BACKGROUND: Because of the slow pharmacokinetics of subcutaneous (SC) insulin, avoiding postprandial hyperglycemia has been a major challenge for an artificial pancreas (AP) using SC insulin without a meal announcement. METHODS: A semiautomated AP with Technosphere® Insulin (TI; MannKind Corporation, Valencia, CA) was designed to combine pulmonary and SC insulin. Manual inhalation of 10 U ultrafast-absorbing TI at mealtime delivers the first, or cephalic, phase of insulin, and an SC insulin pump controlled by zone model predictive controller delivers second-phase and basal insulin. This AP design was evaluated on 100 in silico subjects from the University of Virginia/Padova metabolic simulator using a protocol of two 50 g carbohydrate (CHO) meals and two 15 g CHO snacks. RESULTS: Simulation analysis shows that the semiautomated AP with TI provides 32% and 16% more time in the controller target zone (80-140 mg/dl) during the 4 h postprandial period, with 39 and 20 mg/dl lower postprandial blood glucose peak on average than the pure feedback AP and the AP with manual feed-forward SC bolus, respectively. No severe hypoglycemia (<50 mg/dl) was observed in any cases. CONCLUSIONS: The semiautomated AP with TI provides maximum time in the clinically accepted region when compared with pure feedback AP and AP with manual feed-forward SC bolus. Furthermore, the semiautomated AP with TI provides a flexible operation (optional TI inhalation) with minimal user interaction, where the controller design can be tailored to specific user needs and abilities to interact with the device.
BACKGROUND: Because of the slow pharmacokinetics of subcutaneous (SC) insulin, avoiding postprandial hyperglycemia has been a major challenge for an artificial pancreas (AP) using SC insulin without a meal announcement. METHODS: A semiautomated AP with Technosphere® Insulin (TI; MannKind Corporation, Valencia, CA) was designed to combine pulmonary and SC insulin. Manual inhalation of 10 U ultrafast-absorbing TI at mealtime delivers the first, or cephalic, phase of insulin, and an SC insulin pump controlled by zone model predictive controller delivers second-phase and basal insulin. This AP design was evaluated on 100 in silico subjects from the University of Virginia/Padova metabolic simulator using a protocol of two 50 g carbohydrate (CHO) meals and two 15 g CHO snacks. RESULTS: Simulation analysis shows that the semiautomated AP with TI provides 32% and 16% more time in the controller target zone (80-140 mg/dl) during the 4 h postprandial period, with 39 and 20 mg/dl lower postprandial blood glucose peak on average than the pure feedback AP and the AP with manual feed-forward SC bolus, respectively. No severe hypoglycemia (<50 mg/dl) was observed in any cases. CONCLUSIONS: The semiautomated AP with TI provides maximum time in the clinically accepted region when compared with pure feedback AP and AP with manual feed-forward SC bolus. Furthermore, the semiautomated AP with TI provides a flexible operation (optional TI inhalation) with minimal user interaction, where the controller design can be tailored to specific user needs and abilities to interact with the device.
Authors: Karin Amrein; Martin Ellmerer; Roman Hovorka; Norman Kachel; Dieter Parcz; Stefan Korsatko; Karlheinz Smolle; Sabine Perl; Gerlies Bock; Werner Doll; Gerd Köhler; Thomas R Pieber; Johannes Plank Journal: Diabetes Technol Ther Date: 2010-05 Impact factor: 6.118
Authors: Boris Kovatchev; Claudio Cobelli; Eric Renard; Stacey Anderson; Marc Breton; Stephen Patek; William Clarke; Daniela Bruttomesso; Alberto Maran; Silvana Costa; Angelo Avogaro; Chiara Dalla Man; Andrea Facchinetti; Lalo Magni; Giuseppe De Nicolao; Jerome Place; Anne Farret Journal: J Diabetes Sci Technol Date: 2010-11-01
Authors: Firas H El-Khatib; Steven J Russell; David M Nathan; Robert G Sutherlin; Edward R Damiano Journal: Sci Transl Med Date: 2010-04-14 Impact factor: 17.956
Authors: William L Clarke; Stacey Anderson; Marc Breton; Stephen Patek; Laurissa Kashmer; Boris Kovatchev Journal: J Diabetes Sci Technol Date: 2009-09-01
Authors: Roman Hovorka; Janet M Allen; Daniela Elleri; Ludovic J Chassin; Julie Harris; Dongyuan Xing; Craig Kollman; Tomas Hovorka; Anne Mette F Larsen; Marianna Nodale; Alessandra De Palma; Malgorzata E Wilinska; Carlo L Acerini; David B Dunger Journal: Lancet Date: 2010-02-04 Impact factor: 79.321
Authors: Roman Hovorka; Kavita Kumareswaran; Julie Harris; Janet M Allen; Daniela Elleri; Dongyuan Xing; Craig Kollman; Marianna Nodale; Helen R Murphy; David B Dunger; Stephanie A Amiel; Simon R Heller; Malgorzata E Wilinska; Mark L Evans Journal: BMJ Date: 2011-04-13