**6. Activity-based dynamic insulin infusion system**

In section 3, we have introduced the glucose-insulin regulatory system and applied it to model the OGTT. We came up with our novel DBI, by means of which we can even detect supposedly normal subjects who are at risk of becoming diabetic. Now, we continue on the trail of this glucose-insulin regulatory system, by presenting its application to illustrate how for a diabetic patient the glucose level keeps going up after meal, and how it is regulated by automated infusion of insulin.

Herein, we demonstrate the operation of a Glucose activity-based Dynamic Insulin infusion (or release) system. The current insulin infusion systems are based on the diabetic patient's known activities history, in order to estimate the required insulin amount. These techniques do not allow the patients to deviate too much from their normal daily activities [Naylor et al., 1996]. Hence, our approach focuses on regular sampling of the diabetic patients' blood glucose concentration through a sensor, to compute the required amount of insulin to be released into the blood stream.

The amount of insulin infused to bring the blood glucose concentration down is regulated by a Closed-loop PD (Proportional-Derivative) Control system algorithm (Fig. 13). The closed loop system continuously monitors the blood glucose concentration at 0.5 h interval. Once the system detects that the blood glucose concentration exceeds a predetermined threshold e.g. 120mg/dl [International Diabetes Federation], the system is alarmed and 'calculates' the amount of insulin required [Loh, 2004] to bring the blood glucose concentration below the threshold.

Fig. 13. Block diagram of the Glucose Regulating Insulin Release (GRIR) system: The glucose sensor monitors the existing blood glucose level. The error between the glucose sensor level and the computed expected blood glucose concentration is fed into the Closed-loop PD (Proportional-Derivative) Control system, and its algorithm computes the amount of insulin (x) to be released. Accordingly, the required amount of insulin is released into the blood. This now readjusts the blood glucose level, which is again monitored by the sensor.

Then, Fig. 14 shows the results of the application of the Insulin Infusion Release system of Fig 13. The diabetic subject D18's unaided glucose clinical data is fed into the system. On the Y axis, we have plotted blood-glucose concentration above the patient's glucose concentration of 120 mg/dl (or 1.2 g/l) at time 0 after meal. The insulin is released at 0.5 hour, 1 hour and 1.5 hours after meal. In figure 16, it is seen, how following insulin infusion, the blood glucose comes down. Once the blood glucose concentration drops below the threshold, the controller will stop releasing insulin into the blood stream.

Fig. 14. The subject's unaided blood glucose concentration at time 0 is above 120mg/dl. The system is alarmed and samples the blood glucose concentration at 0.5h (170 mg/dl). The system sends a bolus of insulin 10mU/dl into the blood stream. The system keeps monitoring the resulting blood glucose concentration at 1.0h and 1.5 hour intervals, and infuses computed insulin bolus into the blood stream to bring the blood glucose concentration below the threshold value.

Thus, we have demonstrated the capability of the activity based adaptive dynamic real-time insulin release system. This system is able to protect the users from hyperglycemia.

### **7. Conclusion**

442 Biomedical Science, Engineering and Technology

In section 3, we have introduced the glucose-insulin regulatory system and applied it to model the OGTT. We came up with our novel DBI, by means of which we can even detect supposedly normal subjects who are at risk of becoming diabetic. Now, we continue on the trail of this glucose-insulin regulatory system, by presenting its application to illustrate how for a diabetic patient the glucose level keeps going up after meal, and how it is regulated by

Herein, we demonstrate the operation of a Glucose activity-based Dynamic Insulin infusion (or release) system. The current insulin infusion systems are based on the diabetic patient's known activities history, in order to estimate the required insulin amount. These techniques do not allow the patients to deviate too much from their normal daily activities [Naylor et al., 1996]. Hence, our approach focuses on regular sampling of the diabetic patients' blood glucose concentration through a sensor, to compute the required amount of insulin to be

The amount of insulin infused to bring the blood glucose concentration down is regulated by a Closed-loop PD (Proportional-Derivative) Control system algorithm (Fig. 13). The closed loop system continuously monitors the blood glucose concentration at 0.5 h interval. Once the system detects that the blood glucose concentration exceeds a predetermined threshold e.g. 120mg/dl [International Diabetes Federation], the system is alarmed and 'calculates' the amount of insulin required [Loh, 2004] to bring the blood glucose

*A,G,*ω,*y,y1* 

Blood Pool

Blood Glucose Insulin released into the blood pool

Fig. 13. Block diagram of the Glucose Regulating Insulin Release (GRIR) system: The glucose sensor monitors the existing blood glucose level. The error between the glucose sensor level and the computed expected blood glucose concentration is fed into the Closed-loop PD (Proportional-Derivative) Control system, and its algorithm computes the amount of insulin (x) to be released. Accordingly, the required amount of insulin is released into the blood. This now readjusts the blood glucose level, which is again monitored by the sensor.

Then, Fig. 14 shows the results of the application of the Insulin Infusion Release system of Fig 13. The diabetic subject D18's unaided glucose clinical data is fed into the system. On the Y axis, we have plotted blood-glucose concentration above the patient's glucose concentration of 120 mg/dl (or 1.2 g/l) at time 0 after meal. The insulin is released at 0.5 hour, 1 hour and 1.5 hours after meal. In figure 16, it is seen, how following insulin infusion, the blood glucose comes down. Once the blood glucose concentration drops below

the threshold, the controller will stop releasing insulin into the blood stream.

Blood Glucose Response Computer

x

Controller Insulin Release

System

**6. Activity-based dynamic insulin infusion system** 

automated infusion of insulin.

released into the blood stream.

concentration below the threshold.

Non-Invasive Blood Glucose Sensor

> Computation of New Expected Blood Glucose Concentration

+


This chapter is framed to provide useful insights into: (i) the mechanisms of diabetes; (ii) how the bioengineering analysis of the glucose regulatory system can be employed to diagnose diabetic patients and subjects at risk of becoming diabetic, based on an integrated index composed of parameters of the governing differential equation to simulate blood glucose concentration data of OGTT; (iii) parameters of time-and frequency-domain measures of HRV can be employed to differentiate diabetic subjects from normal subjects; (iii) processing of retinal digital fundus images to characterize retinopathy, and analysis of plantar pressure distribution images of normal subjects, and subjects with diabetes type II without and with neuropathy, (iv) diagnosis of diabetic autonomic neuropathy by means of a novel intregrated index composed of parameters of heartrate variability power-spectrum plots; (v) how we can apply the glucose-insulin regulatory system to illustrate how for a diabetic patient the glucose level keeps going up after meal, and how it is can be regulated by automated infusion of insulin.
