and shared as open source by people living with type 1 diabetes (T1D) years before commercial systems were first available. Now, numerous options for commercial systems exist in some countries, yet tens of thousands of people with diabetes are still choosing Open-Source AID (OS-AID), previously called "do-it-yourself" (DIY) systems, which are noncommercial versions of these open-source AID systems. In this article, we provide point and counterpoint perspectives regarding (1) safety and efficacy, (2) regulation and support, (3) user choice and flexibility, (4) access and affordability, and (5) patient and provider education, for open source and commercial AID systems. The perspectives reflected here include that of a person living with T1D who uses and has developed OS-AID systems, a physician-researcher based in the United States who conducts clinical trials to support development of commercial AID systems and supports people with diabetes using all types of AID, and an endocrinologist with T1D who uses both systems and treats people with diabetes using all types of AID.

Learning personalized self-management routines is pivotal for people with type 1 diabetes (T1D), particularly early in diagnosis. Context-aware technologies, such as hybrid closed-loop (HCL) insulin pumps, are important tools for diabetes self-management. However, clinicians have observed that practices using these technologies involve significant individual differences. We conducted interviews with 20 adolescents and young adults who use HCL insulin pump systems for managing T1D, and we found that these individuals leverage both technological and non-technological means to maintain situational awareness about their condition. We discuss how these practices serve to infrastructure their self-management routines, including medical treatment, diet, and glucose measurement-monitoring routines. Our study provides insights into adolescents' and young adults' lived experiences of using HCL systems and related technology to manage diabetes, and contributes to a more nuanced understanding of how the HCI community can support the contextualized management of diabetes through technology design.

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.

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., Competing Interests: C.B. is a consultant/speaker for Insulet. L.H.M. has received speaking/consulting honoraria from Dexcom and Tandem Diabetes Care and also consults for Beta Bionics and Capillary Biomedical. R.P.W. has received research funding from Dexcom, Eli Lilly, and Tandem Diabetes Care; conference travel support from Dexcom and Eli Lilly; consulting honoraria from Eli Lilly; and speaker honoraria from Dexcom. G.P.F. conducts research sponsored by and has been a consultant/speaker for Abbott, Beta Bionics, Dexcom, Insulet, Medtronic, and Tandem Diabetes Care. No other potential conflicts of interest relevant to this article were reported., (© 2024 by the American Diabetes Association.)

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.

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.

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.

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.

Background: The purpose of this study was to develop and test a new Clinic Tool to assist health care professionals with clinical care of persons with diabetes using the Control-IQ system., Methods: A Clinic Tool was iteratively developed with input from diabetes clinicians, which outlined a systematic process for assessing data, reviewing insulin settings, providing education, and documenting the encounter. Diabetes clinicians were recruited to trial the Clinical Tool in up to five clinical encounters (in-person, telehealth, or telephone). Quantitative surveys and free-text responses, including a knowledge quiz and the System Usability Scale (SUS), were administered to determine clinician satisfaction, confidence, knowledge, and implications for practice., Results: Twenty-nine clinicians (43% endocrinologists, mean 10.7 years in practice) enrolled in the study and completed 89 encounters using the Control-IQ Clinic Tool. Participants spent an average of 10 minutes using the Tool and reported excellent SUS scores within the 90%-95% percentile for usability. Knowledge quiz scores increased in 42% of participants. Both familiarity with Control-IQ and confidence providing clinical care to Control-IQ users significantly improved ( P = .009 and P < .001 respectively). Ninety percent of participants agreed that the Tool will change their clinical care going forward., Conclusion: The Control-IQ Clinical Tool is highly usable and impacted clinical care delivery to Control-IQ users. Tools that serve to improve clinician confidence in delivery of care to diabetes device users should be expanded, leveraged, and studied to assess the impact on adherence and glycemic control for persons with diabetes., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared the following potential conflicts of interest with respect to the research, authorship, and/or publication of this article: LHM has received speaking/consulting honoraria from Tandem Diabetes, Dexcom, and Capillary Biomedical and is a certified trainer for Medtronic Minimed. GPF has received speaking consulting honoraria from Tandem Diabetes, Dexcom, Medtronic, Insulet, Abbott, Lilly, and Beta Bionics. The institution receives research/project grants from Medtronic, Tandem Diabetes, Insulet, Dexcom, Abbott, Lilly, and Beta Bionics. CB, SC, and BM have nothing to disclose.

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.

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.

Background: A composite metric for the quality of glycemia from continuous glucose monitor (CGM) tracings could be useful for assisting with basic clinical interpretation of CGM data., Methods: We assembled a data set of 14-day CGM tracings from 225 insulin-treated adults with diabetes. Using a balanced incomplete block design, 330 clinicians who were highly experienced with CGM analysis and interpretation ranked the CGM tracings from best to worst quality of glycemia. We used principal component analysis and multiple regressions to develop a model to predict the clinician ranking based on seven standard metrics in an Ambulatory Glucose Profile: very low-glucose and low-glucose hypoglycemia; very high-glucose and high-glucose hyperglycemia; time in range; mean glucose; and coefficient of variation., Results: The analysis showed that clinician rankings depend on two components, one related to hypoglycemia that gives more weight to very low-glucose than to low-glucose and the other related to hyperglycemia that likewise gives greater weight to very high-glucose than to high-glucose. These two components should be calculated and displayed separately, but they can also be combined into a single Glycemia Risk Index (GRI) that corresponds closely to the clinician rankings of the overall quality of glycemia (r = 0.95). The GRI can be displayed graphically on a GRI Grid with the hypoglycemia component on the horizontal axis and the hyperglycemia component on the vertical axis. Diagonal lines divide the graph into five zones (quintiles) corresponding to the best (0th to 20th percentile) to worst (81st to 100th percentile) overall quality of glycemia. The GRI Grid enables users to track sequential changes within an individual over time and compare groups of individuals., Conclusion: The GRI is a single-number summary of the quality of glycemia. Its hypoglycemia and hyperglycemia components provide actionable scores and a graphical display (the GRI Grid) that can be used by clinicians and researchers to determine the glycemic effects of prescribed and investigational treatments.

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.

Background: We investigated the potential benefits of automated insulin delivery (AID) among individuals with type 1 diabetes (T1D) in sub-populations of baseline device use determined by continuous glucose monitor (CGM) use status and insulin delivery via multiple daily injections (MDI) or insulin pump., Materials and Methods: In a six-month randomized, multicenter trial, 168 individuals were assigned to closed-loop control (CLC, Control-IQ, Tandem Diabetes Care), or sensor-augmented pump (SAP) therapy. The trial included a two- to eight-week run-in phase to train participants on study devices. The participants were stratified into four subgroups: insulin pump and CGM (pump+CGM), pump-only, MDI and CGM (MDI+CGM), and MDI users without CGM (MDI-only) users. We compared glycemic outcomes among four subgroups., Results: At baseline, 61% were pump+CGM users, 18% pump-only users, 10% MDI+CGM users, and 11% MDI-only users. Mean time in range 70-180 mg/dL (TIR) improved from baseline in the four subgroups using CLC: pump+CGM, 62% to 73%; pump-only, 61% to 70%; MDI+CGM, 54% to 68%; and MDI-only, 61% to 69%. The reduction in time below 70 mg/dL from baseline was comparable among the four subgroups. No interaction effect was detected with baseline device use for TIR ( P = .67) or time below ( P = .77). On the System Usability Questionnaire, scores were high at 26 weeks for all subgroups: pump+CGM: 87.2 ± 12.1, pump-only: 89.4 ± 8.2, MDI+CGM 87.2 ± 9.3, MDI: 78.1 ± 15., Conclusions: There was a consistent benefit in patients with T1D when using CLC, regardless of baseline insulin delivery modality or CGM use. These data suggest that this CLC system can be considered across a wide range of patients.

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., Competing Interests: L.H.M. has received research/education grants from Beta Bionics, Insulet, the Leona M. and Harry B. Helmsley Charitable Trust, the National Institutes of Health, and Tandem Diabetes Care. She has served as a consultant/speaker for Capillary Biomedical, Dexcom, and Tandem Diabetes Care and on an advisory board for Eli Lilly. As of January 2023, she is also employed by Tandom Diabetes Care. H.K.A. has received research grants from Dexcom, Eli Lilly, the Institute for the Advancement of Food and Nutrition Sciences, IM Therapeutics, Mannkind, Medtronic, REMD Biotherapeutics, and Senseonics. He has served as a consultant for Eli Lilly and on advisory boards for Ascensia and Mannkind. G.P.F. has received research grants from Abbott, Beta Bionics, Dexcom, Eli Lilly, Insulet, JDRF, Medtronic, and Tandem Diabetes Care and has served as a consultant/speaker for Abbott, Beta Bionics, Dexcom, Insulet, Eli Lilly, Medtronic, and Tandem Diabetes Care. S.M.O. has received research grants from the AAFP, the Colorado Department of Public Health & Environment, and the Leona M. and Harry B. Helmsley Charitable Trust. He has served on advisory boards for the ADA, ADCES, Cecelia Health, Dexcom, the Jaeb Center for Health Research, Medtronic, the National Committee on Quality Assurance, and Pendulum Therapeutics. S.P. has received research grants from Dexcom, Eli Lilly, JDRF, the Leona M. and Harry B. Helmsley Charitable Trust, Medtronic, the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), and Sanofi and has served on an advisory board for Medtronic. V.N.S. has received research grants from Dexcom, Eli Lilly, Insulet, JDRF, the National Institutes of Health, Novo Nordisk, and Tandem Diabetes Care. He has served as a consultant/speaker for Dexcom and Insulet and on advisory boards for DKSH Singapore, LifeScan, and Medscape. R.P.W. has received research grant support from Dexcom and Tandem Diabetes Care and has served as a consultant/speaker for Tandem Diabetes Care. T.K.O. has received research grants from Abbott, the AAFP, the Leona M. and Harry B. Helmsley Charitable Trust, the National Institute of Nursing Research, and NIDDK. She has served on advisory boards for ADA, ADCES, Cecelia Health, Dexcom, and the Jaeb Center for Health Research. No other potential conflicts of interest relevant to this article were reported., (© 2023 by the American Diabetes Association.)

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., (© 2023 by the American Diabetes Association.)

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.

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.

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.)., (Copyright © 2023 Massachusetts Medical Society.)

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., (© The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society.)

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., Competing Interests: G.P.F. has served as a consultant for Abbott Diabetes Care, an advisory board member for Dexcom, and conducts research sponsored by Medtronic, Dexcom, Bigfoot, Tandem, Insulet, and NovoNordisk. The remaining authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

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.

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., Competing Interests: Conflicts of Interest LHM has received speaking/consulting honoraria from Tandem Diabetes, Dexcom, Inc., Capillary Biomedical, and Lilly. Her institution receives research/project grants from Medtronic, Tandem Diabetes, Beta Bionics, Dexcom, Abbott, and Insulet Corp. PFC has received consulting fees in the last 12 months from Academic Impressions Inc. and speaking fees from Westminster Medical Clinic. GPF has received consulting/speaking/advisory board honoraria for Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly and has received research support from Medtronic, Dexcom, Abbott, Tandem, Insulet, Beta Bionics, and Lilly. The other authors declare that there are no conflicts of interest.

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., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Background: The Tandem Control-IQ (CIQ) system has demonstrated significant glycemic improvements in large randomized controlled and real-world trials. Use of this system is lower in people with type 1 diabetes (T1D) government-sponsored insurance and those with type 2 diabetes (T2D). This analysis aimed to evaluate the performance of CIQ in these groups. Methods and Materials: A retrospective analysis of CIQ users was performed. Users age ≥6 years with a t:slim X2 Pump and >30 days of continuous glucose monitoring (CGM) data pre-CIQ and >30 days post-CIQ technology initiation were included. Results: A total of 4243 Medicare and 1332 Medicaid CIQ users were analyzed among whom 5075 had T1D and 500 had T2D. After starting CIQ, the Medicare beneficiaries group saw significant improvement in time in target range 70-180 mg/dL (TIR; 64% vs. 74%; P  < 0.0001), glucose management index (GMI; 7.3% vs. 7.0%; P  < 0.0001), and the percentage of users meeting American Diabetes Association (ADA) CGM Glucometrics Guidelines (12.8% vs. 26.3%; P  < 0.0001). The Medicaid group also saw significant improvement in TIR (46% vs. 60%; P  < 0.0001), GMI (7.9% vs. 7.5%; P  < 0.0001), and percentage meeting ADA guidelines (5.7% vs. 13.4%; P  < 0.0001). Patients with T2D and either insurance saw significant glycemic improvements. Conclusions: The CIQ system was effective in the Medicare and Medicaid groups in improving glycemic control. The T2D subgroup also demonstrated improved glycemic control with CIQ use. Glucometrics achieved in this analysis are comparable with those seen in previous randomized controlled clinical trials with the CIQ system.

Aims: To evaluate psychosocial outcomes for adults with type 1 diabetes (T1D) using the tubeless Omnipod® 5 Automated Insulin Delivery (AID) System., Methods: A single-arm, multicenter (across the United States), prospective safety and efficacy study of the tubeless AID system included 115 adults with T1D. Participants aged 18-70 years completed questionnaires assessing psychosocial outcomes - diabetes distress (T1-DDS), hypoglycemic confidence (HCS), well-being (WHO-5), sleep quality (PSQI), insulin delivery satisfaction (IDSS), diabetes treatment satisfaction (DTSQ), and system usability (SUS) - before and after 3 months of AID use. Associations among participant characteristics, psychosocial measures and glycemic outcomes were evaluated using linear regression analyses., Results: Adults using the tubeless AID system demonstrated improvements in diabetes-specific psychosocial measures, including diabetes distress, hypoglycemic confidence, insulin delivery satisfaction, diabetes treatment satisfaction, and system usability after 3 months (all P < 0.001). No changes in general well-being or sleep quality were observed. The psychosocial outcomes assessed were not consistently associated with baseline participant characteristics (i.e., age, sex, diabetes duration, glycemic outcomes including percent time in range 70-180 mg/dL, percent time below range < 70 mg/dL, hemoglobin A1c, or insulin regimen)., Conclusions: Use of the Omnipod 5 AID system was associated with significant improvements in diabetes-related psychosocial outcomes for adults with T1D., Clinical Trials Registration Number: NCT04196140., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: Very young children with type 1 diabetes often struggle to achieve glycemic targets, putting them at risk for long-term complications and creating an immense management burden for caregivers. We conducted the first evaluation of the Omnipod 5 Automated Insulin Delivery System in this population., Research Design and Methods: A total of 80 children aged 2.0-5.9 years used the investigational system in a single-arm study for 13 weeks following 14 days of baseline data collection with their usual therapy., Results: There were no episodes of severe hypoglycemia or diabetic ketoacidosis. By study end, HbA1c decreased by 0.55% (6.0 mmol/mol) (P < 0.0001). Time with sensor glucose levels in target range 70-180 mg/dL increased by 10.9%, or 2.6 h/day (P < 0.0001), while time with levels <70 mg/dL declined by median 0.27% (P = 0.0204)., Conclusions: Use of the automated insulin delivery system was safe, and participants experienced improved glycemic measures and reduced hypoglycemia during the study phase compared with baseline., (© 2022 by the American Diabetes Association.)

The publisher of Diabetes Technologies & Therapeutics officially withdraws the Just Accepted version of the article entitled, "Positive Impact of the Bionic Pancreas on Diabetes Control in Youth 6-17 Years Old with Type 1 Diabetes: A Multicenter Randomized Trial," by Laurel H Messer, et al. (epub 28 Jun 2022; DOI: 10.1089/dia.2022.0201) due to its erroneous release before being finalized. The correct version will be republished in due course. The publisher extends its sincerest apologies to the authors of the article and to the journal's readership for this regrettable mishap.

Background: Technology for patients with type 1 diabetes (T1D), including continuous glucose monitoring (CGM), insulin pumps, and hybrid closed-loop (HCL) systems, is improving, being used more commonly in the pediatric population, and impacts glycemic control. Materials and Methods: We evaluated the use of these technologies and their impact on glycemic control among patients with T1D who were seen at the Barbara Davis Center ( n  = 4003) between January 2018 and December 2020, <22 years old, with diabetes duration >3 months. Data were analyzed by age group and technology-use group defined as multiple daily injection with blood glucose meter (MDI/BGM), pump with BGM (pump/BGM), MDI with CGM (MDI/CGM), and pump with CGM (pump/CGM). Glycemic control was compared using analysis of covariance (ANCOVA) and controlling for diabetes duration, race, and insurance. Results: Among 4003 patients, 20% used MDI/BGM (mean hemoglobin A1c [HbA1c] = 10.0%); 14.4% used pump/BGM (mean HbA1c = 10.0%); 15.4% used MDI/CGM (mean HbA1c = 8.6%); and 49.8% used pump/CGM (mean HbA1c = 8.1%). Compared with MDI/BGM patients, MDI/CGM and pump/CGM users had a lower HbA1c and were more likely to reach an HbA1c <7.0% (all P  < 0.0001). Among pump/CGM users, 35% used HCL technology (mean HbA1c = 7.6%) and had a lower HbA1c and were more likely to reach an HbA1c <7% than non-HCL users ( P  < 0.001). Conclusions: CGM use was associated with a lower HbA1c in both MDI and pump users. Pump use was only associated with a lower HbA1c if used with CGM. HCL was associated with the lowest HbA1c. Spanish language and minority race/ethnicity were associated with lower rates of pump and CGM use, highlighting the need to reduce disparities.

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., (© 2022 The Authors. Pediatric Diabetes published by John Wiley & Sons Ltd.)

Combining technologies including rapid insulin analogs, insulin pumps, continuous glucose monitors, and control algorithms has allowed for the creation of automated insulin delivery (AID) systems. These systems have proven to be the most effective technology for optimizing metabolic control and could hold the key to broadly achieving goal-level glycemic control for people with type 1 diabetes. The use of AID has exploded in the past several years with several options available in the United States and even more in Europe. In this article, we review the largest studies involving these AID systems, and then examine future directions for AID with an emphasis on usability.

Background: Hybrid Closed-Loop (HCL) systems aid individuals with type 1 diabetes in improving glycemic control; however, sustained use over time has not been consistent for all users. This study developed and validated prognostic models for successful 12-month use of the first commercial HCL system based on baseline and 1- or 3-month data. Methods and Materials: Data from participants at the Barbara Davis Center ( N  = 85) who began use of the MiniMed 670G HCL were used to develop prognostic models using logistic regression and Lasso model selection. Candidate factors included sex, age, duration of diabetes, baseline hemoglobin A1c (HbA1c), race, ethnicity, insurance status, history of insulin pump and continuous glucose monitor use, 1- or 3-month Auto Mode use, boluses per day, and time in range (TIR; 70-180 mg/dL), and scores on behavioral questionnaires. Successful use of HCL was predefined as Auto Mode use ≥60%. The 3-month model was then externally validated against a sample from Stanford University ( N  = 55). Results: Factors in the final model included baseline HbA1c, sex, ethnicity, 1- or 3-month Auto Mode use, Boluses per Day, and TIR. The 1- and 3-month prognostic models had very good predictive ability with area under the curve values of 0.894 and 0.900, respectively. External validity was acceptable with an area under the curve of 0.717. Conclusions: Our prognostic models use clinically accessible baseline and early device-use factors to identify risk for failure to succeed with 670G HCL technology. These models may be useful to develop targeted interventions to promote success with new technologies.

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., (© 2022 by the American Diabetes Association.)

Objective: To describe real-world outcomes for youth using the Tandem t:slim X2 insulin pump with Control-IQ technology ("Control-IQ") for 6 months at a large pediatric clinic. Methods: Youth with type 1 diabetes, who started Control-IQ for routine care, were prospectively followed. Data on system use and glycemic control were collected before Control-IQ start, and at 1, 3, and 6 months after start. Mixed models assessed change across time; interactions with baseline hemoglobin A1c (HbA1c) and age were tested. Results: In 191 youth (median age 14, 47% female, and median HbA1c 7.6%), percent time with glucose levels 70-180 mg/dL (time-in-range [TIR]) improved from 57% at baseline to 66% at 6 months ( P  < 0.001). The proportion of participants reaching TIR target (>70%) doubled from 23.5% at baseline to 47.8% at 3 months, sustaining at 46.7% at 6 months ( P  < 0.001). Glucose management indicator (approximation of HbA1c) improved from 7.5% at baseline to 7.1% at 3 months and 7.2% at 6 months ( P  < 0.001). Those with higher baseline HbA1c experienced the most substantial improvements in glycemic control. Percent time using the Control-IQ feature was 86.4% at 6 months, and <4% of cohort discontinued use. Conclusion: The Control-IQ system clinically and significantly improved glycemic control in a large sample of youth. System use was high at 6 months, with only a small proportion discontinuing use, indicating potential for sustaining results long term.

Numerous studies have demonstrated the clinical value and safety of insulin pump therapy in type 1 diabetes and type 2 diabetes populations. However, the eligibility criteria for insulin pump coverage required by the Centers for Medicare & Medicaid Services (CMS) discount conclusive evidence that supports insulin pump use in diabetes populations that are currently deemed ineligible. This article discusses the limitations and inconsistencies of the insulin pump eligibility criteria relative to current scientific evidence and proposes workable solutions to address this issue and improve the safety and care of all individuals with diabetes.

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., (© 2021 John Wiley & Sons Ltd.)

Objective: Advances in diabetes technology have transformed the treatment paradigm for type 1 diabetes, yet the burden of disease is significant. We report on a pivotal safety study of the first tubeless, on-body automated insulin delivery system with customizable glycemic targets., Research Design and Methods: This single-arm, multicenter, prospective study enrolled 112 children (age 6-13.9 years) and 129 adults (age 14-70 years). A 2-week standard therapy phase (usual insulin regimen) was followed by 3 months of automated insulin delivery. Primary safety outcomes were incidence of severe hypoglycemia and diabetic ketoacidosis. Primary effectiveness outcomes were change in HbA 1c and percent time in sensor glucose range 70-180 mg/dL ("time in range")., Results: A total of 235 participants (98% of enrolled, including 111 children and 124 adults) completed the study. HbA 1c was significantly reduced in children by 0.71% (7.8 mmol/mol) (mean ± SD: 7.67 ± 0.95% to 6.99 ± 0.63% [60 ± 10.4 mmol/mol to 53 ± 6.9 mmol/mol], P < 0.0001) and in adults by 0.38% (4.2 mmol/mol) (7.16 ± 0.86% to 6.78 ± 0.68% [55 ± 9.4 mmol/mol to 51 ± 7.4 mmol/mol], P < 0.0001). Time in range was improved from standard therapy by 15.6 ± 11.5% or 3.7 h/day in children and 9.3 ± 11.8% or 2.2 h/day in adults (both P < 0.0001). This was accomplished with a reduction in time in hypoglycemia <70 mg/dL among adults (median [interquartile range]: 2.00% [0.63, 4.06] to 1.09% [0.46, 1.75], P < 0.0001), while this parameter remained the same in children. There were three severe hypoglycemia events not attributable to automated insulin delivery malfunction and one diabetic ketoacidosis event from an infusion site failure., Conclusions: This tubeless automated insulin delivery system was safe and allowed participants to significantly improve HbA 1c levels and time in target glucose range with a very low occurrence of hypoglycemia., (© 2021 by the American Diabetes Association.)

Background: Studies of closed-loop control (CLC) in patients with type 1 diabetes (T1D) consistently demonstrate improvements in glycemic control as measured by increased time-in-range (TIR) 70-180 mg/dL. However, clinical predictors of TIR in users of CLC systems are needed. Materials and Methods: We analyzed data from 100 children aged 6-13 years with T1D using the Tandem Control-IQ CLC system during a randomized trial or subsequent extension phase. Continuous glucose monitor data were collected at baseline and during 12-16 weeks of CLC use. Participants were stratified into quartiles of TIR on CLC to compare clinical characteristics. Results: TIR for those in the first, second, third, and fourth quartiles was 54%, 65%, 71%, and 78%, respectively. Lower baseline TIR was associated with lower TIR on CLC ( r  = 0.69, P  < 0.001). However, lower baseline TIR was also associated with greater improvement in TIR on CLC ( r  = -0.81, P  < 0.001). During CLC, participants in the highest versus lowest TIR-quartile administered more user-initiated boluses daily (8.5 ± 2.8 vs. 5.8 ± 2.6, P  < 0.001) and received fewer automated boluses (3.5 ± 1.0 vs. 6.0 ± 1.6, P  < 0.001). Participants in the lowest (vs. the highest) TIR-quartile received more insulin per body weight (1.13 ± 0.27 vs. 0.87 ± 0.20 U/kg/d, P  = 0.008). However, in a multivariate model adjusting for baseline TIR, user-initiated boluses and insulin-per-body-weight were no longer significant. Conclusions: Higher baseline TIR is the strongest predictor of TIR on CLC in children with T1D. However, lower baseline TIR is associated with the greatest improvement in TIR. As with open-loop systems, user engagement is important for optimal glycemic control.