Multicenter closed-loop insulin delivery study points to challenges for keeping blood glucose in a safe range by a control algorithm in adults and adolescents with type 1 diabetes from various sites
Howard Zisser, Eric Renard, Boris Kovatchev, Claudio Cobelli, Angelo Avogaro, Revital Nimri, Lalo Magni, Bruce A Buckingham, H Peter Chase, Francis J Doyle 3rd, John Lum, Peter Calhoun, Craig Kollman, Eyal Dassau, Anne Farret, Jerome Place, Marc Breton, Stacey M Anderson, Chiara Dalla Man, Simone Del Favero, Daniela Bruttomesso, Alessio Filippi, Rachele Scotton, Moshe Phillip, Eran Atlas, Ido Muller, Shahar Miller, Chiara Toffanin, Davide Martino Raimondo, Giuseppe De Nicolao, Roy W Beck, Control to Range Study Group, Howard Zisser, Lois Jovanovic, Alison Wollitzer, Wendy Bevier, Eyal Dassau, Kristin Castorino, Kateryna Markova, Jacqueline Wiley, Erin Beveridge, Nicolas Santibanez, Alexandra Sales, Maia Bradley, Adam Castorino, Boris Kovatchev, Stacey M Anderson, Susan Demartini, Sue Brown, William Clarke, Marc Breton, Stephen Patek, Patrick Keith-Hynes, Colleen Hughes-Karvetski, Molly McElwee, Mary Oliveri, Christian Wakeman, Eric Renard, Anne Farret, Marie-Josee Pelletier, Hugues Chevassus, Jerome Place, Moshe Phillip, Eran Atlas, Revital Nimri, Tal Oron, Alon Farfel, Sharon Demol, Eran Mel, Tal Ben-Ari, Michael Gilon, Ayele Parnes, Ido Muller, Shahar Miller, Alona Hamou, Orna Hermon, Galit Shiovitch-Mantzuri, Galia Fayman, Claudio Cobelli, Chiara Dalla Man, Angelo Avogaro, Daniela Bruttomesso, Alberto Maran, Michele Schiavon, Simone Del Favero, Roberto Visentin, Rachele Scotton, Alessio Filippi, Lalo Magni, Chiara Toffanin, Giuseppe De Nicolao, Simone Mancini, Davide Martino Raimondo, Bruce A Buckingham, Darrell M Wilson, Kari Benassi, Paula Clinton, Breanne P Harris, Satya Shanmugham, Kimberly Caswell, H Peter Chase, David M Maahs, Robert Slover, Sally Sullivan, Laurel Messer, Victoria Gage, Jaime Realsen, Emily Westfall, Hannah Goettle, Francis J Doyle 3rd, Roy W Beck, John Lum, Craig Kollman, Peter Calhoun, Judy Sibayan, Nelly M Njeru, Werner Sauer, John C Pickup, Irl Hirsch, Howard Wolpert, Howard Zisser, Eric Renard, Boris Kovatchev, Claudio Cobelli, Angelo Avogaro, Revital Nimri, Lalo Magni, Bruce A Buckingham, H Peter Chase, Francis J Doyle 3rd, John Lum, Peter Calhoun, Craig Kollman, Eyal Dassau, Anne Farret, Jerome Place, Marc Breton, Stacey M Anderson, Chiara Dalla Man, Simone Del Favero, Daniela Bruttomesso, Alessio Filippi, Rachele Scotton, Moshe Phillip, Eran Atlas, Ido Muller, Shahar Miller, Chiara Toffanin, Davide Martino Raimondo, Giuseppe De Nicolao, Roy W Beck, Control to Range Study Group, Howard Zisser, Lois Jovanovic, Alison Wollitzer, Wendy Bevier, Eyal Dassau, Kristin Castorino, Kateryna Markova, Jacqueline Wiley, Erin Beveridge, Nicolas Santibanez, Alexandra Sales, Maia Bradley, Adam Castorino, Boris Kovatchev, Stacey M Anderson, Susan Demartini, Sue Brown, William Clarke, Marc Breton, Stephen Patek, Patrick Keith-Hynes, Colleen Hughes-Karvetski, Molly McElwee, Mary Oliveri, Christian Wakeman, Eric Renard, Anne Farret, Marie-Josee Pelletier, Hugues Chevassus, Jerome Place, Moshe Phillip, Eran Atlas, Revital Nimri, Tal Oron, Alon Farfel, Sharon Demol, Eran Mel, Tal Ben-Ari, Michael Gilon, Ayele Parnes, Ido Muller, Shahar Miller, Alona Hamou, Orna Hermon, Galit Shiovitch-Mantzuri, Galia Fayman, Claudio Cobelli, Chiara Dalla Man, Angelo Avogaro, Daniela Bruttomesso, Alberto Maran, Michele Schiavon, Simone Del Favero, Roberto Visentin, Rachele Scotton, Alessio Filippi, Lalo Magni, Chiara Toffanin, Giuseppe De Nicolao, Simone Mancini, Davide Martino Raimondo, Bruce A Buckingham, Darrell M Wilson, Kari Benassi, Paula Clinton, Breanne P Harris, Satya Shanmugham, Kimberly Caswell, H Peter Chase, David M Maahs, Robert Slover, Sally Sullivan, Laurel Messer, Victoria Gage, Jaime Realsen, Emily Westfall, Hannah Goettle, Francis J Doyle 3rd, Roy W Beck, John Lum, Craig Kollman, Peter Calhoun, Judy Sibayan, Nelly M Njeru, Werner Sauer, John C Pickup, Irl Hirsch, Howard Wolpert
Abstract
Background: The Control to Range Study was a multinational artificial pancreas study designed to assess the time spent in the hypo- and hyperglycemic ranges in adults and adolescents with type 1 diabetes while under closed-loop control. The controller attempted to keep the glucose ranges between 70 and 180 mg/dL. A set of prespecified metrics was used to measure safety.
Research design and methods: We studied 53 individuals for approximately 22 h each during clinical research center admissions. Plasma glucose level was measured every 15-30 min (YSI clinical laboratory analyzer instrument [YSI, Inc., Yellow Springs, OH]). During the admission, subjects received three mixed meals (1 g of carbohydrate/kg of body weight; 100 g maximum) with meal announcement and automated insulin dosing by the controller.
Results: For adults, the mean of subjects' mean glucose levels was 159 mg/dL, and mean percentage of values 71-180 mg/dL was 66% overall (59% daytime and 82% overnight). For adolescents, the mean of subjects' mean glucose levels was 166 mg/dL, and mean percentage of values in range was 62% overall (53% daytime and 82% overnight). Whereas prespecified criteria for safety were satisfied by both groups, they were met at the individual level in adults only for combined daytime/nighttime and for isolated nighttime. Two adults and six adolescents failed to meet the daytime criterion, largely because of postmeal hyperglycemia, and another adolescent failed to meet the nighttime criterion.
Conclusions: The control-to-range system performed as expected: faring better overnight than during the day and performing with variability between patients even after individualization based on patients' prior settings. The system had difficulty preventing postmeal excursions above target range.
Trial registration: ClinicalTrials.gov NCT01271023.
Figures
Source: PubMed