Diabetes Technology and Therapy in the Pediatric Age Group

Diabetes Care 2024; 47: 346–352

Background

Despite evidence that continuous glucose monitoring (CGM) use is associated with lower HbA1c among children with type 1 diabetes, uptake of this technology remains lower among those with difficulty accessing health care, including those from lower socioeconomic status backgrounds and racial and ethnic minorities. In this study, we sought to explore the impact of rural location in use of CGM technology to guide patient and provider decision making.

Methods

In this retrospective study of electronic health record demographic and visits data from a single diabetes program from January 1, 2018, through December 31, 2021, we compared the odds of completing a visit with (+) and without (2) CGM interpretation between rural-urban commuting area (RUCA) designations.

Results

Among the 13,645 visits completed by 2008 patients with type 1 diabetes younger than age 18 years, we found children living in small rural towns had 31% lower odds (6.3% of CGM+ visits, 8.6% of CGM2 visits; adjusted odds ratio [aOR] 0.69, 95% CI 0.51–0.94) and those living in isolated rural towns had 49% lower odds (2.0% of CGM+ visits, 3.4% of CGM2 visits; aOR 0.51, 95% CI 0.28–0.92) of completing a CGM-billed clinic visit compared with those living in urban areas (70.0% of CGM+ visits, 67.2% of CGM2 visits). We also found significant differences in CGM-billed visits by neighborhood deprivation as well as race/ethnicity and insurance payor.

Conclusions

Geographic location presents a meaningful barrier to access to care for patients living with type 1 diabetes. Further work is needed to identify and address the needs of children and families living in rural areas to improve the care of these patients.

Comments

Diabetes technology improves glycemic outcomes and quality of life for people with diabetes…if they have access. This paper by Tilden and colleagues expands existing evidence indicating that rural geography is a barrier to accessing healthcare for adults with diabetes and find that children in rural areas had significantly lower odds of CGM clinic visits compared to their peers in urban areas. In addition, those children living in isolated rural towns had ever lower odds of CGM visits. These data from 2018 to 2021 in the Vanderbilt Pediatric Diabetes Program add an important barrier to target for equitable diabetes care in Pediatrics. Future studies are required in other states in the United States (and other countries) that identify barriers as a first step and then develop intervention programs to improve access to diabetes technology as an important component of best practices of diabetes care. Now that this particular barrier has been identified healthcare systems need to adapt and develop innovative outreach programs so that rural populations fully benefit from advances in diabetes technology.

Diabetes Technol Ther 2024; 26: 119–124

Background

Continuous glucose monitors (CGMs) use in people with type 1 diabetes (T1D) is associated with lower hemoglobin A1c. At present, CGMs are not approved for inpatient use, a time when close glucose monitoring and intensive insulin management are essential. CGM accuracy data from adult hospitalizations have been published, but pediatric data are limited.

Methods

A retrospective review of Dexcom G6 data from hospitalized youth with T1D assessed CGMs glucose values 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: 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

From 83 unique patients (median age 12.0 years, 68.7% non-Hispanic white, 54.2% male) during 100 admissions, a total of 1,120 POC and 288 laboratory-matched pairs were collected. The MARD for POC values, overall, was 11.8%, 13.5% on the medical floor, and that 7.9% in the intensive care unit. 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

The findings from the 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 and with concomitant medication use.

Comments

Continuous glucose monitor (CGM) use has been increasing in the outpatient setting. However, CGM is not currently approved for use in the inpatient setting. Data is available on the inpatient use of CGM in adults (1, 2); however, there is little data on inpatient CGM use in youth. Cobry et al. reviewed CGM data from youth on Dexcom G6 CGM during hospitalization and compared data to matched (within 5 minute) point-of-care and laboratory glucose values. The data from this retrospective study showed acceptable accuracy of CGM glucoses in hospitalized pediatric patients.

Point-of-care glucoses are standard of care in hospitals, but they only provide glucose data at snapshots in time. CGM has the potential to improve care for hospitalized youth. CGM allows for continuous monitoring of glucoses and visualization of glucose trends with minimal discomfort to the patient. As CGM is a key component of automated insulin delivery (AID) systems, acceptance of inpatient use of CGM is the first step towards evaluation of AID systems inpatient. Additional research should be prioritized to study the accuracy of CGM in hospitalized youth.

Diabetes Care 2023; 46: 2300–2307

Background

Automated insulin delivery (AID) systems have demonstrated potential in significantly enhancing glycemic control in children and adolescents with type 1 diabetes (T1D). Previous meta-analyses indicated benefits of AID systems but often involved inpatient settings or non-randomized trials, particularly in children and adolescents. To address these gaps, this recent meta-analysis of randomized controlled trials (RCTs) compared AID systems with conventional insulin therapy to assess improvements in glycemic control in children and adolescents with T1D in outpatient settings.

Methods

A comprehensive literature search was conducted in PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov up to May 4, 2023. The inclusion criteria were RCTs involving children, adolescents, and young adults aged ≤25 years with T1D in outpatient settings that compared AID systems with conventional insulin therapies and reported continuous glucose monitoring (CGM) outcomes. Conventional insulin therapy included multiple daily insulin injection (MDI), continuous subcutaneous insulin infusion (CSII), and sensor-augmented pump (SAP) with or without low glucose suspend. Key outcomes extracted included percentage of time in range (TIR) (3.9–10 mmol/L), time below range (TBR) (<3.9 mmol/L), and time above range (TAR) (>10 mmol/L). Data were synthesized using random-effects meta-analysis. In addition, a prespecified subgroup analysis was conducted.

Results

Meta-analysis included 25 RCTs encompassing 1345 participants. Participant mean age ranged from 3.9 to 17 years. AID systems significantly increased TIR by 11.38% (95% CI 9.01–13.76) compared to conventional insulin therapy, equating to 164 additional minutes per day within the target range. AID also reduced TAR by 12.19% (95% CI −14.65 to −9.73), equating to 176 min less per day and TBR by 0.59% (95% CI −1.02 to −0.15). These results indicate overall improved glycemic control, although substantial statistical heterogeneity was observed across trials. The favorable effect of AID was consistent when AID was used over 3 months or 6 months and across different subgroups stratified by type of AID system, timing of intervention, study design, mean age, study duration, and comparator. Serious adverse effects, such as severe hypoglycemia and diabetic ketoacidosis, were rare.

Conclusions

AID systems were more effective than conventional insulin therapies in increasing TIR and reducing TAR and TBR for children and adolescents with T1D in outpatient settings. The improvements were consistent both in the short and long term and in different subgroups suggesting consistent benefits of AID systems for glycemic control in pediatric population.

Comments

AID systems, which integrate glucose monitoring technology with glucose-responsive insulin delivery, now enable the achievement of glycemic goals that are still difficult to reach with conventional therapy for the majority of pediatric population (3). Recent recommendations from the National Institute of Health and Care Excellence (NICE) regarding hybrid closed-loop (HCL) systems underscore the growing significance of these advances in diabetes care (4). The use of AID systems is especially essential for the pediatric population, as it not only helps achieve glycemic targets but also significantly enhances quality of life for their families (5).

This meta-analysis confirms the significant advantages of AID systems over conventional insulin therapies in improving glycemic control for children and adolescents with T1D in outpatient settings. Enhanced sensor-based metrics, such as increased TIR and reductions in TAR and TBR, underscore the clinical efficacy of AID systems. Despite observed statistical heterogeneity among the studies, improvements across various subgroups and durations of AID use were consistent. Of note TBR reduction only by 0.59% compared with conventional insulin therapy contrasts meta-analyses of AID use that included older age groups (6). The subgroup analysis showed that the reduction was significant in dual-hormone systems and supervised settings but not in single-hormone systems and unsupervised settings. Therefore, more trials of dual hormone AID in children and adolescents are needed.

In conclusion, despite limitations such as small sample sizes, risk of performance bias, and high heterogeneity across trials, this meta-analysis demonstrates that AID systems offer superior glycemic control for young individuals with T1D compared to conventional treatment. This data supports broader adoption of diabetes management technologies for all youth with T1D (7). Further innovation in diabetes management technologies and studies are needed, especially in younger age groups.

BMC Med 2024; 22: 175

Hybrid closed-loop (HCL) systems seamlessly interface continuous glucose monitoring (CGM) with insulin pumps, employing specialized algorithms and user-initiated automated insulin delivery. This study aimed to assess the efficacy of HCLs at 12 months postinitiation on glycated hemoglobin (HbA1c), time-in-range (TIR), hypoglycemia frequency, and quality of life measures among children and young people (CYP) with type 1 diabetes mellitus (T1DM) and their caregivers in a real-world setting. Conducted between August 1, 2021, and December 10, 2022, the prospective recruitment took place in eight pediatric diabetes centers across England under the National Health Service England’s (NHSE) HCL pilot real-world study.

A cohort of 251 CYP (58% males, mean age 12.3 years) with T1DM participated (89% white, 3% Asian, 4% black, 3% mixed ethnicity, and 1% other). The study utilized three HCL systems: (1) Tandem Control-IQ AP system, which uses the Tandem t:slim X2 insulin pump (Tandem Diabetes Care, San Diego, CA, USA) with the Dexcom G6® CGM (Dexcom, San Diego, CA, USA) sensor; (2) Medtronic MiniMed™ 780G with the Guardian 4 sensor (Medtronic, Northridge, CA, USA); and (3) the CamAPS FX (CamDiab, Cambridge, UK) with the Ypsomed insulin pump (Ypsomed Ltd, Escrick, UK) and Dexcom G6® CGM. All systems were fully funded by the NHS. Results demonstrated significant improvements in HbA1c (average reduction at 12 months 7 mmol/mol; P < 0.001), time-in-range (TIR) (average increase 13.4%; P < 0.001), hypoglycemia frequency (50% reduction), hypoglycemia fear, and quality of sleep (P < 0.001) among CYP over a 12-month period of HCL usage. Additionally, parents and carers experienced improvements in hypoglycemia fear and quality of sleep after 6 and 12 months of use. In addition to the improvements in glycemic management, these findings underscore the positive impact of HCL systems on both the well-being of CYP with T1DM and the individuals caring for them.

Comments

Now that multiple automated insulin delivery systems have been developed and become the standard of care for people with type 1 diabetes access to these systems needs to be expanded. In this study by Ng and colleagues present 1-year data on the real-world experience of children and young people with type 1 diabetes using NHS provided systems: Control IQ, MiniMed 780G, and CamAPS FX. No between system analyses are presented instead results are pooled. At 1-year significant improvements were reported for HbA1c, TIR, hypoglycemia, hypoglycemia fear, and quality of sleep. Positive impacts were also reported for parents and carers for hypoglycemia fear and sleep quality extending the benefit for a healthcare system. The authors also emphasize that as diabetes technology evolves that accuracy, accessibility, and cost will be important factors so that children and young people with type 1 diabetes can benefit from these innovations in care. Such data are necessary to advocate for expanded coverage of diabetes technology.

Diabetes Technol Ther 2023; 25: 755–764

Background

Data analyses strongly support the use of automated insulin delivery (AID) in children and adolescents with type 1 diabetes (T1D), to reach current American Diabetes Association ADA-recommended glycemic goals. Since the availability of the first AID system for pediatric T1D, hybrid closed-loop (HCL) algorithms that adjust insulin delivery to a specific sensor glucose (SG) range or target have advanced to provide automatic correction insulin boluses that further improve glycemia—advanced hybrid closed-loop (AHCL) therapies. MiniMed AHCL algorithm can automatically deliver a correction bolus up to every 5 min, when appropriate, based on glucose target (GT) settings. MiniMed AHCL system use during the pivotal trial in adolescents aged 14–21 years demonstrated significantly reduced hemoglobin A1c (HbA1c), increased time spent in target range (TIR) and lowered time spent below range (TBR, <70 mg/dL) compared with baseline run-in and no severe hypoglycemia or diabetic ketoacidosis (DKA) (8). This study aimed to evaluate the safety and effectiveness of the MiniMed AHCL system in children and adolescents aged 7–17 years with T1D.

Methods

The study was conducted as a single-arm nonrandomized trial involving 160 participants with T1D, aged 7–17 years, across 13 investigational centers. Participants had >6 months of insulin pump therapy use with or without CGM experience at the screening. Following a 25-day run-in period participants used the AHCL system for three months with glucose targets of 100 mg/dL and 120 mg/dL. The study analyzed changes in HbA1c and TIR from baseline to the end of study. The secondary effectiveness endpoints were the overall mean change in percentage of TBR (<70 mg/dL) and time spent above range (TAR, >180 mg/dL). Additional analyses included change in mean sensor glucose (SG), coefficient of variation (CV) of SG, and insulin delivery between the run-in and study periods.

Results

The AHCL system led to a significant reduction in HbA1c from 7.9 ± 0.9% to 7.4 ± 0.7% (P < 0.001). The proportion of participants achieving the consensus recommended HbA1c of < 7.0% increased to 25.7% (35/136) among those using AHCL, compared to 15.6% (25/160) at baseline. Overall, TIR increased from 59.4 ± 11.8% to 70.3 ± 6.5% (P < 0.001), with a mean of 10.9% (2.6 hours/day). There were no significant changes in CV of SG and TBR, except for the nighttime period where the CV of SG was reduced from 34.2—5.3% to 32.9—5.2% (P = 0.003). Using the 100 mg/dL glucose target with a 2-hour active insulin time (AIT) increased mean TIR to 73.4% and reduced time below and above range compared to higher AIT settings. There were no severe hypoglycemia or DKA events during the study.

Conclusions

The MiniMed AHCL system was safe and effective for children and adolescents with T1D, leading to lower HbA1c and increased TIR. The 100 mg/dL glucose target combined with the shortest AIT of 2 hours achieved the highest TIR and lowest times below and above range.

Comments

The study on the use of the MiniMed AHCL system in children and adolescents aged 7–17 years with T1D highlights the safety and efficacy of the MiniMed AHCL system, as shown by clinically significant mean reduction in HbA1c by 0.5% and the increase in TIR by 10.9% in the absence of DKA or severe hypoglycemic events during the three-month trial period.

The study's findings are particularly significant because they align with previous research in older adolescents and adults. The comparison with the older cohort (aged 14–21 years) indicates that the glycemic benefits of the AHCL system are consistent across different age groups, with both groups achieving similar reductions in HbA1c and increases in TIR. This consistency underscores the robustness of the AHCL system in effectively managing blood glucose levels in younger age groups.

An important takeaway from this study is the role of specific pump settings, such as glucose target (GT) and active insulin time (AIT), in optimizing glycemic outcomes. Previous studies have shown that pediatric use of the 100 mg/dL GT and 2-hour AIT demonstrated a greater likelihood of attaining consensus-recommended targets for TIR, TBR, and TAR (9, 10). In the present study, mean TIR increased to 73.4%, and mean TAR and TBR were reduced to 24.4% and 2.2%, respectively, when a small number of participants used the lowest GT and shortest AIT. This suggests that personalized adjustments to these settings can enhance the system's efficacy, making it a valuable tool in the management of pediatric T1D.

However, the study also identifies some limitations, including its nonrandomized design and the underrepresentation of diverse racial/ethnic and socioeconomic groups. Additionally, the exclusion of participants with a baseline HbA1c >10% and the requirement for prior insulin pump experience may mean that the results are not fully applicable to all pediatric T1D population, particularly those with more challenging glycemic control or less experience with diabetes technology.

In conclusion, this study provides compelling evidence for the safe and effective use of the MiniMed AHCL system in pediatric populations, demonstrating significant improvements in glycemic control. It highlights the importance of individualized pump settings for optimizing glycemic outcomes. These findings support the broader adoption of AHCL systems in pediatric diabetes care, especially given the challenges in achieving glycemic targets.

Diabetes Technol Ther 2024; 26 (S3): 76–83

Background

Carbohydrate counting is a well-established tool for self-management of type 1 diabetes (T1D) and can improve glycemic control and potentially reduce long-term complication risk. However, it can also be burdensome, error-prone, and complicated for the patient. A randomized controlled trial was conducted to investigate glycemic control with carbohydrate counting (‘‘flex’’) versus simplified meal announcement (‘‘fix’’) in adolescents with T1D using the MiniMed 780G system. The present study reports follow-up data to 12 months.

Methods

Adolescents with T1D were randomly assigned 1:1 to use the MiniMed 780G system alongside the flex versus fix approaches. Participants were followed for 12 months with outcomes recorded at 3, 6, 9, and 12 months. The primary endpoint was the difference in time-in-range (TIR), and secondary endpoints included glycated hemoglobin (HbA1c) and other glucose and insulin metrics.

Results

At 12 months, TIR (proportion of time with sensor glucose 70–180 mg/dL) was significantly lower in the fix versus flex group (72.9% vs. 80.1%, respectively; P = 0.001). There was no significant difference in HbA1c between the fix (6.8%–0.5%) and flex groups (6.5%–0.5%) at 12 months (P = 0.092), and mean HbA1c was below 7% at all time points in both arms.

Conclusions

Glycemic control with simplified meal announcement was maintained over 12 months. On average, the international consensus targets were met in both arms for all time points. The simplified approach represents a viable alternative to carbohydrate counting, particularly in people who find the latter burdensome; however, carbohydrate counting resulted in superior TIR.

Comments

In this manuscript Petrovski and colleagues present 12-month follow-up of their randomized controlled trial of simplified meal announcement versus precise carbohydrate counting using the MiniMed 780G AHCL system. The data demonstrate maintenance of their initial findings at 1 year. Participants were randomized to either a set of three fixed, personalized, preset carbohydrate amounts corresponding to a regular meal, large meal, or snack (the ‘‘fix’’ group), or to precise carbohydrate counting (the ‘‘flex’’ group). Both groups on average achieved TIR (>70%) and HbA1c (<7%) goals with minimal hypoglycemia; however, those who followed the “precise” carbohydrate counting plan did have 7% more TIR (P = 0.001) and 0.3% lower HbA1c (P = 0.092). One important focus of current diabetes technology research is to reduce the burden of user input required to use automated insulin delivery devices. These data support the current approach and importance of teaching and using carbohydrate counting to optimize glycemic outcomes while also providing data on the magnitude of difference in glycemic outcomes for those who use a 780G and use a simplified “fixed” dosing approach. Of note, again, is that both arms achieved current ISPAD goals. What is unanswered, and most likely highly individualized, is the benefit in quality of life to those who might choose to use a simplified approach. With these data diabetes providers can help quantify the benefits of carbohydrate counting and efforts to bolus precisely so that an individual with diabetes can make their own decision how important the extra 7% TIR is versus the reduction in effort and presumed improvement in quality of life. These data may also reassure many that an occasional miscalculation of carbohydrates can be overcome with a 780G system. Future research will continue to refine automated insulin delivery systems so that user burden decreases especially around meal announcement and the need for it. These data are an encouraging step in that direction and a re-adjustment in dietary education that does not focus so heavily on carbohydrate counting.

Diabetes Care 2024; 47: 1084–1091

Objective

Automated insulin delivery (AID) systems are increasingly used in clinical practice. Medtronic MiniMed 780G (Medtronic, Northridge, CA) is an AID system, also known as advanced hybrid closed-loop (AHCL). There are few real-world data on the 1-year performance of this device in children and adolescents with type 1 diabetes (T1D). The aim was to investigate glucose metrics and identify potential predictors for achieving glycemic outcomes in children and adolescents during their first year of using the MiniMed 780G system.

Methods

This multicenter, longitudinal, real-world study recruited children and adolescents with T1D (n = 368) who began using SmartGuard technology between June 2020 and June 2022. Ambulatory glucose profile data were collected during a 15-day run-in period (baseline), 2 weeks after automatic mode activation, and every 3 months thereafter. The influence of various covariates on glycemic outcomes after one year of MiniMed 780G use was assessed.

Results

After 15 days of using the automatic mode, all glucose metrics improved compared to baseline (P < 0.001), except for time below range (RBR) (P = 0.113) and coefficient of variation (P = 0.330). After one year, time in range (TIR) remained significantly higher than at baseline (75.3% vs. 62.8%, P < 0.001). The mean HbA1c over the study duration was lower than the previous year (6.9 ± 0.6% vs. 7.4 ± 0.9%, P < 0.001). Time spent in the tight range (70–140 mg/dL) was 51.1%, and the glycemia risk index was 27.6. Higher TIR levels were associated with fewer automatic correction boluses (P < 0.001), fewer SmartGuard exits (P = 0.021), and more extended time in automatic mode (P = 0.030). Participants with a baseline HbA1c >8% showed more significant improvement in TIR levels (from 54.3% to 72.3%).

Conclusions

This study highlights the sustained effectiveness of the MiniMed 780G system in youth with T1D. The findings suggest that even children and adolescents with low therapeutic engagement can benefit from SmartGuard technology.

Comments

The safety and efficacy of the MiniMed 780G system have been well-documented through both clinical trials and observational studies (11). This current study further demonstrates that the Advanced Hybrid Closed-Loop (AHCL) system leads to rapid and sustained improvements in glycemic outcomes in real-world settings. Notably, the time spent within target glucose ranges, as universally recommended (12), increased within the first two weeks of AHCL use and remained stable throughout the study period. Additionally, the mean HbA1c value significantly decreased during the first year of AHCL use compared to the previous year, with BMI stability maintained throughout the study period.

Predictors for achieving target recommendations for TIR, glucose management indicator (GMI), and TBR by the end of the study included older age, longer duration in automatic mode, and a lower number of automatic correction boluses. The analysis further revealed that individuals with the highest TIR levels had an average SmartGuard activation time of 96.3%. Notably, the most significant improvements in TIR were observed in individuals who had suboptimal glycemic levels prior to using the AHCL system. This is particularly encouraging for adolescents, given the challenges of managing T1D during this period and the typically suboptimal clinical outcomes.

The strength of this study lies in its large sample size (n = 368) from 25 centers, its relatively long follow-up period of one year, and its comprehensive inclusion of both glucose metrics and clinical data. However, the study's limitations include its exclusive inclusion of centers in Italy, which may limit the generalizability of the findings to other countries. Furthermore, only patients with consistent CGM system use (mean daily use >70%) were included, precluding evaluation of the MiniMed 780G system's effectiveness during partial use.

Diabetes Technol Ther 2024; 26: 198–202

Objective

The onset of type 1 diabetes (T1D) with diabetic ketoacidosis (DKA) is linked to higher long-term glycated hemoglobin levels. This study evaluated whether initiating hybrid-closed-loop (HCL) therapy at the time of T1D diagnosis could prevent the negative impact of DKA on long-term glycemic outcomes.

Methods

In a post hoc analysis from the CLOuD trial (NCT02871089), 51 adolescents who started HCL therapy upon T1D diagnosis were assessed. Glycemic and insulin metrics were compared between those with DKA at diagnosis (n = 17) and those without (n = 34).

Results

Adolescents with and without DKA at diagnosis had similar time in target glucose range (3.9–10.0 mmol/L, 70–180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL), and HbA1c levels at 6, 12, and 24 months. Although insulin requirements at 6 months were higher for those with DKA at diagnosis, the difference was not statistically significant after adjusting for body weight. Residual C-peptide secretion was also similar between the two groups.

Conclusions

HCL therapy initiated at the onset of T1D may mitigate the negative glycemic effects associated with DKA at diagnosis.

Comments

Large observational studies of young patients with T1D have found that those presenting with DKA at diagnosis exhibit higher HbA1c levels over time compared to those who do not present with DKA, independent of demographic and socioeconomic factors (13, 14). Conversely, smaller studies reported that the presence of DKA at diabetes diagnosis was not associated with deteriorated long-term metabolic control in children using modern technologies. These studies concluded that the early implementation of insulin pump therapy into diabetes treatment might mitigate the effect of DKA and lead to long-term HbA1C improvement (15).

Given that data indicate HCL therapy leads to improved glycemic outcomes over the first 24 months compared to standard insulin therapy in young people with new-onset T1D (16, 17), this post hoc analysis assessed whether HCL therapy could additionally mitigate the adverse impact of DKA at diagnosis on long-term glycemic outcomes.

Previous studies have evaluated whether near normalization of glucose levels, instituted immediately after diagnosis of T1D through intensive diabetes management, could preserve pancreatic beta cell function by reducing glucotoxicity. These studies showed that in youths with newly diagnosed T1D, 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 (17).

The current study did not find differences in residual endogenous insulin secretion between those with and without DKA at diagnosis, despite improved glycemic control.

The SEARCH for Diabetes in Youth study previously reported that DKA at onset was associated with increasingly higher HbA1c levels over time, independent of baseline fasting C-peptide (18). Therefore, the effects of DKA at onset on long-term glycemic outcomes may operate through additional pathways beyond those related to residual insulin secretion. This finding emphasizes the current study's results, where HCL therapy was able to mitigate the negative effects of DKA at diagnosis, despite the absence of an effect on residual C-peptide secretion (16).

Promisingly, the current results show that individuals who presented with DKA at diagnosis had similar glycemic outcomes to those who did not present with DKA over the first two years postdiagnosis, with both groups maintaining a mean time in range greater than the 70% recommended by international guidelines. However, the main limitation of the study is the small sample size. Longer follow-up would be of interest to determine if this effect is sustained over the years and whether the use of HCL in maintaining target glycemic control can prevent short- and long-term complications of diabetes despite the absence of residual beta cell function.

Diabetes Res Clin Prac 2024; 210: 111621

Background

The aim was to analyze metabolic outcomes, diabetes impact and device satisfaction in children and adolescents with type 1 diabetes (T1D) in Italy who used different treatment modalities for diabetes care in a real-world context.

Methods

In this multicenter, nationwide, cross-sectional study, 1464 participants were enrolled at a routine clinic visits. Six different treatment modalities were included: MDI + SMBG; MDI + CGM; sensor-augmented pump therapy; predictive management of low glucose; hybrid closed-loop (HCL); advanced hybrid closed-loop (AHCL). An Italian of the Diabetes Impact and Device Satisfaction Scale (DIDS) questionnaire was used to evaluate health-related quality of life.

Results

Children and adolescents treated with AID systems were more likely to have HbA1c ≤ 6.5%, higher time in range (glucose levels 70–180 mg/dL), lower percentage of time with glucose levels above 180 mg/dL, higher device satisfaction, and reduced impact of diabetes. Compared to MDI + CGM, all of the therapeutic modalities, except for MDI + SMBG, had increased device satisfaction. HCL and AHCL were associated with lower diabetes impact compared to MDI + CGM.

Conclusions

Real-world use of automated insulin delivery systems is associated with reduced T1D impact, increased device satisfaction, and achievement of glycemic goals.

Comments

Diabetes technology, including continuous glucose monitoring (CGM), insulin pumps, and automated insulin delivery systems, have been shown to improve clinical outcomes (19) and health-related quality of life (20, 21). Cherubini et al. evaluated clinical and quality of life outcomes in youth with type 1 diabetes (T1D) using different technologies in a nationwide cross-sectional study. Youth using AID systems had the best clinical outcomes and reduced T1D impact on quality of life compared to those using other technologies.

This study highlights the benefits of diabetes technology in improving clinical outcomes and health-related quality of life. The strength of this study was that it was a multicenter study across an entire country demonstrating the consistent benefits of AID systems in youth with T1D. The results of this study further reinforces the need for access to technology for all youth with T1D.

Diabetes Technol Ther 2024; 26: 383–393

Aim

This study aims 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 (T1D) with up to 2 years of use.

Methods

Following the 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 enroll in an extension phase with continued use of the AID system. HbA1c was measured every 3 months for 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

A total of 80 participants completed 18.2 [17.4, 23.4] (median [interquartile range]) total months of AID use, 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. Adverse events included one episode of severe hypoglycemia and one episode of diabetic ketoacidosis.

Conclusions

The Omnipod 5 AID System can be used safely to maintain improvements in glycemic outcomes with up to 2 years of use in very young children with T1D.

Comments

The Omnipod 5 Automated Insulin Delivery (AID) System improved HbA1c and time in range (TIR) glucose 70–180 mg/dL while decreasing time in hypoglycemia in youth 2–5.9 years of age over a 13-week single-arm multicenter pivotal trial (22). Participants in that study were given the option of continuing in the extension phase. HbA1c improvements and increased TIR were maintained during the extension phase.

Management of T1D in young children can be challenging. DeSalvo et al. have shown that the Omnipod 5 AID systems can help improve HbA1c and increase TIR while minimizing hypoglycemia in the 2–5.9-year-old age group over a median of 18 months. This data is important for showing that young children can safely and effectively use AID systems, and use of AID systems should be offered to young children.

Diabetes Technol Ther 2024; 26: 11–23

Background

Omnipod 5 automated insulin delivery system (Omnipod 5) is a wearable tubeless device with an automated insulin delivery (AID) system for managing insulin-requiring diabetes. Omnipod 5 was previously demonstrated to be safe and effective over three months in type 1 diabetes (T1D). However, data on its performance over extended periods was lacking. This study addressed the long-term safety and effectiveness by evaluating the system's performance over a span of up to two years in a diverse population of children, adolescents, and adults with T1D.

Methods

Following a three-month single-arm pivotal trial, participants aged 6 to 70 years were given the option to continue using the Omnipod 5 in an extension phase. Hemoglobin A1c (HbA1c) levels were measured every three months up to 15 months, and continuous glucose monitoring (CGM) data were collected for up to two years. The study’s primary outcomes were changes in HbA1c and time in the target glucose range (TIR). Primary safety outcomes were incidence rates of severe hypoglycemia and diabetic ketoacidosis. Secondary outcomes included differences between the extension phase and the standard therapy phase in various glucose metrics, clinical and system use measures.

Results

Among the 224 participants, which included 110 children (ages 6–13.9 years) and 114 adolescents/adults (ages 14–70 years), the median duration of AID use was 22.3 months. Significant reductions in HbA1c levels were observed and maintained over a 15-month period, decreasing from 7.7% to 7.2% in children and from 7.2% to 6.9% in adolescents/adults. TIR also improved, increasing from 52.4% to 65.9% in children and from 63.6% to 72.9% in adolescents/adults, which corresponds to an increase of 3.2 and 2.2 hours per day, respectively.

The study showed significant improvements in secondary outcomes. Adolescents and adults reduced the percentage of time with glucose levels below 70 mg/dL from 2.05% to 1.23% (P < 0.0001) and the percentage of time below 54 mg/dL by 0.03% (P = 0.0008). In children, the percentage of time with glucose levels below 54 mg/dL increased slightly (P = 0.0049), while the percentage of time below 70 mg/dL remained unchanged. Hyperglycemia time, defined as glucose levels above 180 mg/dL, decreased significantly in both groups, from 45.5% to 32.3% in children (P < 0.0001) and from 33.4% to 25.6% in adolescents/adults (P < 0.0001).

Incidents of severe hypoglycemia and diabetic ketoacidosis were rare, with only one episode of diabetic ketoacidosis and seven episodes of severe hypoglycemia reported. Participants spent a high percentage of time in automated mode, averaging 96.1% in children and 96.3% in adolescents/adults.

Conclusions

The Omnipod 5 proved to be effective and safe for long-term use in individuals with T1D, maintaining improved glycemic control for up to two years. The significant improvements in HbA1c and TIR observed during the initial trial phase were sustained throughout the extension phase. These findings suggest that the Omnipod 5 can offer lasting benefits for glycemic management in children, adolescents, and adults.

Comments

Omnipod 5 was previously evaluated through a pivotal 3-month study, demonstrating its safety and effectiveness in 128 adult/adolescents (aged 14 to 70 years) and 112 children (aged 6 to 13.9 years) with T1D. Results showed a significant increase in TIR and an improvement in HbA1c (23). The study led to Food and Drug Administration (FDA) authorization for the system for individuals aged 6 years and older with T1D.

This subsequent 2-year extension study provides valuable insights into the system's long-term performance. This extended research confirmed that participants continued to experience lower HbA1c and greater TIR, reinforcing the system’s effectiveness over a longer period. The study also highlights the system’s safety, with a low incidence of severe hypoglycemia and diabetic ketoacidosis. Furthermore, the high retention rate, with over 90% of participants choosing to continue using the system, indicates strong user satisfaction.

In summary, the Omnipod 5 has demonstrated effectiveness in managing T1D in various populations. The improvements in glycemic control, along with favorable safety outcomes and high retention rates, are particularly significant for the pediatric group, where diabetes management is often more complex. The extension study further supports the system’s potential for reliable, long-term diabetes management and underscores its role as a valuable option in pediatric care.

Diabetes Technol Ther 2023; 25: 782–789

Background

Omnipod 5 tubeless automated insulin delivery system (Omnipod 5) has been shown to improve glycemic control in clinical trials. However, these trials often include a homogenous group of participants, lacking diversity in race, ethnicity, and socioeconomic status. This study investigated the real-world effectiveness of the Omnipod 5 in a diverse cohort of youth with type 1 diabetes (T1D), comparing glycemic control before and after the initiation of the device. The goal was to assess whether the improvements observed in pivotal trials could be replicated in a broader, more representative population.

Methods

This retrospective study analyzed data from youth aged 2–21 years with T1D who began using the Omnipod 5 at two pediatric academic centers. Baseline continuous glucose monitoring (CGM) data from the 14 days prior to Omnipod 5 initiation were compared with data collected during the first 90 days of device use. Key outcomes included changes in time in range (TIR) and hemoglobin A1c (HbA1c), as well as CGM and insulin pump metrics. Multivariable regression analyses were employed to identify factors influencing TIR and HbA1c, adjusting for variables such as age, sex, race, duration of diabetes, site, diabetic ketoacidosis (DKA) at diagnosis, A1C at diagnosis, insurance type, insulin regimen before Omnipod 5 initiation, and HbA1c or TIR before Omnipod 5 initiation.

Results

The study included 195 youth, primarily non-Hispanic White (78.9%), with a median age of 11.7 years. After 90 days of using Omnipod 5, median TIR increased by 11 percentage points, from 49% to 61% (P < 0.001), and HbA1c decreased by 0.5 percentage points, from 7.5% to 6.9% (P < 0.001). Improvements were observed in all other CGM parameters, including time spent very low (<54 mg/dL), low (<70 mg/dL), high (>180 mg/dL), and very high (>250 mg/dL) (P < 0.01 for all analyses). There was no statistically significant difference in glycemic outcomes by race for TIR and HbA1c. Significant improvements in TIR were observed within the first 9 days and were maintained throughout the study period. Notably, those starting with lower baseline TIR experienced greater relative gains. Decreases in user-initiated boluses and carbohydrate entries were recorded, though they did not affect the overall glycemic improvements.

Conclusions

This study demonstrated that the real-world use of the Omnipod 5 AID system led to substantial improvements in glycemic control, comparable to those reported in clinical trials. The device significantly increased TIR and reduced HbA1c within the first 9 days of AID initiation, with these improvements sustained over the first 90 days of use, despite modest decreases in user-initiated boluses. These findings underscore the potential of Omnipod 5 to positively impact diabetes management across a diverse pediatric population.

Comments

Results from this first real-world study of the Omnipod 5 confirm that the benefits observed in controlled trials extend to a broader population in real-world settings. The improvements in glycemic control, particularly the increase in TIR and reduction in HbA1c, highlight the device's potential to enhance diabetes management among a wider range of racial and socioeconomic groups of youth with T1D. Notably, improvements in TIR observed within the first nine days of initiating Omnipod 5 were sustained throughout the 90-day study period, even with fewer user-administered boluses and carbohydrate entries.

Although real-world studies provide more generalizable findings, the relatively small sample size for non-White and publicly insured youth in this study might have affected the generalizability of the results. Additionally, as this cohort comprised early adopters of Omnipod 5 technology, the mean HbA1c might have been lower than that of the general population of youth with T1D, potentially limiting its representativeness. The retrospective nature of the study also introduced limitations on data availability.

In conclusion, significant improvements in glycemic control in real-world settings underscore the importance of broader use of advanced diabetes technologies in pediatric and adolescent populations with T1D. Addressing barriers to access is crucial to improving health equity in the management of T1D.

Diabetes Technol Ther 2024; 26: 24–32

Background

Adverse events (AE), such as severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), are significant risks of intensive insulin therapy. AE rates are generally very low in advanced hybrid closed-loop (AHCL) clinical studies, but prospective real-world data on AE rates are lacking.

Methods

The Control-IQ Observational (CLIO) study was a single-arm, prospective, longitudinal, postmarket surveillance study of individuals with type 1 diabetes (T1D) age 6 years and older who began the use of t:slim X2 insulin pump with Control-IQ technology in the real-world outpatient setting. Over 12 months, reported AEs were compared to historical data from the T1D Exchange. Patient-reported outcomes were assessed quarterly. All study visits were virtual.

Results

Three thousand one hundred fifty-seven participants enrolled from August 2020 through March 2022. Two thousand nine hundred ninety-eight participants completed through 12 months. The rates of SH were significantly lower than historic rates for children (9.31 vs. 19.31 events/100 patient years, d = 0.29, P < 0.01) and adults (9.77 vs. 29.49 events/100 patient years, d = 0.53, P < 0.01). The rates of DKA were also significantly lower in both groups. The lower observed rates of AEs were independent of baseline hemoglobin A1c or prior insulin delivery method. Time in range 70–180 mg/dL was 70.1% (61.0–78.8) for adults, 61.2% (52.4–70.5) for age 6–13, 60.9% (50.1–71.8) for age 14–17, and 67.3% (57.4–76.9) overall. A reduction in diabetes burden was consistently reported.

Conclusions

Compared to historical data in both children and adults, SH and DKA rates were lower for users of t:slim X2 with Control-IQ technology. In this virtual study design, real-world use of this AHCL system proved safe and effective.

Comments

The rates of adverse events (AE), such as severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), are rare in clinical trials of automated insulin delivery (AID) systems. Graham et al. have shown that AEs in a prospective, longitudinal real-world database on individuals ≥ 6 years of age using Control-IQ technology remain lower than historical data from the T1D Exchange registry.

This study further adds to the growing body of evidence that AID systems can improve clinical outcomes and decrease the rates of AEs in people with T1D. This study compared rates of AEs in Control-IQ users to people from the historical T1D Exchange database. It will be important to compare the rates of AEs to more contemporaneous data from individuals who remain on multiple daily injections ±continuous glucose monitoring (CGM), individuals on sensor-augmented pump, and those on pump therapy alone.

Diabetes Technol Ther 2024; 26: 287–297

Background

The development of insulin delivery technologies for type 1 diabetes (T1D) has led to the concurrent emergence of the open-source automated insulin delivery (OS-AID) systems. These systems, which integrate continuous subcutaneous insulin infusion pump, continuous glucose monitor and an algorithm analyzing fluctuations in glucose and adjusting insulin delivery through the pump, have gained popularity due to their potential benefits in glycemic control and quality of life (24). This study aimed to assess nationwide prevalence, safety, and impact of OS-AID systems on metabolic control and daily life among Danish children and adolescents with T1D.

Methods

This retrospective cohort study identified participants through pediatric diabetes outpatient clinics and social media, collecting data via surveys and medical records. Inclusion criteria were age 2–18 years, T1D and use of an OS-AID system at time of enrollment. Data on glycemic control, and time in range (TIR) were collected from data platforms and compared from the 4 weeks before and up to 24 weeks after initiating an OS-AID system, as well as the latest available 4-week period. From patient records, hemoglobin A1c (HbA1c), weight, and height 6 months before and 6 months after initiating an OS-AID system, as well as the latest available values were collected. Safety was assessed through records of ketoacidosis and severe hypoglycemia, while quality of life was evaluated using psychometric questionnaires.

Results

Out of 2,950 Danish children and adolescents with T1D, 56 were identified as OS-AID users, resulting in a prevalence of 1.89%. Of 31 respondents (16 females), median age 12 [interquartile range: 11–14] years, continuous glucose monitoring (CGM) data were available in 21 participants. The mean duration of OS-AID system use was 2.37 ± 0.86 years. TIR significantly increased from 62.29% at baseline to 70.12% (P < 0.01). HbA1c data, available for 27 participants, showed a decrease from 6.7% to 6.5% (P < 0.05) six months after initiating OS-AID systems. There were no significant changes in safety parameters. Parents reported improved sleep quality, and adolescents reported increased self-efficacy. However, body mass index (BMI) SDS significantly increased after the initiation of OS-AID systems, according to the latest available data.

Conclusions

The study found that the prevalence of OS-AID systems among Danish children and adolescents with T1D was 1.89%. Users experienced significant improvements in glycemic control without an increased risk of severe hypoglycemia or ketoacidosis. Additionally, parents reported improved sleep quality, and adolescent participants noted an increase in self-efficacy, highlighting the benefits of OS-AID systems beyond metabolic control.

Comments

This study was the first to provide a nationwide assessment of OS-AID systems among Danish children and adolescents with T1D. Although the adoption rate of OS-AID systems was relatively low at 1.89%, data from the Danish Registry of Childhood and Adolescent Diabetes, which included 2311 children and adolescents with T1D, revealed that 79.70% used some type of pump and 92.55% used sensors more than 70% of the time. These findings suggest that although OS-AID users made up a small subgroup, they were part of a broader trend toward the increased use of advanced diabetes management technologies.

Significant improvements in TIR and HbA1c observed in this cohort were consistent with findings from international studies (25). Additionally, there was no reported increase in the risk of severe hypoglycemia or ketoacidosis. Despite participants starting with relatively good glycemic control, the use of OS-AID systems led to further improvements, demonstrating their potential to enhance management even in those with glycemia well within target. The study did note a significant increase in BMI SDS, suggesting a potential correlation with higher insulin doses. However, the overall BMI SDS was lower compared to other reports (26). Socioeconomic factors, such as higher educational and occupational levels of their mothers, were associated with OS-AID use.

In conclusion, this study provides a comprehensive nationwide evaluation of OS-AID systems among Danish children and adolescents with T1D. However, the study's reliance on retrospective data, the small number of participants, and the exclusion of users who discontinued OS-AID systems may introduce biases and limit the generalizability of the findings. Although there were clear benefits in glycemic control without an increased risk of severe hypoglycemia or ketoacidosis, the adoption of OS-AID systems remained relatively low and was more common among families with higher socioeconomic status. This may be due to the complexities associated with these systems and the broader availability of commercial alternatives.

Diabetes Care 2024; 47: 660–667

This manuscript is also discussed in Chapter 2, page 42

Objective

Early glycemic optimization is important in young children with type 1 diabetes (T1D) to reduce the risk of complications. Therefore, it is essential to identify strategies to improve the management in these patients and to optimize long-term outcomes. The aim was to compare the demographic, clinical, and therapeutic characteristics of children under 6 years old with T1D across three international registries: the Diabetes Prospective Follow-Up Registry (DPV; Europe), the T1D Exchange Quality Improvement Network (T1DX-QI; United States), and the Australasian Diabetes Data Network (ADDN; Australasia).

Methods

This analysis examined prospective registry data from 2019 to 2021, involving 8004 children.

Results

The mean ± SD ages at diabetes diagnosis were 3.2 ± 1.4 years (DPV and ADDN) and 3.7 ± 1.8 years (T1DX-QI). The mean ± SD diabetes durations were 1.4 ± 1.3 years (DPV), 1.4 ± 1.6 years (T1DX-QI), and 1.5 ± 1.3 years (ADDN). BMI z-scores in the overweight range were reported in 36.2% (DPV), 41.8% (T1DX-QI), and 50.0% (ADDN) of participants. Mean ± SD HbA1c levels varied among the registries: DPV 7.3 ± 0.9% (56 ± 10 mmol/mol), T1DX-QI 8.0 ± 1.4% (64 ± 16 mmol/mol), and ADDN 7.7 ± 1.2% (61 ± 13 mmol/mol). Overall, 37.5% of the children achieved the target HbA1c of <7.0% (53 mmol/mol), with 43.6% in DPV, 25.5% in T1DX-QI, and 27.5% in ADDN. The use of diabetes technologies varied among the registries: insulin pump use was 86.6% (DPV), 46.6% (T1DX-QI), and 39.2% (ADDN), while continuous glucose monitoring (CGM) use was 85.1% (DPV), 57.6% (T1DX-QI), and 70.5% (ADDN). The use of hybrid closed-loop (HCL) systems was uncommon, ranging from 0.5% (ADDN) to 6.9% (DPV).

Conclusions

Across the three major registries, less than 50% of children under 6 years old achieved the target HbA1c of <7.0% (53 mmol/mol). Although most participants used CGM, the use of insulin pumps varied, and HCL system use was rare.

Comments

Managing diabetes in young children presents numerous challenges due to physiological factors such as increased insulin sensitivity, unpredictable dietary and physical activity patterns, and the developmental aspects of cognition and socioemotional growth. In recent years, glycemic control targets for young children with T1D have been revised, with current targets set at HbA1c <7.0% (53 mmol/L) (27, 28). Furthermore, the use and availability of new diabetes technologies have increased (29, 30), with evidence demonstrating significant benefits for young children with T1D who utilize these technologies (31, 32).

This cross-sectional study analyzed a large cohort of young patients from three prospective registries. The primary findings indicated that insulin pump and CGM use were significantly higher in the DPV registry compared to the other two registries. Variations in the uptake of diabetes technology among the registries may be attributed to differences in clinical practices and accessibility of these devices. Additionally, a significantly higher percentage of children in the DPV registry achieved the target HbA1c <7% compared to those in the other registries.

Within the T1DX-QI and ADDN registries, HbA1c levels were notably lower in patients using insulin pumps compared to those using multiple daily injections (MDI). In the T1DX-QI registry, CGM users had significantly lower HbA1c levels compared to those using self-monitoring of blood glucose (SMBG). Comparisons of short-term diabetes complications, such as severe hypoglycemia (SH) and diabetic ketoacidosis (DKA), across registries revealed that only in the T1DX-QI registry did pump users experience significantly lower rates of severe hypoglycemia and DKA compared to MDI users. Additionally, CGM users in the DPV registry had significantly lower incidences of SH, and in the ADDN registry, a lower incidence of hypoglycemia with coma was observed, although no other significant differences were noted.

The International Society for Pediatric and Adolescent Diabetes (ISPAD) has recommended an HbA1c target of <7% (53 mmol/mol) since 2018, whereas the American Diabetes Association (ADA) adopted this target in 2020. These differences in target timelines may partly explain the higher proportion of children achieving HbA1c targets in the DPV registry, followed by ADDN and T1DX-QI, as lower glycemic targets are associated with achieving lower HbA1c levels (33). The differences between the registries in the percent of young patients achieving glycemic targets may also result from disparities in accessibility of the new technological devices.

This study underscores the benefits of utilizing diabetes technologies in young children for improved glycemic control and reduced acute diabetes complications. Both hyperglycemia and hypoglycemia negatively impact the developing brain of young children (34). Therefore, the observed improvements in HbA1c, coupled with low rates of SH, are promising. However, global access to these diabetes technologies remains uneven. Despite strong evidence supporting their use in the ISPAD and ADA guidelines (28, 35), HCL systems were infrequently used across all registries.

A notable strength of this study is the large sample size within each registry. However, limitations include the study's focus on high-income countries, limiting the generalizability of findings to middle- and low-income countries. Additionally, the lack of data on time in range, a new important measure of glycemic control, is a limitation. Insulin delivery method and CGM use varies widely depending on the geographic area and the characteristics of the different health care systems. Therefore, the evaluation of clinical outcomes and treatment modalities in international multicenter registries is essential to determine the impact of these technologies on the achievement of glycemic targets and the occurrence of SH and DKA worldwide.

Identifying factors contributing to discrepancies in glycemic outcomes and technology use among registries may help optimize care for children with T1D.

Diabetes Technol Ther 2023; 25: 765–773

This manuscript is also discussed in Chapter 12, page 356

Objective

Previous studies have shown an overall increase in HbA1c levels in the United States over the past decade. Additionally, health disparities in type 1 diabetes (T1D) outcomes based on race/ethnicity and insurance type continue to exist. This study examines HbA1c trends from 2016 to 2022, stratified by race/ethnicity and insurance type, using a large multicenter national database.

Methods

Glycemic outcomes and diabetes device use trends were evaluated for over 48,000 individuals with T1D from 3 adult and 12 pediatric centers in the T1D Exchange Quality Improvement Collaborative (T1DX-QI). Data from 2016 to 2017 were compared with data from 2021 to 2022.

Results

The mean HbA1c in 2021–2022 was 8.4%, a decrease from the mean HbA1c of 8.7% in 2016–2017 (P < 0.01). An analysis of glycemic change among patient with T1D who contributed data in both study periods also demonstrates significant improvement (mean HbA1c of 8.4% in 2021/2022 compared with 8.5% in 2016/2017 (P < 0.01). During the same period, the percentage of patients using continuous glucose monitors (CGMs), insulin pumps, or hybrid closed-loop (HCL) systems increased by 45%, 12%, and 33%, respectively. However, these improvements were not equitably distributed across racial/ethnic groups or insurance types. Disparities persisted over the 7-year period, with significant gaps in HbA1c (1.2%–1.6%), CGM use (30%), pump use (25%–35%), and HCL system use (up to 20%) between non-Hispanic White (NHW) and non-Hispanic Black (NHB) patients.

Conclusions

Population-level data on outcomes such as HbA1c can provide valuable insights into strategies for improving health among patients with T1D. The T1DX-QI cohort showed significant improvements in HbA1c levels from 2016 to 2022 and increased use of diabetes devices. However, these improvements were not consistent across all racial/ethnic groups or insurance types.

Comments

The study findings indicated a reduction in mean HbA1c from 8.7% in 2016–2017 to 8.4% in 2021–2022 for all patients with T1D seen at the included centers in the T1DX-QI (P < 0.01). This improvement was observed across all age groups. Although racial and ethnic disparities in HbA1c levels persisted when controlling for age, sex, and duration of diabetes, each racial and ethnic group showed a statistically significant improvement in HbA1c. These findings are promising compared to previous data from the T1DX (3).

The observed changes may be attributed to the adjustment in HbA1c targets (28), the initiatives of the T1DX-QI Network—which employs quality improvement, health equity frameworks, and population health principles to enhance outcomes for people with T1D, and the increased implementation of new diabetes technologies. Despite these improvements, significant inequities in HbA1c levels and diabetes device use persisted between NHW and NHB/Hispanic patients with T1D throughout the study period. Although the mean HbA1c decreased over the seven years regardless of insurance type, the reduction was more pronounced for privately insured individuals. Furthermore, a significantly higher percentage of NHW patients had private insurance compared to NHB/Hispanic patients.

The strengths of the study include a large number of participants with a wide age range, diverse ethnicities, and varied socioeconomic statuses. Additionally, the ability to evaluate longitudinal changes in glycemic control in the same patient from 2016 to 2022 adds to the robustness of the findings. However, limitations include the absence of data on the number of patients in each age group and the selection bias of the T1DX-QI centers, which were primarily academic institutions located mainly in the eastern and western regions of the United States, affecting the study's generalizability.

There is a need for funded studies to further evaluate potential contributing factors and to implement innovative programs aimed at reducing the disparities between different ethnic and socio-economic groups.

Diabetes Technol Ther 2023; 25: 774–781

Objective

Since the introduction of insulin pumps therapy in children with diabetes, various approaches have been employed to determine the optimal basal rates. Previously, the DPV registry provided circadian basal rate patterns for different age groups. With the recent increase in pump users and the predominance of short-acting insulin analogues, a new analysis was conducted using a larger data pool.

Methods

All recent basal profiles from type 1 diabetes (T1D) patients using insulin pump therapy or automated insulin dosage (AID) aged 1 to 25 years were included from the DPV 2021 data pool. Profiles that were excluded: night-time-only pump users, human regular insulin users, and those with daily basal rates <0.05 and >1.0 U/kg/day.

Results

In analyzing profiles from young persons (n = 25,718) with T1D, differences were found in daily basal rate patterns across age groups. Additionally, significant differences (P < 0.001) in total daily basal dose were observed between sexes in all age groups except adults. The expected basal-rate pattern also varied based on body mass index, HbA1c, and use of continuous glucose monitoring.

Conclusions

This analysis highlights multiple factors that influence basal patterns and insulin requirements, including age group, sex, overweight, HbA1c, bolus frequency, and sensor use. As circadian basal rates are essential for initiating insulin pump therapy, whether automated or not, a multimodal approach is necessary to estimate optimal basal rates.

Comments

Insulin pump therapy is widely recognized as a standard treatment for patients with T1D. Pediatric specialists often recommend a variable basal rate for insulin pump therapy that aligns with physiological changes, adjusting insulin delivery to match a circadian insulin sensitivity pattern characterized by two peaks: one in the early morning (dawn) and another in the late afternoon (dusk). Analysis of automated insulin delivery (AID) data in pediatric patients also reveals adherence to circadian patterns (36). Therefore, establishing expected circadian profiles is essential for setting initial insulin pump parameters when initiating therapy with AID systems.

In the current study, the shape and hourly distribution of insulin pump basal rate were influenced by factors such age, sex, BMI, number of daily boluses, and diabetes control quality.

The total daily basal rate requirement varied among different groups, with younger patients exhibiting significantly lower absolute mean hourly basal rates.

Notably, the relative proportion of hourly basal rate in the youngest age group (< 6 years) differed significantly from that of other age groups. In this youngest group, the highest percentage of hourly basal rate occurred in the afternoon and evening hours, whereas other age groups exhibited two peaks: one in the early morning and another in the late afternoon.

A key finding of the study is the differential impact of sex across age groups. In the youngest cohort (<6 years), boys and girls required nearly identical amounts of insulin. However, in the 6–12-year-old group, girls required a higher total basal insulin dose and a higher basal insulin dose per kg/day. This sex difference reversed in young adults, potentially due to earlier pubertal onset in girls and increased insulin resistance during puberty. Besides circadian distribution, the total daily basal rate requirement also varied among groups, necessitating consideration of both factors for individualized basal rate settings.

The study's strengths include the large patient sample from multiple centers in four countries, standardized documentation using a single electronic health record software, and centralized data analysis. However, the retrospective design presents limitations, such as the absence of data on physical activity, body composition, nutritional choices, emotional stress, mental health, and menstrual cycle, all of which could influence basal rate patterns.

In conclusion, the patterns of individual basal rates and the total basal insulin required vary based on age, sex, BMI, and daily bolus frequency. These factors are crucial for developing personalized basal insulin recommendations for both insulin pumps and AID systems.

Diabetes Care 2024; 47: 707–711

This manuscript is also discussed in Chapter 2, page 44

Background

Socioeconomic status (SES) impacts technology use in youth with type 1 diabetes (T1D). This analysis explored relationships between SES, technology use and glycemic outcomes in youth with T1D.

Methods

A cross-sectional analysis of HbA_1c data from 2822 Australian youth with T1D in the Australasian Diabetes Data Network (ADDN) T1D was performed. The Index of Relative Socioeconomic Disadvantage (IRSD) was uses to assign SES status bases on residential postcodes. Associations among IRSD quintile, HbA1c, and management regimen were evaluated with linear regression models.

Results

Youth across all IRSD quintiles had lower mean HbA1c with Insulin pump therapy, continuous glucose monitoring, and their concurrent use (P < 0.001). There was no interaction between technology use and IRSD quintile on HbA_1c (P = 0.624), reflecting a similar association of lower HbA_1c with technology use across all IRSD quintiles.

Conclusions

Technology use was associated with lower HbA_1c across all socioeconomic backgrounds. Lower SES quintiles does not preclude glycemic benefits of diabetes technologies, highlighting the need to remove barriers to technology access.

Comments

The use of diabetes technology, including continuous glucose monitoring and insulin pumps, is associated with improved clinical outcomes in youth with type 1 diabetes (T1D). Lomax et al. evaluated the impact of diabetes technology (CGM and/or insulin pump) use on HbA1c across socioeconomic quintiles in the Australasian Diabetes Data Network (ADDN). Although differences in HbA1c continued across all socioeconomic quintiles, youth using diabetes technology had similar improvements in HbA1c outcomes irrespective of socioeconomic quintile.

Youth from lower socioeconomic strata have lower use of diabetes technology (37–39). Although technology does not fully close glycemic outcomes gaps in youth from lower socioeconomic strata, this study, along with others (40, 41), shows that technology use can be beneficial irrespective of socioeconomic status. Therefore, efforts should be made to make technology accessible to all youth with T1D and to encourage its use.

Front Endocrinol (Lausanne) 2023; 14: 1283181

Objective

The objective of this study is to compare parameters of glycemic control among three types of hybrid closed-loop (HCL) systems in children with T1D (CwD) using population-wide data from the national pediatric diabetes registry CENDA.

Methods

CwD aged <19 years treated with Medtronic MiniMed 780G (780G), Tandem t:slim X2 (Control-IQ), or do-it-yourself AndroidAPS (AAPS) systems for >12 months and monitored by CGM >70% of the time were included. HbA1c, times in glycemic ranges, and Glycemia Risk Index (GRI) were used for cross-sectional comparison between the HCL systems.

Results

Data from 512 CwD were analyzed. 780G, Control-IQ, and AAPS were used by 217 (42.4%), 211 (41.2%), and 84 (16.4%) CwD, respectively. The lowest HbA1c value was observed in the AAPS group (44 mmol/mol; IQR 8.0, P < 0.0001 vs any other group), followed by Control-IQ and 780G groups (48 [IQR 11] and 52 [IQR 10] mmol/mol, respectively). All of the systems met the recommended criteria for time in range (78% in AAPS, 76% in 780G, and 75% in Control-IQ users). CwD using AAPS spent significantly more time in hypoglycemia (5% vs 2% in 780G and 3% in Control-IQ) and scored the highest GRI (32, IQR 17). The lowest GRI (27, IQR 15) was seen in 780G users.

Conclusion

Although all HCL systems proved effective in maintaining recommended long-term glycemic control, we observed differences that illustrate strengths and weaknesses of particular systems. Our findings could help in individualizing the choice of HCL systems.

Comments

After decades of research there are now multiple automated insulin delivery systems available around the world, although many regions have limited access due to regulatory, commercial, or health-policy restrictions. Furthermore, many people with diabetes do not have the financial resources to afford automated insulin delivery. However, in those countries where choice is available the question of which system is the best is a common one from people with diabetes as well as for diabetologists. It is unlikely, and probably unnecessary, to have a randomized controlled trial comparing different automated insulin delivery systems. However, the data from the ČENDA registry provide useful information comparing users of the 780G, Control IQ, and AndroidAPS. An important take home message is that the TIR goal was met in all systems, whereas the <4% goal for Time Below Range was exceeded (5%) by AndroidAPS. Multiple limitations are noted appropriately by the authors including those that could not be fully overcome by statistical analyses such as preexisting differences in the groups on each system. The authors conclude that all systems proved effective for children with type 1 diabetes—a welcome and important message. They also suggest that these data could help individualize choice of automated insulin delivery systems. Further, one might hypothesize that such data may incentivize further industry innovation to improve automated insulin delivery systems.

N Engl J Med 2023; 389: 2151–2161

This article is also discussed in Chapter 15, page 412

Background

Teplizumab, a humanized monoclonal antibody to CD3 on T cells, is approved by the Food and Drug Administration to delay the onset of clinical type 1 diabetes (stage 3) in patients 8 years of age or older with preclinical (stage 2) disease. Whether treatment with intravenous teplizumab in patients with newly diagnosed type 1 diabetes can prevent disease progression is unknown.

Methods

In this phase 3, randomized, placebo-controlled trial, we assessed β-cell preservation, clinical end points, and safety in children and adolescents who were assigned to receive teplizumab or placebo for two 12-day courses. The primary end point was the change from baseline in β-cell function, as measured by stimulated C-peptide levels at week 78. The key secondary end points were the insulin doses that were required to meet glycemic goals, glycated hemoglobin levels, time in the target glucose range, and clinically important hypoglycemic events.

Results

Patients treated with teplizumab (217 patients) had significantly higher stimulated C-peptide levels than patients receiving placebo (111 patients) at week 78 (least squares mean difference, 0.13 pmol per milliliter; 95% confidence interval [CI], 0.09 to 0.17; P < 0.001), and 94.9% (95% CI, 89.5 to 97.6) of patients treated with teplizumab maintained a clinically meaningful peak C-peptide level of 0.2 pmol per milliliter or greater, as compared with 79.2% (95% CI, 67.7 to 87.4) of those receiving placebo. The groups did not differ significantly with regard to the key secondary end points. Adverse events occurred primarily in association with administration of teplizumab or placebo and included headache, gastrointestinal symptoms, rash, lymphopenia, and mild cytokine release syndrome.

Conclusions

Two 12-day courses of teplizumab in children and adolescents with newly diagnosed type 1 diabetes showed benefit with respect to the primary end point of preservation of β-cell function, but no significant differences between the groups were observed with respect to the secondary end points

Comments

Pediatric endocrinologists have focused care on treating the glycemic derangements presented by insulin deficiency in type 1 diabetes. Significant progress has been made in the past decade plus to bring us to the current state where continuous glucose monitoring and automated insulin delivery are both standard of care per ISPAD Guidelines with A-level evidence. In parallel, the decades of research addressing the immunologic basis of type 1 diabetes has resulted in multiple studies published in high impact journals demonstrated preservation of c-peptide in people with type 1 diabetes. In the current article by Ramos and colleagues, Teplizumab preserved c-peptide in children and adolescents with newly diagnosed (stage 3) type 1 diabetes to add to existing data (and FDA approval of Teplizumab) to preserve c-peptide in stage 2 type 1 diabetes. The absolute difference in this multicenter randomized placebo-controlled trial in c-peptide at 78 weeks was 0.13 pmol/ml.

The next decade will likely see the transformation of how we care for newly diagnosed youth with type 1 diabetes, as research data accumulates on immunomodulatory interventions to delay—and in the future prevent—the onset of stage 3 type 1 diabetes. The care and education at stage 3 has focused on management of glycemia, but in the future this may be balanced with the addition of immunomodulatory treatment. Much will need to be done with clinical logistics to make future beta-cell preserving therapies available to all. Equitable translation to all who may benefit will require diligence so that disparities in care do not create two-tiered approaches to those newly diagnosed. In addition, as the authors note, this study enrolled mainly white youth (86%) and diversity in immunomodulatory studies (as has been noted in diabetes technology research) needs to include a population representative of those with type 1 diabetes.