Source: http://www.google.com/patents/US7069078?dq=7,194,691
Timestamp: 2017-05-24 04:54:39
Document Index: 85097604

Matched Legal Cases: ['art.\n7', 'art.\n14', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8', 'art 8']

Patent US7069078 - Insulin-mediated glucose uptake monitor - Google PatentsSearch Images Maps Play YouTube News Gmail Drive More »Sign inPatentsAn implanted medical device may detect the onset of impaired glucose tolerance or Type II diabetes. The implanted medical device may have additional functionality. For example, the implanted medical device may be a pacemaker or a pressure monitor, but may also monitor insulin-mediated glucose uptake...http://www.google.com/patents/US7069078?utm_source=gb-gplus-sharePatent US7069078 - Insulin-mediated glucose uptake monitorAdvanced Patent SearchTry the new Google Patents, with machine-classified Google Scholar results, and Japanese and South Korean patents.Publication numberUS7069078 B2Publication typeGrantApplication numberUS 10/127,033Publication dateJun 27, 2006Filing dateApr 22, 2002Priority dateApr 22, 2002Fee statusPaidAlso published asUS20030199925, WO2003088832A1Publication number10127033, 127033, US 7069078 B2, US 7069078B2, US-B2-7069078, US7069078 B2, US7069078B2InventorsRichard HoubenOriginal AssigneeMedtronic, Inc.Export CitationBiBTeX, EndNote, RefManPatent Citations (14), Non-Patent Citations (2), Referenced by (20), Classifications (10), Legal Events (2) External Links: USPTO, USPTO Assignment, EspacenetInsulin-mediated glucose uptake monitor
US 7069078 B2Abstract
An implanted medical device may detect the onset of impaired glucose tolerance or Type II diabetes. The implanted medical device may have additional functionality. For example, the implanted medical device may be a pacemaker or a pressure monitor, but may also monitor insulin-mediated glucose uptake by processing electrical signals from the heart. An implanted medical device that monitors insulin-mediated glucose uptake may be implanted in a patient who has not been diagnosed with impaired glucose tolerance or Type II diabetes, and may give the patient early warning if these conditions develop.
an implantable medical device that receives an electrical signal from a heart, wherein the implantable medical device comprises at least one of a pacemaker, a pacemaker-cardioverter-defibrillator, an implantable pressure monitor, an implantable nerve stimulator, an implantable muscle stimulator, an implantable drug delivery device, and an implantable cardiac monitor; and
a processor coupled to the implantable medical device that monitors insulin-mediated glucose uptake as a function of the electrical signal,
wherein the implantable medical device receives a signal in addition to the electrical signal from the heart.
wherein the processor monitors insulin-mediated glucose uptake by monitoring at least one of a T-wave amplitude in the electrical signal, a Q-T interval in the electrical signal and an S-T elevation in the electrical signal.
3. The system of claim 1, further comprising memory coupled to the processor.
4. The system of claim 1, wherein the implantable medical device and the processor are included in a single implantable device.
5. The system of claim 1, further comprising an electrode coupled to the implantable medical device, wherein the implantable medical device receives the electrical signal from the electrode.
6. The system of claim 5, wherein the electrode is disposed in a chamber of the heart.
7. The system of claim 1, wherein the implantable medical device monitors a condition in addition to insulin-mediated glucose uptake.
wherein the implantable medical device delivers a therapy other than delivery of insulin.
9. The system of claim 1, wherein the implantable medical device analyzes at least one of a heart rhythm and a pressure in the heart.
wherein the implantable medical device delivers at least one of pacing pulses, defibrillation, nerve stimulation and muscle stimulation.
11. An implantable medical device system comprising:
wherein the implantable medical device receives an activity signal from an activity sensor, a pressure signal from a pressure sensor and a temperature signal from a temperature sensor.
12. A medical device system comprising:
a medical device that receives an electrical signal from a heart, wherein the medical device includes at least one of a pacemaker, a pacemaker-cardioverter-defibrillator, a pressure monitor, a nerve stimulator, a muscle stimulator, a drug delivery device, a monitor, and a cardiac monitor; and
a processor coupled to the medical device that monitors insulin-mediated glucose uptake as a function of the electrical signal,
wherein the medical device receives a signal in addition to the electrical signal from the heart.
14. The system of claim 12, further comprising memory coupled to the processor.
15. The system of claim 12, wherein the medical device and the processor are included in a single device.
16. The system of claim 12, further comprising an electrode coupled to the medical device, wherein the medical device receives the electrical signal from the electrode.
17. The system of claim 16, wherein the electrode is disposed in a chamber of the heart.
wherein the medical device monitors a condition in addition to insulin-mediated glucose uptake.
wherein the medical device delivers a therapy other than delivery of insulin.
wherein the medical device delivers at least one of pacing pulses, defibrillation, nerve stimulation and muscle stimulation.
21. A medical device system comprising:
wherein the medical device receives an activity signal from an activity sensor, a pressure signal from a pressure sensor and a temperature signal from a temperature sensor.
22. A medical device system comprising:
wherein the medical device analyzes at least one of a heart rhythm and a pressure in the heart.
The invention relates to patient monitoring systems, and more particularly, to patient monitoring systems that receive an electrical cardiac signal indicative of cardiac activity.
Type II diabetes generally develops in adulthood, and the risk of development of Type II diabetes increases with age. Factors such as obesity also contribute to the risk. A patient suffering from Type II diabetes secretes insulin, but the insulin's target cells are less sensitive to insulin. Symptoms of Type II diabetes are typically slow to appear, and a patient having Type II diabetes may not be aware of his condition. A blood test may show whether the patient has impaired glucose tolerance (IGT), which is often a precursor to Type II diabetes, or compensated Type II diabetes. Unless addressed with treatment such as diet and exercise, these conditions may develop into uncompensated Type II diabetes, a very serious condition.
Patients at risk for diabetes may use a glucose sensor. Most glucose sensors presently in common use are based on electrochemical methods such as the electroenzymatic method where blood glucose is oxidized under glucose-oxidase control, producing gluconic acid and hydrogen peroxide. Alternately, the produced gluconic acid can be determined directly. Both of these sensor types, however, suffer from stability problems. Optical glucose sensors have been tried, but optical sensors may not be feasible for long-term continuous monitoring or for implantable applications.
Poor diet and lack of exercise may not only increase the risk of Type II diabetes, but may increase the risk of heart disease as well. Obesity may, for example, contribute to high blood pressure, which increases the workload of the heart. In addition, the risk of coronary heart disease, like the risk of developing Type II diabetes, increases with age.
In commonly-assigned U.S. Pat. No. 5,741,211 to Renirie, et al., a possible relationship between diabetes mellitus and coronary heart disease was discussed. A correlation between electrocardiogram (ECG) changes and blood glucose was described, and systems and methods were described whereby changes in blood insulin could be monitored as a function of ECG signals. The system applied signal processing to the continuously sensed ECG signals to discriminate selected portions such as the QRS complex and the T-wave. The discriminated portions may be further processed to determine a relationship between the signal and the patient's blood insulin and/or blood glucose levels. The '211 patent is hereby incorporated by reference herein in its entirety.
Long-term monitoring systems and devices known in the art typically involve chemically based sensors. These sensors are typically not medically or economically beneficial for a patient who may be at risk of developing diabetes. Examples of these techniques and/or devices may be found in the issued U.S. Patents listed in Table 1 below.
5,660,163
5,999,848
Gord et al.
6,081,736
6,119,028
6,175,752 B1
6,212,416 B1
6,221,011 B1
6,259,937 B1
6,277,072 B1
6,360,888 B1
The present invention has certain objects. That is, various embodiments of the present invention provide solutions to one or more problems existing in the prior art with respect to insulin and/or glucose monitors. These problems include, for example, the lack of medical or economic benefit associated with implanting an insulin or glucose monitor in a patient who has not been diagnosed as diabetic. The problems also include a lack of robustness of sensors that may be used to perform the monitoring over an extended period of time. Various embodiments of the present invention have the object of solving at least one of the foregoing problems.
It is an object of the invention to monitor the development of IGT or Type II diabetes in a patient with an implanted medical device. In particular, it is an object of the present invention to monitor insulin-mediated glucose uptake, which may be indicative of IGT or Type II diabetes. Because the patient may not have been diagnosed with IGT or Type II diabetes, surgical implantation of such a device may not be justified medically or economically.
In a patient who receives an implanted medical device that principally performs another function, however, the implanted medical device may also monitor insulin-mediated glucose uptake. An implantable cardiac pacemaker, for example, may have a principal function of monitoring the patient's heart rhythms and delivering appropriate therapy to correct arrhythmias. The same pacemaker may be further configured to monitor insulin-mediated glucose uptake as an additional benefit. The implantation of the pacemaker may be justified medically and economically, and may include an implanted insulin-mediated glucose uptake monitor with no additional surgery or inconvenience to the patient. The patient may receive the benefit of monitoring even when the patient has not have been diagnosed with IGT or diabetes, enabling early detection of such conditions.
It is a further object of the invention to enable implantable medical devices of many types to monitor insulin-mediated glucose uptake. Many implantable devices may be configured to receive an electrical signal from the heart, such as an ECG signal or an electrogram (EGM) signal. Other implantable devices may be adapted to receive an electrical signal from the heart. These devices, which may have other principal functions, may also be applied to monitor insulin-mediated glucose uptake.
It is also an object of the invention to provide an early warning in patients who do develop IGT or Type II diabetes. IGT and Type II diabetes typically develop slowly, and early detection may lead to more effective treatment and fewer complications. These conditions often respond to therapy such as administration of glucose lowering agents, changes in diet and/or exercise. When IGT or diabetes is detected early, a greater array of therapeutic options are available to the patient. It is an additional object of the invention to monitor the effectiveness of the therapy.
An additional object of the invention is to provide a robust system for monitoring insulin-mediated glucose uptake. Because the monitoring may take place over an extended period of time, the implanted components should be able to operate for a long time under a wide variety of conditions. Many glucose sensors are ill-suited to long-term monitoring.
Various embodiments of the invention may possess one or more features capable of fulfilling the above objects. The invention analyzes electrical signals from the heart to assess the patient's insulin-mediated glucose uptake. In an exemplary embodiment, the invention analyzes the electrical signals that follow the ingestion of a meal. The invention further employs electrodes as sensors, which are more robust than chemically based sensors. The electrodes may be coupled to an implantable medical device that performs other principal functions, such as a pacemaker, a pacemaker-cardioverter-defibrillator, a pressure monitor, a nerve stimulator, a muscle stimulator, a drug delivery device, and a cardiac monitor. The invention provides additional functionality to the implantable medical device.
The invention may offer one or more advantages in addition to those mentioned above. Patients needing an implantable medical device may receive blood insulin and/or blood glucose monitoring as an added benefit, without the necessity of a separate, dedicated insulin or glucose monitoring device. The techniques of the invention may help identify the development of conditions that otherwise might not be noticed by the patient, and may provide the patient with an early warning of IGT or Type II diabetes. With early warning, the patient may take steps that can slow, and possibly reverse, the progression of the disease.
FIG. 6 is a process diagram that illustrates the physiological relationship between insulin-mediated uptake of glucose and cardiac electrical signals.
FIG. 7 is a diagram of a system including an implantable medical device.
FIG. 8 is a flow diagram showing techniques for collecting and processing data pertaining to the monitoring of blood insulin and/or blood glucose.
Electrical signals detected via pacing and sensing leads 16 and 18 may be used to monitor blood insulin and/or blood glucose using techniques that will be described below. The invention is not limited to the particular embodiment shown in FIG. 1 or to other exemplary embodiments shown in subsequent figures.
The electrogram signal provided by EGM amplifier 94 is employed when IMD 10 is being interrogated by an external programmer to transmit a representation of a cardiac analog electrogram. See, for example, U.S. Pat. No. 4,556,063 to Thompson et al., hereby incorporated by reference herein in its entirety. The electrogram signal may also be useful in monitoring blood insulin and/or blood glucose. Output pulse generator 96 provides amplified pacing stimuli to patient's heart 8 through coupling capacitor 98 in response to a pacing trigger signal provided by digital controller/timer circuit 74 each time either (a) the escape interval times out, (b) an externally transmitted pacing command is received, or (c) in response to other stored commands as is well known in the pacing art. By way of example, output amplifier 96 may correspond generally to an output amplifier disclosed in U.S. Pat. No. 4,476,868 to Thompson, hereby incorporated by reference herein in its entirety.
The present invention is not limited in scope to single-sensor or dual-sensor pacemakers, and is not limited to IMD's comprising activity or pressure sensors only. Nor is the present invention limited in scope to single-chamber pacemakers, single-chamber leads for pacemakers or single-sensor or dual-sensor leads for pacemakers. Thus, various embodiments of the present invention may be practiced in conjunction with one or more leads or with multiple-chamber pacemakers, for example. At least some embodiments of the present invention may be applied equally well in the contexts of single-, dual-, triple- or quadruple- chamber pacemakers or other types of IMD's. See, for example, U.S. Pat. No. 5,800,465 to Thompson et al., hereby incorporated by reference herein in its entirety, as are all U.S. Patents referenced therein. IMD 10 may also be a pacemaker-cardioverter-defibrillator (“PCD”) corresponding to any of numerous commercially available implantable PCD's. Various embodiments of the present invention may be practiced in conjunction with PCD's such as those disclosed in U.S. Pat. No. 5,545,186 to Olson et al., U.S. Pat. No. 5,354,316 to Keimel, U.S. Pat. No. 5,314,430 to Bardy, U.S. Pat. No. 5,131,388 to Pless, and U.S. Pat. No. 4,821,723 to Baker et al., all hereby incorporated by reference herein, each in its respective entirety.
IMD 10 is shown in FIG. 4 in combination with leads 1, 7 and 41, and lead connector assemblies 23, 17 and 6 inserted into connector module 12. Optionally, insulation of the outward facing portion of housing 14 of IMD 10 maybe provided using a plastic coating such as parylene or silicone rubber, as is employed in some unipolar cardiac pacemakers. The outward facing portion, however, may be left uninsulated or some other division between insulated and uninsulated portions may be employed. The uninsulated portion of housing 14 serves as a subcutaneous defibrillation electrode to defibrillate either the atria or ventricles. Lead configurations other that those shown in FIG. 4 may be practiced in conjunction with the present invention, such as those shown in U.S. Pat. No. 5,690,686 to Min et al., hereby incorporated by reference herein in its entirety.
Switch matrix 47 is used to select which of the available electrodes are coupled to wide band (0.5–200 Hz) amplifier 49 for use in digital signal analysis. Selection of electrodes is controlled by microprocessor 51 via data/address bus 53, which selections may be varied as desired. Signals from the electrodes selected for coupling to bandpass amplifier 49 are provided to multiplexer 55, and thereafter converted to multi-bit digital signals by A/D converter 57, for storage in random access memory 59 under control of direct memory access circuit 61. Microprocessor 51 may employ digital signal analysis techniques to characterize the digitized signals stored in random access memory 59 to recognize and classify the patient's heart rhythm employing any of the numerous signal processing methodologies known to the art.
The remainder of the circuitry is dedicated to the provision of cardiac pacing, cardioversion and defibrillation therapies, and, for purposes of the present invention may correspond to circuitry known to those skilled in the art. The following exemplary apparatus is disclosed for accomplishing pacing, cardioversion and defibrillation functions. Pacer timing/control circuitry 63 preferably includes programmable digital counters which control the basic time intervals associated with DDD, VVI, DVI, VDD, AAI, DDI and other modes of single- and dual-chamber pacing well known to the art. Circuitry 63 also preferably controls escape intervals associated with anti-tachyarrhythmia pacing in both the atrium and the ventricle, employing any anti-tachyarrhythmia pacing therapies known to the art.
Alternatively, IMD 10 may be an implantable nerve stimulator or muscle stimulator such as that disclosed in U.S. Pat. No. 5,199,428 to Obel et al., U.S. Pat. No. 5,207,218 to Carpentier et al., or U.S. Pat. No. 5,330,507 to Schwartz, or an implantable monitoring device such as that disclosed in U.S. Pat. No. 5,331,966 issued to Bennet et al., all of which are hereby incorporated by reference herein, each in its respective entirety. The present invention is believed to find wide application to any form of implantable electrical device for use in conjunction with electrical leads. As used herein, IMD 10 encompasses all implantable medical devices of any kind that receive electrical signals from heart 8.
Electrical signals from heart 8 may be used to monitor blood insulin and/or blood glucose levels. In particular, there is a relationship between insulin-mediated uptake of glucose and cardiac monophasic action potential. By monitoring cardiac electrical activity, therefore, insulin-mediated uptake of glucose may also be monitored.
FIG. 6 illustrates a manner in which insulin-mediated uptake of glucose affects cardiac electrical signals. Insulin 100 may be secreted in response to an elevated blood glucose level, which often occurs after ingestion of a meal. Insulin 100 may be secreted by the pancreas or by an implanted insulin delivery device. Insulin 100 facilitates glucose transport into most cells. In particular, a glucose transporter such as GLUT-4 102 helps transport glucose across the cell membrane in response to insulin 100. Insulin 100 further triggers other processes not shown in FIG. 6, such as stimulation of glycogenesis, inhibition of glycogenolysis, inhibition of gluconeognesis, and conversion of ADP to ATP.
In cardiac muscle cells, insulin 100 acts upon the sodium-hydrogen exchanger 104, causing sodium ions to enter the cell and hydrogen ions to leave the cell. As a result, sodium ion concentration inside the cell (Nai +) increases and hydrogen ion concentration inside the cell (Hi +) decreases (106). Because of the intracellular loss of hydrogen ion, pH inside the cell increases (108).
The increase in pH (108) has an effect upon the sodium-potassium pump 110, also called the Na+—K+ ATPase pump. Sodium ions are pumped out of the cell and potassium ions are pumped into the cell. As a result, the concentration of sodium ions inside the cell (Nai +) declines and the concentration of potassium ions outside the cell (Ko +) declines as well (112). The change in ion concentrations on opposite sides of the cell membrane causes the resting membrane potential (Vmem) to become more negative due to hyperpolarization (114). Because the resting membrane potential is negative, hyperpolarization results in an increase in the absolute value of the resting membrane potential. The change in ion concentrations also causes the action potential duration (APD) to increase (114).
In cardiac muscle cells, the APD increase affects the T-wave amplitude in an ECG or an EGM. In particular, the APD increase causes the T-wave amplitude to decrease (116). In particular, the T-wave amplitude decreases in comparison to the amplitude of the R-wave, which may be used as a reference. The T-wave is the electrical signal that accompanies repolarization of the ventricular cardiac muscle.
The APD increase also has an affect on the Q-T interval. In particular, the APD increases the Q-T interval, i.e., the time between the Q-wave, which accompanies the onset of ventricular depolarization, and the T-wave (116). The Q-T interval may be corrected for the RR interval and may be abbreviated Q-Tc.
Furthermore, the change in membrane potential may be observed as an S-T elevation (116). Between the S-wave, which accompanies the end of ventricular depolarization, and the T-wave, which accompanies ventricular repolarization, the electrical signal generated by the heart should be approximately zero volts. The change in membrane potential, however, may manifest itself as an elevated potential between the S-wave and the T-wave.
The effects of insulin-mediated glucose uptake shown in FIG. 6 apply to muscle cells throughout the body. These effects in cardiac muscle cells, however, result in artifacts that may be detected by an implanted device that receives an EGM signal from heart 8. The EGM signal reflects insulin-mediated glucose uptake, and the implanted device can monitor insulin-mediated glucose uptake by monitoring and analyzing the EGM signal. In particular, the implanted device can monitor changes in insulin-mediated glucose uptake by monitoring and analyzing changes in the EGM signal.
FIG. 7 shows a system 120 illustrating an embodiment of the invention, in which EGM signals are used to monitor insulin-mediated glucose uptake. System 120, which may be implantable in a human being or a mammal, includes IMD 10. IMD 10 may be a pacemaker or a pacemaker-cardioverter-defibrillator as illustrated in FIGS. 1–5, but IMD 10 may also be any medical device that receives electrical signals from heart 8. IMD 10 may be, for example, an implantable pressure monitor, an implantable nerve stimulator, an implantable muscle stimulator, an implantable drug delivery device or an implantable monitoring device such as a cardiac monitoring device.
In many cases, IMD 10 may have a principal function other than monitoring insulin-mediated glucose uptake or monitoring the progress of IGT or diabetes. The principal function may be to monitor a signal other than a heart signal, or to diagnose a condition other than insulin-mediated glucose uptake. The principal function may also be a therapeutic function other than delivery of insulin, such as delivery of electrical stimulation or pharmaceutical substances. IMD 10 may have any combination of principal monitoring, diagnostic and/or therapeutic functions.
A pressure monitor, in one example, may monitor blood pressures in one or more chambers of heart 8 via one or more pressure sensors that supply pressure signals to the pressure monitor. In addition to monitoring blood pressures, the pressure monitor may perform diagnostic functions such as estimating cardiac output. A pacemaker, in another example, may monitor heart signals, identify and classify cardiac rhythms, and may delivery therapy to heart 8 in response to certain detected arrhythmias. In devices such as a pressure monitor and a pacemaker, insulin-mediated glucose uptake monitoring may be performed in addition to the other functions. In other words, insulin-mediated glucose uptake monitoring may be “piggy-backed” onto an IMD 10 that may another principal function. A patient may receive a pacemaker because of heart problems, for example, and the pacemaker monitors the patient's EGM for arrhythmias. The same pacemaker may also provide insulin-mediated glucose uptake monitoring as an additional benefit. In these cases, the patient need not have been diagnosed with IGT or diabetes.
When insulin-mediated glucose uptake monitoring is “piggy-backed” onto an IMD, the monitoring may be performed using the pre-existing hardware of the IMD. In particular, the IMD may include hardware, such as sensing electrodes, for receiving cardiac signals. By processing the cardiac signals received via the hardware, the IMD may monitor insulin-mediated glucose uptake without needing significant additional sensing hardware.
In some embodiments of the invention, however, the invention may be a stand-alone device. In other words, the invention may be embodied as an implantable monitoring device that has the principal function of monitoring the progress of IGT or diabetes. Such a device may be provided to a patient who, although not diagnosed with IGT or diabetes, is at risk of developing the disease. Such a device may be provided to a patient who has been diagnosed with IGT or diabetes, and who wishes to monitor the efficacy of treatment.
IMD 10 may receive electrical signals from heart 8 via one or more electrodes disposed upon one or more leads. FIG. 7 shows system 120 with leads, such as leads 122 and 124, with electrodes 126 and 128 disposed thereon. The invention is not limited to two electrodes and two leads, but encompasses any number of electrodes. Moreover, multiple electrodes may be disposed upon a single lead, and it is not necessary to the invention that each electrode have a dedicated lead. When IMD 10 is a pacemaker, electrodes 126 and 128 may serve as sensing and pacing electrodes.
The invention is not limited to any particular electrode placement. When IMD 10 is a pacemaker, for example, electrodes 126, 128 may be placed in or proximate to one or more chambers of heart 8. Electrodes 126, 128 need not be placed in or proximate to heart 8, however, but may be placed such that electrodes 126, 128 can detect the electrical signals of heart 8. In general, the closer electrodes 126, 128 are to heart 8, the more pronounced the signals of interest may be, which may facilitate processing the signals.
IMD 10 may also be coupled to leads, sensors or devices that do not sense the electrical activity of heart 8. When IMD 10 is a pacemaker-cardioverter-defibrillator, for example, system 10 may include a lead 130 that couples IMD 10 to a defibrillation coil electrode 132. Defibrillation coil electrode 132 need not have a dedicated lead 130, but may be coupled to another lead such as lead 122 or lead 124. When IMD 10 is another kind of device, IMD 10 may be coupled to other leads, sensors and/or stimulators, such as a pressure sensor, an activity sensor, a muscle stimulator or a temperature sensor (not shown in FIG. 7).
IMD 10 may be coupled to a processor 134. Processor 134 is associated with memory 136. Memory 136 may store data such as measured parameters related to insulin-mediated glucose uptake. Processor 134 is shown as logically separate from IMD 10, but in practice processor 134 may be housed inside IMD 10, and IMD 10 and processor 134 may be realized as a single implantable device. Processor 134 and memory 136 may be included in microprocessor 51 and random access memory 59 in the embodiment of IMD 10 shown in FIG. 5, for example. Alternatively, processor 134 or memory 136 may be physically separate from IMD 10.
Processor 134 analyzes electrical signals from heart 8 sensed by electrodes 126, 128 and received by IMD 10. Processor 134 may, for example, perform digital signal analysis on the electrical signals. The digital signal analysis may include making measurements of R-wave amplitude, T-wave amplitude and Q-T interval, and monitoring for S-T elevation. Data collected in this way may be stored in memory 136.
Data collected by processor 134 may be retrieved via input/output devices such as remote distribution link 138 or RF telemetry 140. Further, processor 134 may receive information such as data or programming via input/output devices 138, 140. Remote distribution link 138 may provide a channel for uploading or downloading information over a telephone line or over the internet, for example. RF telemetry 140 may communicate information on a dedicated wireless channel. Typically, a patient is required to visit an office of a physician when information is to be uploaded or downloaded via RF telemetry 140.
FIG. 8 illustrates exemplary techniques that may be applied by system 120 for monitoring blood insulin and/or blood glucose. In a typical embodiment, processor 134 is responsible for the monitoring. Processor 134 may, for example, regulate data collection, perform signal analysis and perform computations as needed.
The monitoring techniques may be applied on a regular basis, such as every week or every other week. Typically, a patient's progression toward diabetes is sufficiently gradual that monitoring need not be performed on an hour-to-hour or day-to-day basis. The invention may be applied with any monitoring frequency, however, which may be programmed into processor 134 by the patient's physician. Because system 120 may be powered by a battery such as battery power source 76 shown in FIG. 3, less frequent monitoring may conserve battery life.
Monitoring may be triggered by an ingestion of a meal. Monitoring may be triggered automatically by a sensor that detects a meal, for example, or may be triggered by the patient using a device such as input/output device 138, 140. In a healthy patient, insulin-mediated glucose uptake activity rises from a starting level following a meal. As ingested nutrients are absorbed and enter the blood stream, insulin levels rise to promote cellular uptake of glucose and conversion of carbohydrates into glycogen. Within 30 to 50 minutes after a meal, insulin-mediated glucose uptake activity typically reaches a peak in a healthy patient. Insulin-mediated glucose uptake activity thereafter declines. After about two hours, insulin-mediated glucose uptake activity returns approximately to its starting level. Total absorption of a typical meal takes about four hours.
In a patient with IGT, which is often a precursor to Type II diabetes, insulin-mediated glucose uptake activity following a meal may be morphologically different from the insulin-mediated glucose uptake activity in a healthy patient. In particular, insulin-mediated glucose uptake activity may reach a peak more slowly, may peak at a far lower level than in a healthy patient, and may decline more gradually.
In a patient having Type II diabetes, these differences are more pronounced. Following a meal, insulin-mediated glucose uptake activity peaks at a far lower value than that exhibited by a healthy patient and may not peak for more than an hour after the meal. Instead of showing a marked rise and decline of insulin-mediated glucose uptake activity, a diabetic patient exhibits comparatively little change in insulin-mediated glucose uptake activity following a meal. The absence of marked change in insulin-mediated glucose uptake is due to the cell's reduced sensitivity to insulin.
Because insulin-mediated glucose uptake is reflected in the EGM, analysis of the EGM signal may indicate whether the patient may have IGT or diabetes. In a healthy patient, EGM parameters such as T-wave amplitude, Q-T interval and S-T elevation change following ingestion of a meal, as insulin-mediated glucose uptake takes place. A patient having IGT may show changes in the EGM parameters to a lesser degree, and a patient having diabetes may show few changes in EGM parameters after a meal.
To monitor insulin-mediated glucose uptake, therefore, processor 134 takes a sample of ECG data (150). The monitoring may begin after a meal. The first sample may be taken immediately after the meal or following a waiting period. Sampling (150) may last for about a minute, for example. During one minute of sampling, a typical heart beats about sixty times or more, so each sample includes signals from several cardiac cycles. Processor 134 may then wait in an idle mode (152) for a period of time, such as nine minutes, before taking another sample. Samples may be collected over a time period such as two hours.
While in idle mode, processor 134 may assume a low-power configuration, thereby conserving battery power. Processor 134 may also perform some signal processing while waiting. Processor 134 may, for example, remove the noise from the sample (154) using any of several analog and/or digital techniques. One exemplary technique for removing noise is to average the signals from the several cardiac cycles, generating an average electrical signal for a single cardiac cycle. The sampled signal may be separated into a plurality of cardiac cycle signals, using the R-wave as a reference that separates one cardiac cycle signal from another. The average signal may be generated by summing the individual cardiac cycle signals and dividing by the number of cardiac cycles in the sample. Alternatively, individual cardiac signals may be summed and/or averaged on a beat-to-beat basis during sampling (150).
Another noise reduction technique may include rejection of atypical data. Whether the data are atypical or not may be detected by several techniques. If system 120 includes a pacemaker, for example, system 120 may include logic or algorithms for recognizing and classifying various types of arrhythmia. Sensors such as pH sensors or temperature sensors may also be employed to identify atypical data or eliminate artifacts from the data.
After the waiting period (152) expires, processor 134 may take another sample (150). The number of samples, N, may be varied as desired. When N samples have been taken (156), the sampled data may be processed (158). By performing digital signal analysis on each set of sampled data, and by analyzing parameters such as R-wave and T-wave amplitudes, Q-T interval and S-T elevation, processor 134 can determine the insulin-mediated glucose uptake activity that followed the meal, and how the activity varied over time.
The most recent insulin-mediated glucose uptake activity may then be compared to previous insulin-mediated glucose uptake activity, or to a reference insulin-mediated glucose uptake activity, or both (160). Morphological analysis may include techniques such as performing a simple difference calculation, applying a correlation function, comparing frequency components or using any of a number of statistical tools.
Processor 134 may also monitor the data for trends (162). Processor 134 may compare the most recent insulin-mediated glucose uptake activity to prior insulin-mediated glucose uptake activity, which may have a bearing upon whether the patient is progressing to diabetes.
Another trend-monitoring technique is to compare the most recent insulin-mediated glucose uptake activity to a reference activity. The reference activity may be, for example, the insulin-mediated glucose uptake activity monitored under controlled conditions. The farther the most activity departs from the reference, the greater the likelihood that the patient is progressing toward diabetes.
An additional trend-monitoring technique may be to combine the data pertaining to the most recent samplings with data collected previously by, for example, exponential averaging. Processor 134 may also perform any of several statistical analyses, such as calculation of variance parameters, computation of mean and standard deviation, or computation of maximum minus minimum values. Further, processor 134 may apply techniques such as artificial neural network techniques or fuzzy interferencing or the application of genetic algorithms. The invention is not limited to these trend-monitoring techniques, and any or all of them may be employed. The results of processing, comparing and trend-monitoring may be recorded in memory 136 (164).
There are many variations to the techniques shown in FIG. 8, and the invention encompasses all of the variations. For example, some data processing (158) may be performed following the taking of each sample (150), rather than after the taking of all of the samples. The sampling interval may be longer or shorter than a minute, and the waiting period (152) may be shorter or longer than nine minutes. Samples may be taken over a time frame that is shorter or longer than two hours.
In some circumstances, the processed sampled data may indicate that the patient's condition is very serious. In such cases, processor 134 may initiate a patient alert. A patient alert may include, for example, generation of an audible alarm that informs the patient to see his physician right away.
In many cases, however, the processed sampled data will remain stored in memory 136 until the patient's next scheduled appointment with his physician. During the appointment, the physician may interrogate system 120 via input/output devices 138, 140. The data may be organized in any useful form, and the physician may use the data to determine whether the patient is at risk of developing diabetes. The physician may, for example, order blood tests for diabetes when the data indicates that the patient's insulin-mediated glucose uptake activity is anomalous.
The invention may offer several advantages. One advantage is that patients having an implantable device such as a pacemaker, a pacemaker-cardioverter-defibrillator, an implantable pressure monitor, an implantable nerve stimulator, an implantable muscle stimulator, an implantable drug delivery device or an implantable monitoring device may receive blood insulin and/or blood glucose monitoring with the implantable device. There is no need to implant a separate, dedicated insulin or glucose monitoring device. Moreover, in some embodiments, the implanted device can be configured to provide blood insulin and/or blood glucose monitoring without substantial structural modifications.
In addition, the invention uses electrical sensors that are long-lasting and are often functional under a wide variety of conditions. Chemical-based glucose sensors or insulin sensors may not be as robust as electrical sensors.
Moreover, the techniques of the invention help identify problems that may not be otherwise identified. Type II diabetes develops slowly and usually progresses unnoticed by the patient. The techniques of the invention allow the long-term progress of the condition to be monitored and brought to the attention of the patient and his physician. With warning of the development of IGT or Type II diabetes, the patient and the physician can take preventive steps, apply appropriate treatment, and avoid development of serious complications. So far, there is no cure for diabetes, but treatment such as administration of oral glucose lowering agents, proper diet and exercise and can slow, and even reverse, the progression of the disease. The patient may have more therapeutic options available when the disease is detected early.
The preceding specific embodiments are illustrative of the practice of the invention. It is to be understood, therefore, that other expedients known to those skilled in the art or disclosed herein may be employed without departing from the invention or the scope of the claims. For example, many of the embodiments described above are directed to monitoring insulin-mediated glucose uptake activity for diagnostic purposes. The invention is not limited to diagnostic functions, however. The invention may also include additional diagnostic and/or therapeutic functions. Additional diagnostic functions may include, for example, initiation of further glucose metabolic experiments. Therapeutic functions may include, for example, delivery of medication following analysis of the sampled data.
Although the invention may be applied to track the potential development of diabetes, the invention is not limited to that application. When the patient becomes aware of the development of IGT or Type II diabetes, the patient and the physician may take steps to address the condition. The invention may be applied to monitor the effectiveness of the steps, especially over a long term. The invention includes within its scope all applications of blood glucose or blood insulin monitoring.
The invention further includes within its scope the methods of making and using the systems described above. These methods are not limited to the specific examples described above, but may be adapted to meet the needs of a particular patient. The invention also includes within its scope any of computer-readable media comprising instructions for causing a programmable processor, such as microprocessor, to carry out the techniques described above. Such computer-readable media include, but are not limited to, magnetic and optical storage media. Such computer-readable media may be accessed by an external programmer, for example. Computer-readable media also includes read-only memory such as. erasable programmable read-only memory or flash memory that may be accessed by the implanted processor. These and other embodiments are within the scope of the following claims.
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