Blood glucose control system

Abstract

Techniques are used for adaptation of drug-administration parameters that control insulin delivery in a blood glucose control system. One technique provides long-term adaptation of a nominal basal infusion rate, adapting to longer-term changes in a patient's needs due to growth, illness, hormonal fluctuations, physical activity, aging, etc. Another technique provides adaptation of priming dose size at mealtimes for overall better glycemic control and also adapting to longer-term changes in a patient's needs. Adaptation calculations use a receding-horizon window of recent values of the adapted parameter. Doses of a counter-regulatory agent (e.g., glucagon) may also be delivered in response to information about estimated accumulation of exogenously infused insulin (subcutaneously, intramuscularly, intraperitoneally, or intravenously) and/or the effect insulin might have on glucose levels (blood glucose concentration or interstitial fluid glucose concentration).

What is claimed is: 
     
       1. A sensor-driven glucose control system, comprising:
 an insulin delivery device operative in response to an insulin dose control signal to infuse insulin into the subject; and   a controller operative to generate the insulin dose control signal by:
 (1) continually administering priming doses of insulin at respective times, each priming dose being of a respective amount and having a prescribed interval of action; 
 (2) receiving information regarding total amounts of insulin administered during the prescribed intervals of action, each total amount including an aggregation of total doses administered in response to a glucose level signal; and 
 (3) automatically adapting the amounts of the priming doses in response to a mathematical relationship, over respective periods each spanning multiple prescribed intervals of action, between the amounts of the priming doses and the total amounts of insulin administered during the prescribed intervals of action. 
   
     
     
       2. A sensor-driven glucose control system according to  claim 1 , wherein the mathematical relationship includes a target ratio of the amount of each priming dose to the total amount of insulin administered in each prescribed interval of action. 
     
     
       3. A sensor-driven glucose control system according to  claim 2 , wherein the target ratio has different values over respective time periods of a day, or over different prescribed intervals of action, or both. 
     
     
       4. A sensor-driven glucose control system according to  claim 3 , wherein the time periods have a regularity associated with timing of food consumption. 
     
     
       5. A sensor-driven glucose control system according to  claim 1 , wherein each period is defined by a receding-horizon time window extending back from a present time by a predetermined amount of time. 
     
     
       6. A sensor-driven glucose control system according to  claim 1 , being an autonomous or semi-autonomous control system in which the controller includes a corrective insulin controller that generates the insulin dose control signal in response to the glucose level signal to administer corrective doses of insulin so as to regulate the glucose level signal. 
     
     
       7. A sensor-driven glucose control systemaccording to  claim 1 ,, comprising:
 an insulin delivery device configured to receive an insulin dose control signal and operative in response to the insulin dose control signal to infuse priming doses of insulin to a subject; and 
 a controller configured and operative to generate the insulin dose control signal and send it to the insulin delivery device to:
 (1) continually administer the priming doses of insulin at respective times, each priming dose being of a respective amount and having a prescribed interval of action; 
 (2) receive information regarding total amounts of insulin administered during the prescribed intervals of action, each total amount including an aggregation of total doses administered in response to a glucose level signal; and 
 (3) automatically adapt the amounts of the priming doses in response to a mathematical relationship, over respective periods each spanning multiple prescribed intervals of action, between the amounts of the priming doses and the total amounts of insulin administered during the prescribed intervals of action, 
 
 and further comprising a counter-regulatory agent delivery device configured to receive a counter-regulatory agent dose control signal and operative to infuse a counter-regulatory agent into the subject in response to a the counter-regulatory agent dose control signal, and wherein the controller is operative to generate the counter-regulatory agent dose control signal and send it to the counter-regulatory agent delivery device by performing a calculation generating (1) a raw dose control value based on the glucose level signal, and (2) the counter-regulatory agent dose control signal as a modification of the raw dose control value based on an estimation of an effect of insulin infused into the subject by the insulin delivery device. 
 
     
     
       8. A method of operating a controller for a sensor-driven glucose control system including an insulin delivery device configured to receive an insulin dose control signal and operative in response to an the insulin dose control signal to infuse insulin into the a subject, comprising:
 generating the insulin dose control signal and sending it to the insulin delivery device to continually administer priming doses of insulin at respective times, each priming dose being of a respective amount and having a prescribed interval of action; 
 receiving information regarding total amounts of insulin administered during the prescribed intervals of action, each total amount including an aggregation of total doses administered in response to a glucose level signal; and 
 automatically adapting the amounts of the priming doses in response to a mathematical relationship, over respective periods each spanning multiple prescribed intervals of action, between the amounts of the priming doses and the total amounts of insulin administered during the prescribed intervals of action. 
 
     
     
       9. A method according to  claim 8 , wherein the mathematical relationship includes a target ratio of the amount of each priming dose the priming doses to the total amount amounts of insulin administered in each prescribed interval during the prescribed intervals of action. 
     
     
       10. A method according to  claim 9 , wherein the target ratio has different values over respective time periods of a day, or over different prescribed intervals of action, or both. 
     
     
       11. A method according to  claim 10 , wherein the time periods have a regularity associated with timing of food consumption. 
     
     
       12. A method according to  claim 8 , wherein each period is defined by a receding-horizon time window extending back from a present time by a predetermined amount of time. 
     
     
       13. A method according to  claim 8 , wherein the sensor-driven glucose control system is an autonomous or semi-autonomous control system in which the controller includes a corrective insulin controller that generates the insulin dose control signal in response to the glucose level signal to administer corrective doses of insulin so as to regulate the glucose level signal. 
     
     
       14. A method according to  claim 8 , wherein the sensor-driven glucose control system further includes a counter-regulatory agent delivery device configured to receive a counter-regulatory agent dose control signal and operative to infuse a counter-regulatory agent into the subject in response to a the counter-regulatory agent dose control signal, and wherein the method further includes generating the counter-regulatory agent dose control signal and sending it to the counter-regulatory agent delivery device by performing a calculation generating (1) a raw dose control value based on the glucose level signal, and (2) the counter-regulatory agent dose control signal as a modification of the raw dose control value based on an estimation of an effect of insulin infused into the subject by the insulin delivery device. 
     
     
       15. A sensor-driven glucose control system, comprising:
 a controller configured and operative to generate an insulin dose control signal and send it to an insulin delivery device to:
 (1) continually administer priming doses of insulin at respective times, each priming dose being of a respective amount and having a prescribed interval of action; 
 (2) receive information regarding total amounts of insulin administered during the prescribed intervals of action, each total amount including an aggregation of total doses administered in response to a glucose level signal; and 
 (3) automatically adapt the amounts of the priming doses in response to a mathematical relationship, over respective periods each spanning multiple prescribed intervals of action, between the amounts of the priming doses and the total amounts of insulin administered during the prescribed intervals of action, 
   wherein the controller is operative to generate a counter-regulatory agent dose control signal and send it to a counter-regulatory agent delivery device to cause the counter-regulatory agent delivery device to infuse a counter-regulatory agent into the subject, by performing a calculation generating (1) a raw dose control value based on the glucose level signal, and (2) the counter-regulatory agent dose control signal as a modification of the raw dose control value based on an estimation of an effect of insulin infused into the subject.    
     
     
       16. A method of operating a controller for a sensor-driven glucose control system having an insulin delivery device configured to receive an insulin dose control signal and operative in response to the insulin dose control signal to infuse insulin into a subject, comprising:
 generating the insulin dose control signal and sending it to the insulin delivery device to cause the insulin delivery device to continually administer priming doses of insulin at respective times, each priming dose being of a respective amount and having a prescribed interval of action;   receiving information regarding total amounts of insulin administered during the prescribed intervals of action, each total amount including an aggregation of total doses administered in response to a glucose level signal; and   automatically adapting the amounts of the priming doses in response to a mathematical relationship, over respective periods each spanning multiple prescribed intervals of action, between the amounts of the priming doses and the total amounts of insulin administered during the prescribed intervals of action.    
     
     
       17. A method according to  claim 16 , wherein the mathematical relationship includes a target ratio of the amounts of the priming doses to the total amounts of insulin administered during the prescribed intervals of action.  
     
     
       18. A method according to  claim 17 , wherein the target ratio has different values over respective time periods of a day, or over different prescribed intervals of action, or both.  
     
     
       19. A method according to  claim 18 , wherein the time periods have a regularity associated with timing of food consumption.  
     
     
       20. A method according to  claim 16 , wherein each period is defined by a receding-horizon time window extending back from a present time by a predetermined amount of time.  
     
     
       21. A method according to  claim 16 , wherein the sensor-driven glucose control system is an autonomous or semi-autonomous control system in which the controller includes a corrective insulin controller that generates the insulin dose control signal in response to the glucose level signal to administer corrective doses of insulin so as to regulate the glucose level signal.  
     
     
       22. A method according to  claim 16 , wherein the sensor-driven glucose control system further includes a counter-regulatory agent delivery device configured to receive a counter-regulatory agent dose control signal and operative to infuse a counter-regulatory agent into the subject in response to the counter-regulatory agent dose control signal, and wherein the method further includes generating the counter-regulatory agent dose control signal and sending it to the counter-regulatory agent delivery device by performing a calculation generating (1) a raw dose control value based on the glucose level signal, and (2) the counter-regulatory agent dose control signal as a modification of the raw dose control value based on an estimation of an effect of insulin infused into the subject.