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Background: During MiniMed™ advanced hybrid closed-loop (AHCL) use by adolescents and adults in the pivotal trial, glycated hemoglobin (A1C) was significantly reduced, time spent in range (TIR) was significantly increased, and there were no episodes of severe hypoglycemia or diabetic ketoacidosis (DKA). The present study investigated the same primary safety and effectiveness endpoints during AHCL use by a younger cohort with type 1 diabetes (T1D). Methods: An intention-to-treat population ( N  = 160, aged 7-17 years) with T1D was enrolled in a single-arm study at 13 investigational centers. There was a run-in period (∼25 days) using HCL or sensor-augmented pump with/without predictive low-glucose management, followed by a 3-month study period with AHCL activated at two glucose targets (GTs; 100 and 120 mg/dL) for ∼45 days each. The mean ± standard deviation values of A1C, TIR, mean sensor glucose (SG), coefficient of variation (CV) of SG, time at SG ranges, and insulin delivered between run-in and study were analyzed (Wilcoxon signed-rank test or t -test). Results: Compared with baseline, AHCL use was associated with reduced A1C from 7.9 ± 0.9% ( N  = 160) to 7.4 ± 0.7% ( N  = 136) ( P  < 0.001) and overall TIR increased from the run-in 59.4 ± 11.8% to 70.3 ± 6.5% by end of study ( P  < 0.001), without change in CV, time spent below range (TBR) <70 mg/dL, or TBR <54 mg/dL. Relative to longer active insulin time (AIT) settings ( N  = 52), an AIT of 2 h ( N  = 19) with the 100 mg/dL GT increased mean TIR to 73.4%, reduced TBR <70 mg/dL from 3.5% to 2.2%, and reduced time spent above range (TAR) >180 mg/dL from 28.7% to 24.4%. During AHCL use, there was no severe hypoglycemia or DKA. Conclusions: In children and adolescents with T1D, MiniMed AHCL system use was safe, A1C was lower, and TIR was increased. The lowest GT and shortest AIT were associated with the highest TIR and lowest TBR and TAR, all of which met consensus-recommended glycemic targets. ClinicalTrials.gov ID: NCT03959423.

Background: Safety and significant improvement in overall glycated hemoglobin (A1C) and percentage of time spent in (TIR), below (TBR), and above (TAR) glucose range were demonstrated in the pivotal trial of adolescents and adults using the MiniMed™ advanced hybrid closed-loop (AHCL) system with the adjunctive, calibration-required Guardian™ Sensor 3. The present study evaluated early outcomes of continued access study (CAS) participants who transitioned from the pivotal trial investigational system to the approved MiniMed™ 780G system with the non-adjunctive, calibration-free Guardian™ 4 Sensor (MM780G+G4S). Study data were presented alongside those of real-world MM780G+G4S users from Europe, the Middle East, and Africa. Methods: The CAS participants ( N  = 109, aged 7-17 years and N  = 67, aged >17 years) used the MM780G+G4S for 3 months and data of real-world MM780G+G4S system users ( N  = 10,204 aged ≤15 years and N  = 26,099 aged >15 years) were uploaded from September 22, 2021 to December 02, 2022. At least 10 days of real-world continuous glucose monitoring (CGM) data were required for analyses. Glycemic metrics, delivered insulin and system use/interactions underwent descriptive analyses. Results: Time in AHCL and CGM use were >90% for all groups. AHCL exits averaged 0.1/day and there were few blood glucose measurements (BGMs) (0.8/day-1.0/day). Adults in both cohorts met most consensus recommendations for glycemic targets. Pediatric groups met recommendations for %TIR and %TBR, although not those for mean glucose variability and %TAR, possibly due to low use of recommended glucose target (100 mg/dL) and active insulin time (2 h) settings (28.4% in the CAS cohort and 9.4% in the real-world cohort). The CAS pediatric and adult A1C were 7.2% ± 0.7% and 6.8% ± 0.7%, respectively, and there were no serious adverse events. Conclusions: Early clinical use of the MM780G+G4S was safe and involved minimal BGMs and AHCL exits. Consistent with real-world pediatric and adult use, outcomes were associated with achievement of recommended glycemic targets. Clinical Trial Registration number: NCT03959423.

Objective: To evaluate safety and effectiveness of MiniMed™ 670G hybrid closed loop (HCL) in comparison with continuous subcutaneous insulin infusion (CSII) therapy for 6 months in persons with type 1 diabetes (T1D). Methods: Adults (aged 18-80 years), adolescents, and children (aged 2-17 years) with T1D who were using CSII therapy were enrolled and randomized (1:1) to 6 months of HCL intervention (n = 151, mean age of 39.9 ± 19.8 years) or CSII without continuous glucose monitoring (n = 151, 35.7 ± 18.4 years). Primary effectiveness endpoints included change in A1C for Group 1 (baseline A1C >8.0%), from baseline to the end of study, and difference in the end of study percentage of time spent below 70 mg/dL (%TBR <70 mg/dL) for Group 2 (baseline A1C ≤8.0%), to show superiority of HCL intervention versus control. Secondary effectiveness endpoints were change in A1C and %TBR <70 mg/dL for Group 2 and Group 1, respectively, to show noninferiority of HCL intervention versus control. Primary safety endpoints were rates of severe hypoglycemia and diabetic ketoacidosis (DKA). Results: Change in A1C and difference in %TBR <70 mg/dL for the overall group were significantly improved, in favor of HCL intervention. In addition, a significant mean (95% confidence interval) change in A1C was observed for both Group 1 (-0.8% [-1.1% to -0.4%], P  < 0.0001) and Group 2 (-0.3% [-0.5% to -0.1%], P  < 0.0001), in favor of HCL intervention. The same was observed for difference in %TBR <70 mg/dL for Group 1 (-2.2% [-3.6% to -0.9%]) and Group 2 (-4.9% [-6.3% to -3.6%]) ( P  < 0.0001 for both). There was one DKA event during run-in and six severe hypoglycemic events: two during run-in and four during study (HCL: n = 0 and CSII: n = 4 [6.08 per 100 patient-years]). Conclusions: This RCT demonstrates that the MiniMed 670G HCL safely and significantly improved A1C and %TBR <70 mg/dL compared with CSII control in persons with T1D, irrespective of baseline A1C level.

Introduction: 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). Materials and Methods: 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 t -test. Results: 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, n  = 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% ( n  = 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. Conclusions: 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.

Background: 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., Methods: 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., Results: 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)., Conclusion: 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., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Despite the increasing adoption of insulin pumps and continuous glucose monitoring devices, most people with type 1 diabetes do not achieve their glycemic goals 1 . 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 -1 (3.9-10.0 mmol l -1 ))-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 -7 ). The percentage of readings below 54 mg dl -1 (<3.0 mmol l -1 ) 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.

Background: Hybrid closed loop (HCL) therapy is now available in clinical practice for treatment of type 1 diabetes; however, there is limited research on how to educate patients on this new therapy. The purpose of this quality improvement project was to optimize a HCL education program for pediatric patients with type 1 diabetes (T1D)., Methods: Our multidisciplinary team developed a novel HCL clinical training program for current insulin pump users, using a quality improvement process called the Plan-Do-Study-Act model. Seventy-two patients participated in the HCL training program, which included (1) an in-person group class to reinforce conventional insulin pump and CGM use on the new system, (2) a live video conference class to teach HCL use, and (3) three follow-up phone calls in the first 4 weeks after HCL training to assess system use, make insulin adjustments, and provide targeted reeducation. Diabetes educators collected data during follow-up calls, and patients completed a training satisfaction survey., Results: The quality improvement process resulted in a training program that emphasized education on HCL exits, CGM use, and optimizing insulin to carbohydrate ratio settings. Patients successfully sustained time in HCL in the initial weeks of use and rated the trainings and follow-up calls highly., Conclusions: Ongoing educational support is vital in the early weeks of HCL use. This quality improvement project is the first to examine strategies for implementation of HCL therapy into a large pediatric diabetes center, and may inform best practices for implementation of new diabetes technologies into other diabetes clinics.

Background: This study evaluated the safety and performance of the Guardian™ continuous glucose monitoring (CGM) system in children and adolescents with type 1 diabetes (T1D)., Materials and Methods: Subjects 2-18 years of age (mean ± standard deviation [SD] 13.1 ± 3.9 years) with T1D and duration of diagnosis ≥1 year were enrolled at 11 sites in the United States and wore two Guardian Sensor 3 sensors in the abdomen and/or buttock. Sensors were connected to a transmitter paired with either a Guardian Connect system (i.e., mobile device with software application allowing display of sensor glucose [SG] values) or a Guardian Link 3 transmitter used as a Glucose Sensor Recorder (GSR). There were 145 participants who underwent a 6-h in-clinic frequent sample testing (FST) on day 1 (n = 54), day 3 (n = 48), or day 7 (n = 43) postsensor insertion. During FST, SG values were compared with a Yellow Springs Instrument (YSI) plasma reference every 5-15 min (n = 124, 7-18 years of age; n = 2, 2-6 years of age), or to a self-monitoring of blood glucose (SMBG) reference every 5-30 min (n = 19, 2-6 years of age)., Results: The overall mean absolute relative difference (ARD ± SD) between SG and reference values (YSI or SMBG) when calibrating approximately every 12 h, was 10.9% ± 10.7% (3102 paired points) for sensors communicating with the Guardian Connect system and 11.1% ± 10.6% (2624 paired points) for sensors connected to the GSR. The overall percentage of SG values within ±20% of reference values >80 mg/dL or within 20 mg/dL of reference values ≤80 mg/dL was 87.8% for the Guardian Connect system and 86.7% for the GSR, respectively. There was one device-related adverse event of contact dermatitis, but no serious device-related adverse events., Conclusions: The Guardian CGM system demonstrated good accuracy in children and adolescents. These findings support its use in sensor-integrated insulin pump platforms, as well as a standalone technology, for managing diabetes in pediatric populations.

Objective: 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., Research Design and Methods: 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., Results: 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 ( P < 0.001), and HbA 1c 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%)., Conclusions: 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., (© 2018 by the American Diabetes Association.)

Background: This study evaluated the accuracy and performance of a fourth-generation subcutaneous glucose sensor (Guardian ™ Sensor 3) in the abdomen and arm., Methods: Eighty-eight subjects (14-75 years of age, mean ± standard deviation [SD] of 42.0 ± 19.1 years) with type 1 or type 2 diabetes participated in the study. Subjects wore two sensors in the abdomen that were paired with either a MiniMed ™ 640G insulin pump, or an iPhone ® or iPod ® touch ® running a glucose monitoring mobile application (Guardian Connect system) and a third sensor in the arm, which was connected to a glucose sensor recorder (GSR). Subjects were also asked to undergo in-clinic visits of 12-14 h on study days 1, 3, and 7 for frequent blood glucose sample testing using a Yellow Springs Instrument (YSI) reference., Results: The overall mean absolute relative difference (MARD ± SD) between abdomen sensor glucose (SG) and YSI reference values was 9.6% ± 9.0% and 9.4% ± 9.8% for the MiniMed 640G insulin pump and Guardian Connect system, respectively; and 8.7% ± 8.0% between arm SG and YSI reference values. The percentage of SG values within 20% agreement of the YSI reference value (for YSI >80 mg/dL) was 90.7% with the MiniMed 640G insulin pump, 91.8% with the Guardian Connect system, and 93.1% for GSR-connected arm sensors. Mean functional sensor life, when calibrating 3-4 times/day, was 145.9 ± 39.3 h for sensors paired with the MiniMed 640G insulin pump, 146.1 ± 41.6 h for sensors paired with the Guardian Connect system, and 147.6 ± 40.4 h for sensors connected to the GSR. Responses to survey questions regarding sensor comfort and ease of use were favorable., Conclusions: The Guardian Sensor 3 glucose sensor, whether located in abdomen or the arm, provided accurate glucose readings when compared with the YSI reference and demonstrated functional life commensurate with the intended 7-day use. ClinicalTrials.gov : NCT02246582.

Background: 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., Methods: 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., Results: 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 1c 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., Conclusions: 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 1c, hyperglycemia and hypoglycemia, compared to baseline., Trial Registration: Clinicaltrials.gov identifier: NCT02463097.

Background: The ASPIRE in-clinic study established that automatic suspension of insulin with the threshold suspend (TS) feature reduces the duration of induced hypoglycemia. The study's crossover design allowed the effects of antecedent hypoglycemia to be studied., Subjects and Methods: The study enrolled 50 subjects who exercised until plasma glucose (YSI glucose and lactate analyzer; YSI, Inc., Yellow Springs, OH) reached ≤85 mg/dL. Hypoglycemia was evaluated after the YSI value reached <70 mg/dL. In TS experiments, insulin was stopped for 2 h once a sensor glucose (SG) value of ≤70 mg/dL was detected; in control experiments, basal insulin delivery continued. Subjects were randomly assigned to Group A (TS in Period 1; control in Period 2) or Group B (control in Period 1; TS in Period 2). Experiments were separated by 3-10 days., Results: Hypoglycemia was 63.7 min shorter in Period 1 TS experiments (no preceding control experiment) than in Period 2 TS experiments (one or more preceding control experiment(s)) (P<0.01). The number of experiments prior to a successful TS experiment was lower for Period 1 than for Period 2 (0.36 ± 0.64 vs. 1.57 ± 0.84; P<0.001), as was the cumulative duration of antecedent hypoglycemia (16.6 min vs. 204.6 min; P<0.001). The between-groups difference in hypoglycemia duration was not attributable to differences in SG rates of change, the duration of exercise, or area under the curve of <70 mg/dL × min in the 2 days before the successful experiment (all P>0.3)., Conclusions: The TS feature's ability to mitigate hypoglycemia was decreased by an episode or episodes of prolonged antecedent hypoglycemia, suggesting hypoglycemia begets hypoglycemia. The effect of antecedent hypoglycemia should be taken into consideration in the design of future experiments assessing strategies to reduce hypoglycemia.

Background: 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., Methods: 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., Results: 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., Conclusions: 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.).

Nocturnal hypoglycemia is a barrier to therapy intensification efforts in diabetes. The Paradigm® Veo™ system may mitigate nocturnal hypoglycemia by automatically suspending insulin when a prespecified sensor glucose threshold is reached. ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) In-Home (NCT01497938) was a multicenter, randomized, parallel, adaptive study of subjects with type 1 diabetes. The control arm used sensor-augmented pump therapy. The treatment arm used sensor-augmented pump therapy with threshold suspend, which automatically suspends the insulin pump in response to a sensor glucose value at or below a prespecified threshold. To be randomized, subjects had to have demonstrated ≥2 episodes of nocturnal hypoglycemia, defined as &gt;20 consecutive minutes of sensor glucose values ≤65 mg/dl starting between 10:00 PM and 8:00 AM in the 2-week run-in phase. The 3-month study phase evaluated safety by comparing changes in glycated hemoglobin (A1C) values and evaluated efficacy by comparing the mean area under the glucose concentration time curves for nocturnal hypoglycemia events in the two groups. Other outcomes included the rate of nocturnal hypoglycemia events and the distribution of sensor glucose values. Data from the ASPIRE In-Home study should provide evidence on the safety of the threshold suspend feature with respect to A1C and its efficacy with respect to severity and duration of nocturnal hypoglycemia when used at home over a 3-month period., (© 2013 Diabetes Technology Society.)

Background: The mySentry system (Medtronic Inc.) is the first to amplify and relay continuous glucose monitoring (CGM) and insulin pump data to a remote site within the house. Its usability and acceptability were evaluated in families having a child with type 1 diabetes., Methods: Each enrolled family included a child (age 7-17 years) who used a Paradigm REAL-Time Revel sensor-augmented insulin pump (Medtronic). After a 1-week run-in phase, families set up and used the mySentry system for a 3-week study phase. Opinion surveys were completed by parents, and pump and CGM data were collected and analyzed retrospectively. No formal hypothesis testing was performed, and the study was not powered to detect changes in nocturnal glycemia., Results: Thirty-five families completed the study. Enrolled children (61.1% female) had a mean (± standard deviation) age of 11.9 ± 2.70 years and a mean age at initiation of pump therapy of 7.1 ± 3.19 years. Baseline survey results indicated that most parents were fearful of their unawareness of their children's nocturnal glucose excursions. The mySentry system met the predefined acceptability criteria for general experience, product usability, and training materials. There were no unanticipated device-related adverse effects. Among children who experienced nocturnal hypo- or hyperglycemic episodes in both phases of the study, there was a trend toward less frequent and less prolonged episodes during mySentry use., Conclusion: The mySentry system met all predefined criteria for acceptability and did not demonstrate safety issues. Alerting parents to abnormal glucose values or trends may attenuate nocturnal hypoglycemia and hyperglycemia by prompting appropriate and timely intervention., (© 2013 Diabetes Technology Society.)

Continuing glucose monitoring (CGM) is a relatively new and rapidly developing technology that shows promise for the future management of type 1 diabetes. When used with near-daily frequency, it has a significant effect on improvement of glucose metabolism as measured by HbA1C and reduction of hypoglycemia. It appears to be safe and actually reduces both DKA and severe hypoglycemia. Early studies indicate that it should be cost effective.

Objective: Maintenance of appropriate A1C values and minimization of hyperglycemic excursions are difficult for many pediatric patients with type 1 diabetes. Continuous glucose monitoring (CGM) sensor-augmented pump (SAP) therapy is an alternative to multiple daily injection (MDI) therapy in this population., Research Design and Methods: Sensor-augmented pump therapy for A1C reduction (STAR 3) was a 1-yr trial that included 82 children (aged 7-12) and 74 adolescents (aged 13-18) with A1C values ranging from 7.4 to 9.5% who were randomized to either SAP or MDI therapy. Quarterly A1C values were obtained from all subjects. CGM studies were carried out at baseline, 6 months, and 12 months to quantify glycemic excursions [calculated as area under the glucose concentration-time curve (AUC)] and variability. In the SAP group, sensor compliance was recorded., Results: Baseline A1C values were similar in subjects randomized to the SAP (8.26 ± 0.55%) and MDI groups (8.30 ± 0.53%). All subsequent A1C values showed significant (p < 0.05) treatment group differences favoring SAP therapy. Compared with the MDI group, subjects in the SAP group were more likely to meet age-specific A1C targets and had lower AUC values for hyperglycemia with no increased risk of hypoglycemia. Glucose variability improved in the SAP group compared to the MDI group. Children wore CGM sensors more often and were more likely to reach age-specific A1C targets than adolescents., Conclusions: SAP therapy allows both children and adolescents with marginally or inadequately controlled type 1 diabetes to reduce A1C values, hyperglycemic excursions, and glycemic variability in a rapid, sustainable, and safe manner., (© 2011 John Wiley & Sons A/S.)

Background: The Paradigm®Veo™ System includes a low glucose suspend (LGS) feature which suspends insulin delivery when a prespecified glucose threshold setting is reached by the associated continuous glucose monitoring (CGM) sensor. The ASPIRE (Automation to Simulate Pancreatic Insulin REsponse) study is a multicenter, in-clinic, randomized, crossover study to examine the efficacy of LGS in exercise-induced hypoglycemia., Methods: Insulin-pump users underwent two separate exercise sessions, one with the LGS feature set to suspend insulin (LGS-on) when the CGM-detected glucose concentration was ≤ 70 mg/dl and one with the LGS feature off. Exercise sessions were conducted after an overnight fast and with initial plasma glucose level as measured by the YSI 2300 STAT Plus glucose analyzer (YSI) of 100-140 mg/dl. Subjects exercised until their YSI value fell to ≤ 85 mg/dl; subsequent YSI values <70 mg/dl were recorded for up to 4 h to measure the duration and nadir of hypoglycemia. The protocol required that subjects with YSI values <50 or >300 mg/dl were rescued with carbohydrates or insulin, respectively, based on the provider's recommendation. The primary end point was comparison of duration and severity of hypoglycemia between LGS-on and LGS-off sessions. Secondary end points included areas under the glucose concentration curve, CGM sensor accuracy, and last YSI glucose. Device- and procedure-related adverse events and serious adverse events were recorded., Results: Fifty adults and teenagers (17-58 years) with type 1 diabetes were randomized. Study completion is expected in November 2011., (© 2011 Diabetes Technology Society.)

Purpose: To describe 11 instances of severe diabetic ketoacidosis (DKA) with secondary intracerebral complications (ICCs), nine of whom were treated early and showed complete recovery., Methods: Three hundred and eighty-one episodes of DKA were treated at Denver Children's Hospital (DCH) from January 1989 to December 1999. Nine instances of DKA with ICC were prospectively identified during this time period. Two additional occurrences were identified via a medical records search (total incidence, 2.9%). The signs, symptoms and laboratory values which led to their diagnosis and treatment are identified., Results: All nine children who received early treatment with i.v. mannitol showed complete recovery. An additional patient had central nervous system involvement upon arrival at our hospital and showed almost complete recovery. Another patient suffered a cardiorespiratory arrest before transfer to our hospital and died without being treated for cerebral edema., Conclusion: Prevention of ICCs by the earlier diagnosis of diabetes and by being aware of possible risk factors for cerebral edema is the eventual goal. Based on our experience, mannitol should be given promptly for the treatment of ICCs indicated by the clinical course even if cerebral edema is not documented by a computed tomography (CT) scan.

Objective: The purpose of this study was to determine the feasibility of continuous subcutaneous insulin infusion (CSII) (insulin pump) therapy in routine pediatric diabetes care by comparing the HbA(1c), body mass index (BMI), and hypoglycemic episodes before and after initiation of CSII therapy., Research Design and Methods: Data from 56 patients (7-23 years old) were collected during regularly scheduled visits at a frequency similar to non-CSII patients., Results: The data were analyzed for the entire cohort and 3 subgroups (decreased, stable, or increased HbA(1c)) stratified according to a >/=0.5% change in HbA(1c). The total cohort demonstrated a decrease in HbA(1c) from 8.5% to 8.3%. The decreased cohort (39.4% of the total cohort) demonstrated a significant decrease in HbA(1c) from 8.6% to 7.6%. The mean HbA(1c) of the stable cohort (41.0%) was 8.7%. The increased cohort (19.6%) had an increase in HbA(1c) from 7.8% to 8.8%. Thirty-six patients (64.3%) maintained or achieved a HbA(1c) <8.0% or achieved a HbA(1c) at least 1% lower than their pre-CSII level. Of concern, 6 patients (10.7%) demonstrated a clinically significant increase in HbA(1c) from 8.3% to 9.6%. For the entire cohort, the rate of severe hypoglycemia before and on CSII therapy was 12.3 and 9.5 events per 100 patient-years, respectively. A statistically significant proportion of patients reported a decrease in seizure frequency versus an increase (17.9% vs 1.8%) as well as a decrease in overall hypoglycemic frequency versus an increase (41.1% vs 17.9%). There was not a clinically significant increase in BMI, even in the decreased HbA(1c) cohort., Conclusions: CSII therapy is an appropriate option for some children in routine pediatric diabetes care. It can effectively decrease the HbA(1c) and reduce hypoglycemic episodes, without producing an abnormal increase in BMI.

Objective: The purpose of this study was to determine whether postprandial administration of the new rapid-acting insulin analog Humalog could effectively reduce glucose excursions in children <5 years old., Design: Human Regular insulin given before a meal was compared with the same dose of Humalog after a meal of equal carbohydrate content in five toddlers with insulin-dependent (type 1) diabetes mellitus. In addition, the use of Humalog before a meal was compared with Humalog given after a meal of equal carbohydrate content in five other toddlers. The dose of long-acting insulin was not changed during the study period. Blood glucose levels were determined at fasting and at 1, 2, and 4 hours postprandially., Results: The 2-hour glucose excursions were significantly lower when postprandial Humalog administration was compared with preprandial Human Regular insulin administration. In contrast, glucose excursions were similar when Humalog was taken before or after the meal., Conclusion: These data show that it is efficacious to give Humalog insulin postprandially in toddlers with type 1 diabetes, allowing increased safety for the young child. The insulin dose can be both matched to the actual food intake and timed to give families increased flexibility and control at mealtime.

To evaluate the effectiveness of clonidine on growth-hormone (GH) release in prepubertal children, and to distinguish between a central alpha-adrenergic effect and a corticotropin-cortisol-mediated response, we measured serum glucose, corticotropin, cortisol, and GH concentrations following levodopa, arginine hydrochloride, and clonidine hydrochloride stimulation in 15 euthyroid children who had short stature. We found that clonidine is an effective and safe stimulator of GH release and provided a clearer distinction between GH-deficient and non-GH-deficient young persons than levodopa or arginine. The action of clonidine is not corticotropin-cortisol mediated.