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ObjectiveThe study was conducted in 12 middle schools to determine the prevalence of diabetes, pre-diabetes, and diabetes risk factors in eighth-grade students who were predominantly minority and evaluate the feasibility of collecting physical and laboratory data in schools.Research design and methodsAnthropometric measurements and fasting and 2-h post-glucose load blood draws were obtained from approximately 1,740 eighth-grade students.ResultsMean recruitment rate was 50% per school, 49% had BMI > or = 85th percentile, 40.5% had fasting glucose > or = 100 mg/dl, 0.4% had fasting glucose > or = 126 mg/dl, and 2.0% had 2-h glucose > or = 140 mg/dl and 0.1% > or = 200 mg/dl. Mean fasting insulin value was 30.1 microU/ml, 36.2% had fasting insulin > or = 30 microU/ml, and 2-h mean insulin was 102.1 microU/ml. Fasting and 2-h glucose and insulin values increased across BMI percentiles, and fasting glucose was highest in Hispanic and Native American students.ConclusionsThere was a high prevalence of risk factors for diabetes, including impaired fasting glucose (> or =100 mg/dl), hyperinsulinism suggestive of insulin resistance (fasting insulin > or = 30 microU/ml), and BMI > or = 85th percentile. These data suggest that middle schools are appropriate targets for population-based efforts to decrease overweight and diabetes risk.

Objective: To characterize middle-school students from the HEALTHY study with glycemic abnormalities, specifically high-risk hemoglobin A(1c) (A1C) (hrA1C; A1C = 5.7-6.4%) and impaired fasting glucose (IFG; fasting plasma glucose [FPG] = 100-125 mg/dL).Research Design and Methods: History was collected by self-report, physical measurement was collected by trained study staff, and fasting blood was drawn by trained phlebotomists and analyzed centrally.Results: At baseline, among 3,980 sixth graders, 128 (3.2%) had hrA1C and 635 (16.0%) had IFG. Compared with A1C <5.7%, hrA1C was associated with non-Hispanic black race/ethnicity, family history of diabetes, and higher measurements of BMI, waist circumference, and fasting insulin. Compared with FPG <100 mg/dL, IFG was associated with Hispanic ethnicity; increased BMI, waist circumference, and fasting insulin; higher frequency of high blood pressure; and higher mean triglycerides. Two years later, children with hrA1C persisted as hrA1C in 59.4%, and one child (0.8%) developed A1C ≥6.5%; children with IFG persisted with IFG in 46.9%, and seven children (1.1%) developed FPG ≥126 mg/dL. Those with hrA1C compared with IFG had a higher BMI in sixth grade, which persisted to eighth grade.Conclusions: In the HEALTHY study cohort, hrA1C and IFG define different groups of youth with differentially increased diabetes risk markers. IFG is approximately fivefold more common, but hrA1C is more persistent over time. Optimal screening strategies for diabetes in youth remain unresolved. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To improve glycemic control, a hand-held plastic Insulin Dosage Guide was developed to correct blood glucose levels outside of the target range. RESEARCH DESIGN AND METHODS: Protocol 1: Some 40 children (mean age 10.6 +/- 4.6 years) were randomly assigned for 3 months to use a written-on-paper algorithm or the Insulin Dosage Guide to correct abnormal blood glucose levels. Mean HbAlc, and blood glucose levels and time to teach insulin dosage correction were compared. Protocol 2: The Insulin Dosage Guide was used by 83 subjects (mean age 11.4 +/- 4.3 years) for 1 year, and mean HbAlc levels, blood glucose levels, and number of consecutive high blood glucose values taken before and after the year were compared. Protocol 3: Some 20 patients (mean age 10.1 +/- 3.7 years) using rapid-acting insulin and 64 patients (mean age 15.9 +/- 3.6 years) using an insulin pump and rapid-acting insulin used the Insulin Dosage Guide and had mean blood glucose levels, HbAlc, and percentage of blood glucose levels outside of the target range determined. RESULTS: Protocol 1: There was a significant reduction in mean HbAlc, (P = 0.04) and blood glucose levels (P = 0.05) and in the time needed to teach how to correct blood glucose values using the Insulin Dosage Guide compared with the paper algorithm. Protocol 2: There was a decrease in mean HbAlc, levels (P = 0.0001) and a decrease in the mean number of consecutive blood glucose levels (P = 0.001) over the 1-year time period. Protocol 3: With rapid-acting insulin, there was a significant increase in the percentage of blood glucose levels within the target range (1 month, P = 0.04; at 3 months, P = 0.03). With the insulin pump, there was a high rate (90%) of blood glucose levels in the target range during pump initiation when the Insulin Dosage Guide was used. CONCLUSIONS: This inexpensive hand-held plastic card, which is portable and easy to use, may help patients improve glycemia and successfully manage diabetes. [ABSTRACT FROM AUTHOR]

Objective: HEALTHY is a 3-year middle school intervention program designed to reduce risk factors for type 2 diabetes. The prevalence of diabetes risk factors at baseline in a cohort of 6,358 sixth-grade students is reported.Research Design and Methods: Forty-two schools at seven U.S. sites were randomly assigned to intervention or control. Students participated in baseline data collection during fall of 2006.Results: Overall, 49.3% of children had BMI >or=85th percentile, 16.0% had fasting blood glucose >or=100 mg/dl (<1% had fasting blood glucose >or=126 mg/dl), and 6.8% had fasting insulin >or=30 microU/ml. Hispanic youth were more likely to have BMI, glucose, and insulin levels above these thresholds than blacks and whites.Conclusions: Sixth-grade students in schools with large minority populations have high levels of risk factors for type 2 diabetes. The HEALTHY intervention was designed to modify these risk factors to reduce diabetes incidence. [ABSTRACT FROM AUTHOR]

Background: Use of continuous glucose monitoring (CGM) systems is being rapidly adopted as standard of care for insulin-requiring patients with diabetes. The PROMISE study (NCT03808376) evaluated the accuracy and safety of the next-generation implantable Eversense CGM system for up to 180 days. Methods: This was a prospective multicenter study involving 181 subjects with diabetes at 8 USA sites. All subjects were inserted with a primary sensor. Ninety-six subjects had a second sensor, either an identical sensor or a modified sensor (sacrificial boronic acid [SBA]), inserted in their other arm (53 and 43 subjects, respectively). Accuracy was evaluated by comparing CGM to YSI 2300 glucose analyzer (Yellow Springs Instrument [YSI]) values during 10 clinic visits (day 1-180). Confirmed event detection rates, calibration stability, sensor survival, and serious adverse events (SAEs) were evaluated. Results: For primary sensors, the percent CGM readings within 20%/20% of YSI values was 92.9%; overall mean absolute relative difference (MARD) was 9.1%. The confirmed alert detection rate at 70 mg/dL was 93% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 56%. Sixty-five percent of the primary sensors survived to 180 days. For the SBA sensors, the percent CGM readings within 20%/20% of YSI values was 93.9%; overall MARD was 8.5%. The confirmed alert detection rate at 70 mg/dL was 94% and at 180 mg/dL was 99%. The median percentage of time for one calibration per day was 63%. Ninety percent of the SBA sensors survived to 180 days. No device- or insertion/removal procedure-related SAEs were reported. Conclusion: These data show the next-generation Eversense CGM system had sustained accuracy and safety up to 180 days, with an improved calibration scheme and survival, using the primary or SBA sensors.

Introduction: Continuous glucose monitoring (CGM) systems offer real-time data to facilitate diabetes management. The novel Eversense CGM has been approved in Europe and the US. The unique characteristics are the fully implantable sensor and the sensor life up to 180 days., Areas Covered: This expert review describes the results of clinical trials, and the accuracy and safety of the Eversense system. The overall MARD ranges from 8.5% to 9.4%, the 20/20% agreement rate ranges from 84% to 94%, and the percent of values in zones A and B on the Clarke Error Grid is 99.2%. No device-related serious adverse events have been described during pivotal trial studies. The most frequently reported device- or procedure-related adverse events are sensor adhesive patch location site irritation (0.66%), inability to remove the sensor upon first attempt (0.76%), and location site infection (0.96%). Mean A1c reduction is about 0.4% from pivotal trials and real-world studies., Expert Opinion: The Eversense system is novel and differentiated from transcutaneous CGM systems. The long life, the removable transmitter, and the on-body vibration alerts offer opportunities to properly manage diabetes with both MDI and insulin pump therapy.

Aims: This real-world study evaluated the changes in glycated haemoglobin (HbA1c) and continuous glucose monitoring (CGM) metrics associated with use of the implantable 180-day Eversense CGM System (Eversense) in patients with type 1 diabetes., Materials and Methods: This was a prospective, multicentre, observational study among adult participants aged ≥18 years with type 1 diabetes across seven diabetes-care centres in Italy who had Eversense inserted for the first time. HbA1c was measured at baseline and at 180 days. Changes in time in range [TIR (glucose 70-180 mg/dL)], time above range [TAR (glucose >180 mg/dL)], time below range [TBR (glucose <70 mg/dL)] and glycaemic variability were also assessed. Data were also analysed by previous CGM use and by mode of insulin delivery., Results: One-hundred patients were enrolled (mean age 36 ± 12 years, mean baseline HbA1c 7.4 ± 0.92% [57 ± 10 mmol/mol]). Fifty-six per cent of patients were users of the continuous subcutaneous insulin infusion pump and 45% were previous users of CGM. HbA1c significantly decreased in patients after 180 days of sensor wear (-0.43% ± 0.69%, 5 ± 8 mmol/mol, P < 0.0001). As expected, CGM-naïve patients achieved the greatest reduction in HbA1c (-0.74% ± 0.48%, 8 ± 5 mmol/mol). TIR significantly increased and TAR and mean daily sensor glucose significantly decreased while TBR did not change after 180 days of sensor wear., Conclusions: Real-world clinical use of the Eversense CGM System for 180 days was associated with significant improvements in HbA1c and CGM metrics among adults with type 1 diabetes. The study is registered on clinicaltrials.gov (NCT04160156)., (© 2020 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.)

The Eversense ® Continuous Glucose Monitoring (CGM) System, with the first long-term, implantable glucose sensor, has been commercially available in Europe and South Africa since 2016 for adults with diabetes. The performance of the sensor over multiple, sequential 90- or 180-day cycles from either real-world experience or clinical studies has not been previously published. The Eversense Data Management System (DMS) was used to evaluate the accuracy of General Data Protection Regulation (GDPR)-compliant sensor glucose (SG) values against self-monitoring of blood glucose (SMBG) from June 2016 through August 2019 among patients with at least four sensor cycles from European and South African health care practices. Mean SG and associated measures of variability, glucose management indicator (GMI), and percent and time in various hypoglycemic, euglycemic, and hyperglycemic ranges were calculated for the 24-h time period over each cycle. In addition, transmitter wear time was evaluated across each sensor wear cycle. Among the 945 users included in the analysis, the mean absolute relative difference (standard deviation [SD]) using 152,206, 174,645, 206,024, and 172,587 calibration matched pairs against SMBG was 11.9% (3.6%), 11.5% (4.0%), 11.8% (4.7%), and 11.5% (4.1%) during the first four sensor cycles, respectively. Mean values of the CGM metrics over the first sensor cycle were 156.5 mg/dL for SG, 54.7 mg/dL for SD, 0.35 for coefficient of variation, and 7.04% for GMI. Percent SG at different glycemic ranges was as follows: <54 mg/dL was 1.1% (16 min), <70 mg/dL was 4.6% (66 min), ≥70-180 mg/dL (time in range) was 64.5% (929 min), >180-250 mg/dL was 22.8% (328 min), and >250 mg/dL was 8.1% (117 min). The median transmitter wear time over the first cycle was 83.2%. CGM metrics and wear time were similar over the subsequent three cycles. This real-world evaluation of adult patients with diabetes using the Eversense CGM System in the home setting demonstrated that the implantable sensor provides consistent stable accuracy and CGM metrics over multiple, sequential sensor cycles with no indication of degradation of sensor performance.

Previously, the safety and accuracy of the Eversense continuous glucose monitoring (CGM) system were characterized in three pivotal trials among individuals with type 1 diabetes (T1D) and type 2 diabetes (T2D) with a single 90- or 180-day sensor insertion-removal cycle. The Post-Market Clinical Follow-up (PMCF) registry is a prospective study evaluating the long-term safety and performance of the Eversense CGM system over multiple sensor insertion-removal cycles among adults with T1D and T2D. All patients who had a sensor subcutaneously implanted across 534 participating centers in Europe and South Africa from June 2016 to August 2018 were enrolled. Adverse events (AEs) were recorded at each visit and patients were instructed to inform their clinic if they experienced any AEs between visits. AEs were adjudicated for relatedness to the device, procedure, or drug (dexamethasone acetate). The primary safety endpoint was the rate of related serious adverse events (SAEs) through four sensor insertion-removal cycles. The registry enrolled 3023 patients. As of last follow-up, 5417 sensors had been inserted with a total of 1260 patient-years (PYs) of follow-up: 969 patients had used the system for at least 6 months and 173 patients had used the system for at least 1 year. No related SAEs were reported. The most frequently reported related AEs were sensor location site infection (0.96%; 2.46 events per 100 PYs), inability to remove the sensor upon first attempt (0.76%; 1.90 events per 100 PYs), and adhesive patch location site irritation (0.66%; 1.59 events per 100 PYs). One nonserious allergic reaction to lidocaine was reported, which resolved with administration of an antihistamine. The full intended sensor life was achieved by 91% of 90-day sensors and 75% of 180-day sensors. The PMCF registry provides real-world evidence that the Eversense CGM system is safe over multiple cycles of use.

Background: The Eversense ® Continuous Glucose Monitoring (CGM) System, with the first 90-day implantable sensor, received FDA (Food and Drug Administration) approval in June 2018. No real-world experience has been published. Methods: Deidentified sensor glucose (SG) data from August 1, 2018 to May 11, 2019 in the Eversense Data Management System (DMS) were analyzed for the first 205 patients who reached a 90-day wear period on the Eversense CGM system. The mean SG, standard deviation (SD), median interquartile range, coefficient of variation (CV), glucose measurement index (GMI), and percent and time in minutes across glucose ranges were computed for the 24-h time period, the nighttime (00:00-06:00), and by 30-day wear periods. Sensor accuracy, sensor reinsertion rate, transmitter wear time, and safety data were assessed. Results: Of the 205 patients, 129 identified as type 1, 18 as type 2, and 58 were unreported. Fifty were CGM naive, 112 had prior CGM experience, and 43 were unreported. The mean SG was 161.8 mg/dL, SD was 57.4 mg/dL, CV was 0.35, and GMI was 7.18%. Percent SG at <54 mg/dL was 1.2% (18 min), <70 mg/dL was 4.1% (59.7 min), time in range (≥70-180 mg/dL) was 62.3% (897.7 min), >180-250 mg/dL was 21.9% (315.8 min), and >250 mg/dL was 11.6% (166.7 min). Nighttime values were similar. The glucometric values were similar over 30-day time periods of the sensor wear. The mean absolute relative difference (SD) using 27,708 calibration paired points against home blood glucose meters was 11.2% (11.3%). The sensor reinsertion rate was 78.5%. The median transmitter wear time was 83.6%. There were no related serious adverse events. Conclusion: The Eversense real-world data showed promising glycemic results, sensor accuracy, and safety. These data suggest that the Eversense CGM system is a valuable tool for diabetes management.

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, HbA 1c 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., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Objective: To evaluate the safety of in-home use of the MiniMed™ 670G system with SmartGuard™ technology in children with type 1 diabetes (T1D)., Methods: Participants (N = 105, ages 7-13 years, mean age 10.8 ± 1.8 years) were enrolled at nine centers (eight in the United States and one in Israel) and completed a 2-week baseline run-in phase in Manual Mode followed by a 3-month study phase with Auto Mode enabled. Sensor glucose (SG), glycated hemoglobin (HbA 1c ), percentage of SG values across glucose ranges, and SG variability, during the run-in and study phases were compared. Participants underwent frequent sample testing with i-STAT ® venous reference measurement during a hotel period (6 days/5 nights) to evaluate the system's continuous glucose monitoring performance., Results: Auto Mode was used a median of 81% of the time. From baseline to end of study, overall SG dropped by 6.9 ± 17.2 mg/dL (P < 0.001), HbA 1c decreased from 7.9% ± 0.8% to 7.5% ± 0.6% (P < 0.001), percentage of time in target glucose range (70-180 mg/dL) increased from 56.2% ± 11.4% to 65.0% ± 7.7% (P < 0.001), and the SG coefficient of variation decreased from 39.6% ± 5.4% to 38.5% ± 3.8% (P = 0.009). The percentage of SG values within target glucose range was 68.2% ± 9.1% and that of i-STAT reference values was 65.6% ± 17.7%. The percentage of values within 20%/20 of the i-STAT reference was 85.2%. There were no episodes of severe hypoglycemia or diabetic ketoacidosis during the study phase., Conclusion: In-home use of MiniMed 670G system Auto Mode for 3 months by children with T1D, similar to MiniMed 670G system use by adolescents and adults with T1D, was safe and associated with reduced HbA 1c levels and increased time in target glucose range, compared with baseline.

Background: The Medtronic predictive low-glucose management (PLGM) algorithm automatically stops insulin delivery when sensor glucose (SG) is predicted to reach or fall below a preset low-glucose value within the next 30 min, and resumes delivery after hypoglycemia recovery. The present study evaluated the PLGM algorithm performance of the MiniMed™ 670G system SmartGuard™ "suspend before low" feature in children aged 7-13 years with type 1 diabetes (T1D)., Method: Participants (N = 105, mean ± standard deviation of 10.8 ± 1.8 years) underwent an overnight in-clinic evaluation of the "suspend before low" feature with a preset low limit of 65 mg/dL. After exercise, frequent sample testing (FST) was conducted every 5 min if values were <70 mg/dL; every 15 min if 70-80 mg/dL; and every 30 min if >80 mg/dL. First-day performance of the Guardian™ Sensor 3 glucose sensor and continuous glucose monitoring system was also evaluated., Results: Activation of the "suspend before low" feature occurred in 79 of the 105 participants, 79.7% (63/79) did not result in SG falling below 65 mg/dL. Mean glucose at activation was 102 ± 19 mg/dL and the initial insulin suspension duration was 87.5 ± 32.7 min. Four hours after insulin resumption, mean reference glucose was 130 ± 42 mg/dL. Mean absolute relative difference between the FST reference glucose and SG values on the first day of sensor wear was 11.4%. For the 26 participants in whom the "suspend before low" feature did not activate, none involved a reference glucose value ≤65 mg/dL, suggesting that the PLGM algorithm performed as intended., Conclusion: In children aged 7-13 years with T1D, the "suspend before low" feature of the MiniMed 670G system demonstrated a hypoglycemia prevention rate of nearly 80% after exercise and did not involve rebound hyperglycemia. There were no events of severe hypoglycemia during the evaluation.

Real-world data from the first 3141 patients who completed 3 months of SmartGuard™ Auto Mode-enabled MiniMed™ 670G system use during the MiniMed 670G System Commercial Launch are reported. CareLink™ system data uploaded by real-world patients in the Commercial Launch from March 17, 2017 to December 31, 2017 were deidentified and analyzed. Comparisons of overall and night (10:00 PM-07:00 AM) time spent below, within, and above target glucose range (TIR) (70-180 mg/dL) between the baseline Manual Mode and closed-loop Auto Mode periods were made. These were evaluated alongside data from the 124 patients (aged 14-75 years) who completed the 3-month MiniMed 670G system pivotal trial (NCT 2463097), from June 2, 2015 to March 7, 2016. Real-world patients used Auto Mode a median 80.8% of the time (19 h and 24 min of the day). The overall mean of time spent in TIR was 66.0% during baseline Manual Mode versus 73.3% during Auto Mode (P < 0.001); the mean percentage of sensor glucose values <70 mg/dL was 2.7% versus 2.1% (P < 0.001); and that >180 mg/dL was 31.4% versus 24.6% (P < 0.001). The nighttime and early morning (03:00 AM-06:00 AM) TIR during Auto Mode was greater than that during baseline Manual Mode (nighttime: 77.2% vs. 67.4% [P < 0.001], early morning: 70.9% vs. 84.6% [P < 0.001]). Similar differences between Manual Mode and Auto Mode TIR were observed across different age groups. A slight increase in total insulin delivered was also observed. Consistent with improved glycemic control demonstrated in the pivotal trial, analysis of CareLink system data from >3000 real-world patients who completed 3 months of Auto Mode-enabled MiniMed 670G system use demonstrated increased TIR and decreased time below and above TIR compared with baseline. These improved clinical outcomes were observed across a broad age range of patients with type 1 diabetes.

Introduction: Glycated hemoglobin (A1C) is considered a "gold standard" measure of glycemic control in patients with diabetes and is correlated with a lower risk of diabetes complications and cost savings. This retrospective claims-analysis assessed the impact of A1C reduction on healthcare costs in patients with uncontrolled Type 1 and Type 2 diabetes., Methods: Using a large repository of US health plan administrative data linked to A1C values, patients with a diabetes diagnosis and at least two A1C values between 1 January 2009 and 31 December 2014 were selected to identify changes in A1C and associated changes in healthcare expenditure. We used all medical and pharmacy claims to calculate direct healthcare costs from 1 year prior to the index A1C to 2 years after the index A1C. A propensity score method was used to match patients with decreased A1C to patients whose A1C did not decrease, based on potentially confounding variables. Then, a generalized linear model regression was used to estimate the difference-in-difference (DD) effect on costs between the two groups., Results: Of the 3,197 patients who had a first A1C ≥ 9%, 2,273 patients (71%) had a decrease in A1C (Decreasers) and 924 patients (27%) had an increase in A1C (Non-decreasers). After matching, we compared 912 Decreasers to 912 Non-decreasers. Patients in the former group had average annual healthcare costs that were 24% lower during the first year of follow-up and 17% lower during the second year of follow-up, compared to patients whose A1C did not decrease. This reflected a savings of US$2503 and US$1690, respectively. For both time periods, the outpatient category was the largest contributor to cost savings., Discussion: In our analysis, A1C reduction among patients with T1DM and T2DM was associated with slower growth in healthcare costs within 1-2 years. These findings suggest that programs aimed at reducing A1C over a short timeframe may lead to substantial savings and may be worth pursuing by health plans and other payers.

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: Fasting C-peptide levels are used to differentiate type 1 from type 2 diabetes (T2D), thereby determining eligibility for coverage of continuous subcutaneous insulin infusion (CSII) for patients with T2D., Methods: A total of 168 patients (74 female/94 male, aged 55.5 ± 9.7 years) were randomized to CSII, and 163 patients (77 female/86 male, aged 56.4 ± 9.5 years) were randomized to multiple daily injections (MDI) of insulin and grouped by baseline C-peptide level: group A (≤183 pmol/L [≤0.55 ng/mL]); group B (>183 pmol/L [>0.55 ng/mL]). At 6 months, the MDI group crossed over to CSII. Within- and between-group comparisons were recorded at 6 and 12 months in the entire group and separately for those patients aged ≥65 years., Results: CSII reduced hemoglobin A1c (A1c) equally in groups A ( P = .0006, P = .0022) and B ( P<.0001, P<.0001) at 6 and 12 months, respectively. There was an increase in weight in group A versus group B at 6 months but not 12 months ( P<.03). CSII therapy reduced total daily dose (TDD) of insulin and improved treatment satisfaction similarly in groups A and B. The results for patients aged ≥65 years displayed a similar trend as the entire group., Conclusion: A1c, TDD of insulin, and treatment satisfaction improved for T2D patients using CSII versus MDI therapy, irrespective of baseline C-peptide level. A subgroup of patients aged ≥65 years displayed a similar trend. These results support abandoning C-peptide as a criterion for reimbursing CSII therapy in patients with diabetes., Abbreviations: A1c = hemoglobin A1c; CMS = Centers for Medicare and Medicaid Services; CSII = continuous subcutaneous insulin infusion; DTSQ = Diabetes Treatment Satisfaction Questionnaire; MDI = multiple daily injections; RCT = randomized controlled trials; T1D = type 1 diabetes; T2D = type 2 diabetes; TDD = total daily dose.

Background: Simulations using mathematical models are important for studying, developing, and improving therapies for people with type 1 diabetes., Methods: The Medtronic CareLink ® database was used to create virtual patients with a variety of inter-insulin sensitivities, meal absorption rates, pharmacokinetics, age, and gender. In addition, intra-insulin sensitivities of the virtual patients change over a 24-h cycle., Results: A total of 2087 virtual patients were developed. The time percentage between 70 and 180 mg/dL of the CareLink uploads and the simulated virtual patients was 72.4% (18.6) and 74.1% (16.9), respectively. The time percentage <70 mg/dL of the real continuous glucose monitoring from CareLink uploads and the simulated virtual patients was 1% (2.4) and 1.7% (4.1), respectively. A simulation study with the virtual patients predicted the glycemic distribution after 2 h of insulin suspension as reported in the ASPIRE (Automation to Simulate Pancreatic Insulin Response) clinical trial. The 3 months outcomes of Medtronic's hybrid closed-loop 670G system pivotal trial were also predicted in a simulation study. The time percentage <70 mg/dL was 3.4% and 3.1%, and the time percentage between 71 and 180 mg/dL was 73.8% and 77.7% for 93 pivotal study adults (>18 years) and 90 adult (>28 years) virtual patients, respectively., Conclusion: The Medtronic CareLink database was utilized to generate a large number of virtual patients with a variety of insulin sensitivities, pharmacokinetics, and meal absorption rates. This new simulation model can be potentially used to evaluate and prognosticate the outcomes of studies of artificial pancreas algorithms and systems.

Background: It is estimated that one in 10 people in the US have a diagnosis of diabetes. Type 2 diabetes accounts for 95% of all cases in the US, with annual costs estimated to be $246 billion per year. This study investigated the impact of a glucose-measuring intervention to the burden of type 2 diabetes., Objective: This analysis seeks to understand how professional continuous glucose monitoring (professional CGM) impacts clinical and economic outcomes when compared to patients who are not prescribed professional CGM., Methods: This study utilized a large healthcare claims and lab dataset from the US, and identified a cohort of patients who were prescribed professional CGM as identified by CPT codes 95250 and 95251. It calculated economic and clinical outcomes 1 year before and 1 year after the use of professional CGM, using a generalized linear model., Results: Patients who utilized professional CGM saw an improvement in hemoglobin A1C. The "difference-in-difference" calculation for A1C was shown to be -0.44%. There was no statistically significant difference in growth of total annual costs for people who used professional CGM compared to those who did not ($1,270, p = .08). Patients using professional CGM more than once per year had a -$3,376 difference in the growth of total costs (p = .05). Patients who used professional CGM while changing their diabetes treatment regimen also had a difference of -$3,327 in growth of total costs (p = .0023)., Conclusion: Significant clinical benefits were observed for patients who used professional CGM. Economic benefits were observed for patients who utilized professional CGM more than once within a 1-year period or who used it during a change of diabetes therapy. This suggests that professional CGM may help decrease rising trends in healthcare costs for people with type 2 diabetes, while also improving clinical outcomes.

A 3-month pivotal trial using the MiniMed™ 670G hybrid closed-loop (HCL) system in adolescent and adult patients with type 1 diabetes (T1D), relative to a 2-week baseline run-in period, resulted in increased sensor glucose (SG) values in target range (71-180 mg/dL), reduced HbA1c levels, and no events of diabetic ketoacidosis or severe hypoglycemia ( Clinicaltrials.gov : NCT02463097). This brief report evaluated how prior continuous glucose monitoring (CGM) experience influenced glycemic outcomes, in the same pivotal trial. HbA1c levels and the percentage of SG values in low, high, and in-target ranges were analyzed from participants (n = 124) completing the Hybrid Closed-Loop Pivotal Trial in T1D. There were 78 individuals comprising the prior CGM group and 46 comprising the no prior CGM group. Compared to baseline, HbA1c was reduced from 7.4% ± 0.9% to 6.9% ± 0.7% for the prior CGM group and from 7.5% ± 0.9% to 6.8% ± 0.5% for the no prior CGM group. For those with prior CGM experience, the mean percentage of in-target SG values increased from 66.9% ± 12.5% to 72.6% ± 9.1%, and for those with no prior CGM experience it increased from 66.6% ± 11.7% to 71.5% ± 8.5%. Similar improvement in glucose values in the low and high ranges, relative to baseline, was observed for both groups. Resulting outcomes, from baseline to study end, did not differ between each group. These findings suggest that individuals without prior CGM experience, and those already using CGM, will benefit similarly with use of the FDA-approved MiniMed 670G HCL system therapy.

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: Predictions based on continuous glucose monitoring (CGM) data are the basis for automatic suspension and resumption of insulin delivery by a predictive low-glucose management feature termed "suspend before low," which is part of the Medtronic MiniMed ® 640G combined insulin pump and CGM system. This study assessed the safety and performance characteristics of the system in an in-clinic setting at eight sites., Materials and Methods: In-clinic standardized increases in basal insulin delivery rates were used to induce nocturnal hypoglycemia in subjects (14-75 years) with type 1 diabetes wearing the MiniMed 640G system. The "suspend before low" feature was set at 65 mg/dL, and as a result, the predictive algorithm suspended insulin delivery when the forecasted glucose was predicted to be ≤85 mg/dL in 30 min (a 20 mg/dL safety buffer). Reference plasma glucose values (Yellow Springs Instruments [YSI], Yellow Springs, OH) were used to establish hypoglycemia and were defined as ≥2 consecutive values ≤65 mg/dL., Results: Eighty subjects were screened. Among the 69 successful completers, 27 experienced a hypoglycemic event and 42 did not, a prevention rate of 60%. The mean (±standard deviation) YSI value at the time of pump suspension was 101 ± 18.5 mg/dL, and the mean duration of the 68 "suspend before low" events was 105 ± 27 min. At 120 min after the start of the pump suspension events, the mean YSI value was 102 ± 34.6 mg/dL., Conclusion: The MiniMed 640G "suspend before low" feature prevented 60% of induced predicted hypoglycemic events without significant rebound hyperglycemia.

Among children and adolescents with type 1 diabetes mellitus, the use of insulin pump therapy has increased since its introduction in the early 1980s. Optimal management of type 1 diabetes mellitus depends on sufficient understanding by patients, their families, and healthcare providers on how to use pump technology. The goal for the use of insulin pump therapy should be to advance proficiency over time from the basics taught at the initiation of pump therapy to utilizing advanced settings to obtain optimal glycemic control. However, this goal is often not met, and appropriate understanding of the full features of pump technology can be lacking. The objective of this review is to provide an expert perspective on the advanced features and use of insulin pump therapy, including practical guidelines for the successful use of insulin pump technology, and other considerations specific to patients and healthcare providers.

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: 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 system., Results: Days in which the MiniMed 640G "suspend before low" feature was enabled had lower percentages of SG readings ≤70 mg/dL (3.9 mmol/L) or ≥240 mg/dL (13.3 mmol/L) than days when it was not enabled (P < 0.001 for each). Users who switched from the MiniMed Paradigm Veo system to the MiniMed 640G system had fewer excursions below ≤70 mg/dL (P < 0.001) and ≥240 mg/dL (P < 0.001). SG values following automatically resumed pump suspension events recovered more rapidly and had a more stabilized endpoint than following manually resumed events., Conclusions: Automated insulin management features of the MiniMed 640G system can reduce the frequency of both high and low SG values and help stabilize SG after resumption of insulin delivery., Competing Interests: Author Disclosure Statement A.Z., C.M., P.A., J.B.W., T.L.C., and F.R.K. are or were employees of Medtronic during development of this manuscript. P.C. has received research support from Medtronic.

Background: Hypoglycemia varies between patients with type 1 diabetes and is the main obstacle to therapy intensification. We investigated known and potential risk factors for hypoglycemia in subjects with type 1 diabetes., Method: In the ASPIRE In-Home study (NCT01497938), a randomized trial of the threshold suspend (TS) feature of sensor-augmented insulin pump (SAP) therapy, subjects' propensity to nocturnal hypoglycemia (NH) was established in a 2-week run-in phase and assessed in a 3-month study phase via continuous glucose monitoring. Categorical variables were tested for association with NH rates in both phases., Results: Elevated rates of NH were significantly associated with baseline A1C ≤7%, with bolus insulin deliveries unassisted by the bolus estimation calculator, and with assignment to the control group during the study phase., Conclusions: Routine use of the TS feature and the bolus estimation calculator are strategies that may reduce the risk of NH., (© 2015 Diabetes Technology Society.)

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., Results: The TS feature was enabled on 82% of patient-days. Patient-days in which the TS feature was enabled, compared with patient-days in which it was not, had 69% fewer SG values ≤50 mg/dL (0.64% vs. 2.09%, respectively; P<0.001). The reduction in hypoglycemia seen on TS-enabled days was more pronounced during nighttime than during daytime hours. SG data from full-time users of the TS feature reflected a 62% reduction in values ≤50 mg/dL and a 5.6% reduction in values ≥300 mg/dL compared with data from nonusers (P<0.001 for each). The median SG value at the start of 2-h suspensions was 60 (interquartile range [IQR], 57-66) mg/dL, immediately after was 87 (IQR, 63-123) mg/dL, and 4 h later was 164 (IQR, 117-220) mg/dL., Conclusions: The TS feature, when enabled consistently, reduced hypoglycemic exposure, and for those who had it enabled 100% of the time, hyperglycemia was also reduced.

Background: Predictive low glucose management (PLGM) may help prevent hypoglycemia by stopping insulin pump delivery based on predicted sensor glucose values., Materials and Methods: Hypoglycemic challenges were simulated using the Food and Drug Administration-accepted glucose simulator with 100 virtual patients. PLGM was then tested with a system composed of a Paradigm(®) insulin pump (Medtronic, Northridge, CA), an Enlite™ glucose sensor (Medtronic), and a BlackBerry(®) (Waterloo, ON, Canada)-based controller. Subjects (n=22) on continuous subcutaneous insulin infusion (five females, 17 males; median [range] age, 15 [range, 14-20] years; median [range] diabetes duration, 7 [2-14] years; median [range] glycated hemoglobin, 8.0% [6.7-10.4%]) exercised until the PLGM system suspended insulin delivery or until the reference blood glucose value (HemoCue(®); HemoCue GmbH, Großostheim, Germany) reached the predictive suspension threshold setting., Results: PLGM reduced hypoglycemia (<70 mg/dL) in silico by 26.7% compared with no insulin suspension, as opposed to a 5.3% reduction in hypoglycemia with use of low glucose suspend (LGS). The median duration of hypoglycemia (time spent <70 mg/dL) with PLGM was significantly less than with LGS (58 min vs. 101 min, respectively; P<0.001). In the clinical trial the hypoglycemic threshold during exercise was reached in 73% of the patients, and hypoglycemia was prevented in 80% of the successful experiments. The mean (±SD) sensor glucose at predictive suspension was 92±7 mg/dL, resulting in a postsuspension nadir (by HemoCue) of 77±22 mg/dL. The suspension lasted for 90±35 (range, 30-120) min, resulting in a sensor glucose level at insulin resumption of 97±19 mg/dL., Conclusions: In silico modeling and early feasibility data demonstrate that PLGM may further reduce the severity of hypoglycemia beyond that already established for algorithms that use a threshold-based suspension.

Objective: This study determined the association of continuous glucose monitoring glucose (CGM-glucose) levels at different times of the day with improvement in glycated hemoglobin (HbA1c) levels. The potential application of these data is to focus effort to improve glucose control in patients with type 1 diabetes., Research Design and Methods: Data were analyzed from 196 patients with type 1 diabetes who were randomized to receive sensor-augmented pump therapy in the 1-year STAR 3 trial. CGM-glucose values and HbA1c levels from baseline and after 1 year were evaluated to determine associations of improvement in CGM-glucose at different times of the day with longitudinal improvement in HbA1c., Results: Improvement in HbA1c levels after 1 year was related to improvement in mean CGM-glucose levels in daytime (6 a.m.-midnight), overnight (midnight-6 a.m.), and each mealtime period (P<0.0001 for each). In multivariable analysis, only improvement in breakfast meal period was associated with improvement in HbA1c after 1 year, explaining 59% of the HbA1c improvement using the partial R(2) test. Moreover, among those patients who only improved CGM-glucose in the overnight period there was an associated improvement in breakfast meal period CGM-glucose of 26 ± 22 mg/dL (P<0.01)., Conclusions: Breakfast period glucose improvement had the greatest effect on lowering HbA1c levels in patients with type 1 diabetes. Improving glucose control overnight resulted in subsequent improvement in the breakfast period. Although glucose control should be improved at all times, methods to improve overnight and post-breakfast glucose levels may be of primary importance in improving glucose control in patients with type 1 diabetes.

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.).

Background: In insulin pump therapy, optimization of bolus and basal insulin dose settings is a challenge. We introduce a new algorithm that provides individualized basal rates and new carbohydrate ratio and correction factor recommendations. The algorithm utilizes a mathematical model of blood glucose (BG) as a function of carbohydrate intake and delivered insulin, which includes individualized parameters derived from sensor BG and insulin delivery data downloaded from a patient's pump., Methods: A mathematical model of BG as a function of carbohydrate intake and delivered insulin was developed. The model includes fixed parameters and several individualized parameters derived from the subject's BG measurements and pump data. Performance of the new algorithm was assessed using n = 4 diabetic canine experiments over a 32 h duration. In addition, 10 in silico adults from the University of Virginia/Padova type 1 diabetes mellitus metabolic simulator were tested., Results: The percentage of time in glucose range 80-180 mg/dl was 86%, 85%, 61%, and 30% using model-based therapy and [78%, 100%] (brackets denote multiple experiments conducted under the same therapy and animal model), [75%, 67%], 47%, and 86% for the control experiments for dogs 1 to 4, respectively. The BG measurements obtained in the simulation using our individualized algorithm were in 61-231 mg/dl min-max envelope, whereas use of the simulator's default treatment resulted in BG measurements 90-210 mg/dl min-max envelope., Conclusions: The study results demonstrate the potential of this method, which could serve as a platform for improving, facilitating, and standardizing insulin pump therapy based on a single download of data., (© 2013 Diabetes Technology Society.)