Combining continuous glucose monitoring and insulin pumps to automatically tune the basal insulin infusion in diabetes therapy: a review <s> Algorithms embedded in commercial devices <s> Background: Sensor-augmented insulin pumps may be programmed to suspend insulin delivery in response to hypoglycemia. The Medtronic Paradigm ® Veo™ pump with automatic low glucose suspend (LGS) was released in 2009. Data from 7 months of real-world use of the system were analyzed to assess usage patterns and effectiveness of LGS. Method: Data from 935 patients totaling 49,867 patient days were collected; the LGS feature was on for 82% of these days. A subset of 278 subjects who used the pump for ≥3 months was analyzed separately; these subjects provided 28,401 patient days of data, with LGS used for 92% of the time. Results: <s> BIB001 </s> Combining continuous glucose monitoring and insulin pumps to automatically tune the basal insulin infusion in diabetes therapy: a review <s> Algorithms embedded in commercial devices <s> Abstract Background: The automatic Threshold Suspend (TS) feature of the MiniMed 530G system (Medtronic MiniMed, Inc., Northridge, CA), when enabled, suspends insulin delivery for up to 2 h when the sensor glucose (SG) value reaches a preset threshold. Materials and Methods: SG data from 20,973 patients who enabled the TS feature at their discretion and uploaded pump and sensor data to CareLink® (Medtronic MiniMed, Inc.) from October 15, 2013 to July 21, 2014 were analyzed. Comparisons between 758,382 patient-days wherein the TS feature was enabled at any time and 166,791 patient-days in which it was not enabled were made. Further comparisons were made between data collected during daytime (8:00 a.m. to 10:00 p.m.) and nighttime (10:00 p.m. to 8:00 a.m.) hours. Data from subsets of patients who enabled the TS feature all of the time (n=14,673) versus those who never enabled the TS feature (n=2,249) were also compared. Recovery from hypoglycemia during and after 2-h pump suspension events was also assessed... <s> BIB002 </s> Combining continuous glucose monitoring and insulin pumps to automatically tune the basal insulin infusion in diabetes therapy: a review <s> Algorithms embedded in commercial devices <s> Abstract Background: Automated insulin management features of the MiniMed® 640G sensor-augmented pump system include suspension in response to predicted low sensor glucose (SG) values (“suspend before low”), suspension in response to existing low SG values (“suspend on low”), and automatic restarting of basal insulin delivery upon SG recovery. The effectiveness of these features was evaluated using CareLink® software data. Methods: Anonymized data from MiniMed 640G system users (n = 4818), MiniMed 530G system users (n = 39,219), and MiniMed Paradigm® Veo™ system users (n = 43,193) who voluntarily uploaded pump and sensor data were retrospectively analyzed. Comparisons were made between days in which system features were enabled at any time and those in which they were not. Comparisons were also made between pump suspension events for which insulin delivery was automatically or manually resumed and between glycemic parameters of users who switched from the MiniMed Paradigm Veo system to the MiniMed 640G sy... <s> BIB003
Since the availability of first CGM sensors, insulin pump companies understood the potentiality of exploiting CGM data in real-time to improve insulin infusion and, thus, glucose control. Medtronic Inc. (Northbridge, CA) has been one of the most active companies working at the development of both detection-and prediction-based suspension algorithms. Indeed, Medtronic Inc. launched in 2006 the first system for diabetes management integrating CGM and insulin pump technologies in the same medical device (MiniMed Paradigm REAL-time system). Later on, Medtronic Inc. developed the Medtronic Paradigm Veo (Fig. 3a) , i.e. the first device equipped with an automatic detection-based basal insulin suspension feature, which became commercially available outside the U.S. in 2009. The Paradigm Veo system implemented the low glucose suspend (LGS) feature that suspended basal insulin delivery for up to 2 h when the CGM value measured by the sensor embedded in the system fell below a low glucose threshold, which could be set by the user between 40 and 110 mg/dl. In particular, when the pre-defined threshold was reached, in absence of patient's actions, a 6-h cycle automatically started, in which basal insulin was suspended for 2 h and then re-activated for the next 4 h regardless of CGM measurements. The fixed 4-h re-activation of insulin delivery was introduced to prevent the occurrence of diabetes ketoacidosis. Nevertheless, the patient could manually interrupt the LGS cycle at any time and resume normal basal insulin delivery BIB001 . In the U.S., the first device including automatic detection-based suspension of basal insulin, the MiniMed 530G system (Fig. 3b) , entered the market several years later, in 2013. The system implemented the threshold suspend (TS) feature, which was identical to LGS, except for the range of settable low thresholds that was restricted to 60-90 mg/dl in this second device BIB002 . According to a retrospective study of Paradigm Veo data uploaded on Carelink Therapy Management Software for Diabetes (Carelink), the LGS feature was generally well accepted by the European users, who used the feature on 82% of the time, with the low threshold most commonly set between 50 and 60 mg/dl (data collected from January to July 2010) BIB001 . A similar analysis of MiniMed 530G data uploaded on Carelink showed that 70% of patients always used TS, 19% used it intermittently and the remaining 11% never used the feature (data collected from October 2013 to July 2014) BIB002 . Among MiniMed 530G users, the mean low threshold setting was 62.8 ± 5.8 mg/dl. However, even though the patients had the LGS/TS feature active on most of the time, actually, most of suspension events were manually interrupted by the users. Indeed, the retrospective analysis of Carelink data showed that about 50% of suspension events lasted 5 min or less and only 10% of events had complete 2-h duration BIB001 BIB002 . This suggests that a 2-h suspension may be too long for most of the events, thus users preferred to reactivate basal insulin earlier and/or make their own treatment. A new prediction-based suspension algorithm, called "suspend before low" or Prediction Low Glucose Management (PLGM), was implemented in the SmartGuard feature of the MiniMed 640G (Fig. 3c) , which became commercially available outside the U.S. in 2015. The system automatically suspends basal insulin delivery when glucose concentration is predicted to reach or fall below a preset glucose threshold in the next 30 min and automatically restarts basal insulin on recovery from hypoglycemia  . Specifically, basal insulin delivery is suspended if glucose concentration is below T + 70 mg/dl and predicted to drop below T + 20 mg/dl in the next 30 min, where T is a low threshold that the user can set between 50 and 90 mg/dl. The system automatically resumes basal insulin if glucose is ≥ T + 20 mg/dl, the 30-min ahead predicted glucose value is ≥ T + 40 mg/dl and basal insulin delivery has been suspended for at least 30 min. As in the LGS/TS feature, the user can manually restart basal insulin delivery at any time and the maximum duration of suspension events is 2 h, after which basal insulin delivery is resumed for 4 h regardless of CGM concentration. In the U.S., the SmartGuard feature became commercially available in 2016 as part of the MiniMed 630G system (Fig. 3d) . Besides the new PLGM algorithm, the SmartGuard feature of both MiniMed 640G and MiniMed 630G implements the LGS/TS algorithm as well, which is also called "suspend on low". An analysis of MiniMed 640G real-world data (data uploaded on Carelink from January 2015 to January 2016), showed that "suspend before low" was used on 83% of userdays, "suspend on low" was used on 11% of user-days, while in the remaining 6% of user-days neither "suspend before low" or "suspend on low" were activated BIB003 . With the MiniMed 640G, the percentage of suspension events manually interrupted by the user decreased to 33.51%, 11% of events had maximum duration of 2 h, while in the remaining 55% of events basal insulin delivery was automatically resumed by the PLGM algorithm.