Diabetic hypoglycemia
Encyclopedia
Diabetic hypoglycemia is a low blood glucose level
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"...

 occurring in a person 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...

. It is one of the most common types of 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"...

 seen in emergency department
Emergency department
An emergency department , also known as accident & emergency , emergency room , emergency ward , or casualty department is a medical treatment facility specialising in acute care of patients who present without prior appointment, either by their own means or by ambulance...

s and 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. According to the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP), and based on a sample examined between 2004 and 2005, an estimated 55,819 cases (8.0% of total admissions) involved insulin, and severe hypoglycemia is likely the single most common event.

In general, hypoglycemia occurs when a treatment to lower the elevated blood glucose of diabetes inaccurately matches the body's physiological need, and therefore causes the glucose to fall to a below-normal level.

Etiology

Diabetic hypoglycemia can occur in any person with diabetes who takes any medicine to lower their blood glucose, but severe hypoglycemia occurs most often in people with type 1 diabetes who must take insulin for survival. In type 1 diabetes, iatrogenic hypoglycemia is more appropriately viewed as the result of the interplay of insulin excess and compromised glucose counterregulation rather than as absolute or relative insulin excess alone. Hypoglycemia can also be caused by sulfonylurea
Sulfonylurea
Sulfonylurea derivatives are a class of antidiabetic drugs that are used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta cells in the pancreas.-First generation:* Carbutamide...

s in people with type 2 diabetes, although it is far less common because glucose counterregulation generally remains intact in people with type 2 diabetes. Severe hypoglycemia rarely, if ever, occurs in people with diabetes treated only with diet, exercise, or insulin sensitizers.

For people with insulin-requiring diabetes, hypoglycemia is one of the recurrent hazards of treatment. It limits the achievability of normal glucoses with current treatment methods. Hypoglycemia is a true medical emergency, which requires prompt recognition and treatment to prevent organ and brain damage.

Definition, manifestations and recognition

A commonly used "number" to define the lower limit of normal glucose is 70 mg/dl (3.9 mmol/l), though in someone with diabetes, hypoglycemic symptoms can sometimes occur at higher glucose levels, or may fail to occur at lower. Some textbooks for nursing and pre-hospital care use the range 80 mg/dl to 120 mg/dl (4.4 mmol/l to 6.7 mmol/l). This variability is further compounded by the imprecision of glucose meter
Glucose meter
A glucose meter is a medical device for determining the approximate concentration of glucose in the blood. It is a key element of home blood glucose monitoring by people with diabetes mellitus or hypoglycemia...

 measurements at low levels, or the ability of glucose levels to change rapidly.

Diabetic hypoglycemia can be mild, recognized easily by the patient, and reversed with a small amount of carbohydrate
Carbohydrate
A 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 drunk, or it may be severe enough to cause unconsciousness requiring intravenous dextrose or an injection of glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

. Severe hypoglycemic unconsciousness is one form of diabetic coma
Diabetic coma
Diabetic coma is a reversible form of coma found in people with diabetes mellitus. It is a medical emergency.Three different types of diabetic coma are identified:#Severe diabetic hypoglycemia...

. A common medical definition of severe hypoglycemia is "hypoglycemia severe enough that the person needs assistance in dealing with it." A co-morbidity is the issue of hypoglycemia unawareness.

Symptom
Symptom
A symptom is a departure from normal function or feeling which is noticed by a patient, indicating the presence of disease or abnormality...

s of diabetic hypoglycemia, when they occur, are those of 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"...

: neuroglycopenic
Neuroglycopenia
Neuroglycopenia is a medical term that refers to a shortage of glucose in the brain, usually due to hypoglycemia. Glycopenia affects the function of neurons, and alters brain function and behavior...

, adrenergic
Adrenergic
An adrenergic agent is a drug, or other substance, which has effects similar to, or the same as, epinephrine . Thus, it is a kind of sympathomimetic agent...

, and abdominal. Symptoms and effects can be mild, moderate or severe, depending on how low the glucose falls and a variety of other factors. It is rare but possible for diabetic hypoglycemia to result in brain damage or death. Indeed, an estimated 2-4% of deaths of people with type 1 diabetes mellitus have been attributed to hypoglycemia.

In North America a mild episode of diabetic hypoglycemia is sometimes termed a "low" or an "insulin reaction," and in Europe a "hypo", although all of these terms are occasionally used interchangeably in North America, Europe, Australia and New Zealand. A severe episode is sometimes also referred to as "insulin shock".

In a counter-intuitive manifestation, hypoglycemia can trigger a Somogyi effect
Chronic Somogyi rebound
Chronic Somogyi rebound, also called the Somogyi effect and posthypoglycemic hyperglycemia, is a rebounding high blood sugar that is a response to low blood sugar...

, resulting in a rebounding high blood sugar
Blood sugar
The blood sugar concentration or blood glucose level is the amount of glucose present in the blood of a human or animal. Normally in mammals, the body maintains the blood glucose level at a reference range between about 3.6 and 5.8 mM , or 64.8 and 104.4 mg/dL...

 or 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...

.

Oral intake of glucose

The blood glucose can usually be raised to normal within minutes with 15-20 grams of carbohydrate
Carbohydrate
A 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...

, although overtreatment should be avoided if at all possible. 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, about 4-5 ounces (120-150 mL) of regular (non-diet) soda, about one slice of bread, about 4 crackers, or about 1 serving of most starchy foods. Starch
Starch
Starch or amylum is a carbohydrate consisting of a large number of glucose units joined together by glycosidic bonds. This polysaccharide is produced by all green plants as an energy store...

 is quickly digested to glucose, but adding fat or protein retards digestion. Composition of the treatment should be considered, as fruit juice is typically higher in fructose which takes the body longer to metabolize than simple dextrose alone. Following treatment, symptoms should begin to improve within 5 to 10 minutes, although full recovery may take 10–20 minutes. It should be noted that over treatment does not speed recovery, and will simply produce hyperglycemia afterwards, which ultimately will need to be corrected.

Intravenous glucose

If a person cannot receive oral glucose gel or tablets, such as the case with unconsciousness, seizures, or altered mental status, then emergency personal (EMTs/Paramedics and in-hospital personnel) can establish a peripheral or central IV line and administer a solution containing dextrose and saline. These are normally referred to as Dextrose (Concentration) Water, and come in 5%, 10%, 25% and 50%. Dextrose 5% and 10% come in IV bag and syringe form, and are mainly used in infants and to provide a fluid medium for medications. D10W is given at a 2cc/kg rate for Neonates and Infants. Dextrose 25% is given in children under the age of 8, and Dextrose 50% is given in adults. The Dosage for D50W is one half of the ampule, with verification of IV patency after the half of the amp is given, and a recheck of blood glucose levels before administering the other half. Dextrose 25% and 50% are heavily necrotic due to their hyperosmolarity, and should only be given through a patent IV line - Any infiltration can cause massive tissue necrosis.

Glucagon

Glucagon
Glucagon
Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

 is a hormone that rapidly counters the metabolic effects of insulin in the liver, causing glycogenolysis
Glycogenolysis
Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...

 and release of glucose into the blood. It can raise the glucose by 30–100 mg/dL within minutes in any form of hypoglycemia caused by insulin excess (including all types of diabetic hypoglycemia). It comes in a glucagon emergency rescue kit
Glucagon rescue
Glucagon rescue is the emergency injection of glucagon in case of severe diabetic hypoglycemia. It is needed during seizures and/or unconsciousness by an insulin user who is unable at that point to help themselves...

 which includes tiny vials containing 1 mg, which is a standard adult dose. The glucagon in the vial is a lyophilized pellet, which must be reconstituted with 1 ml of sterile water, included in the "kit". In the widely used Lilly
Eli Lilly and Company
Eli Lilly and Company is a global pharmaceutical company. Eli Lilly's global headquarters is located in Indianapolis, Indiana, in the United States...

 Emergency Kit, the water is contained in a syringe with a large needle for intramuscular injection and must be injected into the vial with the pellet of glucagon before being injected. Glucagon works if given subcutaneously, but absorption and recovery are faster if it is injected deep into a muscle (usually the middle of the outside of the thigh). It has an even more rapid effect when given intravenously but this is rarely practicable. Side effects of glucagon can include nausea and headache, but these can also occur after severe hypoglycemia even when glucagon is not used. Risks of glucagon use are far lower than risks of severe hypoglycemia, and it can usually produce a faster recovery than calling for paramedics and waiting for them to start an intravenous line to give dextrose. If someone uses this kit, they should be seen in an emergency room, as glucagon depletes glycogen
Glycogen
Glycogen is a molecule that serves as the secondary long-term energy storage in animal and fungal cells, with the primary energy stores being held in adipose tissue...

 stores, and can lead to a deadly rebound hypoglycemia.

In the United States, normal use of this kit in the out-of-hospital setting is restricted to EMS units carrying paramedics (EMTs in some states can use glucagon, but most require very specific training to do so).

GlucaPen, an autoinjector in development by Enject, Inc. promises to simplify the delivery of glucagon in a manner similar to EpiPen

Hypoglycemic unawareness

Although one expects hypoglycemic episodes to be accompanied by the typical symptoms (e.g., tremor, sweating, palpitations, etc.), this is not always the case. When hypoglycemia occurs in the absence of such symptoms it is called hypoglycemic unawareness. Especially in people with long-standing type 1 diabetes and those who attempt to maintain glucose levels which are closer to normal, hypoglycemic unawareness is common.

In patients with type 1 diabetes mellitus, as plasma glucose levels fall, insulin levels do not decrease - they are simply a passive reflection of the absorption of exogenous insulin. Also, glucagon levels do not increase. Therefore, the first and second defenses against hypoglycemia are already lost in established type 1 diabetes mellitus. Further, the epinephrine
Epinephrine
Epinephrine is a hormone and a neurotransmitter. It increases heart rate, constricts blood vessels, dilates air passages and participates in the fight-or-flight response of the sympathetic nervous system. In chemical terms, adrenaline is one of a group of monoamines called the catecholamines...

 response is typically attenuated, i.e., the glycemic threshold for the epinephrine response is shifted to lower plasma glucose concentrations, which can be aggravated by previous incidents of hypoglycemia.

The following factors contribute to hypoglycemic unawareness:

a) there may be autonomic neuropathy

b) the brain may have become desensitized to hypoglycemia

c) the person may be using medicines which mask the hypoglycemic symptoms

a) Autonomic neuropathy: During hypoglycemia, the body normally releases epinephrine [more commonly known as adrenalin] and related substances. This serves two purposes: The β-effect of epinephrine is responsible for the palpitations and tremors, giving the patient warning that hypoglycemia is present. The β-effect of epinephrine also stimulates the liver to release glucose (gluconeogenesis
Gluconeogenesis
Gluconeogenesis is a metabolic pathway that results in the generation of glucose from non-carbohydrate carbon substrates such as lactate, glycerol, and glucogenic amino acids....

 and glycogenolysis
Glycogenolysis
Glycogenolysis is the conversion of glycogen polymers to glucose monomers. Glycogen is catabolized by removal of a glucose monomer through cleavage with inorganic phosphate to produce glucose-1-phosphate...

). In other words, the epinephrine warns the patient that hypoglycemia is present and signals the liver to release glucose to reverse it. In the absence of epinephrine release, or when it is attenuated (reduced) during hypoglycemia, the patient may not be aware that his/her glucose level is low. This is termed 'hypoglycemic unawareness'. The problem is compounded since, in the absence of an appropriate epinephrine response, the usual responses of glycogenolysis and gluconeogenesis may also be lost or blunted.

Since epinephrine release is a function of the autonomic nervous system
Autonomic nervous system
The autonomic nervous system is the part of the peripheral nervous system that acts as a control system functioning largely below the level of consciousness, and controls visceral functions. The ANS affects heart rate, digestion, respiration rate, salivation, perspiration, diameter of the pupils,...

, the presence of autonomic neuropathy (i.e., a damaged autonomic nervous system) will cause the epinephrine release in response to hypoglycemia to be lost or blunted. Unfortunately, damage to the autonomic nervous system in the form of autonomic neuropathy is a common complication of long-standing diabetes (especially type 1 diabetes), so the presence of hypoglycemic unawareness may be a sign of autonomic neuropathy, although the autonomic response to hypoglycemia is already impaired in patients with type 1 diabetes mellitus even in the absence of autonomic neuropathy.

Because the autonomic response is, in effect, the body's backup system for responding to hypoglycemia, patients with type 1 diabetes are forced to rely almost exclusively on a backup system for protection, which can unfortunately, deteriorate over time. The reduced autonomic response (including the sympathetic neural norepinephrine and acetylcholine as well as the adrenomedullary epinephrine response) causes the clinical syndrome of hypoglycemia unawareness — loss of the largely neurogenic warning symptoms of developing hypoglycemia.

b) Brain desensitization to hypoglycemia: If a person has frequent episodes of hypoglycemia (even mild ones), the brain becomes "used to" the low glucose and no longer signals for adrenalin to be released during such times. More specifically, there are glucose transporter
Glucose transporter
Glucose transporters are a wide group of membrane proteins that facilitate the transport of glucose over a plasma membrane. Because glucose is a vital source of energy for all life these transporters are present in all phyla...

s located in the brain cells (neurons). These transporters increase in number in response to repeated hypoglycemia (this permits the brain to receive a steady supply of glucose even during hypoglycemia). As a result, what was once the hypoglycemic threshold for the brain to signal adrenalin release becomes lower. Epinephrine is not released, if at all, until the blood glucose level has dropped to even lower levels. Clinically, the result is hypoglycemic unawareness.

Since repeated hypoglycemia is common in people with diabetes who strive to keep their glucose levels near normal, the incidence of hypoglycemic unawareness becomes more prevalent in patients who follow 'intensive treatment' protocols.

The most common treatment for this condition is to liberalize the patient's target glucose levels, in an attempt to decrease the frequency of hypoglycemic episodes. Hypoglycemic unawareness will sometimes disappear when the frequency of hypoglycemic episodes has declined, but this is not always the case.

Blood Glucose Awareness Training (BGAT)

Researchers at University of Virginia Health Sciences Center have developed a psychoeducational program that helps patients identify their blood glucose symptoms more accurately, better predict when hypoglycemia is more likely to occur, and then treat hypoglycemia earlier than they might if they were relying exclusively on blunted autonomic symptoms alone. The program, called Blood glucose awareness training (BGAT), is designed to improve the accuracy of patients' detection and interpretation of relevant BG symptoms and other cues. Unfortunately, awareness of these treatments among certified diabetes educators is surprisingly low, and awareness of the program is not even required to attain certification. The reasons for this are multi-faceted, but a frequent criticism is the fact that a disproportionate share of the certification training is dedicated to issues related to the more common type 2 diabetes. Also, BGAT training is more complex, and requires considerable effort on the part of educators, and many may not view it as justified given the proportion of patients who have type 1 diabetes.

An online version of BGAT has been developed and was being tested, but is expected to be functional in the not-too-distant future. It is called BGAThome, and may bring this useful training program to more people in the future.

c) Beta blocker
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...

 drugs:
These medicines are designed to blunt the β-effect of adrenalin and related substances. Hence, if hypoglycemia occurs in someone who is using this type of drug, he/she may not experience the typical adrenergic warning symptoms such as tremor and palpitations. Again, the result is hypoglycemic unawareness. As noted above, beta blockers will also prevent adrenalin from stimulating the liver to make glucose, and therefore may make the hypoglycemia more severe and/or more protracted. Of all the hypoglycemia symptoms, sweating is typically not blocked by beta blockers.

Animals that can detect hypoglycemia

There has been considerable controversy about whether animals such as dogs can detect hypoglycemia in their diabetic owners, and such reports do occasionally surface in the popular media. In 2008, the UK charity Diabetes UK
Diabetes UK
Diabetes UK is a patient, healthcare professional and research charity dedicated to improving the lives of people with diabetes and to working towards a future without the chronic condition diabetes....

 announced that they were helping to fund a project, performed by researchers at Queen's University Belfast and the University of Lincoln
University of Lincoln
The University of Lincoln is an English university founded in 1992, with origins tracing back to the foundation and association with the Hull School of Art 1861....

, looking at whether dogs really can detect hypoglycemia. This research is being conducted under the supervision of Deborah Wells, at Queen's University Belfast. A report on the project can be found in the Diabetes UK magazine Balance. This article quotes Wells as saying that dogs' acute sense of smell may help them to detect low blood sugar.

Some four years earlier, Alyson Jones had an article published in Balance, discussing this topic. This article cited a research study which suggested that over a third of dogs living with people with diabetes would show behavioural changes when their owner's blood sugar level had dropped to hypoglycemic levels. One suggestion was that dogs could be picking up on pheromones, given that sweating can be a sign of early hypoglycemia; a suggestion made by Chris Laurence, the then veterinary director of the Dogs Trust (formerly the National Canine Defence League). However, the article warned that there was no guarantee that dogs would always detect hypos and that "people with diabetes should not rely on their pets for this".

Dogs have been trained to alert their owner when the owner's blood sugar level is off.

See also

  • Diabetic coma
    Diabetic coma
    Diabetic coma is a reversible form of coma found in people with diabetes mellitus. It is a medical emergency.Three different types of diabetic coma are identified:#Severe diabetic hypoglycemia...

  • Glucagon
    Glucagon
    Glucagon, a hormone secreted by the pancreas, raises blood glucose levels. Its effect is opposite that of insulin, which lowers blood glucose levels. The pancreas releases glucagon when blood sugar levels fall too low. Glucagon causes the liver to convert stored glycogen into glucose, which is...

  • Glucagon rescue
    Glucagon rescue
    Glucagon rescue is the emergency injection of glucagon in case of severe diabetic hypoglycemia. It is needed during seizures and/or unconsciousness by an insulin user who is unable at that point to help themselves...

  • 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"...

  • Diabetic hypoglycemia journal
  • Chronic Somogyi rebound
    Chronic Somogyi rebound
    Chronic Somogyi rebound, also called the Somogyi effect and posthypoglycemic hyperglycemia, is a rebounding high blood sugar that is a response to low blood sugar...

  • Medical response dog
    Medical response dog
    A medical response dog is a specific type of service dog specifically trained to help mitigate an individual's medical disability. Typically, they are dogs whose job does not handle primarily epilepsy or psychiatric-based conditions, though some seizure response dogs or psychiatric service dogs may...

  • Hypo alert dog
    Hypo alert dog
    A hypo alert dog is a type of assistance dog trained to provide alerts to their diabetic owners when their blood sugar levels start to become hypoglycemic and sometimes hyperglycemic also.-Description:...


External links

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