Abstract:
The control of diabetes is an interdisciplinary endeavor, which includes a significant biomedical engineering component, with traditions of success beginning in the early...Show MoreMetadata
Abstract:
The control of diabetes is an interdisciplinary endeavor, which includes a significant biomedical engineering component, with traditions of success beginning in the early 1960s. It began with modeling of the insulin-glucose system, and progressed to large-scale in silico experiments, and automated closed-loop control (artificial pancreas). Here, we follow these engineering efforts through the last, almost 50 years. We begin with the now classic minimal modeling approach and discuss a number of subsequent models, which have recently resulted in the first in silico simulation model accepted as substitute to animal trials in the quest for optimal diabetes control. We then review metabolic monitoring, with a particular emphasis on the new continuous glucose sensors, on the analyses of their time-series signals, and on the opportunities that they present for automation of diabetes control. Finally, we review control strategies that have been successfully employed in vivo or in silico, presenting a promise for the development of a future artificial pancreas and, in particular, discuss a modular architecture for building closed-loop control systems, including insulin delivery and patient safety supervision layers. We conclude with a brief discussion of the unique interactions between human physiology, behavioral events, engineering modeling and control relevant to diabetes.
Published in: IEEE Reviews in Biomedical Engineering ( Volume: 2)
Department of Information Engineering, University of Padova, Padova, Italy
Claudio Cobelli (M'84–SM'90–F'01) was born in Bressanone (Bolzano), Italy, on February 21, 1946. He received the Ph.D. degree (Laurea) in electrical engineering from the University of Padova, Padova, Italy, in 1970.
From 1970 to 1980, he was a Research Fellow of the Institute of System Science and Biomedical Engineering, National Research Council, Padova. From 1973 to 1975 and 1975 to 1981, he was an Associate Professor of...Show More
Claudio Cobelli (M'84–SM'90–F'01) was born in Bressanone (Bolzano), Italy, on February 21, 1946. He received the Ph.D. degree (Laurea) in electrical engineering from the University of Padova, Padova, Italy, in 1970.
From 1970 to 1980, he was a Research Fellow of the Institute of System Science and Biomedical Engineering, National Research Council, Padova. From 1973 to 1975 and 1975 to 1981, he was an Associate Professor of...View more
Department of Information Engineering, University of Padova, Padova, Italy
Chiara Dalla Man was born in Venice, Italy, on March 2, 1977. She received the Ph.D. degree (Laurea) cum laude in electronics engineering from the University of Padova, Padova, Italy, in 2000. She also received the Ph.D degree in biomedical engineering from the University of Padova, and City University London, U.K., in 2005.
From March to September 2004, she was a Visiting Ph.D. Student at the Centre of Measurements and In...Show More
Chiara Dalla Man was born in Venice, Italy, on March 2, 1977. She received the Ph.D. degree (Laurea) cum laude in electronics engineering from the University of Padova, Padova, Italy, in 2000. She also received the Ph.D degree in biomedical engineering from the University of Padova, and City University London, U.K., in 2005.
From March to September 2004, she was a Visiting Ph.D. Student at the Centre of Measurements and In...View more
Department of Information Engineering, University of Padova, Padova, Italy
Giovanni Sparacino was born in Pordenone, Italy, on November 11, 1967. He received the Doctoral degree in electronics engineering cum laude from the University of Padua, Padua, Italy, in 1992, and the Ph.D. degree in biomedical engineering from the Polytechnic of Milan, Milan, Italy, in 1996.
Since 1997, he has been with the University of Padua: from 1997 to 1998, he was a Research Engineer at the Faculty of Medicine; from...Show More
Giovanni Sparacino was born in Pordenone, Italy, on November 11, 1967. He received the Doctoral degree in electronics engineering cum laude from the University of Padua, Padua, Italy, in 1992, and the Ph.D. degree in biomedical engineering from the Polytechnic of Milan, Milan, Italy, in 1996.
Since 1997, he has been with the University of Padua: from 1997 to 1998, he was a Research Engineer at the Faculty of Medicine; from...View more
Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy
Lalo Magni was born in Bormio, Italy, in 1971. He graduated with full marks and honors (summa cum laude) in computer engineering from the University of Pavia, Pavia, Italy, in 1994. He received the Ph.D. degree in electronic and computer engineering in 1998.
From January 1999 to December 2004, he was an Assistant Professor at the University of Pavia, where he has been an Associate Professor since January 2005. From October...Show More
Lalo Magni was born in Bormio, Italy, in 1971. He graduated with full marks and honors (summa cum laude) in computer engineering from the University of Pavia, Pavia, Italy, in 1994. He received the Ph.D. degree in electronic and computer engineering in 1998.
From January 1999 to December 2004, he was an Assistant Professor at the University of Pavia, where he has been an Associate Professor since January 2005. From October...View more
Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy
Giuseppe De Nicolao (SM'01) received the degree in electronic engineering from the Polytechnic of Milan, Italy.
From 1987 to 1988, he was with the Biomathematics and Biostatistics Unit of the Institute of Pharmacological Researches “Mario Negri”, Milano. In 1988, he joined the Italian National Research Council (CNR) as a Research Scientist at the Center of System Theory in Milan, Italy. From 1992 to 2000, he was an Associa...Show More
Giuseppe De Nicolao (SM'01) received the degree in electronic engineering from the Polytechnic of Milan, Italy.
From 1987 to 1988, he was with the Biomathematics and Biostatistics Unit of the Institute of Pharmacological Researches “Mario Negri”, Milano. In 1988, he joined the Italian National Research Council (CNR) as a Research Scientist at the Center of System Theory in Milan, Italy. From 1992 to 2000, he was an Associa...View more
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA
Boris P. Kovatchev received the Ph.D. degree in mathematics (probability and statistics) from Sofia University “St. Kliment Ohridski,” Bulgaria, in 1989.
Currently, he is a Professor in the Department of Psychiatry and Neurobehavioral Sciences and Adjunct Professor of Systems and Information Engineering, University of Virginia, Charlottesville. He is Head of Section Computational Neuroscience and Director of the University...Show More
Boris P. Kovatchev received the Ph.D. degree in mathematics (probability and statistics) from Sofia University “St. Kliment Ohridski,” Bulgaria, in 1989.
Currently, he is a Professor in the Department of Psychiatry and Neurobehavioral Sciences and Adjunct Professor of Systems and Information Engineering, University of Virginia, Charlottesville. He is Head of Section Computational Neuroscience and Director of the University...View more
Contents Department of Information Engineering, University of Padova, Padova, Italy
Claudio Cobelli (M'84–SM'90–F'01) was born in Bressanone (Bolzano), Italy, on February 21, 1946. He received the Ph.D. degree (Laurea) in electrical engineering from the University of Padova, Padova, Italy, in 1970.
From 1970 to 1980, he was a Research Fellow of the Institute of System Science and Biomedical Engineering, National Research Council, Padova. From 1973 to 1975 and 1975 to 1981, he was an Associate Professor of biological systems at the University of Florence and Associate Professor of biomedical engineering at the University of Padova, respectively. In 1981, he became a Full Professor of biomedical engineering at the University of Padova. Since 2000, he has been an Affiliate Professor of bioengineering at the University of Washington, Seattle. Since 2000, he has been Chairman of the Graduate and Ph.D. Program on bioengineering at the University of Padova. His main research activity is in the field of modeling and identification of physiological systems, especially endocrine-metabolic systems. He has published around 280 papers in internationally refereed journals. He is Coeditor of Carbohydrate Metabolism: Quantitative Physiology and Mathematical Modeling (Chichester: Wiley, 1981), Modeling and Control of Biomedical Systems (Oxford: Pergamon, 1989), and Modeling Methodology for Physiology and Medicine (New York: Academic, 2000). He is Coauthor of The Mathematical Modeling of Metabolic and Endocrine Systems (New York: Wiley, 1983); Tracer Kinetics in Biomedical Research: from Data to Model (London: Kluwer Academic/Plenum, 2001) and Introduction to Modeling in Physiology and Medicine (San Diego: Academic, 2008).
Dr. Cobelli is currently an Associate Editor of IEEE Transactions on Biomedical Engineering and Diabetes. He is on the Editorial Board of the American Journal of Physiology: Endocrinology and Metabolism, Diabetes, and Journal of Diabetes Science & Technology. In the past he has been Associate Editor of Mathematical Biosciences and on the Editorial Board of Control Engineering Practice, Diabetes, Nutrition and Metabolism, Diabetologia, and American Journal of Physiology: Modeling in Physiology. He has been Chairman (1999–2004) of the Italian Biomedical Engineering Group and has been Chairman (1990–1993 and 1993–1996) of IFAC TC on Modeling and Control of Biomedical Systems. He is Fellow of BMES.
Claudio Cobelli (M'84–SM'90–F'01) was born in Bressanone (Bolzano), Italy, on February 21, 1946. He received the Ph.D. degree (Laurea) in electrical engineering from the University of Padova, Padova, Italy, in 1970.
From 1970 to 1980, he was a Research Fellow of the Institute of System Science and Biomedical Engineering, National Research Council, Padova. From 1973 to 1975 and 1975 to 1981, he was an Associate Professor of biological systems at the University of Florence and Associate Professor of biomedical engineering at the University of Padova, respectively. In 1981, he became a Full Professor of biomedical engineering at the University of Padova. Since 2000, he has been an Affiliate Professor of bioengineering at the University of Washington, Seattle. Since 2000, he has been Chairman of the Graduate and Ph.D. Program on bioengineering at the University of Padova. His main research activity is in the field of modeling and identification of physiological systems, especially endocrine-metabolic systems. He has published around 280 papers in internationally refereed journals. He is Coeditor of Carbohydrate Metabolism: Quantitative Physiology and Mathematical Modeling (Chichester: Wiley, 1981), Modeling and Control of Biomedical Systems (Oxford: Pergamon, 1989), and Modeling Methodology for Physiology and Medicine (New York: Academic, 2000). He is Coauthor of The Mathematical Modeling of Metabolic and Endocrine Systems (New York: Wiley, 1983); Tracer Kinetics in Biomedical Research: from Data to Model (London: Kluwer Academic/Plenum, 2001) and Introduction to Modeling in Physiology and Medicine (San Diego: Academic, 2008).
Dr. Cobelli is currently an Associate Editor of IEEE Transactions on Biomedical Engineering and Diabetes. He is on the Editorial Board of the American Journal of Physiology: Endocrinology and Metabolism, Diabetes, and Journal of Diabetes Science & Technology. In the past he has been Associate Editor of Mathematical Biosciences and on the Editorial Board of Control Engineering Practice, Diabetes, Nutrition and Metabolism, Diabetologia, and American Journal of Physiology: Modeling in Physiology. He has been Chairman (1999–2004) of the Italian Biomedical Engineering Group and has been Chairman (1990–1993 and 1993–1996) of IFAC TC on Modeling and Control of Biomedical Systems. He is Fellow of BMES.View more
Department of Information Engineering, University of Padova, Padova, Italy
Chiara Dalla Man was born in Venice, Italy, on March 2, 1977. She received the Ph.D. degree (Laurea) cum laude in electronics engineering from the University of Padova, Padova, Italy, in 2000. She also received the Ph.D degree in biomedical engineering from the University of Padova, and City University London, U.K., in 2005.
From March to September 2004, she was a Visiting Ph.D. Student at the Centre of Measurements and Information in Medicine, City University London, U.K. From 2005 to 2007, she was a Post-Doctoral Research Fellow with the Department of Information Engineering of Padova University. Since October 2007, she has been an Assistant Professor in the Faculty of Engineering of Padova University. Her research interests include the field of mathematical modeling of metabolic and endocrine systems.
Dr. Dalla Man is on the Editorial Board of Journal of Diabetes Science and Technology.
Chiara Dalla Man was born in Venice, Italy, on March 2, 1977. She received the Ph.D. degree (Laurea) cum laude in electronics engineering from the University of Padova, Padova, Italy, in 2000. She also received the Ph.D degree in biomedical engineering from the University of Padova, and City University London, U.K., in 2005.
From March to September 2004, she was a Visiting Ph.D. Student at the Centre of Measurements and Information in Medicine, City University London, U.K. From 2005 to 2007, she was a Post-Doctoral Research Fellow with the Department of Information Engineering of Padova University. Since October 2007, she has been an Assistant Professor in the Faculty of Engineering of Padova University. Her research interests include the field of mathematical modeling of metabolic and endocrine systems.
Dr. Dalla Man is on the Editorial Board of Journal of Diabetes Science and Technology.View more
Department of Information Engineering, University of Padova, Padova, Italy
Giovanni Sparacino was born in Pordenone, Italy, on November 11, 1967. He received the Doctoral degree in electronics engineering cum laude from the University of Padua, Padua, Italy, in 1992, and the Ph.D. degree in biomedical engineering from the Polytechnic of Milan, Milan, Italy, in 1996.
Since 1997, he has been with the University of Padua: from 1997 to 1998, he was a Research Engineer at the Faculty of Medicine; from 1999 to 2004, he was an Assistant Professor at the Faculty of Engineering; since 2005, he has been an Associate Professor of biomedical engineering at the Faculty of Engineering. His scientific interests include deconvolution and parameter estimation techniques for the study of physiological systems, hormone time-series analysis, continuous glucose monitoring, and measurement and processing of evoked potentials.
Giovanni Sparacino was born in Pordenone, Italy, on November 11, 1967. He received the Doctoral degree in electronics engineering cum laude from the University of Padua, Padua, Italy, in 1992, and the Ph.D. degree in biomedical engineering from the Polytechnic of Milan, Milan, Italy, in 1996.
Since 1997, he has been with the University of Padua: from 1997 to 1998, he was a Research Engineer at the Faculty of Medicine; from 1999 to 2004, he was an Assistant Professor at the Faculty of Engineering; since 2005, he has been an Associate Professor of biomedical engineering at the Faculty of Engineering. His scientific interests include deconvolution and parameter estimation techniques for the study of physiological systems, hormone time-series analysis, continuous glucose monitoring, and measurement and processing of evoked potentials.View more
Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy
Lalo Magni was born in Bormio, Italy, in 1971. He graduated with full marks and honors (summa cum laude) in computer engineering from the University of Pavia, Pavia, Italy, in 1994. He received the Ph.D. degree in electronic and computer engineering in 1998.
From January 1999 to December 2004, he was an Assistant Professor at the University of Pavia, where he has been an Associate Professor since January 2005. From October 1996 to February 1997 and in March 1998, he was at CESAME, Universitè Catholique de Louvain, Louvain La Neuve, Belgium. From October to November 1997, he was at the University of Twente with the System and Control Group in the Faculty of Applied Mathematics. His current research interests include nonlinear control, predictive control, robust control, process control and glucose concentration control in subjects with diabetes. His research is witnessed by more than 40 papers published in international journals.
Dr. Magni was a Plenary Speaker at the 2nd IFAC Conference “Control Systems Design” (CSD'03), in 2003. In 2005, he was a Keynote Speaker at the NMPC Workshop on Assessment and Future Direction. In 2003, he was a Guest Editor of the Special Issue “Control of Nonlinear Systems with Model Predictive Control” in the International Journal of Robust and Nonlinear Control. He served as an Associate Editor of the IEEE Transactions on Automatic Control. He is an Associate Editor of Automatica. He was subarea Chair for the area “Nonlinear systems optimal and predictive control” at the IFAC Symposium on Nonlinear Control Systems (NOLCOS 2007). He organized the NMPC Workshop on Assessment and Future Direction in September 2008 in Pavia.
Lalo Magni was born in Bormio, Italy, in 1971. He graduated with full marks and honors (summa cum laude) in computer engineering from the University of Pavia, Pavia, Italy, in 1994. He received the Ph.D. degree in electronic and computer engineering in 1998.
From January 1999 to December 2004, he was an Assistant Professor at the University of Pavia, where he has been an Associate Professor since January 2005. From October 1996 to February 1997 and in March 1998, he was at CESAME, Universitè Catholique de Louvain, Louvain La Neuve, Belgium. From October to November 1997, he was at the University of Twente with the System and Control Group in the Faculty of Applied Mathematics. His current research interests include nonlinear control, predictive control, robust control, process control and glucose concentration control in subjects with diabetes. His research is witnessed by more than 40 papers published in international journals.
Dr. Magni was a Plenary Speaker at the 2nd IFAC Conference “Control Systems Design” (CSD'03), in 2003. In 2005, he was a Keynote Speaker at the NMPC Workshop on Assessment and Future Direction. In 2003, he was a Guest Editor of the Special Issue “Control of Nonlinear Systems with Model Predictive Control” in the International Journal of Robust and Nonlinear Control. He served as an Associate Editor of the IEEE Transactions on Automatic Control. He is an Associate Editor of Automatica. He was subarea Chair for the area “Nonlinear systems optimal and predictive control” at the IFAC Symposium on Nonlinear Control Systems (NOLCOS 2007). He organized the NMPC Workshop on Assessment and Future Direction in September 2008 in Pavia.View more
Department of Computer Engineering and Systems Science, University of Pavia, Pavia, Italy
Giuseppe De Nicolao (SM'01) received the degree in electronic engineering from the Polytechnic of Milan, Italy.
From 1987 to 1988, he was with the Biomathematics and Biostatistics Unit of the Institute of Pharmacological Researches “Mario Negri”, Milano. In 1988, he joined the Italian National Research Council (CNR) as a Research Scientist at the Center of System Theory in Milan, Italy. From 1992 to 2000, he was an Associate Professor and, since 2000, he has been a full Professor of model identification in the Department of Computer Science and Systems Engineering of the University of Pavia, Pavia, Italy. In 1991, he held a visiting fellowship at the Department of Systems Engineering of the Australian National University, Canberra. His research interests include Bayesian learning, neural networks, model predictive control, optimal and robust filtering and control, deconvolution techniques, modeling, identification and control of biomedical systems, advanced process control and fault diagnosis for semiconductor manufacturing. On these subjects he has authored or coauthored more than 100 journal papers and is coinventor of two patents.
Dr. De Nicolao was a Keynote Speaker at the IFAC workshop on “Nonlinear model predictive control: Assessment and future directions for research”. From 1999 to 2001, he was an Associate Editor of the IEEE Transactions on Automatic Control and, since 2007, he has been an Associate Editor of Automatica.
Giuseppe De Nicolao (SM'01) received the degree in electronic engineering from the Polytechnic of Milan, Italy.
From 1987 to 1988, he was with the Biomathematics and Biostatistics Unit of the Institute of Pharmacological Researches “Mario Negri”, Milano. In 1988, he joined the Italian National Research Council (CNR) as a Research Scientist at the Center of System Theory in Milan, Italy. From 1992 to 2000, he was an Associate Professor and, since 2000, he has been a full Professor of model identification in the Department of Computer Science and Systems Engineering of the University of Pavia, Pavia, Italy. In 1991, he held a visiting fellowship at the Department of Systems Engineering of the Australian National University, Canberra. His research interests include Bayesian learning, neural networks, model predictive control, optimal and robust filtering and control, deconvolution techniques, modeling, identification and control of biomedical systems, advanced process control and fault diagnosis for semiconductor manufacturing. On these subjects he has authored or coauthored more than 100 journal papers and is coinventor of two patents.
Dr. De Nicolao was a Keynote Speaker at the IFAC workshop on “Nonlinear model predictive control: Assessment and future directions for research”. From 1999 to 2001, he was an Associate Editor of the IEEE Transactions on Automatic Control and, since 2007, he has been an Associate Editor of Automatica.View more
Department of Psychiatry and Neurobehavioral Sciences, University of Virginia, Charlottesville, VA, USA
Boris P. Kovatchev received the Ph.D. degree in mathematics (probability and statistics) from Sofia University “St. Kliment Ohridski,” Bulgaria, in 1989.
Currently, he is a Professor in the Department of Psychiatry and Neurobehavioral Sciences and Adjunct Professor of Systems and Information Engineering, University of Virginia, Charlottesville. He is Head of Section Computational Neuroscience and Director of the University of Virginia Diabetes Technology Program. His research expertise is in biomathematics, specifically modeling of biologic and behavioral processes. In the past 15 years he has been involved in various aspects of diabetes technology development, as well as in the development of quantitative strategies for neurobiological problems. Currently, he is the Principal Investigator of two large projects funded by the National Institutes of Health, and the Principal Investigator of the JDRF Artificial Pancreas Project at the University of Virginia. He is also involved in industry-sponsored translational research. He is author of over 100 scientific publications and coauthor of the textbook Invitation to Biomathematics (Academic, 2008). His academic work includes participation in several international boards and NIH study sections. He holds five patents and is author of 15 other inventions that are currently at various stages of the patenting process.
Dr. Kovatchev is an Associate Editor of IEEE Transactions on Biomedical Engineering and member of the Editorial board of the Journal of Diabetes Science and Technology.
Boris P. Kovatchev received the Ph.D. degree in mathematics (probability and statistics) from Sofia University “St. Kliment Ohridski,” Bulgaria, in 1989.
Currently, he is a Professor in the Department of Psychiatry and Neurobehavioral Sciences and Adjunct Professor of Systems and Information Engineering, University of Virginia, Charlottesville. He is Head of Section Computational Neuroscience and Director of the University of Virginia Diabetes Technology Program. His research expertise is in biomathematics, specifically modeling of biologic and behavioral processes. In the past 15 years he has been involved in various aspects of diabetes technology development, as well as in the development of quantitative strategies for neurobiological problems. Currently, he is the Principal Investigator of two large projects funded by the National Institutes of Health, and the Principal Investigator of the JDRF Artificial Pancreas Project at the University of Virginia. He is also involved in industry-sponsored translational research. He is author of over 100 scientific publications and coauthor of the textbook Invitation to Biomathematics (Academic, 2008). His academic work includes participation in several international boards and NIH study sections. He holds five patents and is author of 15 other inventions that are currently at various stages of the patenting process.
Dr. Kovatchev is an Associate Editor of IEEE Transactions on Biomedical Engineering and member of the Editorial board of the Journal of Diabetes Science and Technology.View more
