title: Modeling Day-to-Day Variability of Glucose-Insulin Regulation Over 12-Week Home Use of Closed-Loop Insulin Delivery.
abstract: Parameters of physiological models of glucose-insulin regulation in type 1 diabetes have previously been estimated using data collected over short periods of time and lack the quantification of day-to-day variability. We developed a new hierarchical model to relate subcutaneous insulin delivery and carbohydrate intake to continuous glucose monitoring over 12 weeks while describing day-to-day variability. Sensor glucose data sampled every 10-min, insulin aspart delivery and meal intake were analyzed from eight adults with type 1 diabetes (male/female 5/3, age 39.9 ± 9.5 years, BMI 25.4 ± 4.4kg/m2, HbA1c 8.4 ± 0.6% ) who underwent a 12-week home study of closed-loop insulin delivery. A compartment model comprised of five linear differential equations; model parameters were estimated using the Markov chain Monte Carlo approach within a hierarchical Bayesian model framework. Physiologically, plausible a posteriori distributions of model parameters including insulin sensitivity, time-to-peak insulin action, time-to-peak gut absorption, and carbohydrate bioavailability, and good model fit were observed. Day-to-day variability of model parameters was estimated in the range of 38-79% for insulin sensitivity and 27-48% for time-to-peak of insulin action. In conclusion, a linear Bayesian hierarchical approach is feasible to describe a 12-week glucose-insulin relationship using conventional clinical data. The model may facilitate in silico testing to aid the development of closed-loop insulin delivery systems.
authors.lastname: Yue Ruan
authors.forename: Malgorzata E
authors.initials: ME
authors.lastname: Wilinska
authors.forename: Hood
authors.initials: H
authors.lastname: Thabit
authors.forename: Roman
authors.initials: R
authors.lastname: Hovorka
mesh_terms: D000328:Adult; D001499:Bayes Theorem; D001786:Blood Glucose / Q000378:metabolism*; D003198:Computer Simulation; D003922:Diabetes Mellitus, Type 1 / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D003936:Diagnosis, Computer-Assisted / Q000379:methods; D004040:Dietary Carbohydrates; D004360:Drug Therapy, Computer-Assisted / Q000379:methods*; D025461:Feedback, Physiological / Q000187:drug effects; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage; D007328:Insulin / Q000008:administration & dosage* / Q000097:blood*; D007333:Insulin Resistance; D008297:Male; D008954:Models, Biological; D015233:Models, Statistical
chemical_list: D001786:Blood Glucose; D004040:Dietary Carbohydrates; D007004:Hypoglycemic Agents; D007328:Insulin