78 results on '"Hovorka, Roman"'
Search Results
2. New closed-loop insulin systems
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Boughton, Charlotte K. and Hovorka, Roman
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- 2021
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3. Glucose Monitoring and Insulin Pump Therapy in the Management of Children and Adolescents with Type 1 Diabetes
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Tauschmann, Martin, Hovorka, Roman, Scaramuzza, Andrea, editor, de Beaufort, Carine, editor, and Hanas, Ragnar, editor
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- 2017
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4. The Artificial Pancreas and Type 1 Diabetes
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Nwokolo, Munachiso, Hovorka, Roman, Nwokolo, Munachiso [0000-0001-7200-6004], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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Pancreas, Artificial ,Blood Glucose ,automated insulin delivery ,type 1 diabetes ,artificial pancreas ,Blood Glucose Self-Monitoring ,Endocrinology, Diabetes and Metabolism ,Biochemistry (medical) ,Clinical Biochemistry ,Biochemistry ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Endocrinology ,Humans ,Hypoglycemic Agents ,Insulin ,hybrid closed-loop - Abstract
Diabetes technologies represent a paradigm shift in type 1 diabetes care. Continuous subcutaneous insulin infusion (CSII) pumps and continuous glucose monitors (CGM) improve glycated hemoglobin (HbA1c) levels, enhance time in optimal glycemic range, limit severe hypoglycemia, and reduce diabetes distress. The artificial pancreas or closed-loop system connects these devices via a control algorithm programmed to maintain target glucose, partially relieving the person living with diabetes of this constant responsibility. Automating insulin delivery reduces the input required from those wearing the device, leading to better physiological and psychosocial outcomes. Hybrid closed-loop therapy systems, requiring user-initiated prandial insulin doses, are the most advanced closed-loop systems commercially available. Fully closed-loop systems, requiring no user-initiated insulin boluses, and dual hormone systems have been shown to be safe and efficacious in the research setting. Clinical adoption of closed-loop therapy remains in early stages despite recent technological advances. People living with diabetes, health care professionals, and regulatory agencies continue to navigate the complex path to equitable access. We review the available devices, evidence, clinical implications, and barriers regarding these innovatory technologies.
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- 2023
5. Hybrid Closed-Loop with Faster Insulin Aspart Compared with Standard Insulin Aspart in Very Young Children with Type 1 Diabetes: A Double-Blind, Multicenter, Randomized, Crossover Study
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Ware, Julia, Allen, Janet M, Boughton, Charlotte K, Cezar, Alina, Hartnell, Sara, Wilinska, Malgorzata E, Thankamony, Ajay, Deakin, Mark, Leyland, Hannah, Phelan, Karen, Thornborough, Keith, Hovorka, Roman, Ware, Julia [0000-0002-4497-0979], Boughton, Charlotte K [0000-0003-3272-9544], and Apollo - University of Cambridge Repository
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Blood Glucose ,Toddlers ,Cross-Over Studies ,Endocrinology, Diabetes and Metabolism ,Aspart ,Very young children ,Artificial pancreas ,Medical Laboratory Technology ,Endocrinology ,Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Double-Blind Method ,Child, Preschool ,Humans ,Hypoglycemic Agents ,Insulin ,Closed-loop insulin delivery ,Faster insulin aspart ,Child ,Insulin Aspart - Abstract
We evaluated the use of hybrid closed-loop (HCL) insulin delivery with faster insulin aspart (Fiasp) in very young children with type 1 diabetes (T1D). In a double-blind, multicenter, randomized, crossover study, children aged 2-6 years with T1D underwent two 8-week periods of HCL using CamAPS FX with Fiasp and standard insulin aspart (IAsp), in random order. Primary endpoint was between-treatment difference in time in target range 3.9-10.0 mmol/L. We randomized 25 participants: mean (±standard deviation) age 5.1 ± 1.3 years, baseline HbA1c 55 ± 9 mmol/mol. Time in range was not significantly different between interventions (64% ± 9% vs. 65% ± 9% for HCL with Fiasp vs. IAsp; mean difference -0.33% [95% confidence interval: -2.13 to 1.47; P = 0.71]). There was no significant difference in time with glucose
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- 2023
6. Closed-loop insulin delivery: update on the state of the field and emerging technologies
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Ware, Julia, Hovorka, Roman, Ware, Julia [0000-0002-4497-0979], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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Blood Glucose ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,automated insulin delivery ,type 1 diabetes ,insulin pump ,Blood Glucose Self-Monitoring ,Humans ,Insulin ,Artificial pancreas ,continuous glucose monitoring ,hybrid closed-loop - Abstract
INTRODUCTION: Over the last five years, closed-loop insulin delivery systems have transitioned from research-only to real-life use. A number of systems have been commercialized and are increasingly used in clinical practice. Given the rapidity of new developments in the field, understanding the capabilities and key similarities and differences of current systems can be challenging. This review aims to provide an update on the state of the field of closed-loop insulin delivery systems, including emerging technologies. AREAS COVERED: We summarize key clinical safety and efficacy evidence of commercial and emerging insulin-only hybrid closed-loop systems for type 1 diabetes. A literature search was conducted and clinical trials using closed-loop systems during free-living conditions were identified to report on safety and efficacy data. We comment on emerging technologies and adjuncts for closed-loop systems, as well as non-technological priorities in closed-loop insulin delivery. EXPERT OPINION: Commercial hybrid closed-loop insulin delivery systems are efficacious, consistently improving glycemic control when compared to standard therapy. Challenges remain in widespread adoption due to clinical inertia and the lack of resources to embrace technological developments by health care professionals.
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- 2022
7. Time spent in hypoglycemia according to age and time-of-day: Observations during closed-loop insulin delivery
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Alwan, Heba, Ware, Julia, Boughton, Charlotte K, Wilinska, Malgorzata E, Allen, Janet M, Lakshman, Rama, Nwokolo, Munachiso, Hartnell, Sara, Bally, Lia, De Beaufort, Carine, Besser, Rachel EJ, Campbell, Fiona M, Davis, Nikki, Denvir, Louise, Evans, Mark L, Fröhlich-Reiterer, Elke, Ghatak, Atrayee, Hofer, Sabine E, Kapellen, Thomas M, Leelarathna, Lalantha, Mader, Julia K, Narendran, Parth, Rami-Mehrar, Birgit, Tauschmann, Martin, Thabit, Hood, Thankamony, Ajay, Hovorka, Roman, Alwan, Heba [0000-0001-5516-6022], Ware, Julia [0000-0002-4497-0979], Boughton, Charlotte K [0000-0003-3272-9544], Lakshman, Rama [0000-0002-4341-1307], Bally, Lia [0000-0003-1993-7672], Besser, Rachel EJ [0000-0002-4645-6324], Mader, Julia K [0000-0001-7854-4233], and Apollo - University of Cambridge Repository
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Adult ,Blood Glucose ,Adolescent ,Endocrinology, Diabetes and Metabolism ,Artificial pancreas ,610 Medicine & health ,Young Adult ,Insulin pump therapy ,Endocrinology ,Insulin Infusion Systems ,360 Social problems & social services ,Insulin, Regular, Human ,Humans ,Insulin ,Hypoglycemic Agents ,Closed-loop insulin delivery ,Child ,Aged ,Retrospective Studies ,Cross-Over Studies ,Middle Aged ,Hypoglycemia ,Medical Laboratory Technology ,Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,Child, Preschool ,Randomized trial - Abstract
Objective: We aimed to assess whether percentage of time spent in hypoglycemia during closed-loop insulin delivery differs by age group and time of day. Methods: We retrospectively analyzed data from hybrid closed-loop studies involving young children (2-7 years), children and adolescents (8-18 years), adults (19-59 years), and older adults (≥60 years) with type 1 diabetes. Main outcome was time spent in hypoglycemia
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- 2023
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8. Simulation Models for In-Silico Evaluation of Closed-Loop Insulin Delivery Systems in Type 1 Diabetes
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Wilinska, Malgorzata E., Hovorka, Roman, Marmarelis, Vasilis, editor, and Mitsis, Georgios, editor
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- 2014
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9. Improving glycemic control in critically ill patients: personalized care to mimic the endocrine pancreas
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Chase, J. Geoffrey, Desaive, Thomas, Bohe, Julien, Cnop, Miriam, De Block, Christophe, Gunst, Jan, Hovorka, Roman, Kalfon, Pierre, Krinsley, James, Renard, Eric, and Preiser, Jean-Charles
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- 2018
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10. Coming of age: the artificial pancreas for type 1 diabetes
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Thabit, Hood and Hovorka, Roman
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- 2016
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11. Short‐term fully closed‐loop insulin delivery using faster insulin aspart compared to standard insulin aspart in type 2 diabetes
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Bally, Lia, Herzig, David, Ruan, Yue, Wilinska, Malgorzata E, Semmo, Mariam, Vogt, Andreas, Wertli, Maria M, Vogt, Bruno, Stettler, Christoph, Hovorka, Roman, Wilinska, Gosia [0000-0003-2739-1753], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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antidiabetic drug ,Adult ,Blood Glucose ,endocrine system diseases ,artificial pancreas ,insulin analogues ,nutritional and metabolic diseases ,insulin pump therapy ,Hypoglycemia ,Insulin Infusion Systems ,Diabetes Mellitus, Type 2 ,Double-Blind Method ,randomized trial ,Humans ,Hypoglycemic Agents ,type 2 diabetes ,closed-loop system ,hormones, hormone substitutes, and hormone antagonists ,Insulin Aspart - Abstract
We evaluated the efficacy and safety of short‐term fully closed‐loop insulin delivery using faster versus standard insulin aspart in type 2 diabetes. Fifteen adults with insulin‐treated type 2 diabetes underwent 22 hours of closed‐loop insulin delivery with either faster or standard insulin aspart in a double‐blind randomised crossover design. Basal‐bolus regimen was replaced by model predictive control algorithm‐directed insulin delivery based on sensor glucose levels. The primary outcome was time with plasma glucose in target range (5.6‐10.0mmol/l) and did not differ between treatments (mean difference [95%CI] ‐3.3% [8.2;1.7], p=0.17). Mean glucose and glucose variability were comparable, as was time spent below and above target range. Hypoglycaemia (
- Published
- 2019
12. Hybrid closed‐loop glucose control with faster insulin aspart compared with standard insulin aspart in adults with type 1 diabetes: A double‐blind, multicentre, multinational, randomized, crossover study
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Boughton, Charlotte K., Hartnell, Sara, Thabit, Hood, Poettler, Tina, Herzig, David, Wilinska, Malgorzata E., Ashcroft, Nicole L., Sibayan, Judy, Cohen, Nathan, Calhoun, Peter, Bally, Lia, Mader, Julia K., Evans, Mark, Leelarathna, Lalantha, Hovorka, Roman, Boughton, Charlotte K. [0000-0003-3272-9544], Herzig, David [0000-0003-1028-9445], Calhoun, Peter [0000-0002-5325-7200], Bally, Lia [0000-0003-1993-7672], Evans, Mark [0000-0001-8122-8987], and Apollo - University of Cambridge Repository
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type 1 diabetes ,artificial pancreas ,aspart ,faster insulin aspart ,continuous glucose monitoring ,ORIGINAL ARTICLES ,insulin pump therapy ,ORIGINAL ARTICLE ,closed‐loop insulin delivery - Abstract
Aim: To evaluate the use of hybrid closed‐loop glucose control with faster‐acting insulin aspart (Fiasp) in adults with type 1 diabetes (T1D). Research Design and Methods: In a double‐blind, multinational, randomized, crossover study, 25 adults with T1D using insulin pump therapy (mean ± SD, age 38 ± 9 years, HbA1c 7.4% ± 0.8% [57 ± 8 mmol/mol]) underwent two 8‐week periods of unrestricted living comparing hybrid closed‐loop with Fiasp and hybrid closed‐loop with standard insulin aspart in random order. During both interventions the CamAPS FX closed‐loop system incorporating the Cambridge model predictive control algorithm was used. Results: In an intention‐to‐treat analysis, the proportion of time sensor glucose was in the target range (3.9–10.0 mmol/L; primary endpoint) was not different between interventions (75% ± 8% vs. 75% ± 8% for hybrid closed‐loop with Fiasp vs. hybrid closed‐loop with standard insulin aspart; mean‐adjusted difference −0.6% [95% CI −1.8% to 0.7%]; p < .001 for non‐inferiority [non‐inferiority margin 5%]). The proportion of time with sensor glucose less than 3.9 mmol/L (median [IQR] 2.4% [1.2%–3.2%] vs. 2.9% [1.7%–4.0%]; p = .01) and less than 3.0 mmol/L (median [IQR] 0.4% [0.2%–0.7%] vs. 0.7% [0.2%–0.9%]; p = .03) was reduced with Fiasp versus standard insulin aspart. There was no difference in mean glucose (8.1 ± 0.8 vs. 8.0 ± 0.8 mmol/L; p = .13) or glucose variability (SD of sensor glucose 2.9 ± 0.5 vs. 2.9 ± 0.5 mmol/L; p = .90). Total daily insulin requirements did not differ (49 ± 15 vs. 49 ± 15 units/day; p = .45). No severe hypoglycaemia or ketoacidosis occurred. Conclusions: The use of Fiasp in the CamAPS FX closed‐loop system may reduce hypoglycaemia without compromising glucose control compared with standard insulin aspart in adults with T1D.
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- 2021
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13. Fully closed-loop insulin delivery improves glucose control of inpatients with type 2 diabetes receiving hemodialysis
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Bally, Lia, Gubler, Philipp, Thabit, Hood, Hartnell, Sara, Ruan, Yue, Wilinska, Malgorzata E, Evans, Mark L, Semmo, Mariam, Vogt, Bruno, Coll, Anthony P, Stettler, Christoph, Hovorka, Roman, Wilinska, Gosia [0000-0003-2739-1753], Evans, Mark [0000-0001-8122-8987], Coll, Anthony [0000-0003-2594-7463], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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glucose control ,Aged, 80 and over ,Blood Glucose ,Male ,hemodialysis ,Insulin Lispro ,artificial pancreas ,610 Medicine & health ,Infusion Pumps, Implantable ,Middle Aged ,Drug Therapy, Computer-Assisted ,Hospitalization ,Insulin Infusion Systems ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Renal Dialysis ,closed-loop insulin delivery ,Humans ,Hypoglycemic Agents ,Kidney Failure, Chronic ,Female ,Insulin Aspart ,Aged ,Monitoring, Physiologic - Abstract
Inpatient diabetes management of those on hemodialysis poses a major challenge. In a post hoc analysis of a randomized controlled clinical trial, we compared the efficacy of fully automated closed-loop insulin delivery vs. usual care in patients undergoing hemodialysis while in hospital. Compared to control patients receiving conventional subcutaneous insulin therapy, those patients receiving closed-loop insulin delivery significantly increased the proportion of time when a continuous glucose monitor was in the target range of 5.6-10.0 mmol/l by 37.6 percent without increasing the risk of hypoglycemia. Thus, closed-loop insulin delivery offers a novel way to achieve effective and safe glucose control in this vulnerable patient population.
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- 2019
14. Reduced burden of diabetes and improved quality of life: Experiences from unrestricted day-and-night hybrid closed-loop use in very young children with type 1 diabetes
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Musolino, Gianluca, Dovc, Klemen, Boughton, Charlotte K, Tauschmann, Martin, Allen, Janet M, Nagl, Katrin, Fritsch, Maria, Yong, James, Metcalfe, Emily, Schaeffer, Dominique, Fichelle, Muriel, Schierloh, Ulrike, Thiele, Alena G, Abt, Daniela, Kojzar, Harald, Mader, Julia K, Slegtenhorst, Sonja, Ashcroft, Nicole, Wilinska, Malgorzata E, Sibayan, Judy, Cohen, Nathan, Kollman, Craig, Hofer, Sabine E, Fröhlich-Reiterer, Elke, Kapellen, Thomas M, Acerini, Carlo L, De Beaufort, Carine, Campbell, Fiona, Rami-Merhar, Birgit, Hovorka, Roman, Kidsap Consortium, Musolino, Gianluca [0000-0002-4313-2834], Dovc, Klemen [0000-0001-9201-2145], Nagl, Katrin [0000-0001-6489-9068], Schierloh, Ulrike [0000-0002-7644-4818], Hofer, Sabine E [0000-0001-6778-0062], Acerini, Carlo L [0000-0003-2121-5871], Rami-Merhar, Birgit [0000-0001-5575-5222], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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Blood Glucose ,Male ,Parents ,Cross-Over Studies ,type 1 diabetes ,artificial pancreas ,Blood Glucose Self-Monitoring ,Infant ,Circadian Rhythm ,very young children ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Caregivers ,Cost of Illness ,Child, Preschool ,Surveys and Questionnaires ,Quality of Life ,closed-loop insulin delivery ,Humans ,Insulin ,Family ,Female ,Child - Abstract
OBJECTIVE: To evaluate the experiences of families with very young children aged 1 to 7 years (inclusive) with type 1 diabetes using day-and-night hybrid closed-loop insulin delivery. METHODS: Parents/caregivers of 20 children aged 1 to 7 years with type 1 diabetes completed a closed-loop experience survey following two 3-week periods of unrestricted day-and-night hybrid closed-loop insulin therapy using Cambridge FlorenceM system at home. Benefits, limitations, and improvements of closed-loop technology were explored. RESULTS: Responders reported reduced burden of diabetes management, less time spent managing diabetes, and improved quality of sleep with closed-loop. Ninety percent of the responders felt less worried about their child's glucose control using closed-loop. Size of study devices, battery performance and connectivity issues were identified as areas for improvement. Parents/caregivers wished for more options to input information to the system such as temporary glucose targets. CONCLUSIONS: Parents/caregivers of very young children reported important quality of life benefits associated with using closed-loop, supporting adoption of this technology in this population.
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- 2019
15. Participants' Experiences of, and Views About, Daytime Use of a Day-and-Night Hybrid Closed-Loop System in Real Life Settings: Longitudinal Qualitative Study
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Lawton, Julia, Blackburn, Maxine, Rankin, David, Allen, Janet M, Campbell, Fiona M, Leelarathna, Lalantha, Tauschmann, Martin, Thabit, Hood, Wilinska, Malgorzata E, Elleri, Daniela, Hovorka, Roman, Wilinska, Gosia [0000-0003-2739-1753], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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Adult ,Blood Glucose ,Male ,Parents ,Closed-loop system ,Time Factors ,User experience ,Adolescent ,Blood Glucose Self-Monitoring ,Artificial pancreas ,Original Articles ,Middle Aged ,Patient Acceptance of Health Care ,Young Adult ,Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Qualitative research ,Humans ,Hypoglycemic Agents ,Insulin ,Female ,Longitudinal Studies ,Medical device - Abstract
OBJECTIVE: To explore individuals' experiences of daytime use of a day-and-night hybrid closed-loop system, their information and support needs, and their views about how future systems could be improved.RESEARCH DESIGN AND METHODS: Twenty-four adults, adolescents, and parents were interviewed before using a hybrid day-and-night closed-loop system and 3 months later, data were analyzed thematically.RESULTS: Participants praised the closed loop's ability to respond to high and low blood glucose in ways which extended beyond their own capabilities and to act as a safety net and mop up errors, such as when a mealtime bolus was forgotten or unplanned activity was undertaken. Participants also described feeling less burdened by diabetes as a consequence and more able to lead flexible, spontaneous lives. Contrary to their initial expectations, and after trust in the system had been established, most individuals wanted opportunities to collaborate with the closed loop to optimize its effectiveness. Such individuals expressed a need to communicate information, such as when routines changed or to indicate different intensities of physical activity. While individuals valued frequent contact with staff in the initial month of use, most felt that their long-term support needs would be no greater than when using an insulin pump.CONCLUSIONS: While participants reported substantial benefits to using the closed loop during the day, they also identified ways in which the technology could be refined and education and training tailored to optimize effective use. Our findings suggest that mainstreaming this technology will not necessarily lead to increased demands on clinical staff.
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- 2019
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16. Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol
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Leelarathna, Lalantha, Dellweg, Sibylle, Mader, Julia K, Barnard, Katharine, Benesch, Carsten, Ellmerer, Martin, Heinemann, Lutz, Kojzar, Harald, Thabit, Hood, Wilinska, Malgorzata E, Wysocki, Tim, Pieber, Thomas R, Arnolds, Sabine, Evans, Mark L, Hovorka, Roman, and AP@Home Consortium
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Adult ,Glycated Hemoglobin ,Male ,Cross-Over Studies ,Time Factors ,Artificial pancreas ,Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Treatment Outcome ,Humans ,Female ,Closed-loop ,Model predictive control ,Continuous glucose monitoring ,Monitoring, Physiologic - Abstract
INTRODUCTION: Despite therapeutic advances, many people with type 1 diabetes are still unable to achieve optimal glycaemic control, limited by the occurrence of hypoglycaemia. The objective of the present study is to determine the effectiveness of day and night home closed-loop over the medium term compared with sensor-augmented pump therapy in adults with type 1 diabetes and suboptimal glycaemic control. METHODS AND ANALYSIS: The study will adopt an open label, three-centre, multinational, randomised, two-period crossover study design comparing automated closed-loop glucose control with sensor augmented insulin pump therapy. The study will aim for 30 completed participants. Eligible participants will be adults (≥18 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c)≥7.5% (58 mmol/mmol) and ≤10% (86 mmol/mmol)). Following a 4-week optimisation period, participants will undergo a 3-month use of automated closed-loop insulin delivery and sensor-augmented pump therapy, with a 4-6 week washout period in between. The order of the interventions will be random. All analysis will be conducted on an intention to treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3 months free living phase. Secondary outcomes include HbA1c changes; mean glucose and time spent above and below target glucose levels. Further, participants will be invited at baseline, midpoint and study end to participate in semistructured interviews and complete questionnaires to explore usability and acceptance of the technology, impact on quality of life and fear of hypoglycaemia. ETHICS AND DISSEMINATION: Ethical approval has been obtained at all sites. Before screening, all participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT01961622 (ClinicalTrials.gov).
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- 2020
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17. Assessing the effectiveness of a 3-month day-and-night home closed-loop control combined with pump suspend feature compared with sensor-augmented pump therapy in youths and adults with suboptimally controlled type 1 diabetes: a randomised parallel study protocol
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Bally, Lia, Thabit, Hood, Tauschmann, Martin, Allen, Janet M, Hartnell, Sara, Wilinska, Malgorzata E, Exall, Jane, Huegel, Viki, Sibayan, Judy, Borgman, Sarah, Cheng, Peiyao, Blackburn, Maxine, Lawton, Julia, Elleri, Daniela, Leelarathna, Lalantha, Acerini, Carlo L, Campbell, Fiona, Shah, Viral N, Criego, Amy, Evans, Mark L, Dunger, David B, Kollman, Craig, Bergenstal, Richard M, Hovorka, Roman, Tauschmann, Martin [0000-0002-2305-2490], Wilinska, Gosia [0000-0003-2739-1753], Acerini, Carlo [0000-0003-2121-5871], Evans, Mark [0000-0001-8122-8987], Dunger, David [0000-0002-2566-9304], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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Adult ,Blood Glucose ,Male ,Time Factors ,Adolescent ,type 1 diabetes ,610 Medicine & health ,Young Adult ,Insulin Infusion Systems ,Protocol ,Journal Article ,Humans ,Hypoglycemic Agents ,Insulin ,Child ,Glycated Hemoglobin ,closed-loop ,artificial pancreas ,Home Care Services ,Hypoglycemia ,United Kingdom ,United States ,Diabetes and Endocrinology ,Diabetes Mellitus, Type 1 ,Treatment Outcome ,Research Design ,Regression Analysis ,Female - Abstract
$\textbf{Introduction:}$ Despite therapeutic advances, many individuals with type 1 diabetes are unable to achieve tight glycaemic target without increasing the risk of hypoglycaemia. The objective of this study is to determine the effectiveness of a 3-month day-and-night home closed-loop glucose control combined with a pump suspend feature, compared with sensor-augmented insulin pump therapy in youths and adults with suboptimally controlled type 1 diabetes. $\textbf{Methods and analysis:}$ The study adopts an open-label, multi-centre, multi-national (UK and USA), randomised, single-period, parallel design and aims for 84 randomised patients. Participants are youths (6-21 years) or adults (>21 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c) ≥7.5% (58 mmol/mol) and ≤10% (86 mmol/mol)). Following a 4-week run-in period, eligible participants will be randomised to a 3-month use of automated closed-loop insulin delivery combined with pump suspend feature or to sensor-augmented insulin pump therapy. Analyses will be conducted on an intention-to-treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3-month free-living phase. Secondary outcomes include HbA1c at 3 months, mean glucose, time spent below and above target; time with glucose levels 16.7 mmol/L, glucose variability; total, basal and bolus insulin dose and change in body weight. Participants' and their families' perception in terms of lifestyle change, daily diabetes management and fear of hypoglycaemia will be evaluated. $\textbf{Ethics and dissemination:}$ Ethics/institutional review board approval has been obtained. Before screening, all participants/guardians will be provided with oral and written information about the trial. The study will be disseminated by peer-reviewed publications and conference presentations. $\textbf{Trial registration number:}$ NCT02523131; Pre-results.
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- 2017
18. Sensor Life and Overnight Closed Loop: A Randomized Clinical Trial
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Tauschmann, Martin, Allen, Janet M., Wilinska, Malgorzata E., Ruan, Yue, Thabit, Hood, Acerini, Carlo L., Dunger, David B., Hovorka, Roman, Tauschmann, Martin [0000-0002-2305-2490], Wilinska, Gosia [0000-0003-2739-1753], Acerini, Carlo [0000-0003-2121-5871], Dunger, David [0000-0002-2566-9304], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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Blood Glucose ,Male ,Cross-Over Studies ,Adolescent ,artificial pancreas ,Blood Glucose Self-Monitoring ,closed loop ,Pilot Projects ,Original Articles ,sensor accuracy ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,sensor life ,Humans ,Hypoglycemic Agents ,Insulin ,continuous glucose monitoring ,Female ,Algorithms - Abstract
BACKGROUND: Closed-loop (CL) systems direct insulin delivery based on continuous glucose monitor (CGM) sensor values. CGM accuracy varies with sensor life, being least accurate on day 1 of sensor insertion. We evaluated the effect of sensor life (enhanced Enlite, Medtronic MiniMed, Northridge, CA) on overnight CL. METHODS: In an open-label, randomized, 2-period, inpatient crossover pilot study, 12 adolescents on insulin pump (age 16.7 ± 1.9 years; HbA1c 66 ± 10 mmol/mol) attended a clinical research facility on 2 overnight occasions. In random order, participants received CL on day 1 or on day 3-4 after sensor insertion. During both periods, glucose was automatically controlled by a model predictive control algorithm informed by sensor glucose. Plasma glucose was measured every 30 to 60 min. RESULTS: During overnight CL (22:30 to 07:30), the proportion of time with plasma glucose readings in the target range (3.9-8.0 mmol/l, primary endpoint) when initiated on day 1 of sensor insertion vs day 3-4 were comparable (58 ± 32% day 1 vs 56 ± 36% day 3-4; P = .34), and there were no significant differences between interventions in terms of mean plasma glucose ( P = .26), percentage time above 8.0 mmol/l ( P = .49), and time spent below 3.9 mmol/l ( P = .93). Sensor accuracy varied with sensor life (mean absolute relative difference 19.8 ± 15.0% on day 1 and 13.7 ± 10.2% on day 3 to 4). Sensor glucose tended to under-read plasma glucose inflating benefits of CL on glucose control. CONCLUSIONS: In spite of differences in sensor accuracy, overnight CL glucose control informed by sensor glucose on day 1 or day 3-4 after sensor insertion was comparable. The model predictive controller appears to mitigate against sensor inaccuracies.
- Published
- 2017
19. Modelling Day-to-Day Variability of Glucose-Insulin Regulation over 12-Week Home Use of Closed-Loop Insulin Delivery
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Ruan, Yue, Wilinska, Malgorzata E, Thabit, Hood, Hovorka, Roman, Wilinska, Gosia [0000-0003-2739-1753], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
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bayesian parameter estimation ,Artificial pancreas ,hierarchical model ,type 1 diabetes (T1D) ,simulation - Abstract
Parameters of physiological models of glucose-insulin regulation in type 1 diabetes have previously been estimated using data collected over short periods of time and lack the quantification of day-to-day variability. We developed a new hierarchical model to relate subcutaneous insulin delivery and carbohydrate intake to continuous glucose monitoring over 12 weeks while describing day-to-day variability. Sensor glucose data sampled every 10 min, insulin aspart delivery and meal intake were analyzed from 8 adults with type 1 diabetes (male/female 5/3, age 39.9±9.5 years, BMI 25.4±4.4 kg/m2, HbA1c 8.4±0.6%) who underwent a 12-week home study of closed-loop insulin delivery. A compartment model comprised five linear differential equations; model parameters were estimated using the Markov chain Monte Carlo approach within a hierarchical Bayesian model framework. Physiologically plausible a posteriori distributions of model parameters including insulin sensitivity, time-to-peak insulin action, time-to-peak gut absorption, and carbohydrate bioavailability, and good model fit were observed. Day-to-day variability of model parameters was estimated in the range of 38 to 79% for insulin sensitivity and 27 to 48% for time-to-peak of insulin action. In conclusion, a linear Bayesian hierarchical approach is feasible to describe a 12-week glucose-insulin relationship using conventional clinical data. The model may facilitate in silico testing to aid the development of closed-loop insulin delivery systems.
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- 2016
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20. Closed-loop control in insulin pumps for type-1 diabetes mellitus: safety and efficacy.
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Fuchs, Julia and Hovorka, Roman
- Subjects
INSULIN pumps ,DIABETES ,TYPE 1 diabetes ,CLOSED loop systems ,GLYCEMIC control - Abstract
Type 1 diabetes is a lifelong disease with high management burden. The majority of people with type 1 diabetes fail to achieve glycemic targets. Algorithm-driven automated insulin delivery (closed-loop) systems aim to address these challenges. This review provides an overview of commercial and emerging closed-loop systems. We review safety and efficacy of commercial and emerging hybrid closed-loop systems. A literature search was conducted and clinical trials using day-and-night closed-loop systems during free-living conditions were used to report on safety data. We comment on efficacy where robust randomized controlled trial data for a particular system are available. We highlight similarities and differences between commercial systems. Study data shows that hybrid closed-loop systems are safe and effective, consistently improving glycemic control when compared to standard therapy. While a fully closed-loop system with minimal burden remains the end-goal, these hybrid closed-loop systems have transformative potential in diabetes care. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
21. Novel Single-Site Device for Conjoined Glucose Sensing and Insulin Infusion: Performance Evaluation in Diabetes Patients During Home-Use.
- Author
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Tschaikner, Mathias, Powell, Kevin, Jungklaus, Miro, Fritz, Martin, Ellmerer, Martin, Hovorka, Roman, Lane, Steve, Pieber, Thomas R., and Regittnig, Werner
- Subjects
GLUCOSE analysis ,PEOPLE with diabetes ,GLUCOSE ,INSULIN ,BLOOD sugar ,TYPE 1 diabetes - Abstract
Objective: This study evaluated a novel diabetes treatment device that combines commercially available continuous glucose monitoring and insulin infusion technology in such a way as to perform insulin delivery and glucose sensing through a single skin insertion site (single-port device). Methods: Ten type 1 diabetes patients used the device for up to six days in their home/work environment for open-loop insulin delivery and glucose sensing. On an additional day, the device was used in combination with an algorithm to perform automated closed-loop glucose control under hospital settings. To assess the performance of the device, capillary blood glucose concentrations were frequently determined and a continuous glucose sensor was additionally worn by the patients. Results: The average mean absolute relative deviation from blood glucose concentrations obtained for the sensor of the device was low (median, 13.0%; interquartile range, 10.5–16.7%; n = 10) and did not differ from that of the additionally worn glucose sensor (versus 13.9%; 11.9–15.3%; P = 0.922). Furthermore, insulin delivery with the single-port device was reliable and safe during home use and, when performed in combination with the control algorithm, was adequate to achieve and maintain near normoglycemia. Conclusion: Our data show the feasibility of open- and closed-loop glucose control in diabetes patients using a device that combines insulin delivery and glucose sensing at a single tissue site. Significance: The reduction in device size and invasiveness achieved by this design may largely increase patient convenience and enhance acceptance of diabetes treatment with continuous glucose monitoring and insulin delivery technology. [ABSTRACT FROM AUTHOR]
- Published
- 2020
- Full Text
- View/download PDF
22. Short‐term fully closed‐loop insulin delivery using faster insulin aspart compared with standard insulin aspart in type 2 diabetes.
- Author
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Bally, Lia, Herzig, David, Ruan, Yue, Wilinska, Malgorzata E., Semmo, Mariam, Vogt, Andreas, Wertli, Maria M., Vogt, Bruno, Stettler, Christoph, and Hovorka, Roman
- Subjects
INSULIN aspart ,TYPE 2 diabetes ,GLUCOSE analysis ,INSULIN - Abstract
We evaluated the efficacy and safety of short‐term fully closed‐loop insulin delivery using faster versus standard insulin aspart in type 2 diabetes. Fifteen adults with insulin‐treated type 2 diabetes underwent 22 hours of closed‐loop insulin delivery with either faster or standard insulin aspart in a double‐blind randomized crossover design. Basal‐bolus regimen was replaced by model predictive control algorithm‐directed insulin delivery based on sensor glucose levels. The primary outcome was time with plasma glucose in target range (5.6–10.0 mmol/L) and did not differ between treatments (mean difference [95% CI] 3.3% [−8.2; 1.7], P = 0.17). Mean glucose and glucose variability were comparable, as was time spent below and above target range. Hypoglycaemia (<3.5 mmol/L) occurred once with faster insulin aspart and twice with standard insulin aspart. Mean total insulin dose was higher with faster insulin aspart (mean difference [95% CI] 3.7 U [0.7; 6.8], P = 0.021). No episodes of severe hypoglycaemia or other serious adverse events occurred. In conclusion, short‐term fully closed‐loop in type 2 diabetes may require higher dose of faster insulin aspart compared with standard insulin aspart to achieve comparable glucose control. [ABSTRACT FROM AUTHOR]
- Published
- 2019
- Full Text
- View/download PDF
23. Assessing the effectiveness of 3 months day and night home closed-loop insulin delivery in adults with suboptimally controlled type 1 diabetes: a randomised crossover study protocol
- Author
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Leelarathna, Lalantha, Dellweg, Sibylle, Mader, Julia K, Barnard, Katharine, Benesch, Carsten, Ellmerer, Martin, Heinemann, Lutz, Kojzar, Harald, Thabit, Hood, Wilinska, Malgorzata E, Wysocki, Tim, Pieber, Thomas R, Arnolds, Sabine, Evans, Mark L, Hovorka, Roman, AP@home consortium, Wilinska, Gosia [0000-0003-2739-1753], Evans, Mark [0000-0001-8122-8987], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Glycated Hemoglobin ,Male ,Cross-Over Studies ,Time Factors ,Artificial pancreas ,Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Treatment Outcome ,Humans ,Female ,Closed-loop ,Model predictive control ,Continuous glucose monitoring ,Monitoring, Physiologic - Abstract
INTRODUCTION: Despite therapeutic advances, many people with type 1 diabetes are still unable to achieve optimal glycaemic control, limited by the occurrence of hypoglycaemia. The objective of the present study is to determine the effectiveness of day and night home closed-loop over the medium term compared with sensor-augmented pump therapy in adults with type 1 diabetes and suboptimal glycaemic control. METHODS AND ANALYSIS: The study will adopt an open label, three-centre, multinational, randomised, two-period crossover study design comparing automated closed-loop glucose control with sensor augmented insulin pump therapy. The study will aim for 30 completed participants. Eligible participants will be adults (≥18 years) with type 1 diabetes treated with insulin pump therapy and suboptimal glycaemic control (glycated haemoglobin (HbA1c)≥7.5% (58 mmol/mmol) and ≤10% (86 mmol/mmol)). Following a 4-week optimisation period, participants will undergo a 3-month use of automated closed-loop insulin delivery and sensor-augmented pump therapy, with a 4-6 week washout period in between. The order of the interventions will be random. All analysis will be conducted on an intention to treat basis. The primary outcome is the time spent in the target glucose range from 3.9 to 10.0 mmol/L based on continuous glucose monitoring levels during the 3 months free living phase. Secondary outcomes include HbA1c changes; mean glucose and time spent above and below target glucose levels. Further, participants will be invited at baseline, midpoint and study end to participate in semistructured interviews and complete questionnaires to explore usability and acceptance of the technology, impact on quality of life and fear of hypoglycaemia. ETHICS AND DISSEMINATION: Ethical approval has been obtained at all sites. Before screening, all participants will be provided with oral and written information about the trial. The study will be disseminated by peer-review publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT01961622 (ClinicalTrials.gov).
- Published
- 2014
24. Modeling Day-to-Day Variability of Glucose?Insulin Regulation Over 12-Week Home Use of Closed-Loop Insulin Delivery.
- Author
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Ruan, Yue, Wilinska, Malgorzata E., Thabit, Hood, and Hovorka, Roman
- Subjects
BLOOD sugar ,INSULIN ,TYPE 1 diabetes ,CARBOHYDRATE metabolism ,EMPIRICAL Bayes methods ,ARTIFICIAL pancreases - Abstract
Parameters of physiological models of glucose–insulin regulation in type 1 diabetes have previously been estimated using data collected over short periods of time and lack the quantification of day-to-day variability. We developed a new hierarchical model to relate subcutaneous insulin delivery and carbohydrate intake to continuous glucose monitoring over 12 weeks while describing day-to-day variability. Sensor glucose data sampled every 10-min, insulin aspart delivery and meal intake were analyzed from eight adults with type 1 diabetes (male/female 5/3, age \text39.9\,\pm \,\text9.5 years, BMI \text25.4\,\pm \,\text4.4 kg/ m^2, HbA1c \text8.4\,\pm \,\text0.6%) who underwent a 12-week home study of closed-loop insulin delivery. A compartment model comprised of five linear differential equations; model parameters were estimated using the Markov chain Monte Carlo approach within a hierarchical Bayesian model framework. Physiologically, plausible a posteriori distributions of model parameters including insulin sensitivity, time-to-peak insulin action, time-to-peak gut absorption, and carbohydrate bioavailability, and good model fit were observed. Day-to-day variability of model parameters was estimated in the range of 38–79% for insulin sensitivity and 27–48% for time-to-peak of insulin action. In conclusion, a linear Bayesian hierarchical approach is feasible to describe a 12-week glucose–insulin relationship using conventional clinical data. The model may facilitate in silico testing to aid the development of closed-loop insulin delivery systems. [ABSTRACT FROM AUTHOR]
- Published
- 2017
- Full Text
- View/download PDF
25. Closed-loop for type 1 diabetes - an introduction and appraisal for the generalist.
- Author
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Bally, Lia, Thabit, Hood, and Hovorka, Roman
- Subjects
TYPE 1 diabetes ,GLUCOSE ,GLYCEMIC index ,INSULIN therapy ,HORMONES ,HYPOGLYCEMIC agents ,INSULIN pumps ,BIOSENSORS ,BLOOD sugar monitoring ,GLYCOSYLATED hemoglobin ,PATIENT monitoring ,QUESTIONNAIRES ,RESEARCH funding ,IMPACT of Event Scale ,STANDARDS ,EQUIPMENT & supplies - Abstract
Background: Rapid progress over the past decade has been made with the development of the 'Artificial Pancreas', also known as the closed-loop system, which emulates the feedback glucose-responsive functionality of the pancreatic beta cell. The recent FDA approval of the first hybrid closed-loop system makes the Artificial Pancreas a realistic therapeutic option for people with type 1 diabetes. In anticipation of its advent into clinical care, we provide a primer and appraisal of this novel therapeutic approach in type 1 diabetes for healthcare professionals and non-specialists in the field.Discussion: Randomised clinical studies in outpatient and home settings have shown improved glycaemic outcomes, reduced risk of hypoglycaemia and positive user attitudes. User input and interaction with existing closed-loop systems, however, are still required. Therefore, management of user expectations, as well as training and support by healthcare providers are key to ensure optimal uptake, satisfaction and acceptance of the technology. An overview of closed-loop technology and its clinical implications are discussed, complemented by our extensive hands-on experience with closed-loop system use during free daily living.Conclusions: The introduction of the artificial pancreas into clinical practice represents a milestone towards the goal of improving the care of people with type 1 diabetes. There remains a need to understand the impact of user interaction with the technology, and its implication on current diabetes management and care. [ABSTRACT FROM AUTHOR]- Published
- 2017
- Full Text
- View/download PDF
26. Stochastic Virtual Population of Subjects With Type 1 Diabetes for the Assessment of Closed-Loop Glucose Controllers.
- Author
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Haidar, Ahmad, Wilinska, Malgorzata E., Graveston, James A., and Hovorka, Roman
- Subjects
GLUCOSE metabolism ,COMPUTER simulation ,TIME-varying systems ,BAYESIAN analysis ,MARKOV chain Monte Carlo ,PEOPLE with diabetes - Abstract
Closed-loop glucose control is an emerging treatment approach to manage type 1 diabetes. Closed-loop systems consist of a continuous glucose monitor, an insulin infusion pump, and a dosing algorithm that directs insulin delivery based on sensor levels. Testing of dosing algorithms in computer simulations may replace animal testing, accelerates development, and saves resources. We propose here a novel approach to generate a virtual population, to be used in metabolic simulators, from routine experimental data through the process that we term “stochastic e-cloning.” We build on a nonlinear physiologically motivated time-varying model of glucose regulation. We adopt the Bayesian approach to estimate model parameters and to obtain the joint posterior probability distribution of time-invariant and time-varying parameters with the use of the Markov chain Monte Carlo methodology. The estimation process combines prior knowledge and experimental data to generate a sample from the posterior distribution, which can be subsequently used to conduct in silico experiments reflecting population and individual variability, and associated uncertainty as closely as possible. The approach is exemplified using data collected in 12 young subjects with type 1 diabetes. We demonstrate unbiased fit to the data, physiological plausibility of parameter estimates, and results of in silico testing using a stochastic virtual subject. [ABSTRACT FROM PUBLISHER]
- Published
- 2013
- Full Text
- View/download PDF
27. Recent advances in closed-loop insulin delivery.
- Author
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Ware, Julia and Hovorka, Roman
- Subjects
TYPE 1 diabetes ,INSULIN ,CLOSED loop systems ,DIABETES in children - Abstract
Since the discovery of insulin 100 years ago, we have seen considerable advances across diabetes therapies. The more recent advent of glucose-responsive automated insulin delivery has started to revolutionise the management of type 1 diabetes in children and adults. Evolution of closed-loop insulin delivery from research to clinical practice has been rapid, and multiple systems are now commercially available. In this review, we summarise key evidence on currently available closed-loop systems and those in development. We comment on dual-hormone and do-it-yourself systems, as well as reviewing clinical evidence in special populations such as very young children, older adults and in pregnancy. We identify future directions for research and barriers to closed-loop adoption, including how these might be addressed to ensure equitable access to this novel therapy. • Type 1 diabetes is a lifelong condition with high management burden. • Glucose-responsive automated insulin delivery improves glycaemic outcomes and quality of life. • Multiple closed-loop systems are commercially available, offering increased choice for users. • Working towards a fully closed-loop system and addressing barriers to adoption should be the focus of future research. [ABSTRACT FROM AUTHOR]
- Published
- 2022
- Full Text
- View/download PDF
28. Coming of age: the artificial pancreas for type 1 diabetes
- Author
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Thabit, Hood and Hovorka, Roman
- Subjects
Blood Glucose ,Pancreas, Artificial ,Closed-loop system ,Continuous glucose monitor ,Control algorithm ,Artificial pancreas ,Review ,3. Good health ,Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Humans ,Insulin ,Insulin pump ,Algorithms - Abstract
The artificial pancreas (closed-loop system) addresses the unmet clinical need for improved glucose control whilst reducing the burden of diabetes self-care in type 1 diabetes. Glucose-responsive insulin delivery above and below a preset insulin amount informed by sensor glucose readings differentiates closed-loop systems from conventional, threshold-suspend and predictive-suspend insulin pump therapy. Insulin requirements in type 1 diabetes can vary between one-third-threefold on a daily basis. Closed-loop systems accommodate these variations and mitigate the risk of hypoglycaemia associated with tight glucose control. In this review we focus on the progress being made in the development and evaluation of closed-loop systems in outpatient settings. Randomised transitional studies have shown feasibility and efficacy of closed-loop systems under supervision or remote monitoring. Closed-loop application during free-living, unsupervised conditions by children, adolescents and adults compared with sensor-augmented pumps have shown improved glucose outcomes, reduced hypoglycaemia and positive user acceptance. Innovative approaches to enhance closed-loop performance are discussed and we also present the outlook and strategies used to ease clinical adoption of closed-loop systems.
29. Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol
- Author
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Boughton, Charlotte, Allen, Janet M, Tauschmann, Martin, Hartnell, Sara, Wilinska, Malgorzata E, Musolino, Gianluca, Acerini, Carlo L, Dunger, Professor David, Campbell, Fiona, Ghatak, Atrayee, Randell, Tabitha, Besser, Rachel, Trevelyan, Nicola, Elleri, Daniela, Northam, Elizabeth, Hood, Korey, Scott, Eleanor, Lawton, Julia, Roze, Stephane, Sibayan, Judy, Kollman, Craig, Cohen, Nate, Todd, John, Hovorka, Roman, and CLOuD Consortium
- Subjects
Glycated Hemoglobin ,closed-loop ,Adolescent ,type 1 diabetes ,artificial pancreas ,Blood Glucose Self-Monitoring ,3. Good health ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Treatment Outcome ,Insulin-Secreting Cells ,Humans ,Hypoglycemic Agents ,Insulin ,Multicenter Studies as Topic ,Child ,Randomized Controlled Trials as Topic - Abstract
INTRODUCTION: Management of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued intensive metabolic control using hybrid closed-loop (CL) insulin delivery following diagnosis of T1D can preserve C-peptide secretion, a marker of residual beta-cell function, compared with standard multiple daily injections (MDI) therapy. METHODS AND ANALYSIS: The study adopts an open-label, multicentre, randomised, parallel design, and aims to randomise 96 participants aged 10-16.9 years, recruited within 21 days of diagnosis with T1D. Following a baseline mixed meal tolerance test (MMTT), participants will be randomised to receive 24 months treatment with conventional MDI therapy or with CL insulin delivery. A further 24-month optional extension phase will be offered to all participants to continue with the allocated treatment. The primary outcome is the between group difference in area under the stimulated C-peptide curve (AUC) of the MMTT at 12 months post diagnosis. Analyses will be conducted on an intention-to-treat basis. Key secondary outcomes are between group differences in time spent in target glucose range (3.9-10 mmol/L), glycated haemoglobin (HbA1c) and time spent in hypoglycaemia (
30. Closed-loop for type 1 diabetes - an introduction and appraisal for the generalist
- Author
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Bally, Lia, Thabit, Hood, and Hovorka, Roman
- Subjects
Type 1 diabetes ,Diabetes Mellitus, Type 1 ,Glycated Hemoglobin A ,Insulin Infusion Systems ,Blood Glucose Self-Monitoring ,Glucose control ,Humans ,Hypoglycemic Agents ,Artificial pancreas ,Closed-loop ,Biosensing Techniques ,3. Good health ,Monitoring, Physiologic - Abstract
BACKGROUND: Rapid progress over the past decade has been made with the development of the 'Artificial Pancreas', also known as the closed-loop system, which emulates the feedback glucose-responsive functionality of the pancreatic beta cell. The recent FDA approval of the first hybrid closed-loop system makes the Artificial Pancreas a realistic therapeutic option for people with type 1 diabetes. In anticipation of its advent into clinical care, we provide a primer and appraisal of this novel therapeutic approach in type 1 diabetes for healthcare professionals and non-specialists in the field. DISCUSSION: Randomised clinical studies in outpatient and home settings have shown improved glycaemic outcomes, reduced risk of hypoglycaemia and positive user attitudes. User input and interaction with existing closed-loop systems, however, are still required. Therefore, management of user expectations, as well as training and support by healthcare providers are key to ensure optimal uptake, satisfaction and acceptance of the technology. An overview of closed-loop technology and its clinical implications are discussed, complemented by our extensive hands-on experience with closed-loop system use during free daily living. CONCLUSIONS: The introduction of the artificial pancreas into clinical practice represents a milestone towards the goal of improving the care of people with type 1 diabetes. There remains a need to understand the impact of user interaction with the technology, and its implication on current diabetes management and care.
31. Assessing the effect of closed-loop insulin delivery from onset of type 1 diabetes in youth on residual beta-cell function compared to standard insulin therapy (CLOuD study): a randomised parallel study protocol
- Author
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Boughton, Charlotte, Allen, Janet M, Tauschmann, Martin, Hartnell, Sara, Wilinska, Malgorzata E, Musolino, Gianluca, Acerini, Carlo L, Dunger, Professor David, Campbell, Fiona, Ghatak, Atrayee, Randell, Tabitha, Besser, Rachel, Trevelyan, Nicola, Elleri, Daniela, Northam, Elizabeth, Hood, Korey, Scott, Eleanor, Lawton, Julia, Roze, Stephane, Sibayan, Judy, Kollman, Craig, Cohen, Nate, Todd, John, and Hovorka, Roman
- Subjects
Diabetes and endocrinology ,closed-loop ,type 1 diabetes ,artificial pancreas ,3. Good health - Abstract
Introduction: Management of newly diagnosed type 1 diabetes (T1D) in children and adolescents is challenging for patients, families and healthcare professionals. The objective of this study is to determine whether continued intensive metabolic control using hybrid closed-loop (CL) insulin delivery following diagnosis of T1D can preserve C-peptide secretion, a marker of residual beta-cell function, compared with standard multiple daily injections (MDI) therapy. Methods and analysis: The study adopts an open-label, multicentre, randomised, parallel design, and aims to randomise 96 participants aged 10–16.9 years, recruited within 21 days of diagnosis with T1D. Following a baseline mixed meal tolerance test (MMTT), participants will be randomised to receive 24 months treatment with conventional MDI therapy or with CL insulin delivery. A further 24-month optional extension phase will be offered to all participants to continue with the allocated treatment. The primary outcome is the between group difference in area under the stimulated C-peptide curve (AUC) of the MMTT at 12 months post diagnosis. Analyses will be conducted on an intention-to-treat basis. Key secondary outcomes are between group differences in time spent in target glucose range (3.9–10 mmol/L), glycated haemoglobin (HbA1c) and time spent in hypoglycaemia (
32. Improving glycemic control in critically ill patients: personalized care to mimic the endocrine pancreas
- Author
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Chase, J Geoffrey, Desaive, Thomas, Bohe, Julien, Cnop, Miriam, De Block, Christophe, Gunst, Jan, Hovorka, Roman, Kalfon, Pierre, Krinsley, James, Renard, Eric, and Preiser, Jean-Charles
- Subjects
Virtual patient ,Critical Illness ,In silico ,Modeling ,Glycemic Load ,Artificial pancreas ,Model based ,Review ,Hypoglycemia ,3. Good health ,Islets of Langerhans ,Glycemic control ,Metabolism ,Hyperglycemia ,Validation ,Humans ,Endocrine function - Abstract
There is considerable physiological and clinical evidence of harm and increased risk of death associated with dysglycemia in critical care. However, glycemic control (GC) currently leads to increased hypoglycemia, independently associated with a greater risk of death. Indeed, recent evidence suggests GC is difficult to safely and effectively achieve for all patients. In this review, leading experts in the field discuss this evidence and relevant data in diabetology, including the artificial pancreas, and suggest how safe, effective GC can be achieved in critically ill patients in ways seeking to mimic normal islet cell function. The review is structured around the specific clinical hurdles of: understanding the patient's metabolic state; designing GC to fit clinical practice, safety, efficacy, and workload; and the need for standardized metrics. These aspects are addressed by reviewing relevant recent advances in science and technology. Finally, we provide a set of concise recommendations to advance the safety, quality, consistency, and clinical uptake of GC in critical care. This review thus presents a roadmap toward better, more personalized metabolic care and improved patient outcomes.
33. Glucose-responsive insulin delivery for type 1 diabetes: The artificial pancreas story
- Author
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Bally, Lia, Thabit, Hood, and Hovorka, Roman
- Subjects
Insulin pump therapy ,Control algorithm ,Artificial pancreas ,Closed-loop ,Continuous glucose monitoring ,3. Good health - Abstract
Insulin replacement therapy is integral to the management of type 1 diabetes, which is characterised by absolute insulin deficiency. Optimal glycaemic control, as assessed by glycated haemoglobin, and avoidance of hyper- and hypoglycaemic excursions have been shown to prevent diabetes-related complications. Insulin pump use has increased considerably over the past decade with beneficial effects on glycaemic control, quality of life and treatment satisfaction. The advent and progress of ambulatory glucose sensor technology has enabled continuous glucose monitoring based on real-time glucose levels to be integrated with insulin therapy. Low glucose and predictive low glucose suspend systems are currently used in clinical practice to mitigate against hypoglycaemia, and provide the first step towards feedback glucose control. The more advanced technology approach, an artificial pancreas or a closed-loop system, gradually increases and decreases insulin delivery in a glucose-responsive fashion to mitigate against hyper- and hypoglycaemia. Randomised outpatient clinical trials over the past 5 years have demonstrated the feasibility, safety and efficacy of the approach, and the recent FDA approval of the first single hormone closed-loop system establishes a new standard of care for people with type 1 diabetes.
34. 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
- Author
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Musolino, Gianluca, Allen, Janet M, Hartnell, Sara, Wilinska, Malgorzata E, Tauschmann, Martin, Boughton, Charlotte, Campbell, Fiona, Denvir, Louise, Trevelyan, Nicola, Wadwa, Paul, DiMeglio, Linda, Buckingham, Bruce A, Weinzimer, Stuart, Acerini, Carlo L, Hood, Korey, Fox, Steven, Kollman, Craig, Sibayan, Judy, Borgman, Sarah, Cheng, Peiyao, and Hovorka, Roman
- Subjects
2. Zero hunger ,Pancreas, Artificial ,closed-loop ,Adolescent ,type 1 diabetes ,artificial pancreas ,Insulins ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Treatment Outcome ,Humans ,Hypoglycemic Agents ,Multicenter Studies as Topic ,Patient Safety ,Child ,Randomized Controlled Trials as Topic - Abstract
INTRODUCTION: Closed-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 ANALYSIS: The 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 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 DISSEMINATION: Cambridge 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 NUMBER: NCT02925299; Pre-results.
35. Fully closed-loop insulin delivery improves glucose control of inpatients with type 2 diabetes receiving hemodialysis
- Author
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Bally, Lia, Gubler, Philipp, Thabit, Hood, Hartnell, Sara, Ruan, Yue, Wilinska, Malgorzata E, Evans, Mark L, Semmo, Mariam, Vogt, Bruno, Coll, Anthony P, Stettler, Christoph, and Hovorka, Roman
- Subjects
glucose control ,Aged, 80 and over ,Blood Glucose ,Male ,hemodialysis ,Insulin Lispro ,artificial pancreas ,Infusion Pumps, Implantable ,Middle Aged ,Drug Therapy, Computer-Assisted ,Hospitalization ,Insulin Infusion Systems ,Treatment Outcome ,Diabetes Mellitus, Type 2 ,Renal Dialysis ,closed-loop insulin delivery ,Humans ,Hypoglycemic Agents ,Kidney Failure, Chronic ,Female ,610 Medicine & health ,Insulin Aspart ,Aged ,Monitoring, Physiologic - Abstract
Inpatient diabetes management of those on hemodialysis poses a major challenge. In a post hoc analysis of a randomized controlled clinical trial, we compared the efficacy of fully automated closed-loop insulin delivery vs. usual care in patients undergoing hemodialysis while in hospital. Compared to control patients receiving conventional subcutaneous insulin therapy, those patients receiving closed-loop insulin delivery significantly increased the proportion of time when a continuous glucose monitor was in the target range of 5.6-10.0 mmol/l by 37.6 percent without increasing the risk of hypoglycemia. Thus, closed-loop insulin delivery offers a novel way to achieve effective and safe glucose control in this vulnerable patient population.
36. Diabetic Ketoacidosis at Onset of Type 1 Diabetes and Glycemic Outcomes with Closed-Loop Insulin Delivery.
- Author
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Lakshman, Rama, Najami, Mazin, Allen, Janet M., Ware, Julia, Wilinska, Malgorzata E., Hartnell, Sara, Thankamony, Ajay, Randell, Tabitha, Ghatak, Atrayee, Besser, Rachel E.J., Elleri, Daniela, Trevelyan, Nicola, Campbell, Fiona M., Hovorka, Roman, and Boughton, Charlotte K.
- Subjects
- *
TYPE 1 diabetes , *DIABETIC acidosis , *GLYCOSYLATED hemoglobin , *INSULIN , *HYPERGLYCEMIA - Abstract
The presence of diabetic ketoacidosis (DKA) at diagnosis of type 1 diabetes (T1D) is associated with higher glycated hemoglobin levels over time. We evaluated whether hybrid-closed loop (HCL) therapy from onset of T1D could prevent the adverse impact of DKA at diagnosis on long-term glycemic outcomes. This was a posthoc analysis from 51 adolescents using HCL from diagnosis of T1D as part of the CLOuD trial (NCT02871089). We compared glycemic and insulin metrics between adolescents with (n = 17) and without (n = 34) DKA at diagnosis. Participants with and without DKA at diagnosis had similar time in target glucose range 3.9–10.0 mmol/L (70–180 mg/dL), time below range (<3.9 mmol/L, <70 mg/dL) and HbA1c at 6, 12, and 24 months. While insulin requirements at 6 months were higher in those with DKA at diagnosis, this was not statistically significant after adjusting for bodyweight. Residual C-peptide secretion was similar between groups. We conclude that HCL therapy may mitigate against the negative glycemic effects of DKA at T1D diagnosis. [ABSTRACT FROM AUTHOR]
- Published
- 2024
- Full Text
- View/download PDF
37. CamAPS FX Hybrid Closed-Loop with Ultra-Rapid Lispro Compared with Standard Lispro in Adults with Type 1 Diabetes: A Double-Blind, Randomized, Crossover Study.
- Author
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Nwokolo, Munachiso, Lakshman, Rama, Hartnell, Sara, Alwan, Heba, Ware, Julia, Allen, Janet M., Wilinska, Malgorzata E., Evans, Mark L., Hovorka, Roman, and Boughton, Charlotte K.
- Subjects
- *
TYPE 1 diabetes , *INSULIN pumps , *GLYCOSYLATED hemoglobin , *ADULTS , *HYPOGLYCEMIA - Abstract
Introduction: To evaluate hybrid closed-loop with ultra-rapid insulin lispro (Lyumjev) compared with hybrid closed-loop with standard insulin lispro in adults with type 1 diabetes. Materials and Methods: In a single-center, double-blind, randomized, crossover study, 28 adults with type 1 diabetes (mean ± standard deviation [SD]: age 44.5 ± 10.7 years, glycated hemoglobin (HbA1c) 7.1 ± 0.9% [54 ± 10 mmol/mol]) underwent two 8-week periods comparing hybrid closed-loop with ultra-rapid insulin lispro and hybrid closed-loop with standard insulin lispro in random order. The same CamAPS FX closed-loop algorithm was used in both periods. Results: In an intention-to-treat analysis, the proportion of time sensor glucose was in target range (3.9–10 mmol/L [70–180 mg/dL]; primary endpoint) was greater with ultra-rapid lispro compared with standard insulin lispro (mean ± SD: 78.7 ± 9.8% vs. 76.2 ± 9.6%; mean difference 2.5 percentage points [95% confidence interval 0.8 to 4.2]; P = 0.005). Mean sensor glucose was lower with ultra-rapid lispro compared with standard insulin lispro (7.9 ± 0.8 mmol/L [142 ± 14 mg/dL] vs. 8.1 ± 0.9 mmol/L [146 ± 16 mg/dL]; P = 0.048). The proportion of time with sensor glucose <3.9 mmol/L [70 mg/dL] was similar between interventions (median [interquartile range] ultra-rapid lispro 2.3% [1.3%–2.7%] vs. standard insulin lispro 2.1% [1.4%–3.3%]; P = 0.33). No severe hypoglycemia or ketoacidosis occurred. Conclusions: The use of ultra-rapid lispro with CamAPS FX hybrid closed-loop increases time in range and reduces mean glucose with no difference in hypoglycemia compared with standard insulin lispro in adults with type 1 diabetes. ClinicalTrials.gov: Trial registration number NCT05257460. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
38. Glucose-responsive insulin delivery for type 1 diabetes: The artificial pancreas story.
- Author
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Bally, Lia, Thabit, Hood, and Hovorka, Roman
- Subjects
- *
INSULIN therapy , *GLUCOSE analysis , *TYPE 1 diabetes , *TREATMENT of diabetes , *ARTIFICIAL pancreases , *DRUG delivery devices - Abstract
Insulin replacement therapy is integral to the management of type 1 diabetes, which is characterised by absolute insulin deficiency. Optimal glycaemic control, as assessed by glycated haemoglobin, and avoidance of hyper- and hypoglycaemic excursions have been shown to prevent diabetes-related complications. Insulin pump use has increased considerably over the past decade with beneficial effects on glycaemic control, quality of life and treatment satisfaction. The advent and progress of ambulatory glucose sensor technology has enabled continuous glucose monitoring based on real-time glucose levels to be integrated with insulin therapy. Low glucose and predictive low glucose suspend systems are currently used in clinical practice to mitigate against hypoglycaemia, and provide the first step towards feedback glucose control. The more advanced technology approach, an artificial pancreas or a closed-loop system, gradually increases and decreases insulin delivery in a glucose-responsive fashion to mitigate against hyper- and hypoglycaemia. Randomised outpatient clinical trials over the past 5 years have demonstrated the feasibility, safety and efficacy of the approach, and the recent FDA approval of the first single hormone closed-loop system establishes a new standard of care for people with type 1 diabetes. [ABSTRACT FROM AUTHOR]
- Published
- 2018
- Full Text
- View/download PDF
39. The artificial pancreas in children and adolescents with type 1 diabetes : bringing closed-loop home
- Author
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Tauschmann, Martin and Hovorka, Roman
- Subjects
616.4 ,type 1 diabetes ,closed-loop insulin delivery ,artificial pancreas ,continuous glucose monitoring ,insulin pump therapy ,children and adolescents - Abstract
Type 1 diabetes is one of the most common chronic conditions in childhood and adolescence. Despite ongoing development of more physiological insulin preparations, recent advancements in insulin pump technology and more accurate blood glucose monitoring, in clinical practice it remains challenging to achieve normoglycaemia whilst reducing the risk of hypoglycaemia, particularly in young people with type 1 diabetes. Closed-loop insulin delivery (the artificial pancreas) is an emerging technology gradually progressing from bench to clinical practice. Closed-loop systems combine glucose sensing with computer-based algorithm informed insulin delivery to provide real-time glucose-responsive insulin administration. The key objective of my thesis is to evaluate the safety, efficacy and utility of closed-loop insulin delivery in children and adolescents with type 1 diabetes outside of the research facility setting. Results of five clinical trials are presented in the main chapters of this thesis. In a mechanistic study, the impact of glucose sensor operation duration on efficacy of overnight closed-loop was investigated comparing closed-loop performance on day 1 of sensor insertion to day 3 to 4 of sensor. Twelve adolescents with type 1 diabetes attended the research facility for two overnight visits. The sequence of the interventions was random. Despite differences in sensor accuracy, overnight CL glucose control informed by sensor glucose on day 1 or day 3-4 after sensor insertion was comparable. The model predictive controller appears to mitigate against sensor inaccuracies. In home settings, overnight closed-loop application was evaluated over three months in 25 children and adolescents with type 1 diabetes aged six to 18 years. The study was conducted at three centres in the UK and adopted a randomised cross-over design. Compared to sensor-augmented pump therapy, overnight home use of closed-loop increased the proportion of time sensor glucose was in target, and reduced mean glucose and hypoglycaemia. Two randomised crossover studies evaluated the safety and efficacy of day-and-night hybrid closed-loop insulin delivery in young people with type 1 diabetes aged 10 to 18 years over seven days, and 21 days, respectively. A total of 24 subjects were enrolled in this single centre trial. Free-living home use of day-and-night closed-loop in suboptimally controlled adolescents with type 1 diabetes was safe, and improved glucose control without increasing the risk of hypoglycaemia. Finally, closed-loop technology was assessed in five very young children (aged one to seven years) with type 1 diabetes in a two-period, crossover study. Closed-loop was used during both 3-week intervention periods, either with standard strength insulin (U100), or with diluted insulin (U20). The order of intervention was random. Free-living home use of day-and-night hybrid closed-loop in very young children with type 1 diabetes was feasible and safe. Glucose control was comparable during both intervention periods. Thus, use of diluted insulin during closed-loop insulin delivery might not be of additional benefit in this population. In conclusion, studies conducted as part of my thesis demonstrate that use of hybrid closed-loop insulin delivery systems in children and adolescents aged one to 18 years in free daily living without remote monitoring or supervision is feasible, safe and effective. My work supports the progression of this technology from research to mainstream clinical practice.
- Published
- 2019
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- View/download PDF
40. Roadmap to the artificial pancreas
- Author
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Hovorka, Roman, Wilinska, Malgorzata E., Chassin, Ludovic J., and Dunger, David B.
- Subjects
- *
ARTIFICIAL organs , *PANCREAS , *INSULIN pumps , *BLOOD sugar monitoring - Abstract
Abstract: Objective: To outline a roadmap to the artificial pancreas (AP) comprising a subcutaneous (sc) glucose monitor, a control algorithm, and an insulin pump delivering sc insulin. Research design and methods: A literature review, personal views, and material from the Juvenile Diabetes Research Foundation have been used to prepare the roadmap. Results: The roadmap identifies sensor reliability but not sensor accuracy as the critical roadblock, which can be addressed by advanced control algorithms combined with safety critical features. It is argued that incremental rather than perfect glucose control should be the objective of the first generation of the AP. Overnight glucose control is more easily achieved than postmeal control and could be the first aim for a commercial AP. Glycated haemoglobin and the risk of hypoglycaemia will remain the primary efficacy and safety measures being accompanied by complementary measures of variability of glucose excursions. Research priorities include the development of AP prototypes incorporating existing glucose monitors with focus on evaluation at home over short- and long-term periods. Conclusions: The AP promises to revolutionise insulin treatment. Building on technological progress in glucose sensing, the true potential of the AP needs to be assessed by building prototypes and evaluations in home settings. [Copyright &y& Elsevier]
- Published
- 2006
- Full Text
- View/download PDF
41. Closed-Loop Insulin Delivery for Glycemic Control in Noncritical Care
- Author
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Lia Bally, Maria M. Wertli, Eveline Andereggen, Christoph Stettler, Hood Thabit, Malgorzata E. Wilinska, Roman Hovorka, Sara Hartnell, Mark L. Evans, Yue Ruan, Anthony P. Coll, University of Zurich, Hovorka, Roman, Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
Blood Glucose ,Male ,Pancreas, Artificial ,medicine.medical_specialty ,medicine.medical_treatment ,030209 endocrinology & metabolism ,610 Medicine & health ,Type 2 diabetes ,2700 General Medicine ,Infusions, Subcutaneous ,Artificial pancreas ,law.invention ,03 medical and health sciences ,Insulin Infusion Systems ,0302 clinical medicine ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,medicine ,Clinical endpoint ,Humans ,Hypoglycemic Agents ,Insulin ,030212 general & internal medicine ,Aged ,Glycemic ,Type 1 diabetes ,business.industry ,General Medicine ,Middle Aged ,medicine.disease ,3. Good health ,Hospitalization ,Diabetes Mellitus, Type 2 ,Female ,10029 Clinic and Policlinic for Internal Medicine ,business - Abstract
BACKGROUND: In patients with diabetes, hospitalization can complicate the achievement of recommended glycemic targets. There is increasing evidence that a closed-loop delivery system (artificial pancreas) can improve glucose control in patients with type 1 diabetes. We wanted to investigate whether a closed-loop system could also improve glycemic control in patients with type 2 diabetes who were receiving noncritical care. METHODS: In this randomized, open-label trial conducted on general wards in two tertiary hospitals located in the United Kingdom and Switzerland, we assigned 136 adults with type 2 diabetes who required subcutaneous insulin therapy to receive either closed-loop insulin delivery (70 patients) or conventional subcutaneous insulin therapy, according to local clinical practice (66 patients). The primary end point was the percentage of time that the sensor glucose measurement was within the target range of 100 to 180 mg per deciliter (5.6 to 10.0 mmol per liter) for up to 15 days or until hospital discharge. RESULTS: The mean (±SD) percentage of time that the sensor glucose measurement was in the target range was 65.8±16.8% in the closed-loop group and 41.5±16.9% in the control group, a difference of 24.3±2.9 percentage points (95% confidence interval [CI], 18.6 to 30.0; P
- Published
- 2018
42. Safety of User-Initiated Intensification of Insulin Delivery Using Cambridge Hybrid Closed-Loop Algorithm
- Author
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Julia Ware, Malgorzata E. Wilinska, Yue Ruan, Janet M. Allen, Charlotte K. Boughton, Sara Hartnell, Lia Bally, Carine de Beaufort, Rachel E. J. Besser, Fiona M. Campbell, Katharine Draxlbauer, Daniela Elleri, Mark L. Evans, Elke Fröhlich-Reiterer, Atrayee Ghatak, Sabine E. Hofer, Thomas M. Kapellen, Lalantha Leelarathna, Julia K. Mader, Womba M. Mubita, Parth Narendran, Tina Poettler, Birgit Rami-Merhar, Martin Tauschmann, Tabitha Randell, Hood Thabit, Ajay Thankamony, Nicola Trevelyan, Roman Hovorka, Ware, Julia [0000-0002-4497-0979], Boughton, Charlotte K [0000-0003-3272-9544], Besser, Rachel EJ [0000-0002-4645-6324], Evans, Mark L [0000-0001-8122-8987], Leelarathna, Lalantha [0000-0001-9602-1962], Mader, Julia K [0000-0001-7854-4233], Thabit, Hood [0000-0001-6076-6997], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
closed-loop ,hypoglycemia ,automated insulin delivery ,type 1 diabetes ,artificial pancreas ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Internal Medicine ,Bioengineering ,610 Medicine & health ,personalized medicine ,610 Medizin und Gesundheit - Abstract
Objective: Many hybrid closed-loop (HCL) systems struggle to manage unusually high glucose levels as experienced with intercurrent illness or pre-menstrually. Manual correction boluses may be needed, increasing hypoglycemia risk with overcorrection. The Cambridge HCL system includes a user-initiated algorithm intensification mode (“Boost”), activation of which increases automated insulin delivery by approximately 35%, while remaining glucose-responsive. In this analysis, we assessed the safety of “Boost” mode. Methods: We retrospectively analyzed data from closed-loop studies involving young children (1-7 years, n = 24), children and adolescents (10-17 years, n = 19), adults (≥24 years, n = 13), and older adults (≥60 years, n = 20) with type 1 diabetes. Outcomes were calculated per participant for days with ≥30 minutes of “Boost” use versus days with no “Boost” use. Participants with Results: Eight weeks of data for 76 participants were analyzed. There was no difference in time spent 300 mg/dL was 1.39 percentage points (1.01 to 1.77; P < .001) higher on “Boost” days, with higher mean glucose and lower time in target range ( P < .001). Conclusions: Use of an algorithm intensification mode in HCL therapy is safe across all age groups with type 1 diabetes. The higher time in hyperglycemia observed on “Boost” days suggests that users are more likely to use algorithm intensification on days with extreme hyperglycemic excursions.
- Published
- 2022
43. Training and Support for Hybrid Closed-Loop Therapy
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Janet M. Allen, Roman Hovorka, Sara Hartnell, Charlotte K. Boughton, Julia Fuchs, Boughton, Charlotte [0000-0003-3272-9544], Fuchs, Julia [0000-0002-4497-0979], Hovorka, Roman [0000-0003-2901-461X], Apollo - University of Cambridge Repository, and Boughton, Charlotte K [0000-0003-3272-9544]
- Subjects
Blood Glucose ,medicine.medical_specialty ,Emerging technologies ,Computer science ,type 1 diabetes ,Endocrinology, Diabetes and Metabolism ,Biomedical Engineering ,Bioengineering ,Artificial pancreas ,Physical medicine and rehabilitation ,Quality of life (healthcare) ,Insulin Infusion Systems ,Commentaries ,Internal Medicine ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,hybrid closed-loop ,Glycemic ,Type 1 diabetes ,training ,artificial pancreas ,Blood Glucose Self-Monitoring ,medicine.disease ,Diabetes Mellitus, Type 1 ,Research studies ,Quality of Life ,Closed loop - Abstract
Hybrid closed-loop therapy is an emerging technology transforming the management of type 1 diabetes (T1D). Research studies demonstrate glycemic and quality of life benefits of hybrid closed-loop therapy for people with T1D. Translating these outcomes into standard clinical practice is critical for reimbursement and improving access to this technology. High-quality training is essential for achieving optimal outcomes with hybrid closed-loop therapy. Basic diabetes skills and tasks are as important, or even more important, with closed-loop therapy than with standard insulin therapy and need to be reiterated. Establishing expectations of hybrid closed-loop therapy clearly at the outset promotes long-term usage and optimal outcomes. We share key aspects of training and support for users of commercially available hybrid closed-loop systems and consider who may benefit from this technology.
- Published
- 2022
- Full Text
- View/download PDF
44. Automated Insulin Delivery in Adults
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Charlotte K. Boughton, Roman Hovorka, Boughton, Charlotte [0000-0003-3272-9544], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Blood Glucose ,Male ,Pancreas, Artificial ,medicine.medical_specialty ,Hospitalized patients ,Endocrinology, Diabetes and Metabolism ,Pregnancy in Diabetics ,Insulin delivery ,Artificial pancreas ,030209 endocrinology & metabolism ,Psychosocial impact ,Article ,Automation ,03 medical and health sciences ,Insulin Infusion Systems ,0302 clinical medicine ,Endocrinology ,Pregnancy ,medicine ,Humans ,Insulin ,Intensive care medicine ,Type 1 diabetes ,business.industry ,Blood Glucose Self-Monitoring ,Equipment Design ,medicine.disease ,Hybrid closed-loop ,Hospitalization ,Clinical Practice ,Diabetes Mellitus, Type 1 ,Clinical evidence ,Hyperglycemia ,030220 oncology & carcinogenesis ,Research studies ,Female ,business ,Inpatient diabetes ,Psychosocial - Abstract
Hybrid closed-loop (artificial pancreas) systems have recently been introduced into clinical practice for adults with type 1 diabetes. This reflects successful translation from research studies in highly supervised settings to evaluation of the technology in free-living home settings. We review the different closed-loop approaches and the key clinical evidence supporting adoption of hybrid closed-loop systems for adults with type 1 diabetes. We also discuss the growing evidence for automated insulin delivery in pregnant women and in hospitalized patients with hyperglycemia. We consider the psychosocial impact of closed-loop systems and the challenges and potential future advancements for automated insulin delivery.
- Published
- 2020
45. Closed-loop technology: a practical guide
- Author
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Hartnell, S, Fuchs, J, Boughton, CK, Hovorka, R, Boughton, Charlotte [0000-0003-3272-9544], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
training and education ,hybrid closed loop ,type 1 diabetes ,artificial pancreas - Abstract
Hybrid closed-loop insulin delivery has been shown to be safe and effective in improving time in target glucose range and reducing the risk of hypoglycaemia for people with type 1 diabetes. Benefits in terms of reduction in diabetes burden have also been demonstrated. After decades of research and development, four hybrid closed-loop systems are now commercially available in the UK with more expected soon. We review the hybrid closed-loop systems currently available – Tandem t:slim with Control-IQ, CamAPS FX, Medtronic MiniMed 670G and second generation, Medtronic MiniMed 780G – and discuss the components and key features of these technologies. As hybrid closed-loop systems become more widely available, education and training of health care professionals and users will be pivotal in ensuring the research benefits are translated into real-world outcomes. Users need to be supported to make appropriate choices about the different systems available and be guided in realistic expectations regarding outcomes. Attention must be given to the key training and education requirements and how these differ from traditional insulin pump therapy. Training and interpretation in reviewing closed-loop data are essential for post-initiation reviews and optimisation. Developments in diabetes technology are progressing rapidly and other hybrid closed-loop systems currently in pivotal clinical trials may soon become commercially available. We also consider other important progress in this field including the use of faster-acting insulin analogues, adjunctive therapies such as SGLT2 inhibitors and dual hormone closed-loop systems.
- Published
- 2021
- Full Text
- View/download PDF
46. Pharmacokinetics of insulin lispro in type 2 diabetes during closed-loop insulin delivery.
- Author
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Ruan, Yue, Thabit, Hood, Kumareswaran, Kavita, and Hovorka, Roman
- Subjects
- *
PHARMACOKINETICS , *TYPE 2 diabetes , *CLOSED loop systems , *DRUG delivery systems , *ACQUISITION of data , *METABOLIC clearance rate - Abstract
Insulin pharmacokinetics is not well understood during continuous subcutaneous insulin infusion in type 2 diabetes (T2D). We analyzed data collected in 11 subjects with T2D [6 male, 9 white European and two of Indian ethnicity; age 59.7(12.1) years, BMI 30.1(3.9) kg/m 2 , fasting C-peptide 1002.2(365.8) pmol/l, fasting plasma glucose 9.6(2.2) mmol/l, diabetes duration 8.0(6.2) years and HbA1c 8.3(0.8)%; mean(SD)] who underwent a 24-h study investigating closed-loop insulin delivery at the Wellcome Trust Clinical Research Facility, Cambridge, UK. Subcutaneous delivery of insulin lispro was modulated every 15 min according to a model predictive control algorithm. Two complementary insulin assays facilitated discrimination between exogenous (lispro) and endogenous plasma insulin concentrations measured every 15–60 min. Lispro pharmacokinetics was represented by a linear two-compartment model whilst parameters were estimated using a Bayesian approach applying a closed-form model solution. The time-to-peak of lispro absorption ( t max ) was 109.6 (75.5–120.5) min [median (interquartile range)] and the metabolic clearance rate ( MCR I ) 1.26 (0.87–1.56) × 10 −2 l/kg/min. MCR I was negatively correlated with fasting C-peptide ( r s = −0.84; P = .001) and with fasting plasma insulin concentration ( r s = −0.79; P = .004). In conclusion, compartmental modelling adequately represents lispro kinetics during continuous subcutaneous insulin infusion in T2D. Fasting plasma C-peptide or fasting insulin may be predictive of lispro metabolic clearance rate in T2D but further investigations are warranted. [ABSTRACT FROM AUTHOR]
- Published
- 2014
- Full Text
- View/download PDF
47. New closed-loop insulin systems
- Author
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Roman Hovorka, Charlotte K. Boughton, Boughton, Charlotte K [0000-0003-3272-9544], Hovorka, Roman [0000-0003-2901-461X], Apollo - University of Cambridge Repository, and Boughton, Charlotte K. [0000-0003-3272-9544]
- Subjects
Adult ,Blood Glucose ,Pancreas, Artificial ,Glucose control ,Computer science ,Endocrinology, Diabetes and Metabolism ,medicine.medical_treatment ,030209 endocrinology & metabolism ,Artificial pancreas ,Review ,Insulin 100 – celebrating 100 years of insulin ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,Insulin Infusion Systems ,Inventions ,Diabetes management ,Internal Medicine ,medicine ,Humans ,Insulin ,030212 general & internal medicine ,Child ,Type 1 diabetes ,Blood Glucose Self-Monitoring ,Correction ,medicine.disease ,Clinical Practice ,Hybrid closed-loop ,Diabetes Mellitus, Type 1 ,Risk analysis (engineering) ,Automated insulin delivery ,Closed loop - Abstract
Graphical abstract Advances in diabetes technologies have enabled the development of automated closed-loop insulin delivery systems. Several hybrid closed-loop systems have been commercialised, reflecting rapid transition of this evolving technology from research into clinical practice, where it is gradually transforming the management of type 1 diabetes in children and adults. In this review we consider the supporting evidence in terms of glucose control and quality of life for presently available closed-loop systems and those in development, including dual-hormone closed-loop systems. We also comment on alternative ‘do-it-yourself’ closed-loop systems. We remark on issues associated with clinical adoption of these approaches, including training provision, and consider limitations of presently available closed-loop systems and areas for future enhancements to further improve outcomes and reduce the burden of diabetes management. Supplementary Information The online version contains a slideset of the figures for download available at 10.1007/s00125-021-05391-w.
- Published
- 2020
48. The Artificial Pancreas
- Author
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Charlotte K. Boughton, Roman Hovorka, Boughton, Charlotte [0000-0003-3272-9544], Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
Pancreas, Artificial ,Transplantation ,medicine.medical_specialty ,Type 1 diabetes ,business.industry ,Insulin ,medicine.medical_treatment ,Insulin delivery ,Usability ,medicine.disease ,Artificial pancreas ,Clinical Practice ,Diabetes Mellitus, Type 1 ,Insulin Infusion Systems ,Diabetes mellitus ,Immunology and Allergy ,Medicine ,Humans ,Hypoglycemic Agents ,business ,Intensive care medicine - Abstract
Purpose of review: Advances in diabetes technologies have enabled the development of artificial pancreas (closed-loop) systems for people with diabetes. We review the key studies which have led to the adoption of the artificial pancreas in clinical practice and consider ongoing challenges and areas for future enhancements. Recent findings: Studies have demonstrated safety and efficacy of closed-loop insulin delivery systems in free-living settings over periods of up to 6 months for children and adults with type 1 diabetes. Since 2017, four hybrid closed-loop systems have been approved by regulatory bodies worldwide, but these systems are not entirely automated, requiring user interaction to deliver mealtime insulin boluses. Improving usability of these devices in the real-world setting is an important challenge. Summary: The artificial pancreas has become the gold standard for the treatment of type 1 diabetes. First generation systems are increasingly being adopted in clinical practice, however further work is required, developing advanced systems and faster acting insulin analogues to allow complete automation and further reduce the burden of type 1 diabetes., upported by the National Institute of Health Research Cambridge Biomedical Research Centre, Efficacy and Mechanism Evaluation National Institute for Health Research, The Leona M. & Harry B. Helmsley Charitable Trust, JDRF, National Institute of Diabetes and Digestive and Kidney Diseases and Diabetes UK.
- Published
- 2020
49. Glucose-responsive insulin delivery for type 1 diabetes: The artificial pancreas story
- Author
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Lia Bally, Roman Hovorka, Hood Thabit, Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
Blood Glucose ,Pancreas, Artificial ,Insulin pump ,medicine.medical_specialty ,medicine.medical_treatment ,Control algorithm ,Pharmaceutical Science ,Artificial pancreas ,030209 endocrinology & metabolism ,Insulin pump therapy ,03 medical and health sciences ,Insulin Infusion Systems ,0302 clinical medicine ,Quality of life ,medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Closed-loop ,030212 general & internal medicine ,Intensive care medicine ,Continuous glucose monitoring ,Feedback, Physiological ,Glycated Hemoglobin ,Type 1 diabetes ,business.industry ,medicine.disease ,Hypoglycemia ,3. Good health ,Clinical trial ,Diabetes Mellitus, Type 1 ,Hyperglycemia ,Ambulatory ,Quality of Life ,business ,Hormone - Abstract
Insulin replacement therapy is integral to the management of type 1 diabetes, which is characterised by absolute insulin deficiency. Optimal glycaemic control, as assessed by glycated haemoglobin, and avoidance of hyper- and hypoglycaemic excursions have been shown to prevent diabetes-related complications. Insulin pump use has increased considerably over the past decade with beneficial effects on glycaemic control, quality of life and treatment satisfaction. The advent and progress of ambulatory glucose sensor technology has enabled continuous glucose monitoring based on real-time glucose levels to be integrated with insulin therapy. Low glucose and predictive low glucose suspend systems are currently used in clinical practice to mitigate against hypoglycaemia, and provide the first step towards feedback glucose control. The more advanced technology approach, an artificial pancreas or a closed-loop system, gradually increases and decreases insulin delivery in a glucose-responsive fashion to mitigate against hyper- and hypoglycaemia. Randomised outpatient clinical trials over the past 5 years have demonstrated the feasibility, safety and efficacy of the approach, and the recent FDA approval of the first single hormone closed-loop system establishes a new standard of care for people with type 1 diabetes.
- Published
- 2018
50. Novel Single-Site Device for Conjoined Glucose Sensing and Insulin Infusion: Performance Evaluation in Diabetes Patients During Home-Use
- Author
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Mathias Tschaikner, Werner Regittnig, Roman Hovorka, Kevin Powell, Miro Jungklaus, Thomas R. Pieber, Steve Lane, Martin Fritz, Martin Ellmerer, Hovorka, Roman [0000-0003-2901-461X], and Apollo - University of Cambridge Repository
- Subjects
Adult ,Blood Glucose ,Male ,Pancreas, Artificial ,Adolescent ,0206 medical engineering ,Biomedical Engineering ,Glucose sensing ,02 engineering and technology ,Artificial pancreas ,Insulin infusion ,Young Adult ,Insulin Infusion Systems ,Interquartile range ,Diabetes mellitus ,Medicine ,Humans ,Hypoglycemic Agents ,Insulin ,Aged ,Type 1 diabetes ,business.industry ,Continuous glucose monitoring ,Blood Glucose Self-Monitoring ,Home use ,Middle Aged ,medicine.disease ,020601 biomedical engineering ,Diabetes Mellitus, Type 1 ,Anesthesia ,Female ,business - Abstract
Objective: This study evaluated a novel diabetes treatment device that combines commercially available continuous glucose monitoring and insulin infusion technology in such a way as to perform insulin delivery and glucose sensing through a single skin insertion site (single-port device). Methods: Ten type 1 diabetes patients used the device for up to six days in their home/work environment for open-loop insulin delivery and glucose sensing. On an additional day, the device was used in combination with an algorithm to perform automated closed-loop glucose control under hospital settings. To assess the performance of the device, capillary blood glucose concentrations were frequently determined and a continuous glucose sensor was additionally worn by the patients. Results: The average mean absolute relative deviation from blood glucose concentrations obtained for the sensor of the device was low (median, 13.0%; interquartile range, 10.5–16.7%; n = 10) and did not differ from that of the additionally worn glucose sensor (versus 13.9%; 11.9–15.3%; P = 0.922). Furthermore, insulin delivery with the single-port device was reliable and safe during home use and, when performed in combination with the control algorithm, was adequate to achieve and maintain near normoglycemia. Conclusion: Our data show the feasibility of open- and closed-loop glucose control in diabetes patients using a device that combines insulin delivery and glucose sensing at a single tissue site. Significance: The reduction in device size and invasiveness achieved by this design may largely increase patient convenience and enhance acceptance of diabetes treatment with continuous glucose monitoring and insulin delivery technology.
- Published
- 2019
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