Real-World Evidence Analysis of a Hybrid Closed-Loop System.

BACKGROUND: We analyzed real-world evidence to assess the performance of the mylife CamAPS FX hybrid closed-loop system. METHODS: Users from 15 countries across different age groups who used the system between May 9, 2022, and December 3, 2022, and who had ≥30 days of continuous glucose monitor data, and ≥30% of closed-loop usage were included in the current analysis (N = 1805). RESULTS: Time in range (3.9-10 mmol/L) was 72.6 ± 11.5% (mean ± SD) for all users and increased by age from 66.9 ± 11.7% for users ≤6 years old to 81.8 ± 8.7% for users ≥65 years. Time spent in hypoglycemia (<3.9 mmol/L) was 2.3% [1.3, 3.6] (median [interquartile range]). Mean glucose and glucose management indicator were 8.4 ± 1.1 mmol/L and 6.9%, respectively. Time using closed-loop was high at 94.7% [90.0, 96.9]. CONCLUSIONS: Glycemic outcomes from the present real-world evidence are comparable to results obtained from previous randomized controlled studies and confirm the efficacy of this hybrid closed-loop system in real-world settings.

Improvement of Selected Psychological Parameters and Quality of Life of Patients With Type 1 Diabetes Mellitus Undergoing Transition From Multiple Daily Injections and Self-Monitoring of Blood Glucose Directly to the MiniMed 780G Advanced Hybrid Closed-Loop System: Post hoc Analysis of a Randomized Control Study.

BACKGROUND: While introducing new technologies and methods of treatment for type 1 diabetes mellitus (T1DM), it seems essential to monitor whether modern technologies in diabetes treatment may improve the psychological and emotional status of patients. OBJECTIVE: This study aims to assess the baseline psychological parameters of patients with T1DM during investigation of the direct transition from multiple daily injections (MDI) and self-monitoring of blood glucose (SMBG) to the MiniMed 780G advanced hybrid closed-loop (AHCL) system and to evaluate changes in the psychological well-being and quality of life (QoL) after the transition in these individuals versus the control group. METHODS: The trial was a 2-center, randomized controlled, parallel group study. In total, 41 patients with T1DM managed with MDI or SMBG were enrolled and randomized either to the AHCL or the MDI+SMBG group. Of these, 37 (90%) participants (mean age 40.3 years, SD 8.0 years; mean duration of diabetes 17.3, SD 12.1 years; mean hemoglobin A1c [HbA1c] 7.2%, SD 1.0%) completed the study (AHCL: n=20, 54%; MDI+SMBG: n=17, 46%). Psychological parameters (level of stress, coping mechanisms, level of anxiety, self-efficacy level, acceptance of illness, locus of control of illness, life satisfaction, QoL) were measured at baseline and at the end of the study using 10 psychological questionnaires. RESULTS: At baseline, the general level of stress of the examined patients was higher than in the general healthy Polish population (P=.001), but coping strategies used in stressful situations were significantly more effective and the level of self-efficacy (P<.001) was much higher than in the general population. The patients in this study accepted their illness more than patients with diabetes from the general Polish population (P<.001), but they felt that their health does not depend on them compared to the general population (P<.001). The overall life satisfaction was similar to that of the general population (P=.161). After 3 months from transition, the AHCL group reported an increase in 4 scales of the QoL-feeling well (P=.042), working (P=.012), eating as I would like (P=.011), and doing normal things (P=.034)-in comparison to the control group, where no significant change occurred. The level of both state anxiety and trait anxiety decreased in the AHCL group: State-Trait Anxiety Inventory (STAI) X1 scores (P=.009), STAI X1 stens (P=.013), and STAI X2 scores (P=.022). The AHCL group became more emotion oriented in stressful situations (Coping Inventory for Stressful Situations [CISS] E; P=.043) and significantly less self-blaming after 3 months of the study (P=.020). CONCLUSIONS: The results indicate that the patients who decided to take part in the transition study were characterized by higher levels of stress than the general healthy population but had better coping strategies and self-efficacy. Furthermore, transitioning from MDI+SMBG treatment to the AHCL in patients naive to technology may significantly improve psychological well-being and QoL within 3 months. The rapidity of these changes suggests that they may be related to the significant improvement in glycemic outcomes but also significantly less burdened diabetes self-management. TRIAL REGISTRATION: ClinicalTrials.gov NCT04616391; https://clinicaltrials.gov/ct2/show/NCT04616391.

Advanced hybrid closed loop therapy versus conventional treatment in adults with type 1 diabetes (ADAPT): a randomised controlled study.

BACKGROUND: Adults with type 1 diabetes who are treated with multiple daily injections of insulin plus intermittently scanned continuous glucose monitoring (isCGM) can have suboptimal glucose control. We aimed to assess the efficacy of an advanced hybrid closed loop (AHCL) system compared with such therapy in this population. METHODS: The Advanced Hybrid Closed Loop Study in Adult Population with Type 1 Diabetes (ADAPT) trial is a prospective, multicentre, open-label, randomised controlled trial that involved 14 centres in three European countries (France, Germany, and the UK). We enrolled patients who were at least 18 years of age, had a type 1 diabetes duration of at least 2 years, HbA1c of at least 8% (64 mmol/mol), and were using multiple daily injections of insulin plus isCGM (cohort A) or real time continuous glucose monitoring (cohort B) for at least 3 months. Here, only results for cohort A are reported. Participants were randomly allocated 1:1 to AHCL therapy or continuation of multiple daily injections of insulin plus continuous glucose monitoring for 6 months with an investigator-blinded block randomisation procedure. Participants and treating clinicians could not be masked to the arm assignment. The primary endpoint was the between-group difference in mean HbA1c change from baseline to 6 months in the intention-to-treat population using AHCL therapy and those using multiple daily injections of insulin plus isCGM. The primary endpoint was analysed using a repeated measures random-effects model with the study arm and period as factors. Safety endpoints included the number of device deficiencies, severe hypoglycaemic events, diabetic ketoacidosis, and serious adverse events. This study is registered with ClinicalTrials.gov, NCT04235504. FINDINGS: Between July 13, 2020, and March 12, 2021, 105 people were screened and 82 randomly assigned to treatment (41 in each arm). At 6 months, mean HbA1c had decreased by 1·54% (SD 0·73), from 9·00% to 7·32% in the AHCL group and 0·20% (0·80) in the multiple daily injections of insulin plus isCGM from 9·07% to 8·91% (model-based difference -1·42%, 95% CI -1·74 to -1·10; p<0·0001). No diabetic ketoacidosis, severe hypoglycaemia, or serious adverse events related to study devices occurred in either group; two severe hypoglycaemic events occurred in the run-in phase. 15 device-related non-serious adverse events occurred in the AHCL group, compared with three in the multiple daily injections of insulin plus isCGM group. Two serious adverse events occurred (one in each group), these were breast cancer (in one patient in the AHCL group) and intravitreous haemorrhage (in one patient in the multiple daily injections of insulin plus isCGM group). INTERPRETATION: In people with type 1 diabetes using multiple daily injections of insulin plus isCGM and with HbA1c of at least 8%, the use of AHCL confers benefits in terms of glycaemic control beyond those that can be achieved with multiple daily injections of insulin plus isCGM. These data support wider access to AHCL in people with type 1 diabetes not at target glucose levels. FUNDING: Medtronic International Trading Sàrl.

Transitioning of People With Type 1 Diabetes From Multiple Daily Injections and Self-Monitoring of Blood Glucose Directly to MiniMed 780G Advanced Hybrid Closed-Loop System: A Two-Center, Randomized, Controlled Study.

OBJECTIVE: The aim of this study was to evaluate the outcomes of transitioning to the MiniMed 780G advanced hybrid closed-loop (AHCL) system in adult individuals with type 1 diabetes mellitus (T1DM) naive to continuous subcutaneous insulin infusion (CSII) and continuous glucose monitoring (CGM) technologies. RESEARCH DESIGN AND METHODS: This was a two-center, randomized, controlled, parallel-group trial with evaluation of individuals with T1DM aged 26-60 years managed with multiple daily injections (MDI) and self-monitoring of blood glucose (BGM) with HbA1c <10%. RESULTS: A total of 41 participants were recruited and randomized to either the AHCL (n = 20) or the MDI+BGM (n = 21) group, and 37 participants (mean ± SD age 40.3 ± 8.0 years, duration of diabetes 17.3 ± 12.1 years, BMI 25.1 ± 3.1 kg/m2, HbA1c 7.2 ± 1.0%) completed the study. Time spent with glucose levels in target range increased from 69.3 ± 12.3% at baseline to 85.0 ± 6.3% at 3 months in the AHCL group, while remaining unchanged in the control group (treatment effect 21.5% [95% CI 15.7, 27.3]; P < 0.001). The time with levels below range (<70 mg/dL) decreased from 8.7 ± 7.3% to 2.1 ± 1.7% in the AHCL group and remained unchanged in the MDI+BGM group (treatment effect -4.4% [95% CI -7.4, -2.1]; P < 0.001). Participants from the AHCL group also had significant improvements in HbA1c levels (treatment effect -0.6% [95% CI -0.9, -0.2]; P = 0.005) and in quality of life (QoL) in specific subscales compared with the MDI+BGM group. CONCLUSIONS: People with T1DM naive to CSII and CGM technologies initiating AHCL significantly and safely improved their glycemic control, as well as their QoL and psychological well-being.

Predictors of time in target glucose range in real-world users of the MiniMed 780G system.

AIM: Automated insulin delivery systems have improved glycaemic control in people with type 1 diabetes mellitus. The analysis investigated predictors of improved sensor glucose time-in-range (TIR; 70-180 mg/dl) based on real-world use of the MiniMed 780G advanced hybrid closed-loop (AHCL) system. METHODS: Data uploaded by MiniMed 780G system users from August 2020-July 2021 were analysed using univariate and multivariable models to identify baseline, demographic and system use characteristics associated with TIR after AHCL initiation (post-AHCL). System settings associated with improved TIR post-AHCL were identified and their impact on time below range (TBR, <70 mg/dl) post-AHCL was explored. RESULTS: In total, 12 870 users were included, of which 2977 had baseline sensor glucose data. Baseline TIR and time in AHCL (defined as the percentage of time the system was in Auto-mode) were positively associated with TIR post-AHCL with larger values predicting greater mean TIR post-AHCL. Characteristics inversely associated with TIR post-AHCL included the percentage of daily basal insulin dose, daily autocorrection dose, number of daily AHCL exits triggered by the system and number of daily alarms, wherein larger values of these characteristics predicted lower mean TIR post-AHCL. System settings that predicted the largest mean TIR post-AHCL were active insulin time of 2 h and glucose target of 100 mg/dl. Active insulin time was not associated with TBR post-AHCL. CONCLUSION: Modifiable factors, including optimized pump settings, can allow users to achieve glycaemic targets with >80% TIR. The findings from this analysis will potentially guide the optimal use of the MiniMed 780G system and facilitate meaningful improvements in safe glycaemic control.

Comparison of MiniMed 780G system performance in users aged younger and older than 15 years: Evidence from 12 870 real-world users.

AIM: To investigate real-world glycaemic outcomes and goals achieved by users of the MiniMed 780G advanced hybrid closed loop (AHCL) system aged younger and older than 15 years with type 1 diabetes (T1D). MATERIALS AND METHODS: Data uploaded by MiniMed 780G system users from 27 August 2020 to 22 July 2021 were aggregated and retrospectively analysed based on self-reported age (≤15 years and >15 years) for three cohorts: (a) post-AHCL initiation, (b) 6-month longitudinal post-AHCL initiation and (c) pre- versus post-AHCL initiation. Analyses included mean percentage of time spent in AHCL and at sensor glucose ranges, insulin delivered and the proportion of users achieving recommended glucose management indicator (GMI < 7.0%) and time in target range (TIR 70-180 mg/dl > 70%) goals. RESULTS: Users aged 15 years or younger (N = 3211) achieved a GMI of 6.8% ± 0.3% and TIR of 73.9% ± 8.7%, while spending 92.7% of time in AHCL. Users aged older than 15 years (N = 8874) achieved a GMI of 6.8% ± 0.4% and TIR of 76.5% ± 9.4% with 92.3% of time in AHCL. Time spent at less than 70 mg/dl was within the recommended target of less than 4% (3.2% and 2.3%, respectively). Similar outcomes were observed for each group (N = 790 and N = 1642, respectively) in the first month following AHCL initiation, and were sustained over the 6-month observation period. CONCLUSIONS: This real-world analysis shows that more than 75% of users with T1D aged 15 years or younger using the MiniMed 780G system achieved international consensus-recommended glycaemic control, mirroring the achievements of the population aged older than 15 years.

Real-world performance of the MiniMed™ 670G system in Europe.

AIM: To evaluate the real-world performance of the MiniMed 670G system in Europe, in individuals with diabetes. MATERIALS AND METHODS: Data uploaded from October 2018 to July 2020 by individuals living in Europe were aggregated and retrospectively analysed. The mean glucose management indicator (GMI), percentage of time spent within (TIR), below (TBR) and above (TAR) glycaemic ranges, system use and insulin consumed in users with 10 or more days of sensor glucose data after initial Auto Mode start were determined. Another analysis based on suboptimally (GMI > 8.0%) and well-controlled (GMI < 7.0%) glycaemia pre-Auto Mode initiation was also performed. RESULTS: Users (N = 14 899) spent a mean of 81.4% of the time in Auto Mode and achieved a mean GMI of 7.0% ± 0.4%, TIR of 72.0% ± 9.7%, TBR less than 3.9 mmol/L of 2.4% ± 2.1% and TAR more than 10 mmol/L of 25.7% ± 10%, after initiating Auto Mode. When compared with pre-Auto Mode initiation, GMI was reduced by 0.3% ± 0.4% and TIR increased by 9.6% ± 9.9% (P < .0001 for both). Significantly improved glycaemic control was observed irrespective of pre-Auto Mode GMI levels of less than 7.0% or of more than 8.0%. While the total daily dose of insulin increased for both groups, a greater increase was observed in the latter, an increase primarily due to increased basal insulin delivery. By contrast, basal insulin decreased slightly in well-controlled users. CONCLUSIONS: Most MiniMed 670G system users in Europe achieved TIR more than 70% and GMI less than 7% while minimizing hypoglycaemia, in a real-world environment. These international consensus-met outcomes were enabled by automated insulin delivery meeting real-time insulin requirements adapted to each individual user.

Predicting Factors Associated with Hypoglycemia Reduction with Automated Predictive Insulin Suspension in Patients at High Risk of Severe Hypoglycemia: An Analysis from the SMILE Randomized Trial.

Background: This analysis from the SMILE randomized study was performed to identify predictive factors associated with the greatest reductions in hypoglycemia with the Medtronic MiniMed™ 640G Suspend before low feature in adults with type 1 diabetes at high risk of severe hypoglycemia. Methods: Clinical and treatment-related factors associated with decreased sensor hypoglycemia (SH) were identified in participants from the intervention arm by univariate and multivariate analyses. Results: The reduction in SH events <54 mg/dL (<3.0 mmol/L) in the intervention group was significantly (P < 0.0001) associated with the baseline mean number of sensor hypoglycemic events (MNSHE) <54 mg/dL. When excluding continuous glucose monitoring (CGM) factors not readily available (MNSHE, duration of SH events, area under the curve, mean amplitude of glycemic excursions), only the baseline mean time spent <54 mg/dL was found to be a significant independent predictor factor (P < 0.0001). Baseline HbA1c, mean self-monitoring of blood glucose (SMBG), and coefficient of variation of SMBG were significant, although weak, predictors in the absence of any CGM data. Conclusions: The greatest reductions in SH events achieved with the MiniMed 640G system with the Suspend before low feature were seen in participants with higher baseline MNSHE. Measuring these (usually uncollected) events can be a useful tool to predict hypoglycemia reduction. ClinicalTrials.gov Registration Identifier NCT02733991.

Native Collagen: Electrospinning of Pure, Cross-Linker-Free, Self-Supported Membrane.

Rebuilding biological environments is crucial when facing the challenges of fundamental and biomedical research. Thus, preserving the native state of biomolecules is essential. We use electrospinning (ES), which is an extremely promising method for the preparation of fibrillar membranes to mimic the ECM of native tissues. Here, we report for the first time (1) the ES of pure and native collagen into a self-supported membrane in absence of cross-linker and polymer support, (2) the preservation of the membrane integrity in hydrated media in absence of cross-linker, and (3) the preservation of the native molecular structure and recovery of the hierarchical assembly of collagen. We use a multiscale approach to characterize collagen native structure at the molecular level using circular dichroism, and to investigate collagen hierarchical organization within the self-supported membrane using a combination of multiphoton and electron microscopies. Finally, we show that the membranes are perfectly suited for cell adhesion and spreading, making them very promising candidates for the development of biomaterials and finding applications in biomedical research.

Efficacy and safety of suspend-before-low insulin pump technology in hypoglycaemia-prone adults with type 1 diabetes (SMILE): an open-label randomised controlled trial.

BACKGROUND: Hypoglycaemia unawareness and severe hypoglycaemia can increase fear of hypoglycaemia and the risk of subsequent hypoglycaemic events. We aimed to assess the safety and efficacy of insulin pump therapy with integrated continuous glucose monitoring (CGM) and a suspend-before-low feature (Medtronic MiniMed 640G with SmartGuard) in hypoglycaemia-prone adults with type 1 diabetes. METHODS: SMILE was an open-label randomised controlled trial done in people aged 24-75 years with type 1 diabetes for 10 years or longer, HbA1c values of 5·8-10·0% (40-86 mmol/mol), and at high risk of hypoglycaemia (recent severe hypoglycaemia or hypoglycaemia unawareness defined by a Clarke or Gold score ≥4). Participants were enrolled from 16 centres (eg, clinics, hospitals, or university medical centres) in Canada, France, Italy, the Netherlands, and the UK. After baseline run-in phase (2 weeks), participants were randomly assigned to the MiniMed 640G pump (continuous subcutaneous insulin infusion) with self-monitoring of blood glucose (control group) or to the MiniMed 640G system with the suspend-before-low feature enabled (intervention group), for 6 months. The study statistician analysing the data was masked to group assignment until final database lock; because of the nature of the intervention, participants and treating clinicians could not be masked to group assignment. The primary outcome was the mean number of sensor hypoglycaemic events, defined as 55 mg/dL (3·1 mmol/L) or lower, and was analysed on an intention-to-treat basis in all randomly assigned participants. This trial is registered with ClinicalTrials.gov, number NCT02733991, and is completed. FINDINGS: Between Dec 7, 2016, and March 27, 2018, 153 participants with a mean age 48·2 [12·4] years were randomly assigned: 77 to the control group (mean age 47·4 [12·5] years) and 76 to the intervention group (mean age 49·0 [12·2] years). After 6 months, the intervention group had significantly fewer hypoglycaemic events per participant per week (1·1 [SD 1·2] vs 4·1 [3·4] mean events, model-based treatment effect -2·9 [95% CI -3·5 to -2·3]; p<0·0001) and fewer severe hypoglycaemic events (instances requiring third-party assistance with carbohydrate or glucagon administration, or other resuscitative actions) overall (three vs 18; p=0·0036). The most common adverse events were hypoglycaemia (observed in ten [13%] of 77 participants in the control group vs four [5%] of 76 in the intervention group) and hyperglycaemia (observed in seven [9%] of 77 vs seven [9%] of 76). No serious adverse device effects or episodes of diabetic ketoacidosis were reported. INTERPRETATION: Insulin pump therapy with integrated CGM and a suspend-before-low feature reduced the frequency of sensor hypoglycaemic and severe hypoglycaemic events in hypoglycaemia-prone adults compared with use of continuous subcutaneous insulin infusion without real-time CGM. These results suggest that this technology could be beneficial in this high-risk population. FUNDING: Medtronic International Trading Sàrl and Medtronic Canada.