Patent Application
20090163825
This invention relates to medical management of patients with diabetes. More particularly this invention relates to the field of hypoglycemia and hyperglycemia alarm systems.
Individuals with diabetes carry the risk of low blood sugar, known as hypoglycemia, usually resulting from an imbalance between food, exercise, and medications, wherein a low blood sugar reaction can cause disorientation, unconsciousness, and sometimes death. If not properly monitored, an individual or medical professional may not be aware that the individual has reached a hyper or hypoglycemic state.
Individuals with diabetes may also be at risk for hyperglycemia, which is an excess of sugar in the blood, and if the individual is not aware of the hyperglycemic state, serious damage and possibly death may ensue.
Diabetic ketoacidosis (DKA) is an acute, major, life-threatening complication of diabetes which mainly occurs in individuals with type 1 diabetes, and less often with type 2 diabetes. DKA is an acute state of severe uncontrolled diabetes that requires emergency treatment with insulin and intravenous fluids. DKA involves an increase in the serum concentration of ketones greater than 5 mEq/L, a blood glucose level of greater than 250 mg/dL although it is usually much higher), blood pH of less than 7.2, and a bicarbonate level of 18 mEq/L or less.
Hypo and hyperglycemia occur in both adults and children, and the risk depends on the degree and progression of the diabetic state. The risk is especially acute during the night or at other times when the individual is sleeping. Because of the life threatening effects of nocturnal hypoglycemia in young children, parents often experience nights with severe anxiety resulting in sleep deprivation for both parents and children trying to monitor the condition.”
Several automated, programmable, continuous glucose monitoring systems that use subcutaneous sensors have become available for diabetic ambulatory patients. For example, diabetic patients can now wear automated, programmable, continuous monitoring systems such as the two FDA approved glucose monitoring systems by Medtronic (Guardian REAL-Time System), and DexCom (STS Continuous Glucose Monitoring System). Those two systems are equipped with out of range patient alarms to notify the patient of large or dangerous deviations in blood glucose. The detection of hypoglycemia allows the patient to take corrective action to prevent potentially devastating complications. Choleau et al. have described the use of a continuous amperometric glucose sensor implanted in rats to predict hypoglycemia (Prevention of Hypoglycemia Using Risk Assessment With a Continuous Glucose Monitoring System, Diabetes 51:3263-3273, 2002).”
The relationship between acetone in exhaled breath and diabetes has been known for some time. For example, Melker, U.S. Pat. No. 6,981,947, assigned to U. of Fla. Research Foundation, Inc., disclosed in Example III measuring endogenous and exogenous compounds such as acetones in exhaled breath, stating that “normally, the exhaled breath of a person contains water vapor, carbon dioxide, oxygen, and nitrogen, and trace concentrations of carbon monoxide, hydrogen and argon, all of which are odorless.” Melker disclosed a sensor to be used as a sensitive detector for these odorants and for the diagnosis of tooth decay, gum disease or a variety of oral, pulmonary and sinus conditions.
Among the vapor phase odorant compounds detected by Mekler are acetone, which is present in diabetics who are in ketoacidosis, and the use of exhaled breath sensing as a highly sensitive method of diagnosing and following the course of treatment of this disease.
However, Mekler did not teach or suggest a system for continuously or periodically measuring acetone and using the measured data to calculate and alarm a hyper or hypoglycemic state.
Fu, U.S. Pat. No. 7,076,371, disclosed a non-invasive diagnostic and monitoring method and system based on odor detection. Fu's system is designed to emulate a biological nose, with numerous sensors, each with a different type of polymer responding differently to various odorant molecules. Fu taught an aerogel with a very large surface area for coating of a polymer, effectively simulating the huge number of same-type biological olfactory cells and their combined response. The polymer provides the necessary electronic and chemical coupling and a piezoelectric crystal is used for the quantitative conversion of trace amounts of odorant molecules to frequency-shift signals and allows detection of the markers of diabetes, for example. Fu also disclosed a heater incorporated with the detector to “refresh” the system so to provide confirmation of the detection of a targeted substance, which Fu said is important for minimizing false positive alarms, thus improving the general reliability of the system. Fu disclosed alternative types of sensors such as GC, HPLC, mass spectrometry, and conducting nanotubes whose conductivity changes as a result of gas absorption. Fu disclosed the relationship between acetone on a person's breath and ketoacidosis.
Other systems intended primarily for use outside of a hospital setting are designed to measure temperature and moisture level of an individual's skin and to determine insulin reaction based on changes in such temperature and moisture. The “Sleep Sentry” is designed to detect hypoglycemia by monitoring temperature and moisture level of the skin of a sleeping diabetic person. If a temperature drop or increased perspiration is detected, an alarm sounds and the wearer of the device is supposed to check his or her blood sugar.
Allen, et al., disclosed in U.S. 2004-0236244 A1 a hand-held medical apparatus for measuring acetone in exhaled breath as an indicator of ketosis and an aid for detection of weight loss via fat metabolism.
Cranley, et al., disclosed in U.S. 2005-0084921 A1 an enzyme based sensor coupled to a detectable signal mediator for measuring acetone and methods for using the sensor to detect disease, weight loss, and bioavailability monitoring of therapeutics.
Although the relationship between acetone in the breath and hypoglycemia in a diabetic is known, and methods for measuring acetone in a person's breath are known, no one has previously suggested a hypoglycemia and hyperglycemia alarm system based on changes in acetone levels in breath.
It is an object of the present invention to provide an improved warning system for sleeping diabetics, a system which is not based on body temperature or skin moisture changes.
It is another object of the present invention to provide an improvement to existing total glycemic control (TGC) procedures by continuously or periodically measuring exhaled breath of a diabetic patient and determining presence of acetone, which is indicative of a hyper or hypoglycemic state of the patient.
Another object of the invention is to detect a hyper or hypoglycemic state in an individual and to provide an alarm when such state is detected.
A further object of the invention is to provide a system which can be used when a diabetic individual is sleeping and at risk of hyper or hypoglycemia, which is minimally invasive and does not require blood analysis, but can detect hyper or hypoglycemia and signal an alarm when hyper or hypoglycemia is detected.
In one aspect, the invention comprises (A) continuously or periodically determining acetone concentration in exhaled breath of a diabetic patient, (B) determining presence of a hyper or hypoglycemic state of the patient by calculating changes in the acetone concentration, and (C) issuing an alarm when the hyper or hypoglycemic state is determined.
In another aspect, the invention comprises a system for signaling a hyper or hypoglycemic state comprising means to continually or periodically measure acetone concentration in exhaled breath comprising a sensor fluidly connected with a subject's nasal passage, for example an infrared sensor, and a programmed controller which can calculate changes in the acetone concentration in the exhaled breath based on data received from the sensor, the controller programmed to determine presence of a hyper or hypoglycemic state based on the calculated changes in acetone concentration, and an audible and/or visual alarm when the presence of a hyper or hypoglycemic state is determined.
The present invention provides continuous measurement of acetone, a volatile metabolite of fat breakdown, in end-tidal gas as a proxy for hyper or hypoglycemic measurement. The invention would not substitute for periodic blood glucose determinations, but would complement glucose testing in a continuous or semi-continuous non-invasive fashion. It would help avoid hyper or hypoglycemic episodes and neurologic damage.
A system which includes plastic tubing, referred to herein as a cannula, which includes one or two nasal extensions and preferably an oral extension adapted to be worn in a subject's nose and mouth, fluidly connected to a source of vacuum, which draws small amounts of exhaled breath from the subject's nose and/or mouth, can be used to obtain samples of the subject's breath. In some embodiments, a thermistor or other temperature measuring device can be used to detect a condition where the cannula extensions are no longer properly placed in the nose and/or mouth, for example if the subject pulls the cannula out while sleeping or the cannula falls out for some other reason. The temperature measuring device or thermistor is electrically connected to the controller and changes in temperature are detected and interpreted. If the temperature shows periodic physiologic variation with respect to time, then the system is properly functioning and the acetone data are valid.
In some embodiments acetone detection is carried out in or adjacent to the nostrils and/or mouth and no tube, cannula, or vacuum is used.
While the invention is capable of being carried out in various embodiments, a few illustrative embodiments will be described in the following detailed description with reference to the drawings.
Referring first to
Referring now to
The acetone analyzer 19 can be a standard infrared gas analyzer 19 set up to detect small quantities of acetone in the exhaled breath of a diabetic individual.
The devices of the invention can be made in a range of sizes to fit an adult down to an infant. The device can be made of suitable plastics materials, known to those skilled in the art. The body and tubes may be made of similar or different plastics materials.
When the patient is ready to sleep, a start button is pressed. The next morning the patient presses the stop button to end the breath monitoring.
In the following discussion and in the claims, the terms “including” and “comprising” are used in an open-ended fashion, and thus should be interpreted to mean “including, but not limited to . . . ”. Also, the term “connect” or “connects” is intended to mean either an indirect or direct connection. Thus, if a first device connects to a second device, that connection may be through a direct connection, or through an indirect connection via other devices. The term “cannula” refers to a respiratory mask (either full or partial) that fluidly couples one or more of a patient's airways to a testing device. Thus, a “nasal cannula” couples at least one naris to the test device. Likewise, an “oral cannula” may couple to a patient's mouth. The word “cannula” alone could thus refer to a nasal cannula, an oral cannula, or a cannula that couples to both a patients nose and mouth.
The controller 24 may comprise a processor which may be a microcontroller, and can have an on-board converter A/D, D/A converter, on-board random access memory (RAM), read only memory (ROM), as well as other on-board circuits, such as circuits that allow the processor to communicate to external devices. The controller 24 may actually be more than one processor but must be programmed to carry out the acetone level detection and alarm functions. The controller 24 may also drive an indicator or display device coupled to the processor, and may be coupled to on and off switches.
As the person 10 inhales, at least a portion of the airflow into the nostrils is drawn through the tubing. The controller can be programmed to recognize the breathing cycles and to determine whether the airflow is due to exhaling or inhaling.
While the invention has been described and illustrated in detail herein, various alternatives and modifications should become apparent to those skilled in this art without departing from the spirit and scope of the invention.
