We evaluated the effect of the MD-Logic system on overnight glycemic control at patients' homes.
Twenty-four patients (aged 12-43 years; average A1c 7.5 ± 0.8%, 58.1 ± 8.4 mmol/mol) were randomly ...assigned to participate in two overnight crossover periods, each including 6 weeks of consecutive nights: one under closed loop and the second under sensor-augmented pump (SAP) therapy at patients' homes in real-life conditions. The primary end point was time spent with sensor glucose levels below 70 mg/dL (3.9 mmol/L) overnight.
Closed-loop nights significantly reduced time spent in hypoglycemia (P = 0.02) and increased the percentage of time spent in the target range of 70-140 mg/dL (P = 0.003) compared with nights when the SAP therapy was used. The time spent in substantial hyperglycemia above 240 mg/dL was reduced by a median of 52.2% (interquartile range IQR 4.8, 72.9%; P = 0.001) under closed-loop control compared with SAP therapy. Overnight total insulin doses were lower in the closed-loop nights compared with the SAP nights (P = 0.04). The average daytime glucose levels after closed-loop operation were reduced by a median of 10.0 mg/dL (IQR -2.7, 19.2; P = 0.017) while lower total insulin doses were used (P = 0.038). No severe adverse events occurred during closed-loop control; there was a single event of severe hypoglycemia during a control night.
The long-term home use of automated overnight insulin delivery by the MD-Logic system was found to be a feasible, safe, and an effective tool to reduce nocturnal hypoglycemia and improve overnight glycemic control in subjects with type 1 diabetes.
OBJECTIVE: Current state-of-the-art artificial pancreas systems are either based on traditional linear control theory or rely on mathematical models of glucose-insulin dynamics. Blood glucose control ...using these methods is limited due to the complexity of the biological system. The aim of this study was to describe the principles and clinical performance of the novel MD-Logic Artificial Pancreas (MDLAP) System. RESEARCH DESIGN AND METHODS: The MDLAP applies fuzzy logic theory to imitate lines of reasoning of diabetes caregivers. It uses a combination of control-to-range and control-to-target strategies to automatically regulate individual glucose levels. Feasibility clinical studies were conducted in seven adults with type 1 diabetes (aged 19-30 years, mean diabetes duration 10 ± 4 years, mean A1C 6.6 ± 0.7%). All underwent 14 full, closed-loop control sessions of 8 h (fasting and meal challenge conditions) and 24 h. RESULTS: The mean peak postprandial (overall sessions) glucose level was 224 ± 22 mg/dl. Postprandial glucose levels returned to <180 mg/dl within 2.6 ± 0.6 h and remained stable in the normal range for at least 1 h. During 24-h closed-loop control, 73% of the sensor values ranged between 70 and 180 mg/dl, 27% were >180 mg/dl, and none were <70 mg/dl. There were no events of symptomatic hypoglycemia during any of the trials. CONCLUSIONS: The MDLAP system is a promising tool for individualized glucose control in patients with type 1 diabetes. It is designed to minimize high glucose peaks while preventing hypoglycemia. Further studies are planned in the broad population under daily-life conditions.
MD-Logic Artificial Pancreas System Atlas, Eran; Nimri, Revital; Miller, Shahar ...
Diabetes care,
05/2010, Volume:
33, Issue:
5
Journal Article
Peer reviewed
Open access
OBJECTIVE
Current state-of-the-art artificial pancreas systems are either based on traditional linear control theory or rely on mathematical models of glucose-insulin dynamics. Blood glucose control ...using these methods is limited due to the complexity of the biological system. The aim of this study was to describe the principles and clinical performance of the novel MD-Logic Artificial Pancreas (MDLAP) System.
RESEARCH DESIGN AND METHODS
The MDLAP applies fuzzy logic theory to imitate lines of reasoning of diabetes caregivers. It uses a combination of control-to-range and control-to-target strategies to automatically regulate individual glucose levels. Feasibility clinical studies were conducted in seven adults with type 1 diabetes (aged 19–30 years, mean diabetes duration 10 ± 4 years, mean A1C 6.6 ± 0.7%). All underwent 14 full, closed-loop control sessions of 8 h (fasting and meal challenge conditions) and 24 h.
RESULTS
The mean peak postprandial (overall sessions) glucose level was 224 ± 22 mg/dl. Postprandial glucose levels returned to <180 mg/dl within 2.6 ± 0.6 h and remained stable in the normal range for at least 1 h. During 24-h closed-loop control, 73% of the sensor values ranged between 70 and 180 mg/dl, 27% were >180 mg/dl, and none were <70 mg/dl. There were no events of symptomatic hypoglycemia during any of the trials.
CONCLUSIONS
The MDLAP system is a promising tool for individualized glucose control in patients with type 1 diabetes. It is designed to minimize high glucose peaks while preventing hypoglycemia. Further studies are planned in the broad population under daily-life conditions.
This randomized, crossover trial compared an artificial-pancreas system with a sensor-augmented pump for nocturnal glucose control in young persons with type 1 diabetes at a diabetes camp. The ...artificial pancreas resulted in less hypoglycemia and tighter glucose control.
Intensive insulin therapy is considered to be the standard treatment for tight blood glucose control in patients with type 1 diabetes, since it prevents long-term complications. Several studies have promoted the use of insulin pumps, glucose sensors, or a combination of the two devices (sensor-augmented pump)
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to improve glucose control. However, the risk of hypoglycemia is still present with the use of all currently available therapies.
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Maintenance of nocturnal euglycemia is extremely important and is challenging, since most cases of severe hypoglycemia occur at night.
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Such episodes account for 75% of total hypoglycemic seizures in children
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and . . .
Background
Artificial pancreas (AP) systems have shown an improvement in glucose control and a reduced risk of nocturnal hypoglycemia under controlled conditions but remain to be evaluated under ...daily‐life conditions.
Objective
To assess the feasibility, safety, and efficacy of the MD‐Logic AP in controlling nocturnal glucose levels in the patient's home.
Methods
Two‐arm study, each covering four consecutive nights comparing the MD‐Logic AP (‘closed‐loop’ arm) with sensor‐augmented pump therapy (‘control’ arm). Fifteen patients (mean age 19 ± 10.4 yr, A1c 7.5 ± 0.5% or 58 ± 5.9 mmol/mol, diabetes duration 9.9 ± 8.2 yr) were randomly assigned either to ‘Group A’ (first ‘closed‐loop’, then ‘control’ arm) or to ‘Group B’ (vice versa). Investigators were masked to treatment intervention. Primary endpoints were the time spent with glucose levels below 70 mg/dL and the percentage of nights in which the mean overnight glucose levels were within 90–140 mg/dL. Endpoint analyses were based on unmodified sensor glucose readings of the four study nights.
Results
Time of glucose levels spent below 70 mg/dL was significantly shorter on the closed‐loop nights than on control nights, median and interquartile range 3.8 (0, 11.6) and 48.7 (0.6, 67.9) min, respectively; p = 0.0034. The percentage of individual nights in which mean overnight glucose level was within 90–140 mg/dL was 67 (33, 88), and 50 (25, 75), under closed‐loop and control nights, respectively, with no statistical difference. Secondary endpoint analyses demonstrated significant improvements in hypoglycemia parameters. No serious adverse events were reported.
Conclusion
This interim analysis demonstrates the feasibility, safety, and efficiency of the MD‐Logic AP system in home use, and demonstrates an improvement over sensor‐augmented pump therapy. (ClinicalTrials.gov identifier NCT01726829).
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Aims
To evaluate the safety, efficacy and need for remote monitoring of the MD‐Logic closed‐loop system during short‐term overnight use at home.
Methods
Seventy‐five patients (38 male; aged 10‐54 ...years; average A1c, 7.8% ± 0.7%, 61.8 ± 7.2 mmol/mol) were enrolled from 3 clinical sites. Patients were randomly assigned to participate in 2 overnight crossover periods, each including 4 consecutive nights, 1 under closed‐loop control and 1 under sensor‐augmented pump (SAP) therapy in the patient's home. Both study arms were supervised using a remote‐monitoring system in a blinded manner. Primary endpoints were time spent with glucose levels below 70 mg/dL and percentage of nights in which mean overnight glucose levels were within 90 to 140 mg/dL.
Results
The median interquartile range percentage of time spent in hypoglycaemia was significantly lower on nights when MD‐Logic was used, compared to SAP therapy (2.07 0, 4.78 and 2.6 0, 10.34, respectively; P = .004) and the percentage of individual nights with a mean overnight glucose level in target was significantly greater (75 42, 75 and 50 25,75, respectively; P = .008). The time spent in target range was increased by a median of 28% (P = .001), with the same amount of insulin (10.69 7.28, 13.94 and 10.416.9, 14.07, respectively; P = .087). The remote monitoring triggered calls for hypoglycaemia at twice the rate during SAP therapy compared to closed‐loop control (62 and 29, respectively; P = .002).
Conclusions
The MD‐Logic system demonstrated a safe and efficient profile during overnight use by children, adolescents and adults with type 1 diabetes and, therefore, provides an effective means of mitigating the risk of nocturnal hypoglycaemia.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
An artificial pancreas (AP) that automatically regulates blood glucose would greatly improve the lives of individuals with diabetes. Such a device would prevent hypo- and hyperglycemia along with ...associated long- and short-term complications as well as ease some of the day-to-day burden of frequent blood glucose measurements and insulin administration.
We conducted a pilot clinical trial evaluating an individualized, fully automated AP using commercial devices. Two trials (n = 22, n(subjects) = 17) were conducted using a multiparametric formulation of model predictive control and an insulin-on-board algorithm such that the control algorithm, or "brain," can be embedded on a chip as part of a future mobile device. The protocol evaluated the control algorithm for three main challenges: 1) normalizing glycemia from various initial glucose levels, 2) maintaining euglycemia, and 3) overcoming an unannounced meal of 30 ± 5 g carbohydrates.
Initial glucose values ranged from 84-251 mg/dL. Blood glucose was kept in the near-normal range (80-180 mg/dL) for an average of 70% of the trial time. The low and high blood glucose indices were 0.34 and 5.1, respectively.
These encouraging short-term results reveal the ability of a control algorithm tailored to an individual's glucose characteristics to successfully regulate glycemia, even when faced with unannounced meals or initial hyperglycemia. To our knowledge, this represents the first truly fully automated multiparametric model predictive control algorithm with insulin-on-board that does not rely on user intervention to regulate blood glucose in individuals with type 1 diabetes.
Artificial pancreas systems may offer a potential major impact on the normalization of metabolic control and preventing hypoglycemic events. This study aims to establish near-normal overnight glucose ...control and reduce the risk of nocturnal hypoglycemia using the MD-Logic Artificial Pancreas (MDLAP), an algorithm that was developed by our research group. This inpatient feasibility study is the first step towards implementing an overnight closed-loop MDLAP system at the patient's home.
Seven patients with type 1 diabetes (three adolescents and four adults; mean±SD age, 20.6±4.7 years; duration of diabetes, 9.6±2.6 years; body mass index, 24.3±3.9 kg/m(2); and glycated hemoglobin, 7.8±0.8%) participated in a total of 14 closed-loop overnight sessions. Each participant underwent two closed-loop inpatient sessions starting at dinner alone and at dinner following exercise. The closed-loop inpatient sessions were compared with data derived from nights spent at home with an open-loop system in a similar scenario to the study protocol.
The mean percentage of time spent in the near normal glucose range of 63-140 mg/dL was 83±16%, and the median (interquartile range) was 85% (78-92%) for the overnight closed-loop sessions compared with 34±31% and 27% (6-57%) in the homecare open-loop setting, respectively. During the overnight closed-loop sessions at dinner alone 92±9% of the sensor values ranged within target range, compared with 73±19% for the sessions following exercise (P=0.03). No hypoglycemic (<63 mg/dL) events occurred during the closed-loop sessions.
Closed-loop insulin delivery under MDLAP is a feasible and safe solution to control overnight glycemia.
Background
Tight glucose control is needed to prevent long‐term diabetes complications; this is hindered by the risk of hypoglycemia, especially at night.
Objective
To assess the safety and efficacy ...of the closed‐loop MD‐Logic Artificial Pancreas (MDLAP), controlling nocturnal glucose levels in patients with type 1 diabetes mellitus (T1DM).
Research design and methods
This was a randomized, multicenter, multinational, crossover trial conducted in Slovenia, Germany, and Israel. Twelve patients with T1DM (age 23.8 ± 15.6 yr; duration of diabetes 13.5 ± 11.9 yr; A1c 8.1 ± 0.8%, mean ± SD) were randomly assigned to participate in two sequential overnight sessions: one using continuous subcutaneous insulin infusion (CSII) and the other, closed‐loop insulin delivery by MDLAP. The primary outcome was the number of hypoglycemic events below 63 mg/dL. Endpoints analyses were based on sensor glucose readings.
Results
Three events of nocturnal hypoglycemia occurred during CSII and none during the closed‐loop control (p = 0.18). The percentage of time spent in the near normal range of 63–140 mg/dL was significantly higher in the overnight closed‐loop sessions 76% (54–85) than during CSII therapy 29% (11–44) p = 0.02, median (interquartile range). The mean overnight glucose level was reduced by 36 mg/dL with closed‐loop insulin delivery (p = 0.02) with a significantly less glucose variability when compared with the CSII nights (p < 0.001).
Conclusion
The results of this study demonstrate the ability of the MDLAP to safely improve overnight glucose control without increased risk of hypoglycemia in patients with T1DM at three different national, geographic, and clinical centers (ClinicalTrials.gov number, NCT 01238406).
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Applying real-time learning into an artificial pancreas system could effectively track the unpredictable behavior of glucose-insulin dynamics and adjust insulin treatment accordingly. We describe a ...novel learning algorithm and its performance when integrated into the MD-Logic Artificial Pancreas (MDLAP) system developed by the Diabetes Technology Center, Schneider Children's Medical Center of Israel, Petah Tikva, Israel.
The algorithm was designed to establish an initial patient profile using open-loop data (Initial Learning Algorithm component) and then make periodic adjustments during closed-loop operation (Runtime Learning Algorithm component). The MDLAP system, integrated with the learning algorithm, was tested in seven different experiments using the University of Virginia/Padova simulator, comprising adults, adolescents, and children. The experiments included simulations using the open-loop and closed-loop control strategy under nominal and varying insulin sensitivity conditions. The learning algorithm was automatically activated at the end of the open-loop segment and after every day of the closed-loop operation. Metabolic control parameters achieved at selected time points were compared.
The percentage of time glucose levels were maintained within 70-180 mg/dL for children and adolescents significantly improved when open-loop was compared with day 6 of closed-loop control (P<0.0001) and remained unaltered for the adult group (P=0.11) during nominal conditions. In varying insulin sensitivity conditions, the percentage of time glucose levels were below 70 mg/dL was significantly reduced by approximately sevenfold (P<0.001). These observations were correlated with significant reduction in the Low Blood Glucose Index (P<0.001).
The new algorithm was effective in characterizing the patient profiles from open-loop data and in adjusting treatment to provide better glycemic control during closed-loop control in both conditions. These findings warrant corroboratory clinical trials.
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