The threshold-suspend feature of sensor-augmented insulin pumps is designed to minimize the risk of hypoglycemia by interrupting insulin delivery at a preset sensor glucose value. We evaluated ...sensor-augmented insulin-pump therapy with and without the threshold-suspend feature in patients with nocturnal hypoglycemia.
We randomly assigned patients with type 1 diabetes and documented nocturnal hypoglycemia to receive sensor-augmented insulin-pump therapy with or without the threshold-suspend feature for 3 months. The primary safety outcome was the change in the glycated hemoglobin level. The primary efficacy outcome was the area under the curve (AUC) for nocturnal hypoglycemic events. Two-hour threshold-suspend events were analyzed with respect to subsequent sensor glucose values.
A total of 247 patients were randomly assigned to receive sensor-augmented insulin-pump therapy with the threshold-suspend feature (threshold-suspend group, 121 patients) or standard sensor-augmented insulin-pump therapy (control group, 126 patients). The changes in glycated hemoglobin values were similar in the two groups. The mean AUC for nocturnal hypoglycemic events was 37.5% lower in the threshold-suspend group than in the control group (980 ± 1200 mg per deciliter 54.4 ± 66.6 mmol per liter × minutes vs. 1568 ± 1995 mg per deciliter 87.0 ± 110.7 mmol per liter × minutes, P<0.001). Nocturnal hypoglycemic events occurred 31.8% less frequently in the threshold-suspend group than in the control group (1.5 ± 1.0 vs. 2.2 ± 1.3 per patient-week, P<0.001). The percentages of nocturnal sensor glucose values of less than 50 mg per deciliter (2.8 mmol per liter), 50 to less than 60 mg per deciliter (3.3 mmol per liter), and 60 to less than 70 mg per deciliter (3.9 mmol per liter) were significantly reduced in the threshold-suspend group (P<0.001 for each range). After 1438 instances at night in which the pump was stopped for 2 hours, the mean sensor glucose value was 92.6 ± 40.7 mg per deciliter (5.1 ± 2.3 mmol per liter). Four patients (all in the control group) had a severe hypoglycemic event; no patients had diabetic ketoacidosis.
This study showed that over a 3-month period the use of sensor-augmented insulin-pump therapy with the threshold-suspend feature reduced nocturnal hypoglycemia, without increasing glycated hemoglobin values. (Funded by Medtronic MiniMed; ASPIRE ClinicalTrials.gov number, NCT01497938.).
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.
The safety and effectiveness of the in-home use of a hybrid closed-loop (HCL) system that automatically increases, decreases, and suspends insulin delivery in response to continuous glucose ...monitoring were investigated.
Adolescents (n = 30, ages 14-21 years) and adults (n = 94, ages 22-75 years) with type 1 diabetes participated in a multicenter (nine sites in the United States, one site in Israel) pivotal trial. The Medtronic MiniMed
670G system was used during a 2-week run-in phase without HCL control, or Auto Mode, enabled (Manual Mode) and, thereafter, with Auto Mode enabled during a 3-month study phase. A supervised hotel stay (6 days/5 nights) that included a 24-h frequent blood sample testing with a reference measurement (i-STAT) occurred during the study phase.
Adolescents (mean ± standard deviation SD 16.5 ± 2.29 years of age and 7.7 ± 4.15 years of diabetes) used the system for a median 75.8% (interquartile range IQR 68.0%-88.4%) of the time (2977 patient-days). Adults (mean ± SD 44.6 ± 12.79 years of age and 26.4 ± 12.43 years of diabetes) used the system for a median 88.0% (IQR 77.6%-92.7%) of the time (9412 patient-days). From baseline run-in to the end of study phase, adolescent and adult HbA
levels decreased from 7.7% ± 0.8% to 7.1% ± 0.6% (P < 0.001) and from 7.3% ± 0.9% to 6.8% ± 0.6% (P < 0.001, Wilcoxon signed-rank test), respectively. The proportion of overall in-target (71-180 mg/dL) sensor glucose (SG) values increased from 60.4% ± 10.9% to 67.2% ± 8.2% (P < 0.001) in adolescents and from 68.8% ± 11.9% to 73.8% ± 8.4% (P < 0.001) in adults. During the hotel stay, the proportion of in-target i-STAT
blood glucose values was 67.4% ± 27.7% compared to SG values of 72.0% ± 11.6% for adolescents and 74.2% ± 17.5% compared to 76.9% ± 8.3% for adults. There were no severe hypoglycemic or diabetic ketoacidosis events in either cohort.
HCL therapy was safe during in-home use by adolescents and adults and the study phase demonstrated increased time in target, and reductions in HbA
hyperglycemia and hypoglycemia, compared to baseline.
Clinicaltrials.gov identifier: NCT02463097.
This trial assessed safety and effectiveness of an advanced hybrid closed-loop (AHCL) system with automated basal (Auto Basal) and automated bolus correction (Auto Correction) in adolescents and ...adults with type 1 diabetes (T1D).
This multicenter single-arm study involved an intent-to-treat population of 157 individuals (39 adolescents aged 14-21 years and 118 adults aged ≥22-75 years) with T1D. Study participants used the MiniMed™ AHCL system during a baseline run-in period in which sensor-augmented pump +/- predictive low glucose management or Auto Basal was enabled for ∼14 days. Thereafter, Auto Basal and Auto Correction were enabled for a study phase (∼90 days), with glucose target set to 100 or 120 mg/dL for ∼45 days, followed by the other target for ∼45 days. Study endpoints included safety events and change in mean A1C, time in range (TIR, 70-180 mg/dL) and time below range (TBR, <70 mg/dL). Run-in and study phase values were compared using Wilcoxon signed-rank test or paired
-test.
Overall group time spent in closed loop averaged 94.9% ± 5.4% and involved only 1.2 ± 0.8 exits per week. Compared with run-in, AHCL reduced A1C from 7.5% ± 0.8% to 7.0% ± 0.5% (<0.001, Wilcoxon signed-rank test,
= 155), TIR increased from 68.8% ± 10.5% to 74.5% ± 6.9% (<0.001, Wilcoxon signed-rank test), and TBR reduced from 3.3% ± 2.9% to 2.3% ± 1.7% (<0.001, Wilcoxon signed-rank test). Similar benefits to glycemia were observed for each age group and were more pronounced for the nighttime (12 AM-6 AM). The 100 mg/dL target increased TIR to 75.4% (
= 155), which was further optimized at a lower active insulin time (AIT) setting (i.e., 2 h), without increasing TBR. There were no severe hypoglycemic or diabetic ketoacidosis events during the study phase.
These findings show that the MiniMed AHCL system is safe and allows for achievement of recommended glycemic targets in adolescents and adults with T1D. Adjustments in target and AIT settings may further optimize glycemia and improve user experience. Clinical Trial Registration number: NCT03959423.
Despite the increasing adoption of insulin pumps and continuous glucose monitoring devices, most people with type 1 diabetes do not achieve their glycemic goals
. This could be related to a lack of ...expertise or inadequate time for clinicians to analyze complex sensor-augmented pump data. We tested whether frequent insulin dose adjustments guided by an automated artificial intelligence-based decision support system (AI-DSS) is as effective and safe as those guided by physicians in controlling glucose levels. ADVICE4U was a six-month, multicenter, multinational, parallel, randomized controlled, non-inferiority trial in 108 participants with type 1 diabetes, aged 10-21 years and using insulin pump therapy (ClinicalTrials.gov no. NCT03003806). Participants were randomized 1:1 to receive remote insulin dose adjustment every three weeks guided by either an AI-DSS, (AI-DSS arm, n = 54) or by physicians (physician arm, n = 54). The results for the primary efficacy measure-the percentage of time spent within the target glucose range (70-180 mg dl
(3.9-10.0 mmol l
))-in the AI-DSS arm were statistically non-inferior to those in the physician arm (50.2 ± 11.1% versus 51.6 ± 11.3%, respectively, P < 1 × 10
). The percentage of readings below 54 mg dl
(<3.0 mmol l
) within the AI-DSS arm was statistically non-inferior to that in the physician arm (1.3 ± 1.4% versus 1.0 ± 0.9%, respectively, P < 0.0001). Three severe adverse events related to diabetes (two severe hypoglycemia, one diabetic ketoacidosis) were reported in the physician arm and none in the AI-DSS arm. In conclusion, use of an automated decision support tool for optimizing insulin pump settings was non-inferior to intensive insulin titration provided by physicians from specialized academic diabetes centers.
Safety and significant improvement in overall glycated hemoglobin (A1C) and percentage of time spent in (TIR), below (TBR), and above (TAR) glucose range were demonstrated in the pivotal trial of ...adolescents and adults using the MiniMed™ advanced hybrid closed-loop (AHCL) system with the adjunctive, calibration-required Guardian™ Sensor 3. The present study evaluated early outcomes of continued access study (CAS) participants who transitioned from the pivotal trial investigational system to the approved MiniMed™ 780G system with the non-adjunctive, calibration-free Guardian™ 4 Sensor (MM780G+G4S). Study data were presented alongside those of real-world MM780G+G4S users from Europe, the Middle East, and Africa.
The CAS participants (
= 109, aged 7-17 years and
= 67, aged >17 years) used the MM780G+G4S for 3 months and data of real-world MM780G+G4S system users (
= 10,204 aged ≤15 years and
= 26,099 aged >15 years) were uploaded from September 22, 2021 to December 02, 2022. At least 10 days of real-world continuous glucose monitoring (CGM) data were required for analyses. Glycemic metrics, delivered insulin and system use/interactions underwent descriptive analyses.
Time in AHCL and CGM use were >90% for all groups. AHCL exits averaged 0.1/day and there were few blood glucose measurements (BGMs) (0.8/day-1.0/day). Adults in both cohorts met most consensus recommendations for glycemic targets. Pediatric groups met recommendations for %TIR and %TBR, although not those for mean glucose variability and %TAR, possibly due to low use of recommended glucose target (100 mg/dL) and active insulin time (2 h) settings (28.4% in the CAS cohort and 9.4% in the real-world cohort). The CAS pediatric and adult A1C were 7.2% ± 0.7% and 6.8% ± 0.7%, respectively, and there were no serious adverse events.
Early clinical use of the MM780G+G4S was safe and involved minimal BGMs and AHCL exits. Consistent with real-world pediatric and adult use, outcomes were associated with achievement of recommended glycemic targets. Clinical Trial Registration number: NCT03959423.
Control-IQ (Tandem Diabetes) is a hybrid closed-loop (HCL) system that users self-initiate after completing online training. Best practices for clinical follow-up are not known. Our quality ...improvement objective was to evaluate the usefulness of an educator-led follow-up program for new HCL users in a type 1 diabetes pediatric clinic.
We implemented an ''HCLCheck-in'' program, first determining when users started HCL, then having diabetes educators contact them for a follow-up call 2-weeks after start. Educators used a Clinical Tool to inform insulin dose and behavior recommendations, and used four benchmarks to determine need for further follow-up: ≥71% HCL use, ≥71% CGM use, ≥60% Time-in-Range (TIR, 70-180 mg/dL), <5% below 70 mg/dL. Family and educator satisfaction were surveyed.
One-hundred-twenty-three youth mean age 13.6 ± 3.7 y, 53.7% female, mean HbA1c 7.6 ± 1.4% (60 mmol/mol) completed an HCLCheck-in call a median (IQR) of 18(15, 21) days post-HCL start. 74 users (60%) surpassed benchmarks with 94% HCL use and 71% TIR. Of the 49 who did not, 16 completed a second call, and improved median TIR 12.5% (p = 0.03). HCL users reported high satisfaction with the program overall median 10 (9, 10) out of 10. Educators spent a median of 45 (32,70) minutes per user and rated satisfaction with the program as 8 (7,9.5) and the Tool as 9 (9, 10).
Our HCLCheck-in program received high satisfaction ratings and resulted in improved TIR for those initially not meeting benchmarks, suggesting users may benefit from early follow-up. Similar programs may be beneficial for other new technologies.
The efficacy of automatic suspension of insulin delivery in induced hypoglycemia among subjects with type 1 diabetes was evaluated.
In this randomized crossover study, subjects used a ...sensor-augmented insulin pump system with a low glucose suspend (LGS) feature that automatically stops insulin delivery for 2 h following a sensor glucose (SG) value ≤70 mg/dL. Subjects fasted overnight and exercised until their plasma glucose (measured with the YSI 2300 STAT Plus™ glucose and lactate analyzer YSI Life Sciences, Yellow Springs, OH) value reached ≤85 mg/dL on different occasions separated by washout periods lasting 3-10 days. Exercise sessions were done with the LGS feature turned on (LGS-On) or with continued insulin delivery regardless of SG value (LGS-Off). The order of LGS-On and LGS-Off sessions was randomly assigned. YSI glucose data were used to compare the duration and severity of hypoglycemia from successful LGS-On and LGS-Off sessions and to estimate the risk of rebound hyperglycemia after pump suspension.
Fifty subjects attempted 134 sessions, 98 of which were successful. The mean±SD hypoglycemia duration was less during LGS-On than during LGS-Off sessions (138.5±76.68 vs. 170.7±75.91 min, P=0.006). During LGS-On compared with LGS-Off sessions, mean nadir YSI glucose was higher (59.5±5.72 vs. 57.6±5.69 mg/dL, P=0.015), as was mean end-observation YSI glucose (91.4±41.84 vs. 66.2±13.48 mg/dL, P<0.001). Most (53.2%) end-observation YSI glucose values in LGS-On sessions were in the 70-180 mg/dL range, and none was >250 mg/dL.
Automatic suspension of insulin delivery significantly reduced the duration and severity of induced hypoglycemia without causing rebound hyperglycemia.
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