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Closed-Loop Systems

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Abstract

Closed-loop systems, so-called artificial pancreas, aim at driving insulin delivery by blood glucose levels in patients with diabetes treated with insulin. They include a continuous glucose monitoring device, a control algorithm and an insulin infusion pump. The control algorithm is the key of the system since it commands insulin infusion in order to maintain blood glucose in a predefined target range or close to a target glucose level. Algorithm prescriptions are based on past, current and predicted glucose levels according to different designs: proportional-integral-derivative (PID), model predictive control (MPC) or fuzzy logic. The last decade has shown dramatic advances toward the use in free-life of closed-loop systems through demonstrations of feasibility, safety and efficacy in successive hospital, transitional and outpatient trials. Permanent innovation has contributed to this progress by more accurate sensors for glucose monitoring, wearable platforms for running algorithms and wireless communication between devices. The approval by the FDA of a first closed-loop insulin delivery system for routine therapy of type 1 diabetes in September 2016 illustrates the maturity reached by the artificial pancreas after about 40 years of development.

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References

  1. Albisser AM, Leibel BS, Ewart TG, Davidovac Z, Botz CK, Zingg W. An artificial endocrine pancreas. Diabetes. 1974;23:389–96.

    Article  CAS  Google Scholar 

  2. Mirouze J, Selam JL, Pham TC, Cavadore D. Evaluation of exogenous insulin homeostasis by the artificial pancreas in insulin-dependent diabetes. Diabetologia. 1977;13:273–8.

    Article  CAS  Google Scholar 

  3. Shichiri M, Kawamori R, Yamasaki Y, Inoue M, Shigeta Y, Abe H. Computer algorithm for the artificial pancreatic beta cell. Artif Organs. 1978;2(Suppl):247–50.

    Google Scholar 

  4. Clemens AH, Chang PH, Myers RW. The development of Biostator, a glucose-controlled insulin infusion system (GCIIS). Horm Metab Res. 1977;(Suppl):23–33.

    Google Scholar 

  5. The Diabetes Control and Complications Trial Research Group (DCCT). The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med. 1993;329:977–86.

    Article  Google Scholar 

  6. Mastrototaro J. The MiniMed Continuous Glucose Monitoring System. Diabetes Technol Ther. 2000;2(Suppl 1):S13–8.

    Article  Google Scholar 

  7. Kovatchev BP, Breton MD, Dalla Man C, Cobelli C. In silico preclinical trials: a proof of concept in closed-loop control of type 1 diabetes. J Diabetes Sci Technol. 2009;3:44–55.

    Article  Google Scholar 

  8. Renard E. Implantable closed loop glucose-sensing and insulin delivery: the future for insulin pump therapy. Curr Opin Pharmacol. 2002;2:708–16.

    Article  CAS  Google Scholar 

  9. Renard E, Costalat G, Chevassus H, Bringer J. Artificial beta cell: clinical experience toward an implantable closed-loop insulin delivery system. Diabetes Metab. 2006;32:497–502.

    Article  CAS  Google Scholar 

  10. Renard E, Place J, Cantwell M, Chevassus H, Palerm CC. Closed-loop insulin delivery using a subcutaneous glucose sensor and intraperitoneal insulin delivery: feasibility study testing a new model for the artificial pancreas. Diabetes Care. 2010;33:121–7.

    Article  CAS  Google Scholar 

  11. Hovorka R, Chassin LJ, Wilinska ME, et al. Closing the loop: the ADICOL experience. Diabetes Technol Ther. 2004;6:307–18.

    Article  CAS  Google Scholar 

  12. Steil GM, Rebrin K, Darwin C, Hariri F, Saad MF. Feasibility of automating insulin delivery for the treatment of type 1 diabetes. Diabetes. 2006;55:3344–50.

    Article  CAS  Google Scholar 

  13. Weinzimer SA, Steil GM, Swan KL, Dziura J, Kurtz N, Tamborlane WV. Fully automated closed-loop insulin delivery versus semi-automated hybrid control in pediatric patients with type 1 diabetes using an artificial pancreas. Diabetes Care. 2008;31:934–9.

    Article  Google Scholar 

  14. Doyle FJ 3rd, Huyett LM, Lee JB, et al. Closed-loop artificial pancreas systems: engineering the algorithms. Diabetes Care. 2014;37:1191–7.

    Article  Google Scholar 

  15. Hovorka R, Allen JM, Elleri D, et al. Manual closed-loop insulin delivery in children and adolescents with type 1 diabetes: a phase 2 randomised crossover trial. Lancet. 2010;375:743–51.

    Article  CAS  Google Scholar 

  16. Kovatchev B, Cobelli C, Renard E, et al. Multinational study of subcutaneous model-predictive closed-loop control in type 1 diabetes mellitus: summary of the results. J Diabetes Sci Technol. 2010;4:1374–81.

    Article  Google Scholar 

  17. Russell SJ, El-Khatib FH, Nathan DM, Magyar KL, Jiang J, Damiano ER. Blood glucose control in type 1 diabetes with a bihormonal bionic endocrine pancreas. Diabetes Care. 2012;35:2148–55.

    Article  CAS  Google Scholar 

  18. Patek SD, Magni L, Dassau E, et al. Modular closed-loop control of diabetes. IEEE Trans Biomed Eng. 2012;29:2986–3000.

    Article  Google Scholar 

  19. Breton M, Farret A, Bruttomesso D, et al. Fully integrated artificial pancreas in type 1 diabetes: modular closed-loop glucose control maintains near normoglycemia. Diabetes. 2012;61:2230–7.

    Article  CAS  Google Scholar 

  20. Phillip M, Battelino T, Atlas E, et al. Nocturnal glucose control with an artificial pancreas at a diabetes camp. N Engl J Med. 2013;368:824–33.

    Article  CAS  Google Scholar 

  21. Luijf YM, Devries JH, Zwinderman K, et al. Day and night closed-loop control in adults with type 1 diabetes mellitus: a comparison of two closed-loop algorithms driving continuous subcutaneous insulin infusion versus patient self-management. Diabetes Care. 2013;36:3882–7.

    Article  CAS  Google Scholar 

  22. Ly TT, Breton MD, Keith-Hynes P, et al. Overnight glucose control win automated, unified safety system in children and adolescents with type 1 diabetes at diabetes camp. Diabetes Care. 2014;37:2310–6.

    Article  CAS  Google Scholar 

  23. Ly TT, Roy A, Grosman D, et al. Day and night closed-loop control using the integrated Medtronic hybrid closed-loop system in type 1 diabetes at diabetes camp. Diabetes Care. 2015;38:1205–11.

    Article  Google Scholar 

  24. Russell SJ, El-Khatib FH, Sinha M, et al. Outpatient glycemic control with a bionic pancreas in type 1 diabetes. N Engl J Med. 2014;371:313–25.

    Article  Google Scholar 

  25. Cobelli C, Renard E, Kovatchev BP, et al. Pilot studies of wearable outpatient artificial pancreas in type 1 diabetes. Diabetes Care. 2012;35:e65–7.

    Article  Google Scholar 

  26. Kovatchev BP, Renard E, Cobelli C, et al. Feasibility of outpatient fully integrated closed-loop control: first studies of wearable artificial pancreas. Diabetes Care. 2013;36:1851–8.

    Article  Google Scholar 

  27. Kovatchev BP, Renard E, Cobelli C, et al. Safety of outpatient closed-loop control: first randomized crossover trials of a wearable artificial pancreas. Diabetes Care. 2014;37:1789–96.

    Article  CAS  Google Scholar 

  28. Del Favero S, Place J, Kropff J, et al. Multicenter outpatient dinner/overnight reduction of hypoglycemia and increased time of glucose in target with a wearable artificial pancreas using modular model predictive control in adults with type 1 diabetes. Diabetes Obes Metab. 2015;17:468–76.

    Article  Google Scholar 

  29. Brown SA, Kovatchev BP, Breton MD, et al. Multinight « bedside » closed-loop control for patients with type 1 diabetes. Diabetes Technol Ther. 2015;17:203–9.

    Article  CAS  Google Scholar 

  30. Nimri R, Muller I, Atlas E, et al. MD-Logic overnight control for 6 weeks of home use in patients with type 1 diabetes: randomized crossover trial. Diabetes Care. 2014;37:3025–32.

    Article  CAS  Google Scholar 

  31. Thabit H, Lubina-Solomon A, Stadler M, et al. Home use of closed-loop insulin delivery for overnight glucose control in adults with type 1 diabetes: a 4-week, multicentre, randomised crossover study. Lancet Diabetes Endocrinol. 2014;2:701–9.

    Article  CAS  Google Scholar 

  32. Kropff J, Del Favero S, Place J, et al. 2 month evening and night closed-loop glucose control in patients with type 1 diabetes under free-living conditions: a randomised crossover trial. Lancet Diabetes Endocrinol. 2015;3:939–47.

    Article  Google Scholar 

  33. Renard E, Farret A, Kropff J, et al. Day-and-night closed-loop glucose control in patients with type 1 diabetes under free-living conditions: results of a single-arm 1-month experience compared with a previously reported feasibility study of evening and night at home. Diabetes Care. 2016;39:1151–60.

    Article  CAS  Google Scholar 

  34. Anderson SM, Raghinaru D, Pinsker JE, et al. Multinational home use of closed-loop control is safe and effective. Diabetes Care. 2016;39:1143–50.

    Article  Google Scholar 

  35. Thabit H, Tauschmann M, Allen JM, et al. Home use of an artificial beta cell in type 1 diabetes. N Engl J Med. 2015;373:2129–40.

    Article  CAS  Google Scholar 

  36. Kovatchev B, Cheng P, Anderson SM, et al. Feasibility of long-term closed-loop control: a multicenter 6-month trial of 24/7 automated insulin delivery. Diabetes Technol Ther. 2017;19:18–24.

    Article  CAS  Google Scholar 

  37. Bergenstal RM, Garg S, Weinzimer SA, et al. Safety of a hybrid closed-loop insulin delivery system in patients with type 1 diabetes. JAMA. 2016;316:1407–8.

    Article  Google Scholar 

  38. Garg SK, Weinzimer SA, Tamborlane WV, et al. Glucose outcomes with the in-home use of a hybrid closed-loop insulin delivery system in adolescents and adults with type 1 diabetes. Diabetes Technol Ther. 2017;19:155–63.

    Article  CAS  Google Scholar 

  39. Buckingham BA, Forlenza GP, Pinsker JE, et al. Safety and feasibility of the OmniPod hybrid closed-loop system in adult, adolescent, and pediatric patients with type 1 diabetes using a personalized model predictive control algorithm. Diabetes Technol Ther. 2018;20:257–62.

    Article  CAS  Google Scholar 

  40. Benhamou PY, Huneker E, Franc S, et al. Customization of home closed-loop insulin delivery in adult patients with type 1 diabetes, assisted with structured remote monitoring: the pilot WP7 Diabeloop study. Acta Diabetol. 2018;55:549–56.

    Article  CAS  Google Scholar 

  41. Blauw H, van Bon AC, Koops R, et al. Performance and safety of an integrated bihormonal artificial pancreas for fully automated glucose control at home. Diabetes Obes Metab. 2016;18:671–7.

    Article  CAS  Google Scholar 

  42. Abitbol A, Rabasa-Lhoret R, Messier V, et al. Overnight glucose control with dual- and single-hormone artificial pancreas in type 1 diabetes with hypoglycemia unawareness: a randomized controlled trial. Diabetes Technol Ther. 2018;20:189–96.

    Article  CAS  Google Scholar 

  43. Thabit H, Hovorka R. Coming of age: the artificial pancreas for type 1 diabetes. Diabetologia. 2016;59:1795–805.

    Article  CAS  Google Scholar 

  44. Bekiari E, Kitsios K, Thabit H, et al. Artificial pancreas treatment for outpatients with type 1 diabetes: systematic review and meta-analysis. BMJ. 2018;361:k1310.

    Article  Google Scholar 

  45. Dassau E, Renard E, Place J, et al. Intraperitoneal insulin delivery provides superior glycaemic regulation to subcutaneous insulin delivery in model predictive control-based fully-automated artificial pancreas in patients with type 1 diabetes: a pilot study. Diabetes Obes Metab. 2017;19:1698–705.

    Article  CAS  Google Scholar 

  46. Gibney M, Xue Z, Swinney M, Bialonczyk D, Hirsch L. Reduced silent occlusions with a novel catheter infusion set (BD FlowSmart): results from two open-label comparative studies. Diabetes Technol Ther. 2016;18:136–43.

    Article  CAS  Google Scholar 

  47. Howsmon DP, Baysal N, Buckingham BA, et al. Real-time detection of infusion site failures in a closed-loop artificial pancreas. J Diabetes Sci Technol. 2018;12:599–607.

    Article  Google Scholar 

  48. Facchinetti A, Sparacino G, Guerra S, et al. Real-time improvement of continuous glucose monitoring accuracy: the smart sensor concept. Diabetes Care. 2013;36:793–800.

    Article  CAS  Google Scholar 

  49. Pinsker JE, Lee JB, Dassau E, et al. Randomized crossover comparison of personalized MPC and PID control algorithms for the artificial pancreas. Diabetes Care. 2016;39:1135–42.

    Article  Google Scholar 

  50. Ly TT, Buckingham BA, DeSalvo DJ, et al. Day and night closed-loop control using the unified safety system in adolescents with type 1 diabetes at camp. Diabetes Care. 2016;39:e106–7.

    Article  CAS  Google Scholar 

  51. Magni L, Forgione M, Toffanin C, et al. Run-to-run tuning of model predictive control for type 1 diabetes subjects: in silico trial. J Diabetes Sci Technol. 2009;3:1091–6.

    Article  Google Scholar 

  52. Messori M, Kropff J, Del Favero S, et al. Individually adaptive artificial pancreas in subjects with type 1 diabetes: a one-month proof-of-concept trial in free-living conditions. Diabetes Technol Ther. 2017;19:560–71.

    Article  CAS  Google Scholar 

  53. Dassau E, Pinsker JE, Kudva YC, et al. Twelve-week 24/7 ambulatory artificial pancreas with weekly adaptation of insulin delivery settings: effect on hemoglobin A1c and hypoglycemia. Diabetes Care. 2017;40:1719–26.

    Article  CAS  Google Scholar 

  54. Forlenza GP, Cameron FM, Ly TT, et al. Fully closed-loop multiple model probabilistic predictive controller artificial pancreas performance in adolescents and adults in a supervised hotel setting. Diabetes Technol Ther. 2018;20:335–43.

    Article  Google Scholar 

  55. Samadi S, Rashid M, Turksoy K, et al. Automatic detection and estimation of unannounced meals for multivariable artificial pancreas system. Diabetes Technol Ther. 2018;20:235–46.

    Article  CAS  Google Scholar 

  56. Weinzimer SA, Sherr JL, Cengiz E, et al. Effect of pramlintide on prandial glycemic excursions during closed-loop control in adolescents and young adults with type 1 diabetes. Diabetes Care. 2012;35:1994–9.

    Article  CAS  Google Scholar 

  57. Sherr JL, Patel NS, Michaud CI, et al. Mitigating meal-related glycemic excursions in an insulin-sparing manner during closed-loop insulin delivery: the beneficial effects of adjunctive pramlintide and liraglutide. Diabetes Care. 2016;39:1127–34.

    Article  CAS  Google Scholar 

  58. El-Khatib FH, Balliro C, Hillard MA, et al. Home use of a bihormonal bionic pancreas versus insulin pump therapy in adults with type 1 diabetes: a multicentre randomised crossover trial. Lancet. 2017;389:369–80.

    Article  CAS  Google Scholar 

  59. Haidar A, Legault L, Matteau-Pelletier L, et al. Outpatient overnight glucose control with dual-hormone artificial pancreas, single-hormone artificial pancreas, or conventional insulin pump therapy in children and adolescents with type 1 diabetes: an open-label, randomised controlled trial. Lancet Diabetes Endocrinol. 2015;3:595–604.

    Article  CAS  Google Scholar 

  60. Taleb N, Emami A, Suppere C, et al. Efficacy of single-hormone and dual-hormone artificial pancreas during continuous and interval exercise in adult patients with type 1 diabetes: randomised controlled crossover trial. Diabetologia. 2016;59(12):2561–71.

    Article  CAS  Google Scholar 

  61. Taleb N, Haidar A, Messier V, et al. Glucagon in the artificial pancreas systems: potential benefits and safety profile of future chronic use. Diabetes Obes Metab. 2017;19(1):13–23.

    Article  CAS  Google Scholar 

  62. Renard E, Cobelli C, Kovatchev BP. Closed loop developments to improve glucose control at home. Diabetes Res Clin Pract. 2013;102:79–85.

    Article  Google Scholar 

  63. Dauber A, Corcia L, Safer J, Agus MS, Einis S, Steil GM. Closed-loop insulin therapy improves glycemic control in children aged <7 years: a randomized controlled trial. Diabetes Care. 2013;36:222–7.

    Article  CAS  Google Scholar 

  64. Del Favero S, Boscari F, Messori M, et al. Randomized summer camp crossover trial in 5- to 9-year-old children: outpatient wearable artificial pancreas is feasible and safe. Diabetes Care. 2016;39:1180–5.

    Article  Google Scholar 

  65. Russell SJ, Hillard MA, Balliro C, et al. Day and night glycaemic control with a bionic pancreas versus conventional insulin pump therapy in preadolescent children with type 1 diabetes: a randomised crossover trial. Lancet Diabetes Endocrinol. 2016;4:233–43.

    Article  Google Scholar 

  66. Kumareswaran K, Thabit H, Leelarathna L, et al. Feasibility of closed-loop insulin delivery in type 2 diabetes: a randomized controlled study. Diabetes Care. 2014;37:1198–203.

    Article  CAS  Google Scholar 

  67. Murphy HR, Elleri D, Allen JM, et al. Closed-loop insulin delivery during pregnancy complicated by type 1 diabetes. Diabetes Care. 2011;34:406–11.

    Article  CAS  Google Scholar 

  68. Stewart ZA, Wilinska ME, Hartnell S, et al. Closed-loop insulin delivery during pregnancy in women with type 1 diabetes. N Engl J Med. 2016;375:644–54.

    Article  CAS  Google Scholar 

  69. Stewart ZA, Wilinska ME, Hartnell S, et al. Day-and-night closed-loop insulin delivery in a broad population of pregnant women with type 1 diabetes: a randomized controlled crossover trial. Diabetes Care. 2018;41(7):1391–9.

    Article  Google Scholar 

  70. Kovatchev B. The artificial pancreas in 2017: the year of transition from research to clinical practice. Nat Rev Endocrinol. 2018;14:74–6.

    Article  Google Scholar 

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Authors and Affiliations

  1. Department of Endocrinology, Diabetes, Nutrition, Montpellier University Hospital, University of Montpellier, Montpellier, France

    Eric Renard

  2. INSERM Clinical Investigation Centre CIC 1411, University of Montpellier, Montpellier, France

    Eric Renard

  3. Institute of Functional Genomics, UMR CNRS 5203, INSERM U1191, University of Montpellier, Montpellier, France

    Eric Renard

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  1. Eric Renard
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Correspondence to Eric Renard .

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Editors and Affiliations

  1. Department of Endocrinology, Centre Hospitalier Universitaire de Caen, CAEN CEDEX 9, France

    Yves Reznik

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Renard, E. (2019). Closed-Loop Systems. In: Reznik, Y. (eds) Handbook of Diabetes Technology. Springer, Cham. https://doi.org/10.1007/978-3-319-98119-2_6

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  • DOI: https://doi.org/10.1007/978-3-319-98119-2_6

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