Closed-loop artificial pancreas using subcutaneous glucose sensing and insulin delivery and a model predictive control algorithm: the Virginia experience.
BACKGROUND
Recent progress in the development of clinically accurate continuous glucose monitors (CGMs), automated continuous insulin infusion pumps, and control algorithms for calculating insulin doses from CGM data have enabled the development of prototypes of subcutaneous closed-loop systems for controlling blood glucose (BG) levels in type 1 diabetes. The use of a new personalized model predictive control (MPC) algorithm to determine insulin doses to achieve and maintain BG levels between 70 and 140 mg/dl overnight and to control postprandial BG levels is presented.


METHODS
Eight adults with type 1 diabetes were studied twice, once using their personal open-loop systems to control BG overnight and for 4 h following a standardized meal and once using a closed-loop system that utilizes the MPC algorithm to control BG overnight and for 4 h following a standardized meal. Average BG levels, percentage of time within BG target of 70-140 mg/dl, number of hypoglycemia episodes, and postprandial BG excursions during both study periods were compared.


RESULTS
With closed-loop control, once BG levels achieved the target range (70-140 mg/dl), they remained within that range throughout the night in seven of the eight subjects. One subject developed a BG level of 65 mg/dl, which was signaled by the CGM trend analysis, and the MPC algorithm directed the discontinuance of the insulin infusion. The number of overnight hypoglycemic events was significantly reduced (p = .011) with closed-loop control. Postprandial BG excursions were similar during closed-loop and open-loop control.


CONCLUSIONS
Model predictive closed-loop control of BG levels can be achieved overnight and following a standardized breakfast meal. This "artificial pancreas" controls BG levels as effectively as patient-directed open-loop control following a morning meal but is significantly superior to open-loop control in preventing overnight hypoglycemia.
Clarke
William L
WL
Division of Pediatric Endocrinology, Department of Pediatrics, University of Virginia Health Sciences Center, Charlottesville, Virginia 22908, USA. wlc@virginia.edu
Anderson
Stacey
S
Breton
Marc
M
Patek
Stephen
S
Kashmer
Laurissa
L
Kovatchev
Boris
B
D000328:Adult; D000465:Algorithms; D001786:Blood Glucose / Q000187:drug effects* / Q000378:metabolism; D015190:Blood Glucose Self-Monitoring / Q000295:instrumentation; D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy*; D019719:Diagnostic Equipment; D004040:Dietary Carbohydrates / Q000378:metabolism; D005260:Female; D006442:Glycated Hemoglobin / Q000378:metabolism; D006801:Humans; D007003:Hypoglycemia / Q000209:etiology / Q000517:prevention & control; D007004:Hypoglycemic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D007332:Insulin Infusion Systems; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D019397:Pancreas, Artificial; D010865:Pilot Projects; D019518:Postprandial Period; D011237:Predictive Value of Tests; D013997:Time Factors; D016896:Treatment Outcome
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; C517652:hemoglobin A1c protein, human