As hybrid closed-loop (HCL) insulin delivery systems permeate clinical practice, it is critical to ensure all with diabetes are afforded the opportunity to benefit from this technology. Indeed, due ...to the suboptimal control achieved by the vast majority of youth with type 1 diabetes (T1D), pediatric patients are positioned to see the greatest benefit from automated insulin delivery systems. To ensure these systems are well poised to deliver the promise of more targeted control, it is essential to understand the unique characteristics and factors of childhood. Herein, the developmental and physiological needs of youth with T1D are reviewed and consideration is given to how HCL could address these issues. Studies of HCL technologies in youth are briefly reviewed. As future-generation closed-loop systems are being devised, features that could make this technology more attractive to youth and to their families are discussed. Integration of HCL has the potential to minimize the burden of this chronic medical condition while improving glycemic control and ultimately allowing our pediatric patients to fulfill the primary goal of childhood, to be a kid.
Despite innovations in insulin therapy since its discovery, most patients living with type 1 diabetes do not achieve sufficient glycemic control to prevent complications, and they experience ...hypoglycemia, weight gain, and major self-care burden. Promising pharmacological advances in insulin therapy include the refinement of extremely rapid insulin analogs, alternate insulin-delivery routes, liver-selective insulins, add-on drugs that enhance insulin effect, and glucose-responsive insulin molecules. The greatest future impact will come from combining these pharmacological solutions with existing automated insulin delivery methods that integrate insulin pumps and glucose sensors. These systems will use algorithms enhanced by machine learning, supplemented by technologies that include activity monitors and sensors for other key metabolites such as ketones. The future challenges facing clinicians and researchers will be those of access and broad clinical implementation.
The MiniMed 670G System is the first commercial hybrid closed-loop (HCL) system for management of type 1 diabetes. Using data from adolescent and young adult participants, we compared insulin ...delivery patterns and time-in-range metrics in HCL (Auto Mode) and open loop (OL). System alerts, usage profiles, and operational parameters were examined to provide suggestions for optimal clinical use of the system.
Data from 31 adolescent and young adult participants (14-26 years old) at three clinical sites in the 670G pivotal trial were analyzed. Participants had a 2-week run-in period in OL, followed by a 3-month in-home study phase with HCL functionality enabled. Data were compared between baseline OL and HCL use after 1 week, 1 month, 2 months, and 3 months.
Carbohydrate-to-insulin (C-to-I) ratios were more aggressive for all meals with HCL compared with baseline OL. Total daily insulin dose and basal-to-bolus ratio did not change during the trial. Time in range increased 14% with use of Auto Mode after 3 months (
< 0.001), and HbA
decreased 0.75%. Auto Mode exits were primarily due to sensor/insulin delivery alerts and hyperglycemia. The percentage of time in Auto Mode gradually declined from 87%, with a final use rate of 72% (-15%).
In transitioning young patients to the 670G system, providers should anticipate immediate C-to-I ratio adjustments while also assessing active insulin time. Users should anticipate occasional Auto Mode exits, which can be reduced by following system instructions and reliably bolusing for meals. Unique 670G system functionality requires ongoing clinical guidance and education from providers.
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.
To determine the effect of verapamil on pancreatic beta cell function in children and adolescents with newly diagnosed type 1 diabetes.
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.
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.
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.
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.
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.
ClinicalTrials.gov Identifier: NCT04233034.
Pivotal trials of automated insulin delivery (AID) closed-loop systems have demonstrated a consistent picture of glycemic benefit, supporting approval of multiple systems by the Food and Drug ...Administration or Conformité Européenne mark receipt. To assess how pivotal trial findings translate to commercial AID use, a systematic review of retrospective real-world studies was conducted.
PubMed and EMBASE were searched for articles published after 2018 with more than five nonpregnant individuals with type 1 diabetes (T1D). Data were screened/extracted in duplicate for sample size, AID system, glycemic outcomes, and time in automation.
Of 80 studies identified, 20 met inclusion criteria representing 171,209 individuals. Time in target range 70-180 mg/dL (3.9-10.0 mmol/L) was the primary outcome in 65% of studies, with the majority of reports (71%) demonstrating a >10% change with AID use. Change in hemoglobin A1c (HbA1c) was reported in nine studies (range 0.1%-0.9%), whereas four reported changes in glucose management indicator (GMI) with a 0.1%-0.4% reduction noted. A decrease in HbA1c or GMI of >0.2% was achieved in two-thirds of the studies describing change in HbA1c and 80% of articles where GMI was described. Time below range <70 mg/dL (<3.9 mmol/L) was reported in 16 studies, with all but 1 study showing stable or reduced levels. Most systems had >90% time in automation.
With larger and more diverse populations, and follow-up periods of longer duration (∼9 months vs. 3-6 months for pivotal trials), real-world retrospective analyses confirm pivotal trial findings. Given the glycemic benefits demonstrated, AID is rapidly becoming the standard of care for all people living with T1D. Individuals should be informed of these systems and differences between them, have access to and coverage for these technologies, and receive support as they integrate this mode of insulin delivery into their lives.
Aims/hypothesis
While the use of insulin pumps in paediatrics has expanded dramatically, there is still considerable variability among countries in the use of pump technology. The present study ...sought to describe differences in metabolic control and pump use in young people with type 1 diabetes using data collected in three multicentre registries.
Methods
Data for the years 2011 and 2012 from 54,410 children and adolescents were collected from the Prospective Diabetes Follow-up Registry (DPV;
n
= 26,198), T1D Exchange (T1DX;
n
= 13,755) and the National Paediatric Diabetes Audit (NPDA;
n
= 14,457). The modality of insulin delivery, based on age, sex and ethnic minority status, and the impact of pump use on HbA
1c
levels were compared.
Results
The overall mean HbA
1c
level was higher in the NPDA (8.9 ± 1.6% 74 ± 17.5 mmol/mol) than in the DPV (8.0 ± 1.6% 64 ± 17.0 mmol/mol,
p <
0.001) and T1DX (8.3 ± 1.4% 68 ± 15.4 mmol/mol,
p <
0.001). Conversely, pump use was much lower in the NPDA (14%) than in the DPV (41%,
p <
0.001) and T1DX (47%,
p <
0.001). In a pooled analysis, pump use was associated with a lower mean HbA
1c
(pump: 8.0 ± 1.2% 64 ± 13.3 mmol/mol vs injection: 8.5 ± 1.7% 69 ± 18.7 mmol/mol,
p <
0.001). In all three registries, those with an ethnic minority status were less likely to be treated with a pump (
p <
0.001) and boys were treated with a pump less often compared with girls (
p <
0.001).
Conclusions/interpretation
Despite similar clinical characteristics and proportion of minority participants, substantial differences in metabolic control exist across the three large transatlantic registries of paediatric patients with type 1 diabetes, which appears to be due in part to the frequency of insulin pump therapy.
Background
To assess the change in rates of pediatric real‐time or intermittent scanning continuous glucose monitoring (CGM) use over the past 5 years, and how it impacts glycemic control, data from ...two registries were compared: the US‐based type 1 diabetes Exchange Registry (T1DX) and the German/Austrian DPV (Prospective Diabetes Follow‐Up Registry).
Methods
Registry participants aged <18 years with T1D duration ≥1 year encompassed 29 007 individuals in 2011 and 29 150 participants in 2016. Demographic data, CGM use and hemoglobin A1c (HbA1c) were obtained from medical records.
Results
CGM use increased from 2011 to 2016 in both registries across all age groups, regardless of gender, ethnic minority status or insulin delivery method. The increase in CGM use was most pronounced in the youngest patients, and usage rates remain lowest for adolescent patients in 2016. For both registries in 2016, mean HbA1c was lower among CGM users regardless of insulin delivery method compared to pump only (P < 0.001) and injection only (P < 0.001), and CGM users were more likely to achieve glycemic target of HbA1c <7.5% (56% vs 43% for DPV and 30% vs 15% for T1DX, P < 0.001). T1DX participants had a higher mean HbA1c compared with DPV despite whether they were CGM users or non‐users; however, the difference was less pronounced in CGM users (P < 0.001).
Conclusions
Pediatric CGM use increased in both registries and was associated with lower mean HbA1c regardless of insulin delivery modality.
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