Improved Glycemic Outcomes With Medtronic MiniMed Advanced Hybrid Closed-Loop Delivery: Results From a Randomized Crossover Trial Comparing Automated Insulin Delivery With Predictive Low Glucose Suspend in People With Type 1 Diabetes

10.2337/figshare.13618910.v1 ◽

2021 ◽

Author(s):

Olivia J Collyns ◽

Renee A Meier ◽

Zara L Betts ◽

Denis SH Chan ◽

Chris Frampton ◽

...

Keyword(s):

Type 1 Diabetes ◽

Closed Loop ◽

Insulin Delivery ◽

Target Range ◽

Study Phase ◽

Pump Therapy ◽

Set Point ◽

Sensor Glucose ◽

Low Glucose

Objective: To study the MiniMed™ Advanced Hybrid Closed-Loop system (AHCL) which includes an algorithm with individualised basal target set points, automated correction bolus function, and improved Auto Mode stability. Research design and Methods: This dual-centre, randomized, open-label, two-sequence cross-over study in automated insulin delivery naïve participants with type 1 diabetes (aged 7-80yrs), compared AHCL to Sensor Augmented Pump therapy with Predictive Low Glucose Management (SAP+PLGM). Each study phase was 4 weeks, preceded by a 2-4 week run-in, and separated by 2-week washout. <a>Results: 59/60 people completed the study (mean age 23.3±14.4yrs). Time in target range (TIR) 3.9-10mmol/L (70-180 mg/dL) favoured AHCL over SAP+PLGM (</a>70.4±8.1 vs 57.9±11.7) by 12.5±8.5% (p<0.001), with greater improvement overnight (18.8±12.9%, p<0.001). All age groups (children (7 – 13 years), adolescents (14 – 21 years), and adults (>22 years) demonstrated improvement, with adolescents showing the largest improvement (14.4±8.4%). Mean sensor glucose (SG) at run in was 9.3±0.9 mmol/L (167±16.2mg/dL) and improved with AHCL (8.5±0.7mmol/L (153±12.6mg/dL) (p < 0.001)), but deteriorated during PLGM (9.5±1.1mmol/L (17±19.8mg/dL), (p<0.001)).. TIR was optimal when the algorithm set point was 5.6 mmol/L (100 mg/dL) compared to 6.7 mmol/L (120 mg/dL), 72.0±7.9% vs 64.6±6.9% respectively with no additional hypoglycemia. Auto Mode was active 96.4±4.0% of the time. <a>The percentage of hypoglycemia at baseline (<3.9mmol/L (70mg/dl) and </a> £ 3.0mmol/L(54mg/dl)) was 3.1±2.1% and 0.5±0.6% respectively. During AHCL percentage time <3.9mmol/L (70mg/dl) improved to 2.1±1.4% (p=0.034) (70mg/dl), and was statistically but not clinically reduced for £ 3.0mmol/L(54mg/dl) (0.5±0.5%, p = 0.025) There was one episode of mild diabetic ketoacidosis attributed to an infusion set failure in combination with an intercurrent illness, which occurred during the SAP+PLGM arm. Conclusions AHCL with automated correction bolus demonstrated significant improvement in glucose control compared to SAP+PLGM. A lower algorithm sensor glucose set point during AHCL resulted in greater TIR, with no increase in hypoglycemia.

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Assessing the efficacy, safety and utility of 6-month day-and-night automated closed-loop insulin delivery under free-living conditions compared with insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, multicentre, multinational, single-period, randomised, parallel group study protocol

BMJ Open ◽

10.1136/bmjopen-2018-027856 ◽

2019 ◽

Vol 9 (6) ◽

pp. e027856 ◽

Cited By ~ 6

Author(s):

Gianluca Musolino ◽

Janet M Allen ◽

Sara Hartnell ◽

Malgorzata E Wilinska ◽

Martin Tauschmann ◽

...

Keyword(s):

Type 1 Diabetes ◽

Children And Adolescents ◽

Closed Loop ◽

Insulin Pump ◽

Insulin Delivery ◽

Open Label ◽

Pump Therapy ◽

Glucose Levels ◽

Sensor Glucose

IntroductionClosed-loop systems titrate insulin based on sensor glucose levels, providing novel means to reduce the risk of hypoglycaemia while improving glycaemic control. We will assess effectiveness of 6-month day-and-night closed-loop insulin delivery compared with usual care (conventional or sensor-augmented pump therapy) in children and adolescents with type 1 diabetes.Methods and analysisThe trial adopts an open-label, multicentre, multinational (UK and USA), randomised, single-period, parallel design. Participants (n=130) are children and adolescents (aged ≥6 and <19 years) with type 1 diabetes for at least 1 year, and insulin pump use for at least 3 months with suboptimal glycaemic control (glycated haemoglobin ≥58 mmol/mol (7.5%) and ≤86 mmol/mol (10%)). After a 2–3 week run-in period, participants will be randomised to 6-month use of hybrid closed-loop insulin delivery, or to usual care. Analyses will be conducted on an intention-to-treat basis. The primary outcome is glycated haemoglobin at 6 months. Other key endpoints include time in the target glucose range (3.9–10 mmol/L, 70–180 mg/dL), mean sensor glucose and time spent above and below target. Secondary outcomes include SD and coefficient of variation of sensor glucose levels, time with sensor glucose levels <3.5 mmol/L (63 mg/dL) and <3.0 mmol/L (54 mg/dL), area under the curve of glucose <3.5 mmol/L (63 mg/dL), time with glucose levels >16.7 mmol/L (300 mg/dL), area under the curve of glucose >10.0 mmol/L (180 mg/dL), total, basal and bolus insulin dose, body mass index z-score and blood pressure. Cognitive, emotional and behavioural characteristics of participants and caregivers and their responses to the closed-loop and clinical trial will be assessed. An incremental cost-effectiveness ratio for closed-loop will be estimated.Ethics and disseminationCambridge South Research Ethics Committee and Jaeb Center for Health Research Institutional Review Office approved the study. The findings will be disseminated by peer-review publications and conference presentations.Trial registration numberNCT02925299; Pre-results.

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Closed-Loop Insulin Delivery Versus Sensor-Augmented Pump Therapy in Older Adults With Type 1 Diabetes (ORACL): A Randomized, Crossover Trial

Diabetes Care ◽

10.2337/dc21-1667 ◽

2021 ◽

pp. dc211667

Author(s):

Sybil A. McAuley ◽

Steven Trawley ◽

Sara Vogrin ◽

Glenn M. Ward ◽

Spiros Fourlanos ◽

...

Keyword(s):

Older Adults ◽

Type 1 Diabetes ◽

Closed Loop ◽

Crossover Trial ◽

Insulin Delivery ◽

Pump Therapy ◽

Randomized Crossover Trial

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Twelve-Week Home Use of Hybrid Closed-Loop Insulin Delivery System vs. Sensor-Assisted Pump Therapy in Adults with Type 1 Diabetes—Intermediate Results of the Multicenter Randomised Crossover Diabeloop WP7 Trial

Diabetes ◽

10.2337/db18-208-or ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 208-OR ◽

Cited By ~ 1

Author(s):

SYLVIA FRANC ◽

PIERRE Y. BENHAMOU ◽

SOPHIE BOROT ◽

LUCY CHAILLOUS ◽

BRIGITTE DELEMER ◽

...

Keyword(s):

Type 1 Diabetes ◽

Delivery System ◽

Closed Loop ◽

Insulin Delivery ◽

Pump Therapy ◽

Insulin Delivery System ◽

Intermediate Results

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Progress with Closed-loop Systems in Type 1 Diabetes

European Endocrinology ◽

10.17925/ee.2010.06.02.31 ◽

2010 ◽

Vol 6 (2) ◽

pp. 31

Author(s):

Lalantha Leelarathna ◽

Roman Hovorka ◽

◽

Keyword(s):

Type 1 Diabetes ◽

Closed Loop ◽

Diabetes Management ◽

Insulin Delivery ◽

Glucose Measurement ◽

Target Range ◽

Advantages And Disadvantages ◽

Closed Loop Systems ◽

Interstitial Glucose

Automated insulin delivery by means of a glucose-responsive closed-loop system has often been cited as the ‘holy grail’ of type 1 diabetes management. Reflecting the technological advances in interstitial glucose measurements and wider use of continuous glucose monitoring, recent research in closed-loop glucose control has focused on the subcutaneous route for glucose measurements and insulin delivery. The primary aim of such systems is to keep blood glucose within the target range while minimising the risk of hypoglycaemia with minimal input from the user. This article examines recent developments in the field of interstitial glucose measurement, limitations of the current generation of devices and implications on the performance of closed-loop systems. Clinical results and the advantages and disadvantages of different closed-loop configurations are summarised. Potential future advances in closed-loop systems are highlighted.

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Progress with Closed-loop Systems in Type 1 Diabetes

US Endocrinology ◽

10.17925/use.2010.06.1.58 ◽

2010 ◽

Vol 06 (01) ◽

pp. 58

Author(s):

Lalantha Leelarathna ◽

Roman Hovorka ◽

◽

Keyword(s):

Type 1 Diabetes ◽

Closed Loop ◽

Diabetes Management ◽

Insulin Delivery ◽

Glucose Measurement ◽

Target Range ◽

Advantages And Disadvantages ◽

Closed Loop Systems ◽

Interstitial Glucose

Automated insulin delivery by means of a glucose-responsive closed-loop system has often been cited as the ‘holy grail’ of type 1 diabetes management. Reflecting the technological advances in interstitial glucose measurements and wider use of continuous glucose monitoring, recent research in closed-loop glucose control has focused on the subcutaneous route for glucose measurements and insulin delivery. The primary aim of such systems is to keep blood glucose within the target range while minimizing the risk of hypoglycemia with minimal input from the user. This article examines recent developments in the field of interstitial glucose measurement, limitations of the current generation of devices and implications on the performance of closed-loop systems. Clinical results and the advantages and disadvantages of different closed-loop configurations are summarized. Potential future advances in closed-loop systems are highlighted.

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Closed-loop driven by control-to-range algorithm outperforms threshold-low-glucose-suspend insulin delivery on glucose control albeit not on nocturnal hypoglycaemia in prepubertal patients with type 1 diabetes in a supervised hotel setting

Diabetes Obesity and Metabolism ◽

10.1111/dom.13482 ◽

2018 ◽

Vol 21 (1) ◽

pp. 183-187 ◽

Cited By ~ 8

Author(s):

Eric Renard ◽

Nadia Tubiana-Rufi ◽

Elisabeth Bonnemaison-Gilbert ◽

Régis Coutant ◽

Fabienne Dalla-Vale ◽

...

Keyword(s):

Type 1 Diabetes ◽

Glucose Control ◽

Closed Loop ◽

Insulin Delivery ◽

Nocturnal Hypoglycaemia ◽

Low Glucose

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Closed-Loop Insulin Delivery Versus Sensor-Augmented Pump Therapy in Older Adults With Type 1 Diabetes (ORACL): A Randomized, Crossover Trial

10.2337/figshare.16924480 ◽

2021 ◽

Author(s):

Sybil A McAuley ◽

Steven Trawley ◽

Sara Vogrin ◽

Glenn M Ward ◽

Spiros Fourlanos ◽

...

Keyword(s):

Older Adults ◽

Type 1 Diabetes ◽

Closed Loop ◽

Crossover Trial ◽

Insulin Delivery ◽

Diabetes Duration ◽

Pump Therapy ◽

Percentage Points ◽

Pump Stage

Objective To assess the efficacy and safety of closed-loop insulin delivery compared with sensor-augmented pump therapy among older adults with type 1 diabetes. <h2>Research Design and Methods</h2> This open-label randomized (1:1), crossover trial compared 4 months of closed-loop versus sensor-augmented pump therapy. Eligible adults were aged ≥60 years, with type 1 diabetes (duration ≥10 years), using an insulin pump. The primary outcome was continuous glucose monitoring (CGM) time in range <a>(TIR; 3.9–10.0 mmol/L</a>). <h2>Results</h2> Thirty participants (mean age 67 years [SD 5]; median type 1 diabetes duration 38 years [IQR 20–47]) were randomized, n=15 to each sequence; all completed the trial. The mean TIR was 75.2% (6.3) during the closed-loop stage and 69.0% (9.1) during the sensor-augmented pump stage (difference 6.2 percentage points [95% CI 4.4, 8.0]; P <0.0001). All prespecified CGM metrics favored closed loop over sensor-augmented pump; benefits were greatest overnight. Closed loop reduced CGM time <3.9 mmol/L during 24 h/day by 0.5 percentage points (0.3, 1.1; P = 0.0005) and overnight by 0.8 percentage points (0.4, 1.1; P <0.0001) compared with sensor-augmented pump. There was no significant difference in HbA1c between closed-loop versus sensor-augmented pump stages (7.3% [7.1–7.5] | 56 mmol/mol [54–59] versus 7.5% [7.1–7.9] | 59 mmol/mol [54–62], respectively; P = 0.13). Three severe hypoglycemia events occurred during the closed-loop stage and two occurred during the sensor-augmented pump stage; no hypoglycemic events required hospitalization. One episode of diabetic ketoacidosis occurred during the sensor-augmented pump stage; no serious adverse events occurred during the closed-loop stage. <h2>Conclusion</h2> Closed-loop therapy is an effective treatment option for older adults with long duration type 1 diabetes and no safety issues were identified. These older adults had higher TIR accompanied by less time below range during closed-loop than sensor-augmented pump therapy. Of particular clinical importance, closed loop reduced the time spent in hypoglycemic range overnight.

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