Glucose meter

Four generations of blood glucose meter, c. 1993-2005. Sample sizes vary from 30 to 0.3 μl. Test times vary from 5 seconds to 2 minutes (modern meters typically provide results in 5 seconds).

A glucose meter (or glucometer) is a medical device for determining the approximate concentration of glucose in the blood. It is a key element of home blood glucose monitoring (HBGM) by people with diabetes mellitus or hypoglycemia. A small drop of blood, obtained by pricking the skin with a lancet, is placed on a disposable test strip that the meter reads and uses to calculate the blood glucose level. The meter then displays the level in mg/dl or mmol/l.

Since approximately 1980, a primary goal of the management of type 1 diabetes and type 2 diabetes mellitus has been achieving closer-to-normal levels of glucose in the blood for as much of the time as possible, guided by HBGM several times a day. The benefits include a reduction in the occurrence rate and severity of long-term complications from hyperglycemia as well as a reduction in the short-term, potentially life-threatening complications of hypoglycemia.

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.

• Coding: Since test strips may vary from batch to batch, some models require the user to manually enter in a code found on the vial of test strips or on a chip that comes with the test strip. By entering the coding or chip into the glucose meter, the meter will be calibrated to that batch of test strips. However, if this process is carried out incorrectly, the meter reading can be up to 4 mmol/L (72 mg/dL) inaccurate. The implications of an incorrectly coded meter can be serious for patients actively managing their diabetes. This may place patients at increased risk of hypoglycemia. Alternatively, some test strips contain the code information in the strip; others have a microchip in the vial of strips that can be inserted into the meter. These last two methods reduce the possibility of user error.

• Volume of blood sample: The size of the drop of blood needed by different models varies from 0.3 to 1 μl. (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.

International Blood Glucose Units of Measure
Country	Unit of Measure Used	Country	Unit of Measure Used
Algeria	mg/dL	Malaysia	mmol/L
Argentina	mg/dL	Malta	mmol/L
Australia	mmol/L	Mexico	mg/dL
Austria	mg/dL	Netherlands	mmol/L
Bahrain	mg/dL	New Zealand	mmmol/L
Bangladesh	mg/dL	Norway	mmol/L
Belgium	mg/dL	Oman	mg/dL
Brazil	mg/dL	Peru	mg/dL
Canada	mmol/L	Philippines	mg/dL
Caribbean Countries	mg/dL	Poland	mg/dL
Chile	mg/dL	Portugal	mg/dL
China	mmol/L	Qatar	mmol/L
Columbia	mg/dL	Russia	mmol/L
Czech Republic	mmol/L	Saudi Arabia	mg/dL
Denmark	mmol/L	Singapore	mmol/L
Equator	mg/dL	Slovakia	mmol/L
Egypt	mg/dL	South Africa	mmol/L
Finland	mmol/L	Spain	mg/dL
France	mg/dL	Sub-Saharan Africa	mg/dL mmol/L
Georgia	mg/dL	Sweden	mmol/L
Germany	mg/dL mmol/L	Switzerland	mmol/L
Greece	mg/dL	Syria	mg/dL
Hong Kong	mmol/L	Taiwan	mg/dL
India	mg/dL	Thailand	mg/dL
Indonesia	mg/dL	Tunisia	mg/dL
Ireland	mmmol/L	Turkey	mg/gL
Israel	mg/dL	Ukraine	mmol/L
Italy	mg/dL	United Arab Emirates (UAE)	mg/dL
Japan	mg/dL	United Kingdom	mmol/L
Jordan	mg/dL	United States	mg/dL
Kazakhstan	mmol/L	Uruguay	mg/dL
Korea	mg/dL	Venezuela	mg/dL
Kuwait	mg/dL	Vietnam	mmol/L
Lebanon	mg/dL	Yemen	mg/dL
Luxembourg	mg/dL

• 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 beta-hydroxybutyrate 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. 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.

Hospital glucose meters

Special glucose meters for multi-patient hospital use are now used. These provide more elaborate quality control records. Their data handling capabilities are designed to transfer glucose results into electronic medical records and the laboratory computer systems for billing purposes.

Cost

The cost of home blood glucose monitoring is substantial due to the cost of the test strips. In 2006, the consumer cost of each glucose strip ranged from about $0.35 to $1.00. Manufacturers often provide meters at no cost to induce use of the profitable test strips. Type 1 diabetics may test as often as 4 to 10 times a day due to the dynamics of insulin adjustment, whereas type 2 typically test less frequently, especially when insulin is not part of treatment.

Batches of counterfeit test strips for some meters have been identified, which have been shown to produce inaccurate results. They should not be used and should be reported to the supposed manufacturer.

Accuracy

Accuracy of glucose meters is a common topic of clinical concern. Blood glucose meters must meet accuracy standards set by the International Organization for Standardization (ISO). According to ISO 15197 Blood glucose meters must provide results that are within 20% of a laboratory standard 95% of the time (for concentrations about 75 mg/dL, absolute levels are used for lower concentrations). However, a variety of factors can affect the accuracy of a test. Factors affecting accuracy of various meters include calibration of meter, ambient temperature, pressure use to wipe off strip (if applicable), size and quality of blood sample, high levels of certain substances (such as ascorbic acid) in blood, hematocrit, dirt on meter, humidity, and aging of test strips. Models vary in their susceptibility to these factors and in their ability to prevent or warn of inaccurate results with error messages. The Clarke Error Grid has been a common way of analyzing and displaying accuracy of readings related to management consequences. More recently an improved version of the Clarke Error Grid has come into use: It is known as the Consensus Error Grid.

History

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 of oxygen consumed by the enzyme.

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'.

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.

On May 1, 2009, one manufacturer reduced the price of their test strip to the NHS, by approximately 50% (distributed in the UK by Ambe Medical Group and led by Patrick O'Neill-Ortiz). This should allow the NHS to save money on strips and perhaps loosen the restrictions on supply a little, but there is one catch - the test strip (Glucoflex-R) is read by eye, not by meter. Critics argue this is not as accurate or convenient as meter testing. The manufacturer cites studies that show the product is just as effective despite not giving an answer to one decimal place, something they argue is unnecessary for control of blood sugar. This debate has already happened in Germany where Glucoflex-R is an established strip for type 2 diabetes (test strips are not subsidized by the German government for people with Type 2 Diabetes). As a footnote, another low cost visually read strip is soon to be available on prescription according to sources at the NHS. How the other manufactures and the NHS react to these developments, remains to be seen.

Another visual strip is also marketed under the brand name Betachek.

At least in North America, hospitals resisted adoption of meter glucose measurements for inpatient diabetes care for over a decade. Managers of laboratories argued that the superior accuracy of a laboratory glucose measurement outweighed the advantage of immediate availability and made meter glucose measurements unacceptable for inpatient diabetes management. Patients with diabetes and their endocrinologists eventually persuaded acceptance. Some health care policymakers still resist the idea that the society would be well advised to pay the consumables (reagents, lancets, etc.) needed.

Home glucose testing was adopted for type 2 diabetes more slowly than for type 1, and a large proportion of people with type 2 diabetes have never been instructed in home glucose testing. This has mainly come about because health authorities are reluctant to bear the cost of the test strips and lancets.

Future

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.

Throughout the 1990s a company in Hagerstown, Maryland, Futrex, Inc., was deep into finding a universal calibration for their meter, the Dream Beam, which relied on near-infrared technology, however in 1996 the company was raided by the FDA and a lawsuit was filed by the SEC charging Futrex, Inc. and its president Robert Rosenthal with fraud due to the belief that no non-invasive meter could accurately measure blood glucose. The raid was due to an unruly employee however critical time and information was lost throughout the raid and lawsuit, and development was ended on the instrument.

It is speculated that within the next decade, meters may be replaced with continuous glucose sensors for many people with diabetes. This will likely decrease complications found in people with diabetes by limiting problems associated with hyperglycemia and hypoglycemia.

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 non-invasive 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, where it won an E-Tech award. This device is currently undergoing clinical testing in the US and Internationally.

Technology

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. This is analogous to throwing a ball and measuring the distance it has covered so as to determine how hard it was thrown. The amperometric method is used by some meters and measures the electrical current generated at a specific point in time by the glucose reaction. This is analogous to throwing a ball and using the speed at which it is travelling at a point in time to estimate how hard it was thrown. The coulometric method can allow for variable test times, whereas the test time on a meter using the amperometric method is always fixed. Both methods give an estimation of the concentration of glucose in the initial blood sample.

The same principle is used in test strips that have been commercialised for the detection of diabetic ketoacidosis (DKA). These test strips use a beta-hydroxybutyrate-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.

Meter use for hypoglycemia

Although the apparent value of immediate measurement of blood glucose might seem to be higher for hypoglycemia than hyperglycemia, meters have been less useful. The primary problems are precision and ratio of false positive and negative results. An imprecision of ±15% is less of a problem for high glucose levels than low. There is little difference in the management of a glucose of 200 mg/dl compared with 260 (i.e., a "true" glucose of 230±15%), but a ±15% error margin at a low glucose concentration brings greater ambiguity with regards to glucose management.

The imprecision is compounded by the relative likelihoods of false positives and negatives in populations with diabetes and those without. People with type 1 diabetes usually have glucose levels above normal, often ranging from 40 to 500 mg/dl (2.2 to 28 mmol/l), and when a meter reading of 50 or 70 (2.8 or 3.9 mmol/l) is accompanied by their usual hypoglycemic symptoms, there is little uncertainty about the reading representing a "true positive" and little harm done if it is a "false positive." However, the incidence of hypoglycemia unawareness, hypoglycemia-associated autonomic failure (HAAF) and faulty counterregulatory response to hypoglycemia make the need for greater reliability at low levels particularly urgent in patients with type 1 diabetes mellitus, while this is seldom an issue in the more common form of the disease, type 2 diabetes mellitus.

In contrast, people who do not have diabetes may periodically have hypoglycemic symptoms but may also have a much higher rate of false positives to true, and a meter is not accurate enough to base a diagnosis of hypoglycemia upon. A meter can occasionally be useful in the monitoring of severe types of hypoglycemia (e.g., congenital hyperinsulinism) to ensure that the average glucose when fasting remains above 70 mg/dl (3.9 mmol/l).

For the purposes of detecting sleep-time hypoglycaemia events an Australian company, Aimedics, is currently developing a non-invasive device called the HypoMon. This device alerts patients or care givers of hypoglycaemic events.

External links

• National Diabetes Information Clearinghouse
• Glucose Meter Comparison Website