The long term objective of this work is to develop new algorithmic approaches to optimize the delivery of insulin in an automated fashion to people with type 1 diabetes. Specifically, we aim to develop a strategy, inspired by run-to-run control theory established by the chemical process industries, that """"""""learns"""""""" from the previous sequence of glucose responses to insulin dosing (over the course of days), and optimally predicts the appropriate strategy for the forthcoming day. The notion of a """"""""cycle"""""""" in engineering will be extended to manage the 24 hour routine of repeated meals, activities, and sleep cycles and the corresponding dosing of insulin. The algorithm will be tested in both simulation and clinical trials for robustness to sensor noise, uncertainty in the patient characterization, variability in the timing of the postprandial glucose peak, and variability in the carbohydrate content in the meals.
The Specific Aims of this project are to: i) construct predictive patient sensitivity models for calculation of optimal insulin dosing from elevated (or depressed) glucose levels, ii) develop run-to-run algorithm for insulin bolus dosing to provide corrections in subsequent days based on previous history of glucose levels and insulin dosage, and iii) evaluate the robustness of the algorithm through meal challenges of varying carbohydrate content.
The aims will blend prototype algorithms that are drawn from systems engineering with validation in a series of clinical tests. The proposed collaboration between systems engineers and renowned diabetes researchers in an established clinical research setting will allow a novel fusion of methods that can be truly characterized as """"""""innovative"""""""". The medical collaborators in the proposal are located at the prestigious Sansum Medical Research Institute, which is located less than 10 miles from the campus of the University of California, Santa Barbara. The exchange of personnel will be facilitated, allowing the student and post-doc supported on this project to work at both the institute and the university over the span of the project.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
5R01DK068706-02
Application #
6940604
Study Section
Special Emphasis Panel (ZDK1-GRB-1 (M1))
Program Officer
Arreaza-Rubin, Guillermo
Project Start
2004-09-01
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2007-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$143,196
Indirect Cost
Name
University of California Santa Barbara
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
094878394
City
Santa Barbara
State
CA
Country
United States
Zip Code
93106
Zisser, Howard; Palerm, Cesar C; Bevier, Wendy C et al. (2009) Clinical update on optimal prandial insulin dosing using a refined run-to-run control algorithm. J Diabetes Sci Technol 3:487-91
Palerm, Cesar C; Zisser, Howard; Jovanovic, Lois et al. (2008) A Run-to-Run Control Strategy to Adjust Basal Insulin Infusion Rates in Type 1 Diabetes. J Process Control 18:258-265
Zisser, Howard C; Bevier, Wendy C; Jovanovic, Lois (2007) Restoring euglycemia in the basal state using continuous glucose monitoring in subjects with type 1 diabetes mellitus. Diabetes Technol Ther 9:509-15
Bevier, Wendy C; Zisser, Howard; Palerm, Cesar C et al. (2007) Calculating the insulin to carbohydrate ratio using the hyperinsulinaemic-euglycaemic clamp-a novel use for a proven technique. Diabetes Metab Res Rev 23:472-8
Palerm, Cesar C; Zisser, Howard; Bevier, Wendy C et al. (2007) Prandial insulin dosing using run-to-run control: application of clinical data and medical expertise to define a suitable performance metric. Diabetes Care 30:1131-6
Palerm, Cesar C; Rodriguez-Fernandez, Maria; Bevier, Wendy C et al. (2006) Robust parameter estimation in a model for glucose kinetics in type 1 diabetes subjects. Conf Proc IEEE Eng Med Biol Soc 1:319-22
Owens, Camelia; Zisser, Howard; Jovanovic, Lois et al. (2006) Run-to-run control of blood glucose concentrations for people with Type 1 diabetes mellitus. IEEE Trans Biomed Eng 53:996-1005
Zisser, Howard; Jovanovic, Lois; Doyle 3rd, Frank et al. (2005) Run-to-run control of meal-related insulin dosing. Diabetes Technol Ther 7:48-57