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In an implantable medical device for monitoring blood-glucose concentration in the blood, metabolic oxygen consumption is derived by measuring physiological metrics related to mixed venous oxygen concentration. Blood-glucose concentration is determined using correlations of blood-glucose concentrati

In an implantable medical device for monitoring blood-glucose concentration in the blood, metabolic oxygen consumption is derived by measuring physiological metrics related to mixed venous oxygen concentration. Blood-glucose concentration is determined using correlations of blood-glucose concentration with measures of metabolic oxygen consumption including oxymetric, temperature, and electrocardiographic data. Additional physiological sensor measurements may be used to enhance the accuracy of the analysis of blood-glucose concentration. By using a combination of oxymetric and other physiological metrics, blood-glucose concentration can be reliably calculated over a wide range. The device compares the blood-glucose concentration with upper and lower acceptable bounds and generates appropriate warning signals if the concentration falls outside the bounds. The device may also control a therapeutic device to maintain blood-glucose concentration within an acceptable range. A calibration technique determines patient-specific parameters for use in the calculation of blood-glucose concentration.

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1. A method comprising: monitoring blood-glucose concentration in blood of a subject using a system implanted in a subject wherein the system has stored relationships therein between blood-glucose concentration and at least a first physiological metric, and wherein the system implanted in the subjec

1. A method comprising: monitoring blood-glucose concentration in blood of a subject using a system implanted in a subject wherein the system has stored relationships therein between blood-glucose concentration and at least a first physiological metric, and wherein the system implanted in the subject performs the steps of(a) obtaining a measure of the first physiological metric using one or more sensors of the system implanted in the subject; and(b) calculating the blood-glucose concentration using the stored relationships and the measure of the first physiological metric without using a measure obtained from an enzymatic sensor;wherein the first physiological metric is a blood oxygen metric. 2. The method of claim 1, wherein: the implanted system has stored relationships therein between blood-glucose concentration, the first physiological metric, and a second physiological metric,step (a) comprises obtaining a measure of the first physiological metric and also a measure of the second physiological metric using one or more sensors and/or electrodes of the system implanted in the subject;step (b) comprises calculating the blood-glucose concentration using the stored relationships, the measure of the first physiological metric, and also the measure of the second physiological metric without using a measure obtained from an enzymatic sensor; andthe second physiological metric is a metric, other than the first physiological metric, selected from the group consisting of a metric of venous oxygen saturation, a metric of arterial oxygen saturation, a metric of hematocrit, a metric of core temperature, a metric of peripheral temperature, a metric of blood pressure, a metric of blood flow, and a metric of heart rate. 3. The method of claim 2, wherein: the system has stored relationships therein between blood-glucose concentration, the first physiological metric, the second physiological metric, and a third physiological metric,step (a) comprises obtaining a measure of the first physiological metric, a measure of the second physiological metric and also a measure of the third physiological metric using one or more sensors and/or electrodes of the system implanted in the subject;step (b) comprises calculating the blood-glucose concentration using the stored relationships, the measure of the first physiological metric, the measure of the second physiological metric and also the measure of the third physiological metric without using a measure obtained from an enzymatic sensor; andthe third physiological metric is a metric, other than the first and second physiological metrics, selected from the group consisting of a metric of venous oxygen saturation, a metric of arterial oxygen saturation, a metric of hematocrit, a metric of core temperature, a metric of peripheral temperature, a metric of blood pressure, a metric of blood flow, and a metric of heart rate. 4. The method of claim 1, wherein the first physiological metric is a metric of venous oxygen saturation, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject. 5. The method of claim 2, wherein the first physiological metric is a metric of venous oxygen saturation, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject. 6. The method of claim 5, wherein the second physiological metric is one of a metric of core temperature and a metric of peripheral temperature, and the measure of the second physiological metric is obtained using a temperature sensor implanted in the subject. 7. The method of claim 5, wherein the second physiological metric is a metric of blood pressure, and the measure of the second physiological metric is obtained using a blood pressure sensor implanted in the subject. 8. The method of claim 3, wherein: the first physiological metric is a metric of venous oxygen saturation, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject, andthe second physiological metric is a metric of one of core temperature and peripheral temperature, and the measure of the second physiological metric is obtained using a temperature sensor implanted in the subject. 9. The method of claim 2, wherein the first physiological metric is a metric of hematocrit, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject. 10. The method of claim 3, wherein: the second physiological metric is a metric of blood pressure, and the measure of the second physiological metric is obtained using a blood pressure sensor implanted in the subject, andthe third physiological metric is a metric of heart rate, and the measure of the third physiological metric is obtained using one or more electrodes implanted in the subject. 11. The method of claim 1, wherein: step (a) comprises obtaining a measure of the first physiological metric using one or more sensors of the system implanted in the subject and also receiving external data from an external device; andstep (b) comprises using the stored relationships, the measure of the first physiological metric and also the external data to calculate the blood-glucose concentration without using a measure obtained from an enzymatic sensor. 12. The method of claim 1, further comprising transmitting the blood-glucose concentration from the implanted system to an external system wherein the external system communicates the blood-glucose concentration to at least one member of the group consisting of: the subject, a physician, a clinician, a nurse, a caregiver and a manufacturer. 13. The method of claim 1, further comprising: causing a warning which can be sensed by the subject if the blood-glucose concentration reaches a threshold. 14. The method of claim 1, further comprising: determining the rate of change of blood-glucose concentration by determining the blood-glucose concentration at a plurality of times during a period; andcausing an alert which can be sensed by the subject in response to the rate of change of glucose concentration. 15. The method of claim 1, further comprising: determining a metric indicative of average blood-glucose concentration during a period of time by determining the blood-glucose concentration at a plurality of times during the period of time. 16. The method of claim 1, wherein the implantable system provides electrical stimulation to an organ of the subject and wherein the method further comprises modifying the electrical stimulation in response to the blood-glucose concentration. 17. An implantable system for monitoring blood-glucose concentration in a subject wherein the system comprises: a memory which has stored therein relationships between blood-glucose concentration and at least a first physiological metric;a first sensor which obtains a measure of the first physiological metric; anda controller which calculates the blood-glucose concentration using the stored relationships and the measure of the first physiological metric;wherein the system is adapted to be implanted in a subject, the first sensor is an implantable oxymeter, and the first physiological metric is a blood oxygen metric; andwherein the system does not include an enzymatic sensor. 18. The system of claim 17, wherein the first sensor is an oxymeter adapted to be implanted in the subject and which obtains a measure of one of venous oxygen saturation, hematocrit, and arterial oxygen saturation. 19. The system of claim 18, further comprising: a second sensor which obtains a measure of a second physiological metric;wherein the memory has stored therein relationships between blood-glucose concentration, the first physiological metric, and the second physiological metric;wherein the second sensor which obtains the measure of the second physiological metric is a sensor, other than the first sensor, selected from a group consisting of an oxymeter adapted to be implanted in the subject which obtains a measure of venous oxygen saturation, an oxymeter adapted to be implanted in the subject which obtains a measure of hematocrit, an oxymeter adapted to be implanted in the subject which obtains a measure of arterial oxygen saturation, a temperature sensor adapted to be implanted in the subject which obtains a measure of peripheral temperature, a temperature sensor adapted to be implanted in the subject which obtains a measure of core temperature, a blood pressure sensor adapted to be implanted in the subject which obtains a measure of blood pressure, a blood flow sensor adapted to be implanted in the subject which obtains a measure of blood flow, and an electrode adapted to be implanted in the subject which obtains a measure of heart-rate; andwherein the controller calculates the blood-glucose concentration using the stored relationships, the measure of the first physiological metric and also the measure of the second physiological metric. 20. The system of claim 19, further comprising: a third sensor which obtains a measure of a third physiological metric;wherein the memory has stored therein relationships between blood-glucose concentration, the first physiological metric, the second physiological metric, and the third physiological metric;wherein the third sensor which obtains the measure of the third physiological metric is a sensor, other than the first and second sensors, selected from the group consisting of an oxymeter adapted to be implanted in the subject which obtains a measure of venous oxygen saturation, an oxymeter adapted to be implanted in the subject which obtains a measure of hematocrit, an oxymeter adapted to be implanted in the subject which obtains a measure of arterial oxygen saturation, a temperature sensor adapted to be implanted in the subject which obtains a measure of peripheral temperature, a temperature sensor adapted to be implanted in the subject which obtains a measure of core temperature, a blood pressure sensor adapted to be implanted in the subject which obtains a measure of blood pressure, a blood flow sensor adapted to be implanted in the subject which obtains a measure of blood flow, and an electrode adapted to be implanted in the subject which obtains a measure of heart-rate; andwherein the controller uses the stored relationships, the measure of the first physiological metric, the measure of the second physiological metric, and also the measure of the third physiological metric to calculate the blood-glucose concentration. 21. The system of claim 18, wherein the second sensor is a temperature sensor adapted to be implanted in the subject and which obtains a measure of one of core body temperature and peripheral body temperature. 22. A method performed by an external device in conjunction with an implantable medical device implanted within a subject, the method comprising: obtaining, using the external device, a blood-glucose concentration of the subject at each of a plurality of times, to thereby obtain a plurality of different blood-glucose concentrations;obtaining, using the implantable medical device, measures of one or more physiological metrics at each of the plurality of times;transmitting, from the implantable medical device to the external device, data indicative of the measures of said one or more physiological metrics obtained at the plurality of times;determining, using the external device, from the data indicative of the measures of said one or more physiological metrics at the plurality of times, parameters which enable the implantable medical device to derive blood-glucose concentrations for the subject from subsequently-obtained measures of said one or more physiological metrics;transmitting the parameters to the implanted device; anddetermining, using the implantable medical device implanted within a subject, the blood-glucose concentration of the subject, using the parameters and the subsequently-obtained measures of said one or more physiological metrics;wherein said one or more physiological metrics include at least one blood oxygen metric. 23. The method of claim 22, wherein said one or more physiological metrics include at least two physiological metrics selected from the group consisting of a metric of venous oxygen saturation, a metric of arterial oxygen saturation, a metric of hematocrit, a metric of core temperature, a metric of peripheral temperature, a metric of blood pressure, a metric of blood flow, and a metric of heart rate. 24. The method of claim 22, wherein said one or more physiological metrics include at least three physiological metrics selected from the group consisting of a metric of venous oxygen saturation, a metric of arterial oxygen saturation, a metric of hematocrit, a metric of core temperature, a metric of peripheral temperature, a metric of blood pressure, a metric of blood flow, and a metric of heart rate. 25. The method of claim 22, wherein said one or more physiological metrics include at least a metric of venous oxygen saturation. 26. The method of claim 22, wherein the method further comprises: administering glucose to the subject, during the obtaining with the implantable device of the measures of said one or more physiological metrics at the plurality of times, in order to increase the blood-glucose concentration of the subject between one of said plurality of times and another of said plurality of times. 27. The method of claim 22, wherein the method further comprises: administering insulin to the subject, during the obtaining with the implantable device of the measures of said one or more physiological metrics at the plurality of times, in order to decrease the blood-glucose concentration of the subject between one of said plurality of times and another of said plurality of times. 28. A method comprising: monitoring blood-glucose concentration in blood of a subject using a system implanted in the subject, wherein the system has stored relationships therein between blood-glucose concentration and a first physiological metric, a second physiological metric, and a third physiological metric, and wherein the system implanted in the subject performs the steps of:(a) obtaining, using one or more sensors and/or electrodes of the system implanted within the subject, a measure of the first physiological metric which is a physiological metric selected from the group consisting of a metric of venous oxygen saturation and a metric of hematocrit,a measure of the second physiological metric which is a physiological metric, other than the first physiological metric, selected from the group consisting of a metric of hematocrit, a metric of core temperature, a metric of peripheral temperature, a metric of blood pressure, a metric of blood flow, and a metric of heart rate, anda measure of the third physiological metric which is a metric, other than the first and second physiological metrics, selected from the group consisting of a metric of hematocrit, a metric of blood pressure, a metric of blood flow, and a metric of heart rate; and(b) calculating the blood-glucose concentration using the stored relationships, the first physiological metric, the second physiological metric, and the third physiological metric. 29. The method of claim 28, wherein the first physiological metric is a metric of venous oxygen saturation, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject. 30. The method of claim 28, wherein: the first physiological metric is a metric of venous oxygen saturation, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject; andthe second physiological metric is a metric of blood pressure, and the measure of the second physiological metric is obtained using a blood pressure sensor implanted in the subject. 31. The method of claim 28, wherein: the first physiological metric is a metric of venous oxygen saturation, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject; andthe second physiological metric is one of a metric of core temperature and peripheral temperature, and the second physiological metric is obtained using a temperature sensor implanted in the subject. 32. The method of claim 28, wherein the first physiological metric is a metric of hematocrit, and the measure of the first physiological metric is obtained using an oxymeter implanted in the subject. 33. The method of claim 28, wherein: the second physiological metric is a metric of blood pressure, and the measure of the second physiological metric is obtained using a sensor implanted in the subject; andthe third physiological metric is a metric of heart rate, and the measure of the third physiological metric is obtained using one or more electrodes implanted in the subject. 34. The method of claim 28, wherein step (b) comprises calculating the blood-glucose concentration using the stored relationships, the measure of the first physiological metric, the measure of the second physiological metric, and the measure of the third physiological metric, without using a measure obtained from an enzymatic sensor. 35. An implantable system for monitoring blood-glucose concentration in a subject wherein the implantable system comprises: a memory which has stored therein relationships between blood-glucose concentration and a first physiological metric, a second physiological metric, and a third physiological metric;one or more implantable sensors and/or electrodes which obtain, a measure of the first physiological metric, wherein the first physiological metric is a blood oxygen metric,a measure of the second physiological metric, wherein the second physiological metric is a metric, other than the first physiological metric, selected from the group consisting of a metric of venous oxygen saturation, a metric of hematocrit, a metric of arterial oxygen saturation, a metric of peripheral temperature, a metric of core temperature, a metric of blood pressure, a metric of blood flow, and a metric of heart-rate, anda measure of the third physiological metric, wherein the third physiological metric is a metric, other than the first and second physiological metrics, selected from the group consisting of a metric of venous oxygen saturation, a metric of hematocrit, a metric of arterial oxygen saturation, a metric of peripheral temperature, a metric of core temperature, a metric of blood pressure, a metric of blood flow, and a metric of heart-rate; anda controller which calculates the blood-glucose concentration using the stored relationships, the measure of the first physiological metric, the measure of the second physiological metric, and the measure of the third physiological metric. 36. The implantable system of claim 35, wherein the measure of the first physiological metric is obtained using an implantable oxymeter, and wherein the first physiological metric is selected from the group consisting of a metric of venous oxygen saturation, a metric of hematocrit, and a metric of arterial oxygen saturation. 37. The implantable system of claim 36, wherein the controller calculates the blood-glucose concentration using the stored relationships, the measure of the first physiological metric, the measure of the second physiological metric, and the measure of the third physiological metric, without using a measure obtained from an enzymatic sensor.