CHARACTERISTICS There are several key characteristics of glucose meters which may differ from model to model: Size:

The average size is now approximately the size of the palm of the hand, though some are smaller or larger. They are battery-powered. Test strips: A consumable element containing chemicals that react with glucose in the drop of blood is used for each measurement. For some models this element is a plastic test strip with a small spot impregnated with glucose oxidase and other components. Each strip is used once and then discarded. Instead of strips, some models use discs that may be used for several readings. Volume of blood sample: The size of the drop of blood needed by different models varies from 0.3 to 1 l. (Older models required larger blood samples, usually defined as a "hanging drop" from the fingertip.) Smaller volume requirements reduce the frequency of unproductive pricks. Alternative site testing: Smaller drop volumes have enabled "alternate site testing" pricking the forearms or other less sensitive areas instead of the fingertips. Although less uncomfortable, readings obtained from forearm blood lag behind fingertip blood in reflecting rapidly changing glucose levels in the rest of the body. Testing times: The times it takes to read a test strip may range from 3 to 60 seconds for different models. Display: The glucose value in mg/dl or mmol/l is displayed in a small window. The preferred measurement unit varies by country: mg/dl are preferred in the U.S., France, Japan, Israel, and India. mmol/l are used in Canada, Australia, China and the UK. Germany is the only country where medical professionals routinely operate in both units of measure. (To convert mmol/l to mg/dl, multiply by 18. To convert mg/dl to mmol/l, divide by 18.) Many machines can toggle between both types of measurements; there have been a couple of published instances in which someone with diabetes has been misled into the wrong action by assuming that a reading in mmol/l was really a very low reading in mg/dl, or the converse. Glucose vs. plasma glucose: Glucose levels in plasma (one of the components of blood) are generally 10%15% higher than glucose measurements in whole blood (and even more after eating). This is important because home blood glucose meters measure the glucose in whole blood while most lab tests measure the glucose in plasma. Currently, there are many meters on the market that give results as "plasma equivalent," even though they are measuring whole blood glucose. The plasma equivalent is calculated from the whole blood glucose reading using an equation built into the glucose meter. This allows patients to easily compare their glucose measurements in a lab test and at home. It is important for patients and

their health care providers to know whether the meter gives its results as "whole blood equivalent" or "plasma equivalent." One model measures betahydroxybutyrate in the blood to detect ketoacidosis (ketosis). Clock/memory: All meters now include a clock that is set for date and time and a memory for past test results. The memory is an important aspect of diabetes care, as it enables the person with diabetes to keep a record of management and look for trends and patterns in blood glucose levels over days. Most memory chips can display an average of recent glucose readings. Data transfer: Many meters now have more sophisticated data handling capabilities. Many can be downloaded by a cable or infrared to a computer that has diabetes management software to display the test results. Some meters allow entry of additional data throughout the day, such as insulin dose, amounts of carbohydrates eaten, or exercise. A number of meters have been combined with other devices, such as insulin injection devices, PDAs, and even Game Boys.[2] A radio link to an insulin pump allows automatic transfer of glucose readings to a calculator that assists the wearer in deciding on an appropriate insulin dose.

HISTORY and DEVELOPMENT In 1962, Leland Clark and Ann Lyons at the Cincinnati Children's Hospital developed the first glucose enzyme electrode. It relied on a thin layer of glucose oxidase on an oxygen electrode. The sensor worked by measuring the amount of oxygen consumed by the enzyme.[4] Another early glucose meter was the Ames Reflectance Meter by Anton H. Clemens. It was used in American hospitals in the 1970s. It was about 10 inches long. It needed connection to an electrical outlet for power. A moving needle indicated the blood glucose after about a minute. Home glucose monitoring was demonstrated to improve glycemic control of type 1 diabetes in the late 1970s, and the first meters were marketed for home use around 1980. The two models initially dominant in North America in the 1980s were the Glucometer whose trademark is owned by Bayer and the Accu-chek meter (by Roche). Consequently, these brand names have become synonymous with the generic product to many health care professionals. In Britain, a health care professional or a patient may refer to "taking a BM": "Mrs X's BM is 5", etc. BM stands for Boehringer Mannheim, now called Roche, who produced test strips called 'BM-test'.[5][6] Test strips that changed color and could be read visually, without a meter, were also widely used in the 1980s. They had the added advantage that they could be cut longitudinally to save money. As meter accuracy and insurance coverage

improved, they lost popularity. However, a generic version of the BM is marketed under the brand name Glucoflex-R. There is a UK Pharmaceutical company (Ambe Medical Group) who have the executive rights for distribution within the United Kingdom. Another visual strip is also marketed under the brand name Betachek.

Development of noninvasive devices may enable continuous monitoring. Research is being done on noninvasive methods for measuring blood glucose, such as using infrared or near-infrared light, electric currents, and ultrasound. One noninvasive glucose meter has been approved by the U.S. FDA: The GlucoWatch G2 Biographer is designed to be worn on the wrist and uses electric fields to draw out body fluid for testing. The device does not replace conventional blood glucose monitoring. One limitation is that the GlucoWatch is not able to cope with perspiration at the measurement site. Sweat must be allowed to dry before measurement can resume. Due to this limitations and others, the product is no longer on the market. The market introduction of noninvasive blood glucose measurement by spectroscopic measurement methods, in the field of near-infrared (NIR), by extracorporal measuring devices, failed so far because at this time, the devices measure tissue sugar in body tissues and not the blood sugar in blood fluid. To determine blood glucose, the measuring beam of infrared light, for example, has to penetrate the tissue for measurement of blood glucose. There are currently three CGMS (continuous glucose monitoring system) available. The first is Medtronic's Minimed Paradigm RTS with a sub-cutaneous probe attached to a small transmitter (roughly the size of a quarter) that sends interstitial glucose levels to a small pager sized receiver every five minutes. As well, the DexCom STS System is available (2Q 2006). It is a hypodermic probe with a small transmitter. The receiver is about the size of a cell phone and can operate up to five feet from the transmitter. Aside from a two-hour calibration period, monitoring is logged at five-minute intervals for up to 72 hours. The user can set the high and low glucose alarms. The third CGMS available is the FreeStyle Navigator from Abbott Laboratories. There is currently an effort to develop an integrated treatment system with a glucose meter, insulin pump, and wristop controller, as well as an effort to integrate the glucose meter and a cell phone. These glucose meter/cellular phone combinations are under testing and currently cost $149 USD retail. Testing strips are proprietary and available only through the manufacturer (no insurance availability). These "Glugophones" are currently offered in three forms: as a dongle for the iPhone, an add-on pack for LG model UX5000, VX5200, and LX350 cell phones, as well as an add-on pack for the Motorola Razr cell phone. This limits providers to AT&T and Verizon. Similar systems have been tested for a longer time

in Finland. An Israeli company by the name of Cnoga Medical Ltd. has developed a noninvasive Glucometer. CNOGA's technology is based on real-time tissue photography, Tissue image color is processed in real-time providing the temporary color distribution using dynamic range of at least 36 color-depth representing over 6.8^10 color combination, then by using sophisticated mathematical algorithm. They will start marketing the device early 2011. Recent advances in cellular data communications technology have enabled the development of glucose meters that directly integrate cellular data transmission capability, enabling the user to both transmit glucose data to the medical caregiver and receive direct guidance from the caregiver on the screen of the glucose meter. The first such device, from Telcare, Inc., was exhibited at the 2010 CTIA International Wireless Expo,[9] where it won an E-Tech award. This device is currently undergoing clinical testing in the US and Internationally. Many glucose meters employ the oxidation of glucose to gluconolactone catalyzed by glucose oxidase (sometimes known as GOx). Others use a similar reaction catalysed instead by another enzyme, glucose dehydrogenase (GDH). This has the advantage of sensitivity over glucose oxidase but is more susceptible to interfering reactions with other substances. The first-generation devices relied on the same colorimetric reaction that is still used nowadays in glucose test strips for urine. Besides glucose oxidase, the test kit contains a benzidine derivative, which is oxidized to a blue polymer by the hydrogen peroxide formed in the oxidation reaction. The disadvantage of this method was that the test strip had to be developed after a precise interval (the blood had to be washed away), and the meter needed to be calibrated frequently. Most glucometers today use an electrochemical method. Test strips contain a capillary that sucks up a reproducible amount of blood. The glucose in the blood reacts with an enzyme electrode containing glucose oxidase (or dehydrogenase). The enzyme is reoxidized with an excess of a mediator reagant, such as a ferricyanide ion, a ferrocene derivative or osmium bipyridyl complex. The mediator in turn is reoxidised by reaction at the electrode,which generates an electrical current. The total charge passing through the electrode is proportional to the amount of glucose in the blood that has reacted with the enzyme. The coulometric method is a technique where the total amount of charge generated by the glucose oxidation reaction is measured over a period of time. The same principle is used in test strips that have been commercialised for the detection of diabetic ketoacidosis (DKA). These test strips use a betahydroxybutyrate-dehydrogenase enzyme instead of a glucose oxidising enzyme and have been used to detect and help treat some of the complications that can result from prolonged hyperglycaemia.

Blood alcohol sensors using the same approach, but with alcohol dehydrogenase enzymes, have been tried and patented but have not yet been successfully commercially developed. The most promising method for continuous monitoring of glucose levels are implantable enzymatic sensors, such as the Medtronic-MiniMed CGMS (above). This sensor can be implanted in the subcutaneous tissue using a specialized tool designed to minimize tissue damage. The sensor is connected by wire to a pagersized unit which records data that can later be downloaded onto a computer. The tip of the sensor is made of a membrane selectively permeable to glucose. Once the glucose passes through the membrane, it is oxidized by the enzyme glucose oxidase. Reduced glucose oxidase can then be oxidized by reacting with molecular oxygen, forming hydrogen peroxide as a by-product. At the electrode surface, hydrogen peroxide is oxidized into water, generating a current which can be measured and correlated to the glucose concentration outside the membrane (see above right). This type of device requires at least four finger sticks per day for calibration, but with a lag time of approximately four minutes, it is more effective as a continuous glucose sensor that its transcutaneous counterpart.