Glucose meter
Encyclopedia
Medical device
A medical device is a product which is used for medical purposes in patients, in diagnosis, therapy or surgery . Whereas medicinal products achieve their principal action by pharmacological, metabolic or immunological means. Medical devices act by other means like physical, mechanical, thermal,...
for determining the approximate concentration of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...
in the blood
Blood
Blood is a specialized bodily fluid in animals that delivers necessary substances such as nutrients and oxygen to the cells and transports metabolic waste products away from those same cells....
. It is a key element of home blood glucose monitoring
Blood glucose monitoring
Blood glucose monitoring is a way of testing the concentration of glucose in the blood . Particularly important in the care of diabetes mellitus, a blood glucose test is performed by piercing the skin to draw blood, then applying the blood to a chemically active disposable 'test-strip'...
(HBGM) by people with diabetes mellitus
Diabetes mellitus
Diabetes mellitus, often simply referred to as diabetes, is a group of metabolic diseases in which a person has high blood sugar, either because the body does not produce enough insulin, or because cells do not respond to the insulin that is produced...
or hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
. A small drop of blood, obtained by pricking the skin with a lancet
Blood lancet
A blood lancet, or simply lancet, is a small medical implement used for blood sampling. A blood lancet is similar to a small scalpel but with a double-edged blade or needle. Lancets are used to make punctures to obtain small blood specimens, are generally disposable, and are commonly used in the...
, 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
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
as well as a reduction in the short-term, potentially life-threatening complications of hypoglycemia
Diabetic hypoglycemia
Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals...
.
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 batteryBattery (electricity)An electrical battery is one or more electrochemical cells that convert stored chemical energy into electrical energy. Since the invention of the first battery in 1800 by Alessandro Volta and especially since the technically improved Daniell cell in 1836, batteries have become a common power...
-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 oxidaseGlucose oxidaseThe glucose oxidase enzyme is an oxido-reductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. In cells, it aids in breaking the sugar down into its metabolites....
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-hydroxybutyrateBeta-hydroxybutyratebeta-Hydroxybutyric acid is a ketone body. It is a chiral compound having two enantiomers, D-3-hydroxybutyric acid and L-3-hydroxybutyric acid. Like the other ketone bodies , levels of beta-hydroxybutyrate are raised in ketosis...
in the blood to detect ketoacidosis (ketosisKetosisKetosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...
).
- Clock/memory: All meters now include a clock that is set by the user 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 and weeks. Most memory chips can display an average of recent glucose readings. A known deficiency of all current meters is that the clock is often not set to the correct time (ie - due to time changes, static electricity, etc...) and therefore has the potential to misrepresent the time of the past test results making pattern management difficult.
- 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 softwareDiabetes management softwareDiabetes Management Software refers to software tools that run on personal computers and personal digital assistants to help persons with Type 1 and Type 2 diabetes manage the data associated with:*test results from a glucose meter*diabetes logbooks...
to display the test results. Some meters allow entry of additional data throughout the day, such as insulinInsulinInsulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....
dose, amounts of carbohydrateCarbohydrateA carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
s eaten, or exercise. A number of meters have been combined with other devices, such as insulin injection devices, PDAsPersonal digital assistantA personal digital assistant , also known as a palmtop computer, or personal data assistant, is a mobile device that functions as a personal information manager. Current PDAs often have the ability to connect to the Internet...
, cellular transmitters and even Game BoyGame BoyThe , is an 8-bit handheld video game device developed and manufactured by Nintendo. It was released in Japan on , in North America in , and in Europe on...
s. A radio link to an insulin pumpInsulin pumpThe insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
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 recordElectronic medical record
An electronic medical record is a computerized medical record created in an organization that delivers care, such as a hospital or physician's office...
s and the laboratory
Medical laboratory
A medical laboratory or clinical laboratory is a laboratory where tests are done on clinical specimens in order to get information about the health of a patient as pertaining to the diagnosis, treatment, and prevention of disease.-Departments:...
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
Counterfeit
To counterfeit means to illegally imitate something. Counterfeit products are often produced with the intent to take advantage of the superior value of the imitated product...
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 StandardizationInternational Organization for Standardization
The International Organization for Standardization , widely known as ISO, is an international standard-setting body composed of representatives from various national standards organizations. Founded on February 23, 1947, the organization promulgates worldwide proprietary, industrial and commercial...
(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
Ascorbic acid
Ascorbic acid is a naturally occurring organic compound with antioxidant properties. It is a white solid, but impure samples can appear yellowish. It dissolves well in water to give mildly acidic solutions. Ascorbic acid is one form of vitamin C. The name is derived from a- and scorbutus , the...
) in blood, hematocrit
Hematocrit
The hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...
, dirt on meter, humidity
Humidity
Humidity is a term for the amount of water vapor in the air, and can refer to any one of several measurements of humidity. Formally, humid air is not "moist air" but a mixture of water vapor and other constituents of air, and humidity is defined in terms of the water content of this mixture,...
, 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
Clarke error grid
The Clarke Error Grid Analysis was developed in 1987 to quantify clinical accuracy of patient estimates of their current blood glucose as compared to the blood glucose value obtained in their meter. It was then used to quantify the clinical accuracy of blood glucose estimates generated by meters...
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
Consensus Error Grid
The consensus error grid was developed as a new tool for evaluating the accuracy of a blood glucose meter. In recent times, the consensus error grid has been used increasingly by blood glucose meter manufacturers in their clinical studies. It was published in August 2000 by Joan L. Parkes, Stephen...
.
History
In 1962, Leland ClarkLeland Clark
Leland C. Clark Jr. was an American biochemist born in Rochester, New York. He is most well known as the inventor of the Clark electrode, a device used for measuring oxygen in blood, water and other liquids. Clark is considered the "Father of Biosensors", and the modern-day glucose sensor used...
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 1981. The two models initially dominant in North America in the 1980s were the Glucometer, introduced on November 1981#November 5, 1981 whose trademark
Trademark
A trademark, trade mark, or trade-mark is a distinctive sign or indicator used by an individual, business organization, or other legal entity to identify that the products or services to consumers with which the trademark appears originate from a unique source, and to distinguish its products or...
is owned by Bayer
Bayer
Bayer AG is a chemical and pharmaceutical company founded in Barmen , Germany in 1863. It is headquartered in Leverkusen, North Rhine-Westphalia, Germany and well known for its original brand of aspirin.-History:...
and the Accu-chek
Accu-chek
Accu-Chek is the brand of blood sugar-testing devices and Insulin Pumps manufactured by Roche Diagnostics, largely for the diabetic market.Accu-Chek Blood Glucose Monitor Kits contain:...
meter (by Roche). Consequently, these brand
Brand
The American Marketing Association defines a brand as a "Name, term, design, symbol, or any other feature that identifies one seller's good or service as distinct from those of other sellers."...
names have become synonymous with the generic product
Genericized trademark
A genericized trademark is a trademark or brand name that has become the colloquial or generic description for, or synonymous with, a general class of product or service, rather than as an indicator of source or affiliation as intended by the trademark's holder...
to many health care professionals. In Britain
United Kingdom
The United Kingdom of Great Britain and Northern IrelandIn the United Kingdom and Dependencies, other languages have been officially recognised as legitimate autochthonous languages under the European Charter for Regional or Minority Languages...
, 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, hospital
Hospital
A hospital is a health care institution providing patient treatment by specialized staff and equipment. Hospitals often, but not always, provide for inpatient care or longer-term patient stays....
s resisted adoption of meter glucose measurements for inpatient diabetes care for over a decade. Managers of laboratories
Medical laboratory
A medical laboratory or clinical laboratory is a laboratory where tests are done on clinical specimens in order to get information about the health of a patient as pertaining to the diagnosis, treatment, and prevention of disease.-Departments:...
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
Minimed Paradigm
MiniMed Paradigm is a series of insulin pumps manufactured by Medtronic for patients with diabetes mellitus. The pump operates with a single AAA battery and uses a piston-plunger pump to infuse a programmed amount of insulin into the patient through a length of tubing...
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
Insulin pump
The insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin infusion therapy.The device includes:...
, 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
IPhone
The iPhone is a line of Internet and multimedia-enabled smartphones marketed by Apple Inc. The first iPhone was unveiled by Steve Jobs, then CEO of Apple, on January 9, 2007, and released on June 29, 2007...
, an add-on pack for LG
LG
LG may refer to:*LG Corp., a South Korean electronics and petrochemicals conglomerate*LG Electronics, an affiliate of the South Korean LG Group which produces electronic products* Lawrence Graham, a London headquartered firm of business lawyers...
model UX5000, VX5200, and LX350 cell phones, as well as an add-on pack for the Motorola
Motorola
Motorola, Inc. was an American multinational telecommunications company based in Schaumburg, Illinois, which was eventually divided into two independent public companies, Motorola Mobility and Motorola Solutions on January 4, 2011, after losing $4.3 billion from 2007 to 2009...
Razr cell phone. This limits providers to AT&T
AT&T
AT&T Inc. is an American multinational telecommunications corporation headquartered in Whitacre Tower, Dallas, Texas, United States. It is the largest provider of mobile telephony and fixed telephony in the United States, and is also a provider of broadband and subscription television services...
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 oxidaseGlucose oxidase
The glucose oxidase enzyme is an oxido-reductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. In cells, it aids in breaking the sugar down into its metabolites....
(sometimes known as GOx). Others use a similar reaction catalysed instead by another enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
, glucose dehydrogenase
Glucose dehydrogenase (acceptor)
In enzymology, a glucose dehydrogenase is an enzyme that catalyzes the chemical reactionThus, the two substrates of this enzyme are D-glucose and acceptor, whereas its two products are D-glucono-1,5-lactone and reduced acceptor....
(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
Colorimetry
Colorimetry is "the science and technology used to quantify and describe physically the human color perception."It is similar to spectrophotometry, but is distinguished by its interest in reducing spectra to the physical correlates of color perception, most often the CIE 1931 XYZ color space...
reaction that is still used nowadays in glucose test strips for urine. Besides glucose oxidase, the test kit contains a benzidine
Benzidine
Benzidine, the trivial name for 4,4'-diaminobiphenyl, is the solid organic compound with the formula 2. This aromatic amine is a component of a test for cyanide and also in the production of dyes...
derivative, which is oxidized to a blue polymer by the hydrogen peroxide
Hydrogen peroxide
Hydrogen peroxide is the simplest peroxide and an oxidizer. Hydrogen peroxide is a clear liquid, slightly more viscous than water. In dilute solution, it appears colorless. With its oxidizing properties, hydrogen peroxide is often used as a bleach or cleaning agent...
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
Ferricyanide
Ferricyanide is the anion [Fe6]3−. It is also called hexacyanoferrate and in rare, but systematic nomenclature, hexacyanidoferrate...
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
Coulometry
Coulometry is the name given to a group of techniques in analytical chemistry that determine the amount of matter transformed during an electrolysis reaction by measuring the amount of electricity consumed or produced....
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 hypoglycemiaHypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
than hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
, 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
Congenital hyperinsulinism
Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and...
) to ensure that the average glucose when fasting remains above 70 mg/dl (3.9 mmol/l).