Diabetes, described as a group of metabolic diseases in which the person has high blood glucose (blood sugar), either because insulin production is inadequate, or because the body’s cells do not respond properly to insulin, or both.
Normally, the pancreas produces the right amount of insulin to accommodate the quantity of sugar. The cause of Type I diabetes is genetically based, coupled with an abnormal immune response. Frequent urination, increased thirst, extreme hunger, unexplained weight loss, extreme fatigue, blurred vision, irritability, nausea and vomiting. Any Type I symptom, plus: unexplained weight gain, pain, cramping, tingling or numbness in your feet, unusual drowsiness, frequent vaginal or skin infections, dry, itchy skin and slow healing sores. The beta cells in the pancreas of people with type 1 diabetes are not able to produce insulin.
For people without diabetes, the pancreas releases a number of hormones for glucose homeostasis.
Diabetic Retinopathy (DR) is the leading cause of blindness among working adults in developed countries such as Singapore and United States. Patients usually develop DR after 10 years of having diabetes (sometimes earlier).Uncontrolled diabetes allows unusually high levels of blood sugar to accumulate in and damage the tiny blood vessels in the eye. As more and more the blood vessels become clogged, the blood supply to the retina is cut off. Also known as background diabetic retinopathy, is the earlier stage of DR.This condition is usually identified by the deposits formed around the retina due to leakage from the blood vessels. The advanced stage of NPDR which is responsible for most of the vision loss in diabetes.As NPDR progresses into PDR, larger blood vessels become blocked. If you are interested in the types of treatment available for DA, see my article on Treatment for Diabetic Retinopathy.
Diabetes is a condition in which the body either does not produce enough, or does not properly respond to, insulin, a hormone produced in the pancreas that enables cells to absorb glucose in order to turn it into energy. All people with Type 1 diabetes, and many with Type 2 diabetes, must take additional insulin to control the disease. Prior to self monitoring of blood glucose, insulin was usually injected only twice daily by people with Type 1 diabetes, leading to very rudimentary control.
Self monitoring of blood glucose is accomplished using a blood glucose meter and test strips, pictured in Figure 1. The meter interrogates the strip in order to measure the blood glucose concentration, typically requiring about 5-10 seconds. The test strips described in the above procedure can be either optical, in which glucose-derived electrons effect a change in the color of an indicating dye molecule, or electrochemical, in which case the glucose-derived electrons are routed directly through the external meter, and counted. The electrochemical blood glucose test strip (EBGTS) is a very small volume (often about one µl or less) disposable electrochemical cell, which is contacted with whole blood. This electrical current is produced by the very selective oxidation of glucose in the blood sample, which is catalyzed by two reagents which are precoated inside the test strip: (i) an enzyme, which reacts directly with the glucose molecule to remove its two available electrons, and (ii) a mediator molecule, which takes (either singly or as a pair) the two electrons from the enzyme, and transports them to the working electrode, where they can be measured. The enzyme and mediator act as a sort of electron bucket brigade to transport electrons from glucose to the working electrode. This approach was pioneered by Anthony Turner at Cranfield University and Allen Hill at Oxford in 1984. The sample chamber, which is a miniature electrochemical cell, generally is formed from a number of elements and Figure 5 shows these in a cut-away view of an exemplary glucose test strip. When blood is added to an EBGTS, and the proper potential is applied across the electrodes, current flows as glucose is oxidized. Three different curves are shown, corresponding to low, medium, and high blood glucose levels. All EBGTS produce a time varying current (like that in Figure 6) which must be analyzed to deduce a glucose concentration. A mathematical analysis of the declining portion of the current-time curve (termed a Cottrell analysis) can be performed. The surface area and surface roughness of the working electrode must be highly reproducible to insure that current-time curves are reproducible from strip to strip. Coulometric strips are less common; they function by exhaustively depleting the glucose in the strip.
The internal volume of the sample chamber must be highly reproducible to insure that the analyzed volume is constant from strip to strip. Coulometric strips have very robust performance, and are less susceptible to external influences such as variable temperature or hematocrit (red blood cell count), although it is possible to compensate for these effects in amperometric strips.
Once a signal, whether charge or current, is extracted from the EBGTS, it must be converted to blood glucose concentration. The blood samples are tested in a highly accurate laboratory glucose analyzer, called the reference method, to determine the reference glucose value for each sample. The slope and intercept of the resulting line are used to assign a calibration code to the EBGTS.
The user inputs this code into the meter, before self testing, which allows the meter to accurately convert the electrochemical signal to a blood glucose value. This process is shown in Figure 7, a plot of charge against reference glucose for a batch of EBGTS.
In the calibration above, the strips are tested with whole blood, while the reference value is obtained from plasma derived from the same whole blood samples. All EBGTS include an enzyme and a mediator, described conceptually above, to ferry electrons from glucose to the working electrode. In addition to the fundamental structural elements described above, many EBGTS are equipped with advanced features to enhance the user experience.
Most EBGTS are equipped with some means of determining that the sample chamber is entirely filled with blood. Generally, calibration codes, corresponding to a particular batch of strips, are entered into the meter by the user, either manually or through insertion of a calibration “chip,” that accompanies the strip vial. Precise manufacturing control of the sensitivity of the produced strips, such that their performance is highly reproducible from batch to batch. Adding an indicating mark to the strip that the meter can use to assign a calibration code. Both systems are currently in use, and automatically coded strips make up an increasing share of EBGTS.


Historically, measures have been taken during strip design to minimize the hematocrit effect, for example, excluding red blood cells from near the working electrode surface. Glucose oxidase was first employed in EBGTS, and is still used in a few commercially available test strips, although its use is declining, since it reacts rapidly with oxygen. Glucose oxidase has been largely supplanted by the dehydrogenases, which do not react appreciably with oxygen.
Rapid reactivity with both the enzyme and the working electrode material of the particular strip in question.
Capable of being easily stabilized in the oxidized state; this reduces spurious non-glucose related background currents. A few commonly used mediators are: (i) ferricyanide, (ii) 1,10-phenanthroline quinone, and (iii) osmium-based mediators.
In general, as the potential of the mediator increases, the strip becomes more liable to spurious currents from electrochemical interferents such as ascorbate, urate, and acetaminophen. Electrochemical Glucose Sensors and Their Applications in Diabetes Management, Adam Heller and Ben Feldman “Chemical Reviews” Vol. The Technology Behind Glucose Meters: Test Strips, Joachim Hones, Peter Muller, and Nigel Surridge, “Diabetes Technology and Therapeutics” Vol. Recent Progress in Analytical Instrumentation for Glycemic Control in Diabetic and Critically Ill Patients, Venkata R. Listings of electrochemistry books, review chapters, proceedings volumes, and full text of some historical publications are also available in the Electrochemistry Science and Technology Information Resource (ESTIR).
Diabetes is a lifelong disease characterized by high levels of the sugar glucose in the blood. Gestational diabetes occurs when a woman without obvious diabetes develops high blood sugar during pregnancy. There is a lot women with gestational diabetes can do to maintain good health through pregnancy and minimize complications. Patients with high blood sugar will typically experience frequent urination, they will become increasingly thirsty and hungry. However, if the person has diabetes, either the pancreas produces little or no insulin or the cells do not respond normally to the insulin. Medical experts believe that Type II diabetes has a genetic component, but that other factors also put people at risk for the disease.
It is a lot easier to pretend nothing is wrong than it is to take the steps required to stay healthy. To make up for lack of blood supply, the eye attempts to grow new blood vessels.However, these immature blood vessels are feeble and can leak easily. They even grow in the wrong places such as on the surface of the retina and into the vitreous gel. This blockage builds up pressure in the eye and may result into glaucoma, a particularly severe condition that can cause permanent vision loss. In diabetes, the body either fails to make enough insulin (Type 1 diabetes), or does not properly respond to its own insulin (Type 2 diabetes). In order to effectively control Type 1 diabetes, insulin should be injected four or more times daily, including before every meal.
The insulin doses were not usually varied, but could be guided over the long term by the measurement of the glucose concentration in urine.
Current meters are handheld, with simple intuitive user interfaces that are usually activated automatically by insertion of a test strip. For various reasons, including accuracy and the ability to measure extremely small blood volumes, electrochemical strips have gained the advantage in recent years, and now comprise a growing majority of the test strip market.
It then produces, in conjunction with a test meter, an electrical current which is proportional to the blood glucose concentration. Their work was first incorporated into a commercially available device in 1988, the ExacTech strip shown in Figure 3. The working electrode was also coated with a mixture of ferrocene (mediator) and glucose oxidase (enzyme). This size is dominated by ergonomic (handling) concerns, since the actual sample chamber (which fills with blood) is only a few mm long, and is located at the top of the strips in Figure 4.
Two strips of thin plastic onto which the electrodes and chemical reagents (both described below) can be attached or coated.
This separates the two plastic supports, creating an internal space, more or less in the shape of a rectangular solid, which can fill with blood.
This is the portal through which electrons from glucose can enter the meter to be measured.
This is the portal through which glucose derived electrons re-enter the strip after measurement. These include principally the enzyme and mediator (described conceptually above in Figure 2), as well as a host of other reagents, including preservatives (to improve shelf life), surfactants (to help blood fill the strip quickly) and film formers (to distribute all of the reagents evenly within the strip), among others. The peak currents are proportional to the glucose concentration, although for this particular strip, designed for coulometric analysis, that relationship is non-linear.
Typically the current is measured 5-15 seconds after the strip is filled with blood, and that current level is directly proportional to the glucose concentration. In these strips, the total charge, or area under the current-time curve is measured, and is proportional to the glucose concentration. The batches can be quite large, several hundred thousand strips, and a few hundred are typically selected at regular intervals to test. This process, known as plasma calibration, allows glucose test strips to report a plasma glucose concentration, even though they are actually filled with whole blood during use. This is important, because a partially filled chamber can lead to erroneous, generally low, results. Their outputs are compared, and must correlate closely in order for the strip to be deemed full.
However, it is desirable to entirely bypass this process, since user error is always a possibility. In this process, strips are rejected, and disposed of, if their performance does not meet very stringent performance criteria. An alternate approach is to measure the hematocrit, and correct the reported blood glucose value.


EBGTS made with glucose oxidase produce currents that are dependent on the amount of dissolved oxygen in the blood sample, which is heavily dependent on the hematocrit (% red blood cells) in the sample. In that sense, low potential mediators are more desirable, although alternate strategies (such as a second working electrode with no deposited enzyme) can be used to quantify, then correct for interferent currents. High blood sugar is caused by the body’s inability to make insulin or respond to insulin normallyGlucose comes from food and is the main energy source for the body.Insulin is the hormone produced by the pancreas that is responsible for telling organs such as the liver, muscle, and fat to remove glucose from the blood.
This typically happens late in pregnancy, around 28 weeks or later.Gestational diabetes places the mother and baby at risk pregnancy complications such as macrosomia (largebaby), pre-eclampsia (high blood pressure) and birth injury. Percent increase in the odds of each complication was adjusted for potential confounders including, but not limited to, maternal age, BMI, height, smoking status, and family history of diabetes. Healthy meal planning, physical activity, and blood sugar monitoring are important parts of managing gestational diabetes.
This panel of tests can be performed during the first and second trimester to screen for gestational diabetes risk before diagnosis is typically made. Sugar builds up in the blood, overflows into the urine and then passes from the body unused.
Many people with Type II do not discover they have diabetes until they are treated for a complication such as heart disease, blood vessel disease, stroke, blindness, skin ulcers, kidney problems, nerve trouble or impotence. But family members can play an important role in helping their loved one with diabetes, take the steps they need to control their diabetes. Such leakages cause several complications which may damage the eyea€™s retina thus resulting in vision loss. This causes glucose to accumulate in the blood, leading to complications of the eyes, kidney, heart and circulatory system, among others. This requires frequent self monitoring of the blood glucose concentration, in order to know how much insulin to inject. Urine glucose measurement is far inferior to blood glucose measurement, since (i) glucose only appears in the urine when it has exceeded a threshold level in blood, which varies from person to person, and (ii) the urine measurement integrates a glucose value over the time required for the bladder to fill. Meters also, to varying extents, have the ability to store, recall, and graph past blood glucose measurements. The electrodes were exposed, unlike current EBGTS, which generally enclose the electrodes in a thin capillary chamber.
The other (bottom) end of the strips contains electrical contacts for communicating with a blood glucose meter.
It is generally constructed from either a mixture of silver and silver chloride, or an inert material similar such as carbon, platinum or gold. Instead, the area under the current-time curves varies directly with glucose in a linear fashion. In the broadest sense, the analysis can be either amperometric, in which the instantaneous current at a particular time is proportional to glucose, or coulometric, in which the integrated charge underneath the entire curve is proportional to glucose. Although it may take a considerable amount of time for all the glucose to react, in practice the current-time curve assumes a reproducible exponential shape after a few seconds, and can be easily extrapolated.
The chemical details of some of the most commonly used ones are described in the Appendix.
Older strips relied on visual confirmation of fill, but that process has been automated in newer strips. For example, hematocrit can be measured by using an extra pair of electrodes to measure the conductivity of the blood sample, by applying an ac signal between the electrodes.
For this reason, use of PQQ-GDH is decreasing, and the FDA has recently restricted its use in new commercial products. When there is not enough insulin, or these organs can’t respond to insulin, less glucose gets into cells to be stored for energy.
In fact, 80 – 90% of women with gestational diabetes can be managed with lifestyle therapy alone.
Identification of gestational diabetes risk allows women to make lifestyle changes earlier to improve health and wellness throughout pregnancy. Becoming physically active on a regular basis is one of the most important lifestyle changes that an individual with diabetes can make for control of the condition as well as long-term health. Typically, before a meal, the patient measures his blood glucose concentration, then calculates the required insulin dosage, based on (i) the measured glucose value, (ii) planned carbohydrate consumption, (iii) known insulin sensitivity, and (iv) a target glucose concentration. From left: Accuchek Aviva, True Track, Precision Xtra, FreeStyle Lite, Ascensia Contour, Nova, Arkray, One Touch Ultra, Agamatrix. Therefore the required blood volume (about 10 µl) was much larger than that used by today’s strips. In approximately one second, the current peaks, indicating that the strip has filled with blood. This leads to an analysis time similar to that for amperometric strips, about 5 seconds for the fastest analyses. Conductivity is a strong function of hematocrit, so this is an effective form of correction. Enzymes typically are deposited on at least the working electrode, and sometimes on one entire side of the sample chamber, and are codeposited with buffers and stabilizing agents, such as bovine serum albumin. Women with blood sugar levels that cannot be controlled with lifestyle changes will require insulin injections. If the blood glucose concentration can be effectively controlled, then the long term complications described above can be forestalled.
The test time, 30 seconds, was also considerably larger than the 5-10 seconds common today. The current then decreases, as glucose is consumed, causing its concentration in the vicinity of the working electrode to decrease.
As regulatory standards become more stringent, this sort of correction is likely to increase.
A series of continuous innovations has led to the much improved performance available today.



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Comments

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    Author: 777777
  2. 11.07.2015 at 16:47:53


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    Author: mikrob