Hypoglycemia
Encyclopedia
Hypoglycemia or hypoglycæmia (not to be confused with 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...

) is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood" (Gr.
Greek language
Greek is an independent branch of the Indo-European family of languages. Native to the southern Balkans, it has the longest documented history of any Indo-European language, spanning 34 centuries of written records. Its writing system has been the Greek alphabet for the majority of its history;...

 υπογλυκαιμία, from hypo-, glykys, haima). It can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose
Glucose
Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

 to the brain
Human brain
The human brain has the same general structure as the brains of other mammals, but is over three times larger than the brain of a typical mammal with an equivalent body size. Estimates for the number of neurons in the human brain range from 80 to 120 billion...

, resulting in impairment of function (neuroglycopenia
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...

). Effects can range from mild dysphoria
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...

 to more serious issues such as seizures, unconsciousness
Unconsciousness
Unconsciousness is the condition of being not conscious—in a mental state that involves complete or near-complete lack of responsiveness to people and other environmental stimuli. Being in a comatose state or coma is a type of unconsciousness. Fainting due to a drop in blood pressure and a...

, and (rarely) permanent brain damage
Brain damage
"Brain damage" or "brain injury" is the destruction or degeneration of brain cells. Brain injuries occur due to a wide range of internal and external factors...

 or death
Death
Death is the permanent termination of the biological functions that sustain a living organism. Phenomena which commonly bring about death include old age, predation, malnutrition, disease, and accidents or trauma resulting in terminal injury....

.

The most common forms of hypoglycemia occur as a complication of treatment of 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...

 with insulin
Insulin
Insulin is a hormone central to regulating carbohydrate and fat metabolism in the body. Insulin causes cells in the liver, muscle, and fat tissue to take up glucose from the blood, storing it as glycogen in the liver and muscle....

 or oral medications. Hypoglycemia is less common in non-diabetic persons, but can occur at any age. Among the causes are excessive insulin
Hyperinsulinism
Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal. Normal insulin secretion and blood levels are closely related to the level of glucose in the blood, so that a given level of insulin can be normal for one blood glucose level but low or high for another...

 produced in the body (hyperinsulinemia
Hyperinsulinemia
Hyperinsulinemia, or hyperinsulinaemiais a condition which there is excess levels of insulin circulating in the blood than expected relative to the level of glucose. While it is often mistaken for diabetes or hypoglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and...

), inborn errors of metabolism, medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

s and poison
Poison
In the context of biology, poisons are substances that can cause disturbances to organisms, usually by chemical reaction or other activity on the molecular scale, when a sufficient quantity is absorbed by an organism....

s, alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....

, hormone
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 deficiencies, prolonged starvation
Starvation
Starvation is a severe deficiency in caloric energy, nutrient and vitamin intake. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, death...

, alterations of metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 associated with infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...

, and organ failure.

Hypoglycemia is treated by restoring the blood glucose level to normal by the ingestion or administration of dextrose or carbohydrate foods. In more severe circumstances it is treated by injection or infusion 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...

. Recurrent hypoglycemia may be prevented by reversing or removing the underlying cause, by increasing the frequency of meal
Meal
A meal is an instance of eating, specifically one that takes place at a specific time and includes specific, prepared food.Meals occur primarily at homes, restaurants, and cafeterias, but may occur anywhere. Regular meals occur on a daily basis, typically several times a day...

s, with medication
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...

s like diazoxide
Diazoxide
Diazoxide is a potassium channel activator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions...

, octreotide
Octreotide
Octreotide is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone...

, or glucocorticoid
Glucocorticoid
Glucocorticoids are a class of steroid hormones that bind to the glucocorticoid receptor , which is present in almost every vertebrate animal cell...

s, or by surgical
Surgery
Surgery is an ancient medical specialty that uses operative manual and instrumental techniques on a patient to investigate and/or treat a pathological condition such as disease or injury, or to help improve bodily function or appearance.An act of performing surgery may be called a surgical...

 removal of much of the pancreas
Pancreas
The pancreas is a gland organ in the digestive and endocrine system of vertebrates. It is both an endocrine gland producing several important hormones, including insulin, glucagon, and somatostatin, as well as a digestive organ, secreting pancreatic juice containing digestive enzymes that assist...

.

The level of blood glucose low enough to define hypoglycemia may be different for different people, in different circumstances, and for different purposes, and occasionally has been a matter of controversy. Most healthy adults maintain fasting
Fasting
Fasting is primarily the act of willingly abstaining from some or all food, drink, or both, for a period of time. An absolute fast is normally defined as abstinence from all food and liquid for a defined period, usually a single day , or several days. Other fasts may be only partially restrictive,...

 glucose levels above 4.0 mmol/L (72 mg/dl), and develop symptoms of hypoglycemia when the glucose falls below 4 mmol/L. It can sometimes be difficult to determine whether a person's symptoms are due to hypoglycemia. Criteria referred to as Whipple's triad
Whipple's triad
Whipple's triad is a collection of three criteria that suggest a patient's symptoms result from hypoglycemia that may indicate insulinoma...

 are used to determine a diagnosis of 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


Hypoglycemia (common usage)
Hypoglycemia (common usage)
In modern Western culture, "hypoglycemia" has taken on a colloquial meaning distinct from the medical condition of that name. Whereas the medical usage is defined by measurable low blood glucose, this common usage is used to describe a condition characterized by shakiness, moodiness, brain fog,...

 is also a term in popular culture and alternative medicine
Alternative medicine
Alternative medicine is any healing practice, "that does not fall within the realm of conventional medicine." It is based on historical or cultural traditions, rather than on scientific evidence....

 for a common, often self-diagnosed, condition characterized by shakiness and altered mood and thinking, but without measured low glucose or risk of severe harm. It is treated by changing eating patterns.

Definition

In those treated for diabetes a diagnosis of hypoglycemia can be made based on the presence of a low blood sugar alone. Otherwise Whipple's triad is required which include symptoms consistent with hypoglycemia, a low blood sugar, and resolution of these symptoms once the blood sugar improves.

Throughout a 24 hour period blood plasma glucose levels are generally maintained between 4-8 mmol/L (72 and 144 mg/dL). Although 3.3 or 3.9 mmol/L (60 or 70 mg/dL) is commonly cited as the lower limit of normal glucose, symptoms of hypoglycemia usually do not occur until 2.8 to 3.0 mmol/L.(50 to 54 mg/dl)

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.

Glucose concentrations are expressed as milligrams per deciliter (mg/dL or mg/100 mL) in the United States, Japan, Spain, France, Belgium, Egypt, Saudi Arabia and Colombia, while millimoles per liter
Litér
- External links :*...

 (mmol/L or mM) are the 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/dmol (the molar mass
Molar mass
Molar mass, symbol M, is a physical property of a given substance , namely its mass per amount of substance. The base SI unit for mass is the kilogram and that for amount of substance is the mole. Thus, the derived unit for molar mass is kg/mol...

 of glucose). For example, a glucose concentration of 90 mg/dL is 5.0 mmol/L or 5.0 mM.

Method of measurement

Blood glucose levels discussed in this article are venous
Vein
In the circulatory system, veins are blood vessels that carry blood towards the heart. Most veins carry deoxygenated blood from the tissues back to the heart; exceptions are the pulmonary and umbilical veins, both of which carry oxygenated blood to the heart...

 plasma or serum
Blood plasma
Blood plasma is the straw-colored liquid component of blood in which the blood cells in whole blood are normally suspended. It makes up about 55% of the total blood volume. It is the intravascular fluid part of extracellular fluid...

 levels measured by standard, automated glucose oxidase
Glucose oxidase
The glucose oxidase enzyme is an oxido-reductase that catalyses the oxidation of glucose to hydrogen peroxide and D-glucono-δ-lactone. In cells, it aids in breaking the sugar down into its metabolites....

 methods used in medical laboratories
Medical laboratory
A medical laboratory or clinical laboratory is a laboratory where tests are done on clinical specimens in order to get information about the health of a patient as pertaining to the diagnosis, treatment, and prevention of disease.-Departments:...

. For clinical purposes, plasma and serum levels are similar enough to be interchangeable. Arterial
Artery
Arteries are blood vessels that carry blood away from the heart. This blood is normally oxygenated, exceptions made for the pulmonary and umbilical arteries....

 plasma or serum levels are slightly higher than venous levels, and capillary
Capillary
Capillaries are the smallest of a body's blood vessels and are parts of the microcirculation. They are only 1 cell thick. These microvessels, measuring 5-10 μm in diameter, connect arterioles and venules, and enable the exchange of water, oxygen, carbon dioxide, and many other nutrient and waste...

 levels are typically in between. 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. On the other hand, whole blood glucose levels (e.g., by fingerprick meters
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...

) are about 10%-15% lower than venous plasma levels. 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. 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.

Two other factors significantly affect glucose measurement: hematocrit
Hematocrit
The hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...

 and delay after blood drawing
Phlebotomy
Phlebotomy is the process of making an incision in a vein.It is associated with the following concepts:* Venipuncture, the practice of collecting venous blood samples* The main practice of a phlebotomist, an individual trained to draw blood...

. The disparity between venous and whole blood concentrations is greater when the hematocrit is high, as in newborn infants, or adults with polycythemia
Polycythemia
Polycythemia is a disease state in which the proportion of blood volume that is occupied by red blood cells increases...

. High neonatal hematocrits are particularly likely to confound glucose measurement by meter. Second, unless the specimen is drawn into a fluoride
Sodium fluoride
Sodium fluoride is an inorganic chemical compound with the formula NaF. A colorless solid, it is a source of the fluoride ion in diverse applications. Sodium fluoride is less expensive and less hygroscopic than the related salt potassium 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
Leukocytosis
Leukocytosis is a raised white blood cell count above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, and is observed in certain parasitic infections...

. The delay that occurs when blood is drawn at a satellite site and transported to a central laboratory hours later for routine processing is a common cause of mildly low glucose levels in general chemistry panels.

Age differences

Children's blood sugar levels are often slightly lower than adults'. Overnight fasting glucose levels are below 70 mg/dL (3.9 mM) in 5% of healthy adults, but up to 5% of children can be below 60 mg/dL (3.3 mM) in the morning fasting state. As the duration of fasting is extended, a higher percentage of infants and children will have mildly low plasma glucose levels, usually without symptoms. The normal range of newborn blood sugars continues to be debated. 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 the first day after birth.

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
Hormone
A hormone is a chemical released by a cell or a gland in one part of the body that sends out messages that affect cells in other parts of the organism. Only a small amount of hormone is required to alter cell metabolism. In essence, it is a chemical messenger that transports a signal from one...

 defense mechanisms (adrenaline and 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...

) are normally activated as it drops below a threshold level (about 55 mg/dL (3.0 mM) for most people), producing the typical hypoglycemic symptoms of shakiness and dysphoria
Dysphoria
Dysphoria is medically recognized as a mental and emotional condition in which a person experiences intense feelings of depression, discontent and indifference to the world around them.Mood disorders can induce dysphoria, often with a heightened risk of suicide, especially in...

. Obvious impairment may not occur until the glucose falls below 40 mg/dL (2.2 mM), and many healthy people may occasionally have glucose levels below 65 in the morning without apparent effects. Since the brain effects of hypoglycemia, termed neuroglycopenia
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...

, determine whether a given low glucose is a "problem" for that person, most doctors use the term hypoglycemia only when a moderately low glucose level is accompanied by symptoms or brain effects.

Determining the presence of both parts of this definition is not always straightforward, as hypoglycemic symptoms and effects are vague and can be produced by other conditions; people with recurrently low glucose levels can lose their threshold symptoms so that severe neuroglycopenic impairment can occur without much warning, and many measurement methods (especially glucose meters) are imprecise at low levels.

Diabetic hypoglycemia
Diabetic hypoglycemia
Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals...

 represents a special case with respect to the relationship of measured glucose and hypoglycemic symptoms for several reasons. First, although home glucose meter readings are often misleading, the probability that a low reading, whether accompanied by symptoms or not, represents real hypoglycemia is much higher in a person who takes insulin than in someone who does not. Second, because injected insulin cannot be "turned off," diabetic hypoglycemia has a greater chance of progressing to serious impairment if not treated, compared to most other forms of hypoglycemia. Third, because glucose levels are often above normal for long periods of time (hours, days, or months) in persons with diabetes, hypoglycemic symptoms may sometimes occur at higher thresholds than in people whose blood sugar is usually normal. For all of these reasons, higher meter glucose thresholds are often considered "hypoglycemic" in people with diabetes.

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. Because of all of the statistical and measurement variations listed above, the Endocrine Society recommends that a diagnosis of hypoglycemia as problem for an individual person be based on the combination of a low glucose level and evidence of adverse effects.

Signs and symptoms

Hypoglycemic symptoms and manifestations can be divided into those produced by the counterregulatory hormones (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...

/adrenaline and glucagon) triggered by the falling glucose, and the neuroglycopenic effects produced by the reduced brain sugar.

Adrenergic manifestations

  • Shakiness, anxiety
    Anxiety
    Anxiety is a psychological and physiological state characterized by somatic, emotional, cognitive, and behavioral components. The root meaning of the word anxiety is 'to vex or trouble'; in either presence or absence of psychological stress, anxiety can create feelings of fear, worry, uneasiness,...

    , nervousness
  • Palpitation
    Palpitation
    A palpitation is an abnormality of heartbeat that causes a conscious awareness of its beating, whether it is too slow, too fast, irregular, or at its normal frequency. The word may also refer to this sensation itself...

    s, tachycardia
    Tachycardia
    Tachycardia comes from the Greek words tachys and kardia . Tachycardia typically refers to a heart rate that exceeds the normal range for a resting heart rate...

  • Sweat
    SWEAT
    SWEAT is an OLN/TSN show hosted by Julie Zwillich that aired in 2003-2004.Each of the 13 half-hour episodes of SWEAT features a different outdoor sport: kayaking, mountain biking, ice hockey, beach volleyball, soccer, windsurfing, rowing, Ultimate, triathlon, wakeboarding, snowboarding, telemark...

    ing, feeling of warmth (although sweat glands have muscarinic receptors, thus "adrenergic manifestations" is not entirely accurate)
  • Pallor
    Pallor
    Pallor is a reduced amount of oxyhaemoglobin in skin or mucous membrane, a pale color which can be caused by illness, emotional shock or stress, stimulant use, lack of exposure to sunlight, anaemia or genetics....

    , coldness, clamminess
  • Dilated pupils (mydriasis)
  • Feeling of numbness "pins and needles
    Paresthesia
    Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...

    " (paresthesia)

Glucagon manifestations

  • Hunger
    Hunger (motivational state)
    Hunger is a sensation experienced when one is required to eat food. In contrast Satiety is the absence of hunger; it is the sensation of feeling full. Appetite is another sensation experienced with eating, however, it differs from hunger; it is the desire to eat food without a physiological need...

    , borborygmus
    Borborygmus
    Borborygmus also known as stomach growling, rumbling, gurgling, grumbling or wambling, is the rumbling sound produced by the contraction of muscles in the stomach and intestines of animals, including humans...

  • Nausea
    Nausea
    Nausea , is a sensation of unease and discomfort in the upper stomach with an involuntary urge to vomit. It often, but not always, precedes vomiting...

    , vomiting, abdominal discomfort
    Abdominal pain
    Abdominal pain can be one of the symptoms associated with transient disorders or serious disease. Making a definitive diagnosis of the cause of abdominal pain can be difficult, because many diseases can result in this symptom. Abdominal pain is a common problem...

  • Headache
    Headache
    A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...


Neuroglycopenic manifestations

  • Abnormal mentation, impaired judgment
  • Nonspecific dysphoria, moodiness, depression, crying, exaggerated concerns
  • Negativism, irritability, belligerence, combativeness, rage
    Rage (emotion)
    Rage is a feeling of intense anger. It is associated with the Fight-or-flight response and oftentimes activated in response to an external cue, such as the murder of a loved one. The phrase, 'thrown into a fit of rage,' expresses the immediate nature of rage that occurs before deliberation. If left...

  • Personality change, emotional lability
  • Fatigue
    Fatigue (physical)
    Fatigue is a state of awareness describing a range of afflictions, usually associated with physical and/or mental weakness, though varying from a general state of lethargy to a specific work-induced burning sensation within one's muscles...

    , weakness, apathy, lethargy, daydreaming, sleep
    Sleep
    Sleep is a naturally recurring state characterized by reduced or absent consciousness, relatively suspended sensory activity, and inactivity of nearly all voluntary muscles. It is distinguished from quiet wakefulness by a decreased ability to react to stimuli, and is more easily reversible than...

  • Confusion, amnesia
    Amnesia
    Amnesia is a condition in which one's memory is lost. The causes of amnesia have traditionally been divided into categories. Memory appears to be stored in several parts of the limbic system of the brain, and any condition that interferes with the function of this system can cause amnesia...

    , dizziness, delirium
    Delirium
    Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...

  • Staring, "glassy" look, blurred vision, double vision
    Diplopia
    Diplopia, commonly known as double vision, is the simultaneous perception of two images of a single object that may be displaced horizontally, vertically, or diagonally in relation to each other...

  • Flashes of light in the field of vision
  • Automatic behavior, also known as automatism
  • Difficulty speaking, slurred speech
  • Ataxia
    Ataxia
    Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...

    , incoordination, sometimes mistaken for "drunkenness
    Drunkenness
    Alcohol intoxication is a physiological state that occurs when a person has a high level of ethanol in his or her blood....

    "
  • Focal or general motor deficit, paralysis
    Paralysis
    Paralysis is loss of muscle function for one or more muscles. Paralysis can be accompanied by a loss of feeling in the affected area if there is sensory damage as well as motor. A study conducted by the Christopher & Dana Reeve Foundation, suggests that about 1 in 50 people have been diagnosed...

    , hemiparesis
    Hemiparesis
    Hemiparesis is weakness on one side of the body. It is less severe than hemiplegia - the total paralysis of the arm, leg, and trunk on one side of the body. Thus, the patient can move the impaired side of his body, but with reduced muscular strength....

  • Paresthesia
    Paresthesia
    Paresthesia , spelled "paraesthesia" in British English, is a sensation of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. It is more generally known as the feeling of "pins and needles" or of a limb "falling asleep"...

    , headache
    Headache
    A headache or cephalalgia is pain anywhere in the region of the head or neck. It can be a symptom of a number of different conditions of the head and neck. The brain tissue itself is not sensitive to pain because it lacks pain receptors. Rather, the pain is caused by disturbance of the...

  • Stupor, coma, abnormal breathing
  • Generalized or focal seizure
    Seizure
    An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

    s


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 also vary by age, by severity of the hypoglycemia and the speed of the decline. In young children, vomiting can sometimes accompany morning hypoglycemia with ketosis
Ketosis
Ketosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...

. In older children and adults, moderately severe hypoglycemia can resemble mania
Mania
Mania, the presence of which is a criterion for certain psychiatric diagnoses, is a state of abnormally elevated or irritable mood, arousal, and/ or energy levels. In a sense, it is the opposite of depression...

, mental illness, drug intoxication, or drunkenness. In the elderly, hypoglycemia can produce focal stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...

-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, as well as previous incidence.

In newborns, hypoglycemia can produce irritability, jitters, myoclonic jerks, cyanosis
Cyanosis
Cyanosis is the appearance of a blue or purple coloration of the skin or mucous membranes due to the tissues near the skin surface being low on oxygen. The onset of cyanosis is 2.5 g/dL of deoxyhemoglobin. The bluish color is more readily apparent in those with high hemoglobin counts than it is...

, respiratory distress, apneic
Apnea
Apnea, apnoea, or apnœa is a term for suspension of external breathing. During apnea there is no movement of the muscles of respiration and the volume of the lungs initially remains unchanged...

 episodes, sweating, hypothermia
Hypothermia
Hypothermia is a condition in which core temperature drops below the required temperature for normal metabolism and body functions which is defined as . Body temperature is usually maintained near a constant level of through biologic homeostasis or thermoregulation...

, somnolence, hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...

, refusal to feed, and seizures or "spells." Hypoglycemia can resemble asphyxia
Asphyxia
Asphyxia or asphyxiation is a condition of severely deficient supply of oxygen to the body that arises from being unable to breathe normally. An example of asphyxia is choking. Asphyxia causes generalized hypoxia, which primarily affects the tissues and organs...

, hypocalcemia, sepsis
Sepsis
Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...

, 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
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...

 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
Glycogen storage disease
Glycogen storage disease is the result of defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism involved in these processes...

, when chronic hypoglycemia before diagnosis may be better tolerated than acute hypoglycemia after treatment is underway.

Hypoglycemic symptoms can also occur when one is sleeping. Examples of symptoms during sleep can include damp bed sheets or clothes from perspiration. Having nightmares or the act of crying out can be a sign of hypoglycemia. Once the individual is awake they may feel tired, irritable, or confused and these may be signs of hypoglycemia as well.

In nearly all cases, hypoglycemia that is 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.

Causes

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. 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....

ized patients, especially in intensive care unit
Intensive Care Unit
thumb|220px|ICU roomAn intensive-care unit , critical-care unit , intensive-therapy unit/intensive-treatment unit is a specialized department in a hospital that provides intensive-care medicine...

s 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
Iatrogenesis
Iatrogenesis, or an iatrogenic artifact is an inadvertent adverse effect or complication resulting from medical treatment or advice, including that of psychologists, therapists, pharmacists, nurses, physicians and dentists...

. Once identified, these types of hypoglycemia are readily reversed and prevented, and the underlying disease becomes the primary problem.

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 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....

 admission and unpleasant starvation testing. Perhaps the most common inadequacy of 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...

 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.

Newborn infants

Hypoglycemia is a common problem in critically ill or extremely low birthweight infants. If not due to maternal 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...

, 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.
  • Transient neonatal hypoglycemia
    • Prematurity, intrauterine growth retardation, perinatal asphyxia
      Perinatal asphyxia
      Perinatal asphyxia or neonatal asphyxia is the medical condition resulting from deprivation of oxygen to a newborn infant that lasts long enough during the birth process to cause physical harm, usually to the brain...

    • Maternal hyperglycemia due to diabetes or iatrogenic glucose administration
    • Sepsis
    • Prolonged fasting (e.g., due to inadequate breast milk or condition interfering with feeding)
  • Congenital hypopituitarism
  • Congenital hyperinsulinism
    Congenital hyperinsulinism
    Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and...

    , several types, both transient and persistent
  • Inborn errors of carbohydrate metabolism
    Inborn error of metabolism
    Inborn errors of metabolism comprise a large class of genetic diseases involving disorders of metabolism. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances into others...

     such as glycogen storage disease

Young children

Single episodes of hypoglycemia may occur due to gastroenteritis
Gastroenteritis
Gastroenteritis is marked by severe inflammation of the gastrointestinal tract involving both the stomach and small intestine resulting in acute diarrhea and vomiting. It can be transferred by contact with contaminated food and water...

 or fasting, but recurrent episodes nearly always indicate either an inborn error of metabolism, congenital hypopituitarism, or congenital hyperinsulinism. A list of common causes:
  • Prolonged fasting
    • Diarrhea
      Diarrhea
      Diarrhea , also spelled diarrhoea, is the condition of having three or more loose or liquid bowel movements per day. It is a common cause of death in developing countries and the second most common cause of infant deaths worldwide. The loss of fluids through diarrhea can cause dehydration and...

      l illness in young children, especially rotavirus
      Rotavirus
      Rotavirus is the most common cause of severe diarrhoea among infants and young children, and is one of several viruses that cause infections often called stomach flu, despite having no relation to influenza. It is a genus of double-stranded RNA virus in the family Reoviridae. By the age of five,...

       gastroenteritis
  • Idiopathic ketotic hypoglycemia
    Ketotic hypoglycemia
    Ketotic hypoglycemia is a medical term used in two ways: broadly, to refer to any circumstance in which low blood glucose is accompanied by ketosis, and in a much more restrictive way to refer to recurrent episodes of hypoglycemic symptoms with ketosis and, often, vomiting, in young children...

  • Isolated growth hormone deficiency
    Growth hormone deficiency
    Growth hormone deficiency is a medical condition in which the body does not produce enough growth hormone . Growth hormone, also called somatotropin, is a polypeptide hormone which stimulates growth and cell reproduction...

    , hypopituitarism
  • Insulin excess
    Hyperinsulinemic hypoglycemia
    Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin.-Causes:...

    • Hyperinsulinism due to several congenital disorders of insulin secretion
    • Insulin injected for type 1 diabetes
    • Hyperinsulin Hyperammonia syndrome (HIHA) due to Glutamate dehydrogenase 1
      Glutamate Dehydrogenase 1
      GLUD1 is a mitochondrial matrix enzyme, with a key role in the nitrogen and glutamate metabolism and the energy homeostasis. GLUD1 is expressed at high levels in liver, brain, pancreas and kidney, but not in muscle. In the pancreatic cells, GLUD1 is thought to be involved in insulin secretion...

       gene. Can cause mental retardation and epilepsy in severe cases.
  • Gastric dumping syndrome
    Gastric dumping syndrome
    Gastric dumping syndrome, or rapid gastric emptying is a condition where ingested foods bypass the stomach too rapidly and enter the small intestine largely undigested. It happens when the upper end of the small intestine, the duodenum, expands too quickly due to the presence of hyperosmolar food...

     (after gastrointestinal surgery)
  • Other congenital metabolic diseases; some of the common include
    • Maple syrup urine disease
      Maple syrup urine disease
      Maple syrup urine disease , also called branched-chain ketoaciduria, is an autosomal recessive metabolic disorder affecting branched-chain amino acids. It is one type of organic acidemia...

       and other organic acidurias
    • Type 1 glycogen storage disease
      Glycogen storage disease
      Glycogen storage disease is the result of defects in the processing of glycogen synthesis or breakdown within muscles, liver, and other cell types. GSD has two classes of cause: genetic and acquired. Genetic GSD is caused by any inborn error of metabolism involved in these processes...

    • Type III glycogen storage disease. Can cause less severe hypoglycemia than type I
    • Phosphoenolpyruvate carboxykinase deficiency, causes metabolic acidosis and severe hypoglycemia.
    • Disorders of fatty acid oxidation
    • Medium chain acylCoA dehydrogenase deficiency (MCAD
      MCAD
      MCAD may refer to:* Massachusetts Commission Against Discrimination* Mechanical computer-aided design* Medium chain acyl dehydrogenase deficiency* Microsoft Certified Application Developer* Minneapolis College of Art and Design...

      )
    • Familial Leucine sensitive hypoglycemia
  • Accidental ingestions
    • 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, propranolol and others
    • Ethanol (mouthwash, "leftover morning-after-the-party drinks")

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
Reactive hypoglycemia
Reactive hypoglycemia, or postprandial hypoglycemia, is a medical term describing recurrent episodes of symptomatic hypoglycemia occurring within 4 hours after a high carbohydrate meal in people who do not have diabetes...

 pattern, but this is also the peak age for idiopathic postprandial syndrome
Idiopathic postprandial syndrome
Idiopathic postprandial syndrome is a medical term describing a collection of symptoms popularly attributed to hypoglycemia but without demonstrably low blood glucose levels.People with this condition suffer from recurrent episodes of altered mood and cognitive...

, and recurrent "spells" in this age group can be traced to orthostatic hypotension
Orthostatic hypotension
Orthostatic hypotension, also known as postural hypotension, orthostasis, and colloquially as head rush or dizzy spell, is a form of hypotension in which a person's blood pressure suddenly falls when the person stands up or stretches. The decrease is typically greater than 20/10 mm Hg, and may be...

 or hyperventilation
Hyperventilation
Hyperventilation or overbreathing is the state of breathing faster or deeper than normal, causing excessive expulsion of circulating carbon dioxide. It can result from a psychological state such as a panic attack, from a physiological condition such as metabolic acidosis, can be brought about by...

 as often as demonstrable hypoglycemia.
  • Insulin-induced hypoglycemia
    • Insulin injected for type 1 diabetes
    • Factitious insulin injection (Munchausen syndrome
      Munchausen syndrome
      Münchausen syndrome is a psychiatric factitious disorder wherein those affected feign disease, illness, or psychological trauma to draw attention or sympathy to themselves. It is also sometimes known as hospital addiction syndrome or hospital hopper syndrome...

      )
    • Insulin-secreting pancreatic tumor
    • Reactive hypoglycemia and idiopathic postprandial syndrome
  • Addison's disease
    Addison's disease
    Addison’s disease is a rare, chronic endocrine disorder in which the adrenal glands do not produce sufficient steroid hormones...

  • Sepsis
    Sepsis
    Sepsis is a potentially deadly medical condition that is characterized by a whole-body inflammatory state and the presence of a known or suspected infection. The body may develop this inflammatory response by the immune system to microbes in the blood, urine, lungs, skin, or other tissues...


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
      Munchausen syndrome
      Münchausen syndrome is a psychiatric factitious disorder wherein those affected feign disease, illness, or psychological trauma to draw attention or sympathy to themselves. It is also sometimes known as hospital addiction syndrome or hospital hopper syndrome...

      )
    • Excessive effects of oral diabetes drugs, beta-blockers, or drug interactions
    • Insulin-secreting neuroendocrine tumor (insulinoma) of the pancreas
    • Alcohol induced hypoglycemia often linked with ketoacidosis (depletion of NAD+ leads to a block of gluconeogenesis)
    • Alimentary (rapid jejunal emptying with exaggerated insulin response)
      • After gastrectomy dumping syndrome or bowel bypass surgery or resection
    • Reactive hypoglycemia
      Reactive hypoglycemia
      Reactive hypoglycemia, or postprandial hypoglycemia, is a medical term describing recurrent episodes of symptomatic hypoglycemia occurring within 4 hours after a high carbohydrate meal in people who do not have diabetes...

       and idiopathic postprandial syndrome
  • Tumor hypoglycemia, Doege-Potter syndrome
    Doege-Potter syndrome
    Doege-Potter syndrome is a paraneoplastic syndrome in which hypoglycemia is associated with the presence of one or more non-islet fibrous tumors in the pleural cavity. The hypoglycemia is the result of the tumors producing insulin-like growth factor 2...

  • Acquired adrenal insufficiency
    Adrenal insufficiency
    Adrenal insufficiency is a condition in which the adrenal glands, located above the kidneys, do not produce adequate amounts of steroid hormones , primarily cortisol, but may also include impaired aldosterone production which regulates sodium, potassium and water retention...

  • Acquired hypopituitarism
    Hypopituitarism
    Hypopituitarism is the decreased secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain...

  • Immunopathologic hypoglycemia

Pathophysiology of hypoglycemia

Like most animal tissues, brain metabolism
Metabolism
Metabolism is the set of chemical reactions that happen in the cells of living organisms to sustain life. These processes allow organisms to grow and reproduce, maintain their structures, and respond to their environments. Metabolism is usually divided into two categories...

 depends primarily on glucose for fuel in most circumstances. A limited amount of glucose can be derived from 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...

 stored in astrocyte
Astrocyte
Astrocytes , also known collectively as astroglia, are characteristic star-shaped glial cells in the brain and spinal cord...

s, 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
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 and into the neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...

s 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 judgment usually becomes obvious below 40 mg/dl (2.2 mM). Seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s 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
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 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....

 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 into a 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...

, 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
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...

, and availability of alternative fuels. It has been frequently found that those Type 1 diabetics found "dead in bed" in the morning after suspected severe hypoglycemia had some underlying coronary pathology that led to an induced fatal heart attack. Recently, several of these individuals found "dead in bed" were wearing Continuous Glucose Monitors, which provided a history of glucose levels prior to the fatal event. It has been found in several cases, that the fatal event was preceded by at least two hours of blood glucose levels under 40 mg/dl, possibly lower as the continuous glucose monitors are not accurate at levels below 40 mg/dl. The individuals failed to respond to the audible alarms produced by the continuous glucose monitor which may have been "alarming" for many hours prior to the fatal event. The vast majority of symptomatic hypoglycemic episodes result in no detectable permanent harm.

Diagnosis

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
Ketosis
Ketosis is a state of elevated levels of ketone bodies in the body. It is almost always generalized throughout the body, with hyperketonemia, that is, an elevated level of ketone bodies in the blood. Ketone bodies are formed by ketogenesis when the liver glycogen stores are depleted...

 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
Glucose tolerance test
A glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of...

, 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.

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
Cornstarch
Corn starch, cornstarch, cornflour or maize starch is the starch of the corn grain obtained from the endosperm of the corn kernel.-History:...

 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
Diazoxide
Diazoxide is a potassium channel activator, which causes local relaxation in smooth muscle by increasing membrane permeability to potassium ions...

 or octreotide
Octreotide
Octreotide is an octapeptide that mimics natural somatostatin pharmacologically, though it is a more potent inhibitor of growth hormone, glucagon, and insulin than the natural hormone...

. 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
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...

 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
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...

, or by making lifestyle changes to reduce stress. See the following section of this article.

Treatment

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

The blood glucose can be raised to normal within minutes by taking (or receiving) 10-20 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...

. 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
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 (unless the person is taking acarbose
Acarbose
Acarbose is an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay , in North America as Precose , and in Canada as Prandase...

), 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 personnel such as EMTs and paramedics, or in-hospital personnel can establish an IV and give intravenous dextrose, concentrations varying depending on age (infants are given 2 ml/kg dextrose 10%, children are given dextrose 25%, and adults are given 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
Intramuscular injection
Intramuscular injection is the injection of a substance directly into a muscle. In medicine, it is one of several alternative methods for the administration of medications . It is used for particular forms of medication that are administered in small amounts...

. More treatment information can be found in the article diabetic hypoglycemia
Diabetic hypoglycemia
Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals...

.

One situation where starch may be less effective than glucose or sucrose is when a person is taking acarbose
Acarbose
Acarbose is an anti-diabetic drug used to treat type 2 diabetes mellitus and, in some countries, prediabetes. It is a generic sold in Europe and China as Glucobay , in North America as Precose , and in Canada as Prandase...

. Since acarbose and other alpha-glucosidase inhibitor
Alpha-glucosidase inhibitor
Alpha-glucosidase inhibitors are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates . Carbohydrates are normally converted into simple sugars , which can be absorbed through the intestine...

s prevents starch and other sugars from being broken down into monosaccharide
Monosaccharide
Monosaccharides are the most basic units of biologically important carbohydrates. They are the simplest form of sugar and are usually colorless, water-soluble, crystalline solids. Some monosaccharides have a sweet taste. Examples of monosaccharides include glucose , fructose , galactose, xylose...

s 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.

See also

  • 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...

  • Glucose
    Glucose
    Glucose is a simple sugar and an important carbohydrate in biology. Cells use it as the primary source of energy and a metabolic intermediate...

  • Diabetes
  • 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...

  • Diabetic hypoglycemia
    Diabetic hypoglycemia
    Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals...

  • Diabetic hypoglycemia journal
  • Hyperinsulinemic hypoglycemia
    Hyperinsulinemic hypoglycemia
    Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin.-Causes:...

  • Congenital hyperinsulinism
    Congenital hyperinsulinism
    Congenital hyperinsulinism is a medical term referring to a variety of congenital disorders in which hypoglycemia is caused by excessive insulin secretion. Congenital forms of hyperinsulinemic hypoglycemia can be transient or persistent, mild or severe. These conditions are present at birth and...

  • Idiopathic hypoglycemia
    Idiopathic hypoglycemia
    Idiopathic hypoglycemia is, literally, a medical condition in which the glucose level in the blood is abnormally low due to an undeterminable cause. This is considered an incomplete and unsatisfactory diagnosis by physicians and is rarely used by endocrinologists, as it implies an unfinished...

  • Idiopathic postprandial syndrome
    Idiopathic postprandial syndrome
    Idiopathic postprandial syndrome is a medical term describing a collection of symptoms popularly attributed to hypoglycemia but without demonstrably low blood glucose levels.People with this condition suffer from recurrent episodes of altered mood and cognitive...

  • Reactive hypoglycemia
    Reactive hypoglycemia
    Reactive hypoglycemia, or postprandial hypoglycemia, is a medical term describing recurrent episodes of symptomatic hypoglycemia occurring within 4 hours after a high carbohydrate meal in people who do not have diabetes...

  • Ketotic hypoglycemia
    Ketotic hypoglycemia
    Ketotic hypoglycemia is a medical term used in two ways: broadly, to refer to any circumstance in which low blood glucose is accompanied by ketosis, and in a much more restrictive way to refer to recurrent episodes of hypoglycemic symptoms with ketosis and, often, vomiting, in young children...

  • Spontaneous hypoglycemia
    Spontaneous hypoglycemia
    The term "spontaneous hypoglycemia" was coined by the physician Seale Harris.It is a vague term that is currently considered to be too imprecise to be useful by doctors interested in hypoglycemia, though it may have historical value....

  • Insulinoma
    Insulinoma
    An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin.Beta cells secrete insulin in response to increases in blood glucose. The resulting increase in insulin acts to lower blood glucose back to normal levels at which point further secretion of insulin is...


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