Diabetes mellitus modeling and short-term prediction based on blood glucose measurements.

Insulin-Dependent Diabetes Mellitus (IDDM) is a chronic disease characterized by the inability of the pancreas to produce sufficient amounts of insulin. Daily compensation of the deficiency requires 4-6 insulin injections to be taken daily, the aim of this insulin therapy being to maintain normoglycemia - i.e., a blood glucose level between 4 and 7mmol/l. To determine the quantity and timing of these injections, various different approaches are used. Currently, mostly qualitative and semi-quantitative models and reasoning are used to design such a therapy. Here, an attempt is made to show how system identification and control may be used to estimate predictive quantitative models to be used in design of optimal insulin regimens. The system was divided into three subsystems, the insulin subsystem, the glucose subsystem and the insulin-glucose interaction. The insulin subsystem aims to describe the absorption of injected insulin from the subcutaneous depots and the glucose subsystem the absorption of glucose from the gut following a meal. These subsystems were modeled using compartment models and proposed models found in the literature. Several black-box models and grey-box models describing the insulin/glucose interaction were developed and analyzed. These models were fitted to real data monitored by an IDDM patient. Many difficulties were encountered, typical of biomedical systems: Non-uniform and scarce sampling, time-varying dynamics and severe nonlinearities were some of the difficulties encountered during the modeling. None of the proposed models were able to describe the system accurately in all aspects during all conditions. However, all the linear models shared some dynamics. Based on the estimated models, short-term blood glucose predictors for up to two-hour-ahead blood glucose prediction were designed. Furthermore, we explored the issues that arise when applying prediction theory and control to short-term blood glucose prediction.