noninvasive blood glucose monitoring involves either radiation or fluid extraction. With radi- ation technology, an energy beam is 1) applied to the body, ...
R e v i e w s / C o m m e n t a r i e s / P o s i t i o n T E C H N I C A L
Statements
A R T I C L E
Noninvasive Blood Glucose Monitoring DAVID C. KLONOFF, MD, FACP
The concentration of glucose in the blood may soon be measured noninvasively, without puncturing the ringer to obtain a drop of blood. Current prototype devices for this purpose require greater accuracy and miniaturization to be commercially viable. No such device has been approved for marketing by the U.S. Food and Drug Administration. The technology used for noninvasive blood glucose monitoring involves either radiation or fluid extraction. With radiation technology, an energy beam is 1) applied to the body, 2) modified proportionate to the concentration of glucose in the blood, and 3) measured. The blood glucose concentration is then calculated. With fluid extraction technology, a body fluid containing glucose in a concentration proportionate to the blood glucose concentration is extracted and measured. The blood glucose concentration is then calculated. The most promising technologies are 1) nearinfrared light spectroscopy, 2) far-infrared radiation spectroscopy, 3) radio wave impedance, 4) optical rotation of polarized light, 5) fluid extraction from skin, and 6) interstitial fluid harvesting. Each method has features predictive of commercial viability, as well as technical problems to overcome.
N
ew technology could lead to a revolutionary advance in the treatment of diabetes. Innovative methods for noninvasive blood glucose monitoring are being developed. Noninvasive blood glucose measurements are based on one of two types of technology: 1) radiation (Fig. 1) or 2) fluid extraction (Fig. 2). The most promising technologies for use in a noninvasive blood glucose monitoring system are I) near-infrared light (NIR) spectroscopy, 2) far-infrared radiation (FIR) spectroscopy, 3) radio wave impedance, 4) optical rotation of polarized light, 5) fluid extraction from skin, and 6) interstitial fluid harvesting. Other technologies are being evaluated but appear less practical. Methods 1-4 use radiation technology and methods 5-6 use fluid extraction technology (Table 1). The physicochemical basis for these noninvasive blood glucose monitoring technologies is well described, but almost no data has been published supporting their efficacy. The dearth of data that describe the accuracy, precision, and reliability of these technologies, let alone that compare these technologies, has led to skepticism about the concept of noninvasive blood glucose monitoring. Publication
of performance data for each device that becomes licensed is anticipated. This article describes the principles behind, but not the efficacy of, each promising method for noninvasive blood glucose monitoring. These technologies are described because they are inherently worth understanding, even in the absence of an actual analysis of their efficacy.
TECHNOLOGY NIR spectroscopy NIR spectroscopy is the only noninvasive blood glucose monitoring technology ever reviewed by a public Food and Drug Administration (FDA) panel for marketing approval. Although approval was not granted, press coverage of the hearing in 1996 (1) resulted in heightened public awareness of the competition to produce a noninvasive blood glucose monitoring system and of NIR spectroscopy as a technology that might make such monitoring possible (2). The term "near-infrared light" refers to the use of an external light source with wavelengths in the infrared spectrum near the wavelengths of visible light. An NIR
From the Department of Medicine, University of California at San Francisco, San Francisco, California. Address correspondence to David C. Klonoff, MD, FACP, Metabolic Research Unit, Room HSW-1141, University of California at San Francisco, San Francisco, CA 94143-0540. Received for publication 21 June 1996 and accepted in revised form 24 October 1996. F'DA, Food and Drug Administration; FIR, far-infrared radiation; NIR, near-infrared light.
DIABETES CARE, VOLUME 20, NUMBER 3, MARCH
1997
source can pass through or be reflected by a body part. Glucose and other body constituents absorb a small amount of the light at each wavelength (3). Spectroscopy, an established technology used to measure energy containing many wavelengths, detects the amount of NIR absorbed at each wavelength by comparing a reference beam with the detection beam that has passed through or is reflected by the body (4,*)). With spectroscopy, a data processing technique known as chemometrics or multivariate analysis simultaneously analyzes the amount of light absorption at selected wavelengths for each blood glucose level. A polynomial formula is generated that converts the sum of the relative contributions of absorption at the selected wavelengths to the blood glucose concentration (6). This technology is used in oximetry to measure the oxygen saturation of blood. The major problem with using NIR spectroscopy for blood glucose monitoring is the necessity for frequent recalibration. NIR spectroscopy does not measure one signal specific for glucose, but rather many signals that are neither specific for glucose nor linked to glucose levels in a linear fashion. Glucose is responsible for
