HOW(?) & WHY(?) Liquid-Eating & Intermittent-Fasting can be so beneficial to your Health...

Wednesday 4 June 2008

Low Blood Sugar-HYPOglycemia-What the Surgeon says...


"Every Day And In Every Way I Am Getting Better And Better" ...
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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 with proneness to HYPOglycemia.

A small drop of blood obtained by pricking the skin with a lancet is placed on a disposable test strip, which 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 has been the achievement of 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

A glucose meter being used in Brasília, Brazil.Photo by Wilson Dias
A glucose meter being used in Brasília, Brazil.
Photo by Wilson Dias

There are several key characteristics of glucose meters that 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 most models this element is a plastic test strip with a small spot impregnated with glucose oxidase and other components. Each strip can only be used once and is 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 enter in a code that may be found on the vial of test strips, or 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 4mmol/L inaccurate. The implications of an incorrectly coded meter can be serious for patients actively managing their diabetes. For miscoded meters, the probability of making an insulin dose error of 2 units is 50%. The probability of making an insulin dose error of 3 units is 24%, compared to 0.49% when using a no coding meter. This may place patients at increased risk of hypoglycaemia.
    Bayer's No Coding Technology involves a range of meters and test strips with automatic coding.[1]
  • Volume of blood sample: The size of the drop of blood needed by different models varies from 0.3 to 10 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 US, mmol/l in Canada and Europe. To convert mmol/l of glucose to mg/dl, multiply by 18. To convert mg/dl of glucose to mmol/l, divide by 18 or multiply by 0.055. Many machines can toggle between both types of measurements and 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. Recent production U.S.-marketed machines are pre-set at the factory for mg/dl and cannot be changed.
  • Glucose [BG] vs. Plasma glucose [PBG]: 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 you and your healthcare provider to know whether your meter gives its results as "whole blood equivalent" or "plasma equivalent."
  • 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.[1] 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. One model also measures beta-hydroxybutyrate in the blood to detect ketoacidosis (ketosis).
  • Hospital glucose meters: Special glucose meters for multi-patient hospital use are now used. These provide more elaborate quality control records, and the data handling capabilities are designed to transfer glucoses 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 test as often as 10 to 12 times a day due to the dynamics of insulin adjustment, whereas type 2 test less frequently, especially when insulin is not part of treatment.

Some batches of counterfeit test strips for some meters have been identified, and these have been shown to produce inaccurate results[2]. 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. Nearly all of the meters have similar accuracy (±10-15%) when used optimally. However, a variety of factors can affect the accuracy of a test. Factors affecting accuracy of various meters have included calibration of meter, ambient temperature, pressure use to wipe off strip, size of blood sample, high levels of certain drugs 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 is 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 - this is known as the Consensus Error Grid.

History

The earliest glucose meter was the Ames Reflectance Meter by Anton H. Clemens. It was used in American hospitals in the 70's. It was about 10 inches long. It needed connection to an electrical outlet for the 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[3] and the Accu-Chek meter (by Roche). Consequently, these brand names have become synonymous with the generic product to many health care professionals.

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 with scissors longitudinally to save money. As meter accuracy and insurance coverage improved, they lost popularity and are no longer marketed.

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.

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.

Future

Development of noninvasive devices may enable continuous monitoring. Research is being done on noninvasive methods for measuring blood glucose, such as using electric currents and ultrasound.

There is one noninvasive glucose meter that has been approved by the FDA: The GlucoWatch G2 Biographer is designed to be worn on the wrist, and it 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 system is not able to cope with perspiration at the measurement site. The sweat must be allowed to dry before measurement can resume. Due to these 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 the present 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.[4]

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 2 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 5 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. High and low glucose alarms are user-settable.

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 $149.00 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 addon pack for LG model UX5000, VX5200, and LX350 cell phones, as well as an addon pack for the Motorola Razr cell phone. This limits providers to AT&T for the iPhone and Verizon for the others.

Technology

Many glucose meters employ the oxidation of glucose to gluconolactone catalyzed by glucose oxidase. Others use a similar reaction catalysed instead by another enzyme, Glucose Dehydrogenase (GHD). 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 and an enzyme electrode containing glucose oxidase. The enzyme is reoxidized with an excess of ferrocyanide ion. The total charge passing through the electrode is measured and is proportional to the concentration of glucose in the blood. The coulometric method is a technique used to define a reaction where the amount of charge measured over a fixed time is measured. The amperometric method is used by some meters that allows the reaction to go to completion and where the total charge transfer is measured. The coulometric method allows for a fixed test time, whereas test times with a meter using the amperometric techique can vary.

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."

In contrast, people who do not have diabetes but periodically have hypoglycemic symptoms will 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 glucoses when fasting remain above 70 mg/dl (3.9 mmol/l).

YouTube Videos of Blood Glucose Meters

External links used as references

References

  1. ^ Healthcare Professionals -- Products and Services. Bayer Healthcare. Retrieved on 2008-01-30.
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HYPOglycemia (HYPOglycaemia in British English) is the medical term for a pathologicglucose (sugar) in the blood. The term hypoglycemia literally means "under-sweet blood" (Gr. hypo-, glykys, haima). Hypoglycemia can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose as fuel to the brain, resulting in impairment of function (neuroglycopenia). Derangements of function can range from vaguely "feeling bad" to coma and (rarely) permanent brain damage or death. Hypoglycemia can arise from many causes and can occur at any age. state produced by a lower than normal level of

The most common forms of moderate and severe hypoglycemia occur as a complication of treatment of diabetes mellitus with insulin or certain oral medications. Hypoglycemia is usually treated by the ingestion or administration of dextrose, or foods digestible to glucose.

Endocrinologists (specialists in hormones, including those which regulate glucose metabolism) typically consider the following criteria (referred to as Whipple's triad) as proving that individual's symptoms can be attributed to hypoglycemia:

  1. Symptoms known to be caused by hypoglycemia
  2. Low glucose at the time the symptoms occur
  3. Reversal or improvement of symptoms or problems when the glucose is restored to normal

However, not everyone has accepted these suggested diagnostic criteria, and even the level of glucose low enough to define HYPOglycemia has been a source of controversy in several contexts. For many purposes, plasma glucose levels below 70 mg/dl or 3.9 mmol/L are considered HYPOglycemic; these issues are detailed below ...


Defining hypoglycemia

No single glucose value alone serves to define the medical condition termed hypoglycemia for all people and purposes. Throughout the 24 hour cycles of eating, digestion, and fasting, blood plasma glucose levels are generally maintained within a range of 70-140 mg/dL (3.9-7.8 mmol/L) for healthy humans.[1] Although 60 or 70 mg/dL (3.3 or 3.9 mmol/L) is commonly cited as the lower limit of normal glucose, different values (typically below 40, 50, 60, or 70 mg/dL) have been defined as low for different populations, clinical purposes, or circumstances.

The precise level of glucose considered low enough to define hypoglycemia is dependent on (1) the measurement method, (2) the age of the person, (3) presence or absence of effects, and (4) the purpose of the definition. While there is no disagreement as to the normal range of blood sugar, debate continues as to what degree of hypoglycemia warrants medical evaluation or treatment, or can cause harm.[2][3][4]

This article expresses glucose in milligrams per deciliter (mg/dL or mg/100 mL) as is customary in the United States, while millimoles per litre (mmol/L or mM) are the SI (International System) units used in most of the rest of the world. Glucose concentrations expressed as mg/dL can be converted to mmol/L by dividing by 18.0 g/mol (the molar mass of glucose). For example, a glucose concentration of 90 mg/dL is 5.0 mmol/L or 5.0 mM.

Measurement method

Blood glucose levels discussed in this article are venous plasma or serum levels measured by standard, automated glucose oxidase methods used in medical laboratories. For clinical purposes, plasma and serum levels are similar enough to be interchangeable. Arterial plasma or serum levels are slightly higher than venous levels, and capillary levels are typically in between.[5] This difference between arterial and venous levels is small in the fasting state but is amplified and can be greater than 10% in the postprandial state.[6] On the other hand, whole blood glucose levels (e.g., by fingerprick meters) are about 10%-15% lower than venous plasma levels.[5] Furthermore, available fingerstick glucose meters are only warranted to be accurate to within 15% of a simultaneous laboratory value under optimal conditions, and home use in the investigation of hypoglycemia is fraught with misleading low numbers.[7][8] In other words, a meter glucose reading of 39 mg/dL could be properly obtained from a person whose laboratory serum glucose was 53 mg/dL; even wider variations can occur with "real world" home use.

Ironically, most meters sold are routinely tested for accuracy at the high-end of the scale, sometimes up to 800 mg/dL, despite the fact that there is little immediate danger from hyperglycemia, whereas there is very real immediate danger from HYPOglycemia, making accuracy at the low-end extremely critical.

Two other factors significantly affect glucose measurement: hematocrit and delay after phlebotomy. The disparity between venous and whole blood concentrations is greater when the hematocrit is high,[6] as in newborn infants, or adults with polycythemia. High neonatal hematocrits are particularly likely to confound glucose measurement by meter. Second, unless the specimen is drawn into a fluoride tube or processed immediately to separate the serum or plasma from the cells, the measurable glucose will be gradually lowered by in vitro metabolism of the glucose at a rate of approximately 7 mg/dL/hr, or even more in the presence of leukocytosis.[9][10][6]

Age differences

Surveys of healthy children and adults show that plasma glucoses below 60 mg/dL (3.3 mM) or above 100 mg/dL (5.6 mM) are found in less than 5% of samples after an overnight fast.[11] In infants and young children up to 10% have been found to be below 60 mg/dL after an overnight fast.[citation needed] As the duration of fasting is extended, plasma glucose levels can fall further, even in healthy people. In other words, many healthy people can occasionally have glucose levels in the hypoglycemic range without symptoms or disease.

The normal range of newborn blood sugars continues to be debated. Surveys and experience have revealed blood sugars often below 40 mg/dL (2.2 mM), rarely below 30 mg/dL (1.7 mM),[citation needed] in apparently healthy full-term infants on the first day after birth. It has been proposed that newborn brains are able to use alternate fuels when glucose levels are low more readily than adults. Experts continue to debate the significance and risk of such levels, though the trend has been to recommend maintenance of glucose levels above 60-70 mg/dL after the first day after birth. In ill, undersized, or premature newborns, low blood sugars are even more common, but there is a consensus that sugars should be maintained at least above 50 mg/dL[citation needed] (2.8 mM) in such circumstances. Some experts advocate 70 mg/dL[citation needed] as a therapeutic target, especially in circumstances such as hyperinsulinism where alternate fuels may be less available.

Presence or absence of effects

Research in healthy adults shows that mental efficiency declines slightly but measurably as blood glucose falls below 65 mg/dL (3.6 mM) in many people. Hormonal defense mechanisms (adrenaline and glucagon) are activated as it drops below a threshold level (about 55 mg/dL for most people), producing the typical symptoms of shakiness and dysphoria. On the other hand, obvious impairment does not often occur until the glucose falls below 40 mg/dL, and up to 10% of the population may occasionally have glucose levels below 65 in the morning without apparent effects. Brain effects of hypoglycemia, termed neuroglycopenia, determine whether a given low glucose is a "problem" for that person, and hence some people tend to use the term HYPOglycemia only when a moderately low glucose is accompanied by symptoms.

Even this criterion is complicated by the facts that A) hypoglycemic symptoms are vague and can be produced by other conditions; B) people with persistently or recurrently low glucose levels can lose their threshold symptoms so that severe neuroglycopenic impairment can occur without much warning; and C) many measurement methods (especially glucose meters) are imprecise at low levels.

Diabetic hypoglycemia represents a special case with respect to the relationship of measured glucose and hypoglycemic symptoms for several reasons. Although home glucose meter readings are sometimes misleading, the probability that a low reading accompanied by symptoms represents real hypoglycemia is higher in a person who takes insulin. Second, the hypoglycemia has a greater chance of progressing to more serious impairment if not treated, compared to most other forms of hypoglycemia that occur in adults. Third, because glucose levels are above normal most of the time in people with diabetes, hypoglycemic symptoms may occur at higher thresholds than in people who are normoglycemic most of the time. For all of these reasons, people with diabetes usually use higher meter glucose thresholds to determine hypoglycemia.

Purpose of definition

For all of the reasons explained in the above paragraphs, deciding whether a blood glucose in the borderline range of 45-75 mg/dL (2.5-4.2 mM) represents clinically problematic hypoglycemia is not always simple. This leads people to use different "cutoff levels" of glucose in different contexts and for different purposes.

Pathophysiology

Like most animal tissues, brain metabolism depends primarily on glucose for fuel in most circumstances. A limited amount of glucose can be derived from glycogen stored in astrocytes, but it is consumed within minutes. For most practical purposes, the brain is dependent on a continual supply of glucose diffusing from the blood into the interstitial tissue within the central nervous system and into the neurons themselves.

Therefore, if the amount of glucose supplied by the blood falls, the brain is one of the first organs affected. In most people, subtle reduction of mental efficiency can be observed when the glucose falls below 65 mg/dl (3.6 mM). Impairment of action and judgement usually becomes obvious below 40 mg/dl (2.2 mM). Seizures may occur as the glucose falls further. As blood glucose levels fall below 10 mg/dl (0.55 mM), most neurons become electrically silent and nonfunctional, resulting in coma. These brain effects are collectively referred to as neuroglycopenia.

The importance of an adequate supply of glucose to the brain is apparent from the number of nervous, hormonal and metabolic responses to a falling glucose level. Most of these are defensive or adaptive, tending to raise the blood sugar via glycogenolysis and gluconeogenesis or provide alternative fuels. If the blood sugar level falls too low the liver converts a storage of glycogen into glucose and releases it into the bloodstream, to prevent the person going in to a diabetic coma, for a short period of time.

Brief or mild hypoglycemia produces no lasting effects on the brain, though it can temporarily alter brain responses to additional hypoglycemia. Prolonged, severe hypoglycemia can produce lasting damage of a wide range. This can include impairment of cognitive function, motor control, or even consciousness. The likelihood of permanent brain damage from any given instance of severe hypoglycemia is difficult to estimate, and depends on a multitude of factors such as age, recent blood and brain glucose experience, concurrent problems such as hypoxia, and availability of alternative fuels. The vast majority of symptomatic hypoglycemic episodes result in no detectable permanent harm.[12]

Signs and symptoms

Hypoglycemic symptoms and manifestations can be divided into those produced by the counterregulatory hormones (epinephrine/adrenaline and glucagon) triggered by the falling glucose, and the neuroglycopenic effects produced by the reduced brain sugar.

Adrenergic manifestations

Glucagon manifestations

NeuroGlycoPenic manifestations ...

Not all of the above manifestations occur in every case of hypoglycemia. There is no consistent order to the appearance of the symptoms, if symptoms even occur. Specific manifestations may vary by age and by severity of the hypoglycemia. In young children, vomiting can sometimes accompany morning hypoglycemia with ketosis. In older children and adults, moderately severe hypoglycemia can resemble mania, mental illness, drug intoxication, or drunkenness. In the elderly, hypoglycemia can produce focal stroke-like effects or a hard-to-define malaise. The symptoms of a single person may be similar from episode to episode, but are not necessarily so and may be influenced by the speed at which glucose levels are dropping, and previous incidence.

In newborns, HYPOglycemia can produce irritability, jitters, myoclonic jerks, cyanosis, respiratory distress, apneic episodes, sweating, hypothermia, somnolence, hypotonia, refusal to feed, and seizures or "spells". HYPOglycemia can resemble asphyxia, hypocalcemia, sepsis, or heart failure.

In both young and old patients, the brain may habituate to low glucose levels, with a reduction of noticeable symptoms despite NeuroGlycoPenic impairment. In insulin-dependent diabetic patients this phenomenon is termed HYPOglycemia unawareness and is a significant clinical problem when improved glycemic control is attempted. Another aspect of this phenomenon occurs in type I glycogenosis, when chronic hypoglycemia before diagnosis may be better tolerated than acute hypoglycemia after treatment is underway.

Nearly always, hypoglycemia severe enough to cause seizures or unconsciousness can be reversed without obvious harm to the brain. Cases of death or permanent neurological damage occurring with a single episode have usually involved prolonged, untreated unconsciousness, interference with breathing, severe concurrent disease, or some other type of vulnerability. Nevertheless, brain damage or death has occasionally resulted from severe HYPOglycemia.

Determining the cause

Hundreds of conditions can cause hypoglycemia. Common causes by age are listed below. While many aspects of the medical history and physical examination may be informative, the two best guides to the cause of unexplained hypoglycemia are usually

  1. the circumstances
  2. a critical sample of blood obtained at the time of hypoglycemia, before it is reversed.

The circumstances of hypoglycemia provide most of the clues to diagnosis

Circumstances include the age of the patient, time of day, time since last meal, previous episodes, nutritional status, physical and mental development, drugs or toxins (especially insulin or other diabetes drugs), diseases of other organ systems, family history, and response to treatment. When hypoglycemia occurs repeatedly, a record or "diary" of the spells over several months, noting the circumstances of each spell (time of day, relation to last meal, nature of last meal, response to carbohydrate, and so forth) may be useful in recognizing the nature and cause of the hypoglycemia.

An especially important aspect is whether the patient is seriously ill with another problem. Severe disease of nearly all major organ systems can cause hypoglycemia as a secondary problem. Hospitalized patients, especially in intensive care units or those prevented from eating, can suffer hypoglycemia from a variety of circumstances related to the care of their primary disease. Hypoglycemia in these circumstances is often multifactorial or even iatrogenic. Once identified, these types of hypoglycemia are readily reversed and prevented, and the underlying disease becomes the primary problem.

Apart from determining nutritional status and identifying whether there is likely to be an underlying disease more serious than hypoglycemia, the physical examination of the patient is only occasionally helpful. Macrosomia in infancy usually indicates hyperinsulinism. A few syndromes and metabolic diseases may be recognizable by clues such as hepatomegaly or micropenis.

Response to treatment, especially the amount of carbohydrate needed to reverse or prevent recurrence of HYPOglycemia, may provide important clues as well. When 15-30 grams of sugar or starch are given by mouth, a low blood glucose will usually rise by 18-36 mg/dl (1-2 mmol/l) within 5-10 minutes, relieving HYPOglycemia symptoms within 10 minutes[citation needed]. It may take longer to recover from severe hypoglycemia with unconsciousness or seizure even after restoration of normal blood glucose. When a person has not been unconscious, failure of carbohydrate to reverse the symptoms in 10-15 minutes increases the likelihood that hypoglycemia was not the cause of the symptoms. When severe hypoglycemia has persisted in a hospitalized patient, the amount of glucose required to maintain satisfactory blood glucose levels becomes an important clue to the underlying etiology. Glucose requirements above 10 mg/kg/minute in infants, or 6 mg/kg/minute in children and adults are strong evidence for hyperinsulinism. In this context this is referred to as the glucose infusion rate (GIR). Finally, the blood glucose response to glucagon given when the glucose is low can also help distinguish among various types of hypoglycemia. A rise of blood glucose by more than 30 mg/dl (1.70 mmol/l) suggests insulin excess as the probable cause of the hypoglycemia.

In less obvious cases, a "critical sample" may provide the diagnosis

In the majority of children and adults with recurrent, unexplained hypoglycemia, the diagnosis may be determined by obtaining a sample of blood during hypoglycemia. If this critical sample is obtained at the time of HYPOglycemia, before it is reversed, it can provide information that would otherwise require a several-thousand-dollar hospital admission and unpleasant starvation testing. Perhaps the most common inadequacy of emergency department care in cases of unexplained HYPOglycemia is the failure to obtain at least a basic sample before giving glucose to reverse it.

Part of the value of the critical sample may simply be the proof that the symptoms are indeed due to hypoglycemia. More often, measurement of certain hormones and metabolites at the time of hypoglycemia indicates which organs and body systems are responding appropriately and which are functioning abnormally. For example, when the blood glucose is low, hormones which raise the glucose should be rising and insulin secretion should be completely suppressed.

The following is a brief list of hormones and metabolites which may be measured in a critical sample. Not all tests are checked on every patient. A "basic version" would include insulin, cortisol, and electrolytes, with C-peptide and drug screen for adults and growth hormone in children. The value of additional specific tests depends on the most likely diagnoses for an individual patient, based on the circumstances described above. Many of these levels change within minutes, especially if glucose is given, and there is no value in measuring them after the hypoglycemia is reversed. Others, especially those lower in the list, remain abnormal even after hypoglycemia is reversed, and can be usefully measured even if a critical specimen is missed. Although interpretation in difficult cases is beyond the scope of this article, for most of the tests, the primary significance is briefly noted.

  • Glucose: needed to document actual hypoglycemia
  • Insulin: any detectable amount is abnormal during hypoglycemia, but physician must know assay characteristics
  • Cortisol: should be high during hypoglycemia if pituitary and adrenals are functioning normally
  • Growth hormone: should rise after hypoglycemia if pituitary is functioning normally
  • Electrolytes and total carbon dioxide: electrolyte abnormalities may suggest renal or adrenal disease; mild acidosis is normal with starvation hypoglycemia; usually no acidosis with hyperinsulinism
  • Liver enzymes: elevation suggests liver disease
  • Ketones: should be high during fasting and hypoglycemia; low levels suggest hyperinsulinism or fatty acid oxidation disorder
  • Beta-hydroxybutyrate: should be high during fasting and hypoglycemia; low levels suggest hyperinsulinism or fatty acid oxidation disorder
  • Free fatty acids: should be high during fasting and hypoglycemia; low levels suggest hyperinsulinism; high with low ketones suggests fatty acid oxidation disorder
  • Lactic acid: high levels suggest sepsis or an inborn error of gluconeogenesis such as glycogen storage disease
  • Ammonia: if elevated suggests hyperinsulinism due to glutamate dehydrogenase deficiency, Reye syndrome, or certain types of liver failure
  • C-peptide: should be low or undetectable; if elevated suggests hyperinsulinism; low c-peptide with high insulin suggests exogenous (injected) insulin
  • Proinsulin: detectable levels suggest hyperinsulinism; levels disproportionate to a detectable insulin level suggest insulinoma
  • Ethanol: suggests alcohol intoxication
  • Toxicology screen: can detect many drugs causing hypoglycemia, especially for sulfonylureas
  • Insulin antibodies: if positive suggests repeated insulin injection or antibody-mediated hypoglycemia
  • Urine organic acids: elevated in various characteristic patterns in several types of organic aciduria
  • Carnitine, free and total: low in certain disorders of fatty acid metabolism and certain types of drug toxicity and pancreatic disease
  • Thyroxine and TSH: low T4 without elevated TSH suggests hypopituitarism or malnutrition
  • Acylglycine: elevation suggests a disorder of fatty acid oxidation
  • Epinephrine: should be elevated during hypoglycemia
  • Glucagon: should be elevated during hypoglycemia, except in the case of type 1 diabetes mellitus where irreparable damage is done to the cells which produce this counterregulatory hormone.
  • IGF-1: low levels suggest hypopituitarism or chronic malnutrition
  • IGF-2: low levels suggest hypopituitarism; high levels suggest non-pancreatic tumor hypoglycemia
  • ACTH: should be elevated during hypoglycemia; unusually high ACTH with low cortisol suggests Addison's disease
  • Alanine or other plasma amino acids: abnormal patterns may suggest certain inborn errors of amino acid metabolism or gluconeogenesis
  • Somatostatin should be elevated during hypoglycemia as it acts to inhibit insulin production and increase blood glucose level

Further diagnostic steps

When suspected hypoglycemia recurs and a critical specimen has not been obtained, the diagnostic evaluation may take several paths. However good nutrition and prompt intake is essential.

When general health is good, the symptoms are not severe, and the person can fast normally through the night, experimentation with diet (extra snacks with fat or protein, reduced sugar) may be enough to solve the problem. If it is uncertain whether "spells" are indeed due to hypoglycemia, some physicians will recommend use of a home glucose meter to test at the time of the spells to confirm that glucoses are low. This approach may be most useful when spells are fairly frequent or the patient is confident that he or she can provoke a spell. The principal drawback of this approach is the high rate of false positive or equivocal levels due to the imprecision of the currently available meters: both physician and patient need an accurate understanding of what a meter can and cannot do to avoid frustrating and inconclusive results.

In cases of recurrent hypoglycemia with severe symptoms, the best method of excluding dangerous conditions is often a diagnostic fast. This is usually conducted in the hospital, and the duration depends on the age of the patient and response to the fast. A healthy adult can usually maintain a glucose level above 50 mg/dl (2.8 mM) for 72 hours, a child for 36 hours, and an infant for 24 hours. The purpose of the fast is to determine whether the person can maintain his or her blood glucose as long as normal, and can respond to fasting with the appropriate metabolic changes. At the end of the fast the insulin should be nearly undetectable and ketosis should be fully established. The patient's blood glucose levels are monitored and a critical specimen is obtained if the glucose falls. Despite its unpleasantness and expense, a diagnostic fast may be the only effective way to confirm or refute a number of serious forms of hypoglycemia, especially those involving excessive insulin.

A traditional method for investigating suspected hypoglycemia is the oral glucose tolerance test, especially when prolonged to 3, 4, or 5 hours. Although quite popular in the United States in the 1960s, repeated research studies have demonstrated that many healthy people will have glucose levels below 70 or 60 during a prolonged test, and that many types of significant hypoglycemia may go undetected with it. This combination of poor sensitivity and specificity has resulted in its abandonment for this purpose by physicians experienced in disorders of glucose metabolism.

Causes

There are several ways to classify hypoglycemia. The following is a list of the more common causes and factors which may contribute to hypoglycemia grouped by age, followed by some causes that are relatively age-independent. See causes of hypoglycemia for a more complete list grouped by etiology.

HYPOglycemia in newborn infants

Hypoglycemia is a common problem in critically ill or extremely low birthweight infants. If not due to maternal hyperglycemia, in most cases it is multifactorial, transient and easily supported. In a minority of cases hypoglycemia turns out to be due to significant hyperinsulinism, hypopituitarism or an inborn error of metabolism and presents more of a management challenge.

HYPOglycemia in young children

Single episodes of hypoglycemia may occur due to gastroenteritis or fasting, but recurrent episodes nearly always indicate either an inborn error of metabolism, congenital hypopituitarism, or congenital hyperinsulinism. A list of common causes:

HYPOglycemia in older children and young adults

by far the most common cause of severe hypoglycemia in this age range is insulin injected for type 1 diabetes. Circumstances should provide clues fairly quickly for the new diseases causing severe hypoglycemia. All of the congenital metabolic defects, congenital forms of hyperinsulinism, and congenital hypopituitarism are likely to have already been diagnosed or are unlikely to start causing new hypoglycemia at this age. Body mass is large enough to make starvation hypoglycemia and idiopathic ketotic hypoglycemia quite uncommon. Recurrent mild hypoglycemia may fit a reactive hypoglycemia pattern, but this is also the peak age for idiopathic postprandial syndrome, and recurrent "spells" in this age group can be traced to orthostatic hypotension or hyperventilation as often as demonstrable hypoglycemia.

  • Insulin-induced hypoglycemia
    • Insulin injected for type 1 diabetes
    • Factitious insulin injection (Munchausen syndrome)
    • Insulin-secreting pancreatic tumor
    • Reactive hypoglycemia and idiopathic postprandial syndrome
  • Addison's disease
  • Sepsis

HYPOglycemia in older adults

The incidence of hypoglycemia due to complex drug interactions, especially involving oral hypoglycemic agents and insulin for diabetes rises with age. Though much rarer, the incidence of insulin-producing tumors also rises with advancing age. Most tumors causing hypoglycemia by mechanisms other than insulin excess occur in adults.

  • Insulin-induced hypoglycemia
    • Insulin injected for diabetes
    • Factitious insulin injection (Munchausen syndrome)
    • Excessive effects of oral diabetes drugs, beta-blockers, or drug interactions
    • Insulin-secreting pancreatic tumor
    • Alimentary (rapid jejunal emptying with exaggerated insulin response)
    • Reactive hypoglycemia and idiopathic postprandial syndrome
  • Tumor hypoglycemia, Doege-Potter syndrome
  • Acquired adrenal insufficiency
  • Acquired hypopituitarism
  • Immunopathologic hypoglycemia [13]

Treatment and prevention

Management of hypoglycemia involves immediately raising the blood sugar to normal, determining the cause, and taking measures to hopefully prevent future episodes.

Reversing acute hypoglycemia

The blood glucose can be raised to normal within minutes by taking (or receiving) 10-20 grams of carbohydrate. It can be taken as food or drink if the person is conscious and able to swallow. This amount of carbohydrate is contained in about 3-4 ounces (100-120 ml) of orange, apple, or grape juice although fruit juices contain a higher proportion of fructose which is more slowly metabolized than pure dextrose, alternatively, about 4-5 ounces (120-150 ml) of regular (non-diet) soda may also work, as will about one slice of bread, about 4 crackers, or about 1 serving of most starchy foods. Starch is quickly digested to glucose (unless the person is taking acarbose), but adding fat or protein retards digestion. Symptoms should begin to improve within 5 minutes, though full recovery may take 10-20 minutes. Overfeeding does not speed recovery and if the person has diabetes will simply produce hyperglycemia afterwards.

If a person is suffering such severe effects of hypoglycemia that they cannot (due to combativeness) or should not (due to seizures or unconsciousness) be given anything by mouth, medical personal such as EMTs and Paramedics, or in-hospital personel can establish an IV and give intravenous Dextrose, concentrations varying depending on age (Infants are given 2cc/kg Dextrose 10%, Children Dextrose 25%, and Adults Dextrose 50%). Care must be taken in giving these solutions because they can be very necrotic if the IV is infiltrated. If an IV cannot be established, the patient can be given 1 to 2 milligrams of Glucagon in an intramuscular injection. More treatment information can be found in the article diabetic hypoglycemia.

One situation where starch may be less effective than glucose or sucrose is when a person is taking acarbose. Since acarbose and other alpha-glucosidase inhibitors prevents starch and other sugars from being broken down into monosaccharides that can be absorbed by the body, patients taking these medications should consume monosaccharide-containing foods such as glucose tablets, honey, or juice to reverse hypoglycemia.

Prevention

The most effective means of preventing further episodes of hypoglycemia depends on the cause.

The risk of further episodes of diabetic hypoglycemia can often (but not always) be reduced by lowering the dose of insulin or other medications, or by more meticulous attention to blood sugar balance during unusual hours, higher levels of exercise, or alcohol intake.

Many of the inborn errors of metabolism require avoidance or shortening of fasting intervals, or extra carbohydrates. For the more severe disorders, such as type 1 glycogen storage disease, this may be supplied in the form of cornstarch every few hours or by continuous gastric infusion.

Several treatments are used for hyperinsulinemic hypoglycemia, depending on the exact form and severity. Some forms of congenital hyperinsulinism respond to diazoxide or octreotide. Surgical removal of the overactive part of the pancreas is curative with minimal risk when hyperinsulinism is focal or due to a benign insulin-producing tumor of the pancreas. When congenital hyperinsulinism is diffuse and refractory to medications, near-total pancreatectomy may be the treatment of last resort, but in this condition is less consistently effective and fraught with more complications.

Hypoglycemia due to hormone deficiencies such as hypopituitarism or adrenal insufficiency usually ceases when the appropriate hormone is replaced.

Hypoglycemia due to dumping syndrome and other post-surgical conditions is best dealt with by altering diet. Including fat and protein with carbohydrates may slow digestion and reduce early insulin secretion. Some forms of this respond to treatment with a glucosidase inhibitor, which slows starch digestion.

Reactive hypoglycemia with demonstrably low blood glucose levels is most often a predictable nuisance which can be avoided by consuming fat and protein with carbohydrates, by adding morning or afternoon snacks, and reducing alcohol intake.

Idiopathic postprandial syndrome without demonstrably low glucose levels at the time of symptoms can be more of a management challenge. Many people find improvement by changing eating patterns (smaller meals, avoiding excessive sugar, mixed meals rather than carbohydrates by themselves), reducing intake of stimulants such as caffeine, or by making lifestyle changes to reduce stress. See the following section of this article.

HYPOglycemia as American folk medicine

Hypoglycemia is also a term of contemporary American folk medicine which refers to a recurrent state of symptoms of altered mood and subjective cognitive efficiency, sometimes accompanied by adrenergic symptoms, but not necessarily by measured low blood glucose. Symptoms are primarily those of altered mood, behavior, and mental efficiency. This condition is usually treated by dietary changes which range from simple to elaborate. Advising people on management of this condition is a significant "sub-industry" of alternative medicine. More information about this form of "hypoglycemia", with far more elaborate dietary recommendations, is available on the internet and in health food stores. Most of these websites and books describe a conflation of reactive hypoglycemia and idiopathic postprandial syndrome but do not recognize a distinction. The value of most of their recommendations is unproven from a controlled, empirical scientific perspective.

References

  1. ^ Philip E. Cryer (1997). Hypoglycemia: pathophysiology, diagnosis, and treatment. Oxford [Oxfordshire]: Oxford University Press. ISBN 0-19-511325-X.
  2. ^ Koh TH, Eyre JA, Aynsley-Green A (1988). "Neonatal hypoglycaemia--the controversy regarding definition". Arch. Dis. Child. 63 (11): 1386-8. PMID 3202648.
  3. ^ Cornblath M, Schwartz R, Aynsley-Green A, Lloyd JK (1990). "Hypoglycemia in infancy: the need for a rational definition. A Ciba Foundation discussion meeting". Pediatrics 85 (5): 834-7. PMID 2330247.
  4. ^ Cornblath M, Hawdon JM, Williams AF, Aynsley-Green A, Ward-Platt MP, Schwartz R, Kalhan SC (2000). "Controversies regarding definition of neonatal hypoglycemia: suggested operational thresholds". Pediatrics 105 (5): 1141-5. doi:10.1542/peds.105.5.1141. PMID 10790476.
  5. ^ a b Tustison WA, Bowen AJ, Crampton JH (1966). "Clinical interpretation of plasma glucose values". Diabetes 15 (11): 775-7. PMID 5924610.
  6. ^ a b c [edited by] John Bernard Henry (1979). Clinical diagnosis and management by laboratory methods. Philadelphia: Saunders. ISBN 0-7216-4639-5.
  7. ^ Clarke WL, Cox D, Gonder-Frederick LA, Carter W, Pohl SL (1987). "Evaluating clinical accuracy of systems for self-monitoring of blood glucose". Diabetes Care 10 (5): 622-8. doi:10.2337/diacare.10.5.622. PMID 3677983.
  8. ^ Gama R, Anderson NR, Marks V (2000). "'Glucose meter hypoglycaemia': often a non-disease". Ann. Clin. Biochem. 37 ( Pt 5): 731-2. PMID 11026531.
  9. ^ de Pasqua A, Mattock MB, Phillips R, Keen H (1984). "Errors in blood glucose determination". Lancet 2 (8412): 1165. PMID 6150231.
  10. ^ Horwitz DL (1989). "Factitious and artifactual hypoglycemia". Endocrinol. Metab. Clin. North Am. 18 (1): 203-10. PMID 2645127.
  11. ^ Samuel Meites, editor-in-chief; contributing editors, Gregory J. Buffone... [et al.] (1989). Pediatric clinical chemistry: reference (normal) values. Washington, D.C: AACC Press. ISBN 0-915274-47-7.
  12. ^ edited by Allen I. Arieff, Robert C. Griggs (1992). Metabolic brain dysfunction in systemic disorders. Boston: Little, Brown. ISBN 0-316-05067-9.
  13. ^ The Hypoglycemic states - Hypoglycemia. The Hypoglycemic states. Armenian Medical Network (2007).

See also

External links


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