Surgery – Diagnostic testing – Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
2001-01-18
2002-11-26
Walberg, Teresa (Department: 3742)
Surgery
Diagnostic testing
Measuring or detecting nonradioactive constituent of body...
Reexamination Certificate
active
06487429
ABSTRACT:
BACKGROUND OF THE INVENTION
1. Field of the Invention
The invention relates to non-invasive measurement of blood analyte levels. More particularly the invention relates to a process for calibrating a NIR spectrometer to a test subject using targeted glycemic profiles to obtain a wide range of reference blood glucose values, thereby increasing the robustness of the calibration and minimizing the possibility that the calibration is correlated to variables other than glucose.
2. Description of Related Art
NIR (near-IR) spectroscopy has long been studied for use in measurement of blood analytes, particularly glucose. The degree of physiologic and anatomical variation encountered in the general population has rendered it exceedingly difficult to develop an instrument that can be used to make blood glucose measurements on any subject. However, calibration of an instrument to a single individual is possible, and it produces measurements with sufficient accuracy to make the instrument clinically valuable. In general, the calibration process involves acquiring invasive glucose samples for reference values and concurrently making noninvasive spectral measurements. After the reference values and spectral data have been divided into a multivariate calibration set and a test set, used to insure accuracy of the calibration, a mathematical algorithm is developed that makes a blood glucose prediction from a new spectral sample.
It is desirable that the spectra making up the calibration set and test set, and subsequent sample spectra, be as free of noise from sampling factors as possible. For example, P. Cooper and T. Barker, Individual calibration of blood glucose for supporting noninvasive self-monitoring blood glucose (sic), PCT Application Ser. No. WO98/37805 (Feb. 26, 1997) teach a procedure for calibrating a noninvasive glucose monitor to an individual for self-monitoring of blood glucose levels. Spectroscopic samples are gathered at the subject's skin surface using a noninvasive glucose monitor. During sampling, the skin surface is repeatedly moved relative to the sampling probe, so that several samples are gathered, each from a slightly different measurement site. Then, a mean spectrum is calculated from the samples taken at the various sites. Thus, the influence on the spectral measurement of skin variability is minimized. At the same time, the subject's blood glucose level is measured using an invasive blood glucose-monitoring instrument. During the data-gathering phase of the calibration procedure, a glucose excursion is induced. Subsequently, blood sugar level is restored to basal level through the administration of exogenous insulin.
Moreover, it is essential that the reference glucose values do not correlate to any other sampling factor; for example skin temperature, skin humidity, room temperature, time, or other blood analytes. Cooper, et al. decorrelate to the various sampling factors by selecting a small fraction of up to sixty days worth of data with correlation constraints. While the teachings of Cooper, et al. recognize the importance of minimizing noise in the spectral data from various sampling factors, and provide strategies for such control, they do not address the need for an efficient calibration regimen, that can be accomplished in a short period of time.
Glucose excursions are often induced through the intravenous administration of dextrose, a disaccharide composed of two glucose subunits, during procedures commonly known as euglycemic insulin clamp techniques. Over the course of a procedure of this type, exogenous insulin may be infused at a rate that maintains a constant plasma insulin level above a fasting level. The glucose infusion is delivered via an indwelling catheter at a rate based on plasma glucose measurements done at five-minute intervals. When the plasma glucose level falls below basal level, the glucose infusion rate is increased to return plasma to basal levels. Conversely, glucose infusion is decreased or the insulin infusion increased when plasma glucose exceeds basal levels. The total amount of glucose infused over time, or the M value, comprises an index of insulin action on glucose metabolism. See Consensus development conference on insulin resistance,
Diabetes Care,
vol. 21 (2) p. 310 (1998). A typical profile resulting from this procedure would resemble a straight line, but a stepped increase or decrease in blood glucose may also be obtained. See Preservation of physiological responses to hypoglycemia two days after antecedent hypoglycemia in patients with IDDM,
Diabetes Care,
vol. 20 (8) p. 1293 (1997). Although euglycemic clamp studies are effective for quantifying the amount of insulin required to achieve a particular glycemic pattern, they suffer the disadvantage of being highly impractical in clinical settings. Additionally, they entail a significant amount of risk to the patient, and they generally meet with poor patient acceptance.
There exists, therefore, a need in the art for an efficient, low-risk method of calibrating a noninvasive glucose monitor to an individual patient that minimizes or eliminates correlation of reference glucose data to sampling factors such as skin temperature, skin humidity, room temperature, time, or other blood analytes. It would be advantageous to provide targeted, information rich, glycemic profiles for use in calibrating the noninvasive glucose monitor to individual subjects. It would be further advantageous to provide such glycemic profiles in pairs, in which one of the pair is anti-correlated to the other, so that the anti-correlated profiles are mirror images of each other. It would be a great advantage to provide a method of calibrating a noninvasive glucose monitor to a subject in which the subject's blood glucose level is dynamically manipulated through the controlled oral ingestion of calculated amounts of carbohydrate in such a manner as to reproduce the patterns of the anti-correlated profiles; during which time, noninvasive spectral measurements and determinations of blood glucose level would be made at regular intervals, thus degrading ancillary correlations to glucose and providing uncorrelated reference values for the calibration. Furthermore, it would be useful to provide a formula for reliably calculating the required amount of carbohydrate to produce a targeted glycemic profile in a test subject.
SUMMARY OF THE INVENTION
The invention provides a low-risk method of calibrating a noninvasive glucose monitor to an individual subject that minimizes or eliminates correlation of reference glucose data to sampling factors such as skin temperature, skin humidity, room temperature, time, or other blood analytes. Anti-correlated pairs of targeted glycemic profiles are provided, in which one profile of the pair is the inverse of the other. A formula is provided for calculating the amount of carbohydrate a subject must ingest orally in order to produce a glucose excursion that reproduces that of one of the target profiles. Advantageously, the formula employs a numerical index of a subject's sensitivity to carbohydrate challenges. Rapid-acting insulin is administered to lower blood glucose levels at a rate that duplicates that of a target profile. On successive calibration visits, first one profile of a pair and then the inverse profile are produced in a subject. Throughout the course of a visit, noninvasive spectral measurements are made at predetermined intervals. Concurrently, blood glucose levels are measured with a conventional, invasive blood glucose monitor. After the reference values and spectral data have been divided into a multivariate calibration set and a test set, used to insure accuracy of the calibration, a mathematical algorithm is developed that makes a blood glucose prediction from a new spectral sample. Thus, a calibration is provided that avoids correlating glucose to sampling factors.
In a preferred embodiment of the invention, anti-correlated target profiles are provided that include a single glucose excursion within a predetermined time period. In a sec
Blank Thomas B.
Hockersmith Linda
Monfre Stephen L.
Ruchti Timothy L.
Glenn Michael A.
Patel Vinod D
Peil Christopher
Sensys Medical Inc.
Walberg Teresa
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