Predictive Low Glucose Suspend System Research Articles

A sensor-augmented pump with a predictive low-glucose suspend system could lead to an optimal time in target range during pregnancy in Japanese women with type 1 diabetes.

It is challenging for pregnant women with type 1 diabetes to maintain optimum glucose level to attain good neonatal outcomes. This study evaluated the efficacy of sensor-augmented insulin pump (SAP) with a predictive low-glucose suspend (PLGS) system in pregnant Japanese women with type 1 diabetes. SAP with PLGS was used in 11 of the 22 women with type 1 diabetes who delivered between 2011 and 2021 at the two medical institutions in Japan. Glucose management, insulin delivery suspension time (IST) and neonatal outcomes were retrospectively studied. In SAP with PLGS cases (n = 11), average glycated hemoglobin levels were < 6.5% throughout the pregnancy, and the time in range (TIR, 63-140mg/dl) was > 70% in the second and third trimesters. PLGS was safely used without inducing ketoacidosis. Positive correlation was observed between IST and TIR (r = 0.62, p < 0.01). Negative correlation was observed between IST and time below range (TBR) (r = - 0.40, p = 0.02), and IST and time above range (TAR) (r = - 0.45, p = 0.01). Total daily insulin dose was adequately increased without increasing hypoglycemia. There was only one heavy-for-date HFD) infant among the 11 newborns in SAP with PLGS cases. In cases without SAP (n = 11), target glycemic levels were difficult to achieve and there were 5 HFD infants among the 11 newborns. SAP with PLGS was safely and effectively used in pregnant women with type 1 diabetes to achieve target glucose levels without increasing the risk of hypoglycemia, which may have led to good neonatal outcomes. The online version contains supplementary material available at 10.1007/s13340-024-00716-7.

Factors affecting the prolongation of glycemic time in range among children with type 1 diabetes using continuous glucose monitoring systems: A case control study

BackgroundTime in range is a reliable measure of the risk of diabetes complications. High percentage of patients with diabetes fail to achieve the recommended time in range (TIR) target of 70–180 mg/dl (3.9–10 mmol/l) >70%.ObjectiveThis study aimed to identify factors influencing TIR prolongation.MethodsChildren aged 1–17 years with >1-year type 1 diabetes (T1D) duration, treated with continuous subcutaneous insulin infusion (CSII) ≥3 months, using continuous glucose monitoring (CGM) or intermittently scanned CGM (is-CGM) ≥1 month, and with a registration time >70% were included. Data were collected during routine diabetology visits at an outpatient clinic. Insulin pump and CGM or is-CGM reports in the most recent 14 days were recorded using a dedicated software. Legal caregivers were also asked to complete a questionnaire on how the patients use the insulin pump functions and eating habits.ResultsA sample of 110 patients was categorized into two groups: those with TIR >70% and TIR ≤70%. TIR ≤70% group presented with repeated hyperglycemia and a high glycemic variability coefficient of variation. We noted an acceptable hypoglycemia rate (3%), regardless of the TIR value. Patients with TIR >70% predominantly used predictive low glucose suspend system, maintained adequate intervals between insulin delivery and meal consumption, used the “bolus calculator” function, and more frequently created electronic reports.ConclusionsHyperglycemia and high glycemic variability prevent patients from achieving the target TIR. Advanced features in the CGM systems, premeal insulin bolus, and patients’ involvement in diabetes treatment are the main factors contributing to TIR prolongation.

920-P: Effects of Hybrid Closed-Loop System on Glycemic Control and Psychological Aspects in Persons with Type 1 Diabetes Treated with Sensor-Augmented Pump—A Prospective Single-Center Observational Study

Introduction Since the Medtronic 770G hybrid closed-loop (HCL) system was approved in Japan in 2022, we evaluated the effects of the HCL system on glycemic control and psychological aspects in persons with type 1 diabetes mellitus (T1DM) treated with the Medtronic 640G predictive low glucose suspend (PLGS) system. Materials and Methods In a 3-month prospective observational study, 21 people with T1DM (mean age: 48.7 years; male: 5 people) treated with PLGS system were enrolled. The participants switched to the 770G system, where the algorithm maintains glucose levels at 120 mg/dl, and in 3 months the percentage of time in blood glucose range (TIR) 70-180 mg/dl and glycated hemoglobin level (HbA1c) were evaluated. Self-reported questionnaires were administered at baseline and in 3 months to assess their satisfaction, emotional distress, and quality of life (QoL), using Diabetes treatment satisfaction questionnaire status (DTSQs), Problem area in diabetes scale (PAID), and Diabetes therapy-related QoL (DTR-QoL), respectively. Results In 3 months, TIR increased from 63.2 ± 13.7% to 72.7 ± 11.1% (mean ± standard deviation) (P &amp;lt; 0.0005), whereas time above blood glucose range (TAR) 181-250 mg/dl decreased from 26.9 ± 9.1% to 19.7 ± 7.2 % (P &amp;lt; 0.0005). TAR &amp;gt; 250 mg/dl, time below blood glucose range (TBR) 54-69 mg/dl and TBR &amp;lt; 54 mg/dl did not differ significantly. HbA1c decreased from 7.7 ± 1.0% to 7.2 ± 0.8% (P = 0.0013). There were no significant changes in DTSQs, PAID, and DTR-QOL in 3 months (DTSQs 26.7 ± 6.0 compared with baseline 26.9 ± 4.0, P = 0.87, PAID 52.3 ± 17.9 compared with baseline 54.0 ± 16.3, P = 0.48, DTR-QoL 50.1 ± 19.0 compared with baseline 47.0 ± 16.9, P = 0.38). Conclusion HCL system could increase TIR, compared with PLGS system, without worsening treatment satisfaction, emotional distress, and QoL. This study suggested HCL system is useful for Japanese people with T1DM. Disclosure T. Akiyama: None. K. Orime: None. T. Yamakawa: None.

Hypoglycemia and glycemic variability of people with type 1 diabetes with lower and higher physical activity loads in free-living conditions using continuous subcutaneous insulin infusion with predictive low-glucose suspend system

IntroductionMaintaining glycemic control during and after physical activity (PA) is a major challenge in type 1 diabetes (T1D). This study compared the glycemic variability and exercise-related diabetic management strategies of...

Comparison of two advanced hybrid closed loop in a pediatric population with type 1 diabetes: a real-life observational study.

The Advanced Hybrid Closed Loop (AHCL) systems have provided the potential to ameliorate glucose control in children with Type 1 Diabetes. The aim of the present work was to compare metabolic control obtained with 2 AHCL systems (Medtronic 780G system and Tandem Control IQ system) in a pediatric real-life clinical context. It is an observational, real-life, monocentric study; thirty one children and adolescents (M:F = 15:16, age range 7.6-18years, mean age 13.05 ± 2.4years, Diabetes duration > 1year) with T1D, previously treated with Predictive Low Glucose Suspend (PLGS) systems and then upgraded to AHCL have been enrolled. CGM data of the last four weeks of "PLGS system" (PRE period) with the first four weeks of AHCL system (POST period) have been compared. For both AHCL systems, Medtronic 780G and Tandem Control IQ, respectively TIR at 4weeks significantly increased, from 65.7 to 70.5% (p < 0.01) and from 64.8 to 70.1% (p < 0.01). (p < 0.01). The comparison between CGM metrics of the 2 evaluated systems doesn't show difference at baseline (last four weeks of PLGS system) and after four weeks of AHCL use. To our knowledge, this study is the first real-life one comparing 2 AHCL systems in a pediatric population with T1D. It shows an improvement in glucose control when upgrading to AHCL. The comparison between the two AHCL systems did not show significant differences in the analyzed CGM metrics, meaning that the algorithms currently available are equally effective in promoting glucose control.

Predictive low-glucose suspend system and glycemic variability

Predictive low-glucose suspend system and glycemic variability

Survey about do-it-yourself closed loop systems in the treatment of diabetes in Germany.

Continuous glucose monitoring (CGM) improves treatment with lower blood glucose levels and less patient effort. In combination with continuous insulin application, glycemic control improves and hypoglycemic episodes should decrease. Direct feedback of CGM to continuous subcutaneous insulin application, using an algorithm is called a closed-loop (CL) artificial pancreas system. Commercial devices stop insulin application by predicting hypoglycemic blood glucose levels through direct interaction between the sensor and pump. The prediction is usually made for about 30 minutes and insulin delivery is restarted at the previous level if a rise in blood glucose is predicted within the next 30 minutes (hybrid closed loop system, HCL this is known as a predictive low glucose suspend system (PLGS)). In a fully CL system, sensor and pump communicate permanently with each other. Hybrid closed-loop (HCL) systems, which require the user to estimate the meal size and provide a meal insulin basis, are commercially available in Germany at the moment. These systems result in fewer hyperglycemic and hypoglycemic episodes with improved glucose control. Open source initiatives have provided support by building do-it-yourself CL (DIYCL) devices for automated insulin application since 2014, and are used by a tech-savvy subgroup of patients. The first commercial hybrid CL system has been available in Germany since September 2019. We surveyed 1054 patients to determine which devices are currently used, which features would be in demand by potential users, and the benefits of DIYCL systems. 9.7% of these used a DIYCL system, while 50% would most likely trust these systems but more than 85% of the patients would use a commercial closed loop system, if available. The DIYCL users had a better glucose control regarding their time in range (TIR) and glycated hemoglobin (HbA1c).

Dual-Hormone Closed-Loop System Using a Liquid Stable Glucagon Formulation Versus Insulin-Only Closed-Loop System Compared With a Predictive Low Glucose Suspend System: An Open-Label, Outpatient, Single-Center, Crossover, Randomized Controlled Trial.

To assess the efficacy and feasibility of a dual-hormone (DH) closed-loop system with insulin and a novel liquid stable glucagon formulation compared with an insulin-only closed-loop system and a predictive low glucose suspend (PLGS) system. In a 76-h, randomized, crossover, outpatient study, 23 participants with type 1 diabetes used three modes of the Oregon Artificial Pancreas system: 1) dual-hormone (DH) closed-loop control, 2) insulin-only single-hormone (SH) closed-loop control, and 3) PLGS system. The primary end point was percentage time in hypoglycemia (<70 mg/dL) from the start of in-clinic aerobic exercise (45 min at 60% VO2max) to 4 h after. DH reduced hypoglycemia compared with SH during and after exercise (DH 0.0% [interquartile range 0.0-4.2], SH 8.3% [0.0-12.5], P = 0.025). There was an increased time in hyperglycemia (>180 mg/dL) during and after exercise for DH versus SH (20.8% DH vs. 6.3% SH, P = 0.038). Mean glucose during the entire study duration was DH, 159.2; SH, 151.6; and PLGS, 163.6 mg/dL. Across the entire study duration, DH resulted in 7.5% more time in target range (70-180 mg/dL) compared with the PLGS system (71.0% vs. 63.4%, P = 0.044). For the entire study duration, DH had 28.2% time in hyperglycemia vs. 25.1% for SH (P = 0.044) and 34.7% for PLGS (P = 0.140). Four participants experienced nausea related to glucagon, leading three to withdraw from the study. The glucagon formulation demonstrated feasibility in a closed-loop system. The DH system reduced hypoglycemia during and after exercise, with some increase in hyperglycemia.

1017-P: Effects of the T:slim X2 Insulin Pump with Basal-IQ Technology on Glycemic Control in a Pediatric Urban Academic Diabetes Practice

The predictive low glucose suspend (PLGS) algorithm of the t:slimx2 insulin pump with Basal-IQ technology, which is used with the Dexcom G6 continuous glucose monitor (CGM), has been shown to reduce hypoglycemia, though the effect on glucose variability longitudinally in a real-world pediatric population is unknown. We hypothesized that children and adolescents who obtain their care at an urban, academic diabetes center and use the PLGS algorithm would have improved glycemic outcomes, compared to their previous method of diabetes care. We recruited pediatric patients aged 6-18 years old with T1D for &amp;gt;1 year prior to starting the PLGS system. At baseline, glycemic control was assessed using CGM or fingerstick glucose metrics. For the 3 month timepoint, Tandem T:connect software was used. Of the 97 pediatric patients at our center with T1D for &amp;gt;1 year using the PLGS system, 41 pediatric subjects (51.2% female) with a median age of 13.6 years (range 6.6-17.8) and 3 month follow-up data were eligible for analysis. Baseline CSII and CGM use were 87.8% and 92.7%, respectively. Subjects were using Basal-IQ for a median of 92% of the time with 6 suspensions per day in the 2 weeks prior to 3 month follow-up. HbA1c, mean glucose, and percent time in range improved from 7.5%, 186 mg/dl and 51.9% on their previous diabetes care to 7.35%, 171 mg/dl and 57% after 3 months of Basal-IQ use (p= 0.005, p=0.03 and p=0.001). Percent time glucose below 55 mg/dl was a median of 0% at baseline and also at follow-up. There were no significant differences in coefficient of variation, percent time glucose below 70 mg/dl, and percent time glucose above 180 mg/dl. There were also no episodes of DKA or severe hypoglycemia after initiation of Basal-IQ in this cohort. The t:slim x2 insulin pump with Basal-IQ technology resulted in improved HbA1c, mean glucose, and percent time in range in pediatric patients after 3 months of use, without an increase in hypoglycemia or adverse events. 6 month data is being analyzed. Disclosure A. Weiner: None. E. Robinson: None. R. Gandica: None. Funding National Institutes of Health (T32DK065522-14)

How does a predictive low glucose suspend (PLGS) system tackle pediatric lifespan challenges in diabetes treatment? Real world data analysis

The aim of the study was to assess the benefits of a predictive low glucose suspend (PLGS) system in real-life in children and adolescents with type 1 diabetes of different age and age-related clinical challenges. Real life retrospective and descriptive analysis included 44 children (26 girls) with type 1 diabetes who were introduced to PLGS system. We divided them in three age groups: I (3-6 years old, n = 12), II (7-10 y/o, n = 16), III (11-19 y/o, n = 16). All children and their caregivers received unified training in self-management during PLGS therapy. Patients' data included: age, HbA1C levels, sex. While from the CGM metric, we obtained: time of sensor use (SENSuse), time in range (TiR): in, below and over target range and average blood glycemia (AVG), insulin suspension time (INSsusp). SENSuse was 93% in total, with 92%, 94%, and 87% in age groups I, II, III, respectively. In total the reduction of mean HbA1C from 7.61% to 6.88% (P < .05), while for the I, II, and III it was 7.46% to 6.72%, 6.91% to 6.41%, and 8.46 to 7.44%, respectively (P < .05). Although we observed a significant reduction of HbA1C, the time below target range was minimal. Specific findings included: group I-longest INSsusp (17%), group II-lowest glycemic variability (CV) (36%), and group III-highest AVG (169 mg/dL). There was a reverse correlation between suspend before low and age (-0.32, P < .05). In group I CV reduced TiR in target range (TiRin) (-0.82, P < .05), in group II use of complex boluses increased TiRin (0.52, P < .05). In group III higher CV increased HbA1C (0.64, P < .05) while reducing TiRin (-0.72, P < .05). PLGS is a suitable and safe therapeutic option for children with diabetes of all age and it is effective in addressing age-specific challenges. PLGS improves glycemic control in children of all age, positively affecting its different parameters.

1038-P: Results of Interim Analysis of a Randomized Crossover Study in Type 1 Diabetes (T1D) of a Dual-Hormone Closed-Loop System with Xerisol™ Glucagon vs. Insulin-Only Closed-Loop System vs. a Predictive Low Glucose Suspend System

Dual-hormone systems show promise to reduce hypoglycemia, but require a stable liquid glucagon formulation. XeriSol™ glucagon is a shelf-stable glucagon product for this use. Nineteen subjects with T1D are completing a single-center three-day outpatient study comparing control modes of the Oregon Artificial Pancreas system: 1) dual hormone (DH) closed-loop with Novolog™ insulin and XeriSol™ glucagon, 2) insulin-only single hormone (SH) closed-loop, 3) insulin-only predictive low glucose suspend system (PLGS). In clinic aerobic exercise (45 minutes at 60% VO2max) and home exercise was completed with each arm. SH and DH used automated exercise detection to adaptively dose insulin/glucagon for predicted hypoglycemia and tailored mealtime dosing based on past meal responses with an adaptive algorithm. An interim analysis after 7 subjects was completed for safety. The primary outcome measures are % time 70-180 mg/dL and % time &amp;lt;70 mg/dL for the 3-day study and the 4-hour period from start of exercise until the next meal. From start of exercise until the next meal, DH showed a clinically meaningful reduction of time in hypoglycemia compared with PLGS and SH. For the entire study, DH showed a clinically meaningful lower time &amp;lt;70mg/dL. No serious events or unexpected side effects occurred. Disclosure L.M. Wilson: None. P.G. Jacobs: Stock/Shareholder; Self; Pacific Diabetes Technologies. N. Resalat: None. R. Reddy: None. J. El Youssef: None. D. Branigan: None. J.A. Leitschuh: Other Relationship; Self; AgaMatrix. B. Senf: None. V. Gabo: None. J.R. Castle: Advisory Panel; Self; Novo Nordisk Inc., Zealand Pharma A/S. Consultant; Self; Dexcom, Inc. Research Support; Self; Dexcom, Inc., Xeris Pharmaceuticals, Inc. Funding JDRF

Efficacy of an Overnight Predictive Low-Glucose Suspend System in Relation to Hypoglycemia Risk Factors in Youth and Adults With Type 1 Diabetes.

We developed a system to suspend insulin pump delivery overnight when the glucose trend predicts hypoglycemia. This predictive low-glucose suspend (PLGS) system substantially reduces nocturnal hypoglycemia without an increase in morning ketosis. Evaluation of hypoglycemia risk factors that could potentially influence the efficacy of the system remains critical for understanding possible problems with the system and identifying patients that may have the greatest benefit when using the system. The at-home randomized trial consisted of 127 study participants with hemoglobin A1c (A1C) of ≤8.5% (mmol/mol) for patients aged 4-14 years and ≤8.0% for patient aged 15-45 years. Factors assessed included age, gender, A1C, diabetes duration, daily percentage basal insulin, total daily dose of insulin (units/kg-day), bedtime BG, bedtime snack, insulin on board, continuous glucose monitor (CGM) rate of change (ROC), day of the week, time system activated, daytime exercise intensity, and daytime CGM-measured hypoglycemia. The PLGS system was effective in preventing hypoglycemia for each factor subgroup. There was no evidence that the PLGS system was more or less effective in preventing hypoglycemia in any one subgroup compared with the other subgroups based on that factor. In addition, the effect of the system on overnight hyperglycemia did not differ in subgroups. The PLGS system tested in this study effectively reduced hypoglycemia without a meaningful increase in hyperglycemia across a variety of factors.

In-home nighttime predictive low glucose suspend experience in children and adults with type 1 diabetes.

Overnight predictive low glucose suspend (PLGS) reduces hypoglycemia across all ages; however, there are no reports on behavior or experience differences across age groups, especially in pediatrics. As run-in for a subsequent randomized clinical trial (RCT), 127 subjects (50% male) ages 4-45 yr utilized the experimental PLGS system nightly for 5-10 nights (PLGS active phase). We analyzed the number of blood glucose (BG) checks and boluses given per age group. During the subsequent 42 night RCT phase, we analyzed sensor use, skin reactions, errors, and reasons why the experimental system was not used. In 821 nights of active PLGS, subjects ages 4-6 yr (and their parents) tested BG levels 75% of nights compared with 65% of nights (7-10 yr), 53% of nights (11-14 yr), 33% of nights (15-25 yr), and 28% of nights (26-45 yr), respectively (p < 0.001). Likewise, youngest subjects (and parents) administered insulin boluses 56% of nights during active PLGS use compared with 48%, 33%, 20%, and 25%, respectively (p < 0.001). This was unrelated to study requirements. During the RCT phase, subjects 4-6 yr experienced more frequent and severe skin reactions (p = 0.02), while adult subjects (26-45 yr) wore individual sensors a median of 26 h longer than the youngest subjects (p < 0.001). Technical problems with the sensor (errors, miscalibrations, etc.), traveling, and BG levels >270 at bedtime (study requirement) were primary contributors to non-system use. Understanding the different use patterns and challenges in pediatrics and adolescence is needed to direct patient education to optimize use of PLGS and future artificial pancreas systems.

Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis.

OBJECTIVENocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor–based overnight predictive low-glucose suspend (PLGS) system.RESEARCH DESIGN AND METHODSIn two age-groups of children with type 1 diabetes (11–14 and 4–10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight.RESULTSMedian time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11–14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4–10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11–14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4–10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis.CONCLUSIONSIn 4–14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher.

A novel method to detect pressure-induced sensor attenuations (PISA) in an artificial pancreas.

Continuous glucose monitors (CGMs) provide real-time interstitial glucose concentrations that are essential for automated treatment of individuals with type 1 diabetes. Miscalibration, noise spikes, dropouts, or pressure applied to the site (e.g., lying on the site while sleeping) can cause inaccurate glucose signals, which could lead to inappropriate insulin dosing decisions. These studies focus on the problem of pressure-induced sensor attenuations (PISAs) that occur overnight and can cause undesirable pump shut-offs in a predictive low glucose suspend system. The algorithm presented here uses real-time CGM readings without knowledge of meals, insulin doses, activity, sensor recalibrations, or fingerstick measurements. The real-time PISA detection technique was tested on outpatient "in-home" data from a predictive low-glucose suspend trial with over 1125 nights of data. A total of 178 sets were created by using different parameters for the PISA detection algorithm to illustrate its range of available performance. The tracings were reviewed via a web-based analysis tool by an engineer with an extensive expertise on analyzing clinical datasets and ~3% of the CGM readings were marked as PISA events which were used as the gold standard. It is shown that 88.34% of the PISAs were successfully detected by the algorithm, and the percentage of false detections could be reduced to 1.70% by altering the algorithm parameters. Use of the proposed PISA detection method can result in a significant decrease in undesirable pump suspensions overnight, and may lead to lower overnight mean glucose levels while still achieving a low risk of hypoglycemia.

A randomized trial of a home system to reduce nocturnal hypoglycemia in type 1 diabetes.

OBJECTIVEOvernight hypoglycemia occurs frequently in individuals with type 1 diabetes and can result in loss of consciousness, seizure, or even death. We conducted an in-home randomized trial to determine whether nocturnal hypoglycemia could be safely reduced by temporarily suspending pump insulin delivery when hypoglycemia was predicted by an algorithm based on continuous glucose monitoring (CGM) glucose levels.RESEARCH DESIGN AND METHODSFollowing an initial run-in phase, a 42-night trial was conducted in 45 individuals aged 15–45 years with type 1 diabetes in which each night was assigned randomly to either having the predictive low-glucose suspend system active (intervention night) or inactive (control night). The primary outcome was the proportion of nights in which ≥1 CGM glucose values ≤60 mg/dL occurred.RESULTSOvernight hypoglycemia with at least one CGM value ≤60 mg/dL occurred on 196 of 942 (21%) intervention nights versus 322 of 970 (33%) control nights (odds ratio 0.52 [95% CI 0.43–0.64]; P < 0.001). Median hypoglycemia area under the curve was reduced by 81%, and hypoglycemia lasting >2 h was reduced by 74%. Overnight sensor glucose was >180 mg/dL during 57% of control nights and 59% of intervention nights (P = 0.17), while morning blood glucose was >180 mg/dL following 21% and 27% of nights, respectively (P < 0.001), and >250 mg/dL following 6% and 6%, respectively. Morning ketosis was present <1% of the time in each arm.CONCLUSIONSUse of a nocturnal low-glucose suspend system can substantially reduce overnight hypoglycemia without an increase in morning ketosis.

Frequency of morning ketosis after overnight insulin suspension using an automated nocturnal predictive low glucose suspend system.

OBJECTIVETo assess the effect of overnight insulin pump suspension in an automated predictive low glucose suspend system on morning blood glucose and ketone levels in an attempt to determine whether routine measurement of ketone levels is useful when a closed-loop system that suspends insulin delivery overnight is being used.RESEARCH DESIGN AND METHODSData from an in-home randomized trial of 45 individuals with type 1 diabetes (age range 15–45 years) were analyzed, evaluating an automated predictive low glucose pump suspension system in which blood glucose, blood ketone, and urine ketone levels were measured on 1,954 mornings.RESULTSOne or more pump suspensions occurred during 744 of the 977 intervention nights (76%). The morning blood ketone level was ≥0.6 mmol/L after 11 of the 744 nights (1.5%) during which a pump suspension occurred and 2 of the 233 nights (0.9%) during which there was no suspension compared with 11 of 977 control nights (1.1%). The morning blood ketone level was ≥0.6 mmol/L after only 2 of 159 nights (1.3%) with a pump suspension exceeding 2 h. Morning fasting blood glucose level was not a good predictor of the presence of blood ketones.CONCLUSIONSRoutine measurement of blood or urine ketones during use of an automated pump suspension system using continuous glucose monitoring, whether threshold based or predictive, is not necessary. Recommendations for checking ketone levels should be no different when a patient is using a system with automated insulin suspension than it is for conventional diabetes self-management.

Sensitivity Analysis of a Predictive Pump Suspension System to Treat People with Type 1 Diabetes

The primary goal of a low glucose suspend system is to reduce the risk of overnight hypoglycemia (low blood glucose) in individuals with type 1 diabetes by reducing/suspending insulin infusion. We have developed a Kalman filter-based algorithm, combined with a number of safety rules, to implement a predictive low glucose suspend system that shuts off an insulin pump based on a prediction of hypoglycemia 30-70 minutes in the future. This system has been studied in over 2,000 nights in an outpatient-home environment. In this paper, based on an analysis of this data, we isolate the effects of the individual rules in part by simulating their removal from the existing data. Specifically, we decompose the basal insulin into small boluses and, using a model of insulin pharmacodynamic action (the time effect of insulin on blood glucose), alter the real data corresponding to the addition or removal of basal insulin via simulation. Our results show that limiting the total suspension to 180 minutes per night prevents excessive suspension in cases where the average calibration is an excessive 58 mg/dl, above the mean of 18 mg/dl. Further, we also show that a simple threshold algorithm that suspends below 100 mg/dl if the glucose level is flat or falling, is comparable in performance. Lastly, we show that the Kalman filter at the heart of this algorithm reduces the time spent below 70 mg/dl by 50% at the expense of a mean rise of 12 mg/dl in morning glucose levels.

Outpatient Safety Assessment of an In-Home Predictive Low-Glucose Suspend System with Type 1 Diabetes Subjects at Elevated Risk of Nocturnal Hypoglycemia

Nocturnal hypoglycemia is a common problem with type 1 diabetes. In the home setting, we conducted a pilot study to evaluate the safety of a system consisting of an insulin pump and continuous glucose monitor communicating wirelessly with a bedside computer running an algorithm that temporarily suspends insulin delivery when hypoglycemia is predicted. After the run-in phase, a 21-night randomized trial was conducted in which each night was randomly assigned 2:1 to have either the predictive low-glucose suspend (PLGS) system active (intervention night) or inactive (control night). Three predictive algorithm versions were studied sequentially during the study for a total of 252 intervention and 123 control nights. The trial included 19 participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0-7.7%) who were current users of the MiniMed Paradigm® REAL-Time Revel™ System and Sof-sensor® glucose sensor (Medtronic Diabetes, Northridge, CA). With the final algorithm, pump suspension occurred on 53% of 77 intervention nights. Mean morning glucose level was 144±48 mg/dL on the 77 intervention nights versus 133±57 mg/dL on the 37 control nights, with morning blood ketones >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on intervention than control nights, with at least one value ≤70 mg/dL occurring on 16% versus 30% of nights, respectively, with the final algorithm. This study demonstrated that the PLGS system in the home setting is safe and feasible. The preliminary efficacy data appear promising with the final algorithm reducing nocturnal hypoglycemia by almost 50%.