Hypoglycemia, also called low blood sugar, is a fall in
blood sugar
Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...
to levels below normal, typically below 70 mg/dL (3.9 mmol/L).
Whipple's triad
Whipple's triad is a collection of three signs (called Whipple's criteria) that suggests that a patient's symptoms result from hypoglycaemia that may indicate insulinoma. The essential conditions are symptoms of hypoglycaemia, low blood plasma g ...
is used to properly identify hypoglycemic episodes. It is defined as blood glucose below 70 mg/dL (3.9 mmol/L), symptoms associated with hypoglycemia, and resolution of symptoms when blood sugar returns to normal. Hypoglycemia may result in headache
Headache is the symptom of pain in the face, head, or neck. It can occur as a migraine, tension-type headache, or cluster headache. There is an increased risk of depression in those with severe headaches.
Headaches can occur as a result ...
, tiredness, clumsiness, trouble talking, confusion
In medicine, confusion is the quality or state of being bewildered or unclear. The term "acute mental confusion" , fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness
Loss may refer to:
Arts, entertainment, and media Music
* ''Loss'' (Bass Communion album) (2006)
* ''Loss'' (Mull Historical Society album) (2001)
*"Loss", a song by God Is an Astronaut from their self-titled album (2008)
* Losses "(Lil Tjay son ...
, seizures
An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or neural oscillation, synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much o ...
, or death
Death is the irreversible cessation of all biological functions that sustain an organism. For organisms with a brain, death can also be defined as the irreversible cessation of functioning of the whole brain, including brainstem, and brain ...
. Symptoms typically come on quickly.
The most common cause of hypoglycemia is medications
A medication (also called medicament, medicine, pharmaceutical drug, medicinal drug or simply drug) is a drug used to diagnose, cure, treat, or prevent disease. Drug therapy (pharmacotherapy) is an important part of the medical field and rel ...
used to treat diabetes such as insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
s, and biguanide
Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea.
Synthesis
Biguanide can be obtained from ...
s. Risk is greater in diabetics who have eaten less than usual, recently exercised, or consumed alcohol
Alcohol most commonly refers to:
* Alcohol (chemistry), an organic compound in which a hydroxyl group is bound to a carbon atom
* Alcohol (drug), an intoxicant found in alcoholic drinks
Alcohol may also refer to:
Chemicals
* Ethanol, one of sev ...
. Other causes of hypoglycemia include severe illness, sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, kidney failure
Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...
, liver disease
Liver disease, or hepatic disease, is any of many diseases of the liver. If long-lasting it is termed chronic liver disease. Although the diseases differ in detail, liver diseases often have features in common.
Signs and symptoms
Some of the sig ...
, hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
deficiency, tumors
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
such as insulinoma
An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a min ...
s or non-B cell tumors, inborn errors of metabolism
Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substra ...
, several medications, and alcohol. Low blood sugar may occur in otherwise healthy newborns who have not eaten for a few hours.
Hypoglycemia is treated by eating a sugary food or drink, for example glucose tablets or gel, apple juice, soda, or candy. The person must be conscious
Consciousness, at its simplest, is sentience and awareness of internal and external existence. However, the lack of definitions has led to millennia of analyses, explanations and debates by philosophers, theologians, linguisticians, and scien ...
and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). If a person is not able to take food by mouth, glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
by injection or insufflation may help. The treatment of hypoglycemia unrelated to diabetes includes treating the underlying problem.
Among people with diabetes, prevention starts with learning the signs and symptoms of hypoglycemia. Diabetes medications, like insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
s, and biguanide
Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea.
Synthesis
Biguanide can be obtained from ...
s can also be adjusted or stopped to prevent hypoglycemia. Frequent and routine blood glucose testing is recommended. Some may find continuous glucose monitors with insulin pumps to be helpful in the management of diabetes and prevention of hypoglycemia.
Definition
Blood sugar levels naturally fluctuate throughout the day, however ''hypoglycemia'', also called ''low blood sugar'' or ''low blood glucose,'' is when blood sugar levels drop below 70 mg/dL (3.9 mmol/L).
Blood sugar levels are generally maintained between 70 and 110 mg/dL (3.9-6.1 mmol/L). Although 70 mg/dL (3.9 mmol/L) is the lower limit of normal glucose, symptoms of hypoglycemia usually do not occur until 55 mg/dL (3.0 mmol/L) or lower. The blood glucose level at which symptoms of hypoglycemia develop in someone with several prior episodes of hypoglycemia may be even lower.
Whipple's triad
The symptoms of low blood sugar alone are not specific enough to characterize a hypoglycemic episode. A single blood sugar reading below 70 mg/dL is also not specific enough characterize a hypoglycemic episode. ''Whipple's triad
Whipple's triad is a collection of three signs (called Whipple's criteria) that suggests that a patient's symptoms result from hypoglycaemia that may indicate insulinoma. The essential conditions are symptoms of hypoglycaemia, low blood plasma g ...
'' is a set of three conditions that need to be met in order to accurately characterize a hypoglycemic episode.
The three conditions are the following:
# The signs and symptoms of hypoglycemia are present (see section below on ''Signs and Symptoms'')
# A low blood glucose measurement is present, typically less than 70 mg/dL (3.9 mmol/L)
# The signs and symptoms of hypoglycemia resolve after blood glucose levels have returned to normal
Age
The biggest difference in blood glucose levels between the adult and pediatric population occurs in newborns during the first 48 hours of life. After the first 48 hours of life, the Pediatric Endocrine Society cites that there is little difference in blood glucose level and the use of glucose between adults and children. During the 48 hour neonatal period, the neonate adjusts glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
and epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
levels following birth, which may cause temporary hypoglycemia. As a result, there has been difficulty in developing guidelines on interpretation and treatment of low blood glucose in neonates aged less than 48 hours. Following a data review, the Pediatric Endocrine Society concluded that neonates aged less than 48 hours begin to respond to hypoglycemia at serum glucose levels of 55–65 mg/dL (3.0-3.6 mmol/L). This is contrasted by the value in adults, children, and older infants, which is approximately 80–85 mg/dL (4.4-4.7 mmol/L).
In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults. Whipple's triad is used to identify hypoglycemia in children who can communicate their symptoms.
Differential diagnosis
Other conditions that may present similarly to hypoglycemia include the following:
* Alcohol or drug intoxication
Substance intoxication is a transient condition of altered consciousness and behavior associated with recent use of a substance. It is often maladaptive and impairing, but reversible. If the symptoms are severe, the term "substance intoxicatio ...
* Cardiac arrhythmia
Arrhythmias, also known as cardiac arrhythmias, heart arrhythmias, or dysrhythmias, are irregularities in the heartbeat, including when it is too fast or too slow. A resting heart rate that is too fast – above 100 beats per minute in adults ...
* Valvular heart disease
Valvular heart disease is any cardiovascular disease process involving one or more of the four valves of the heart (the aortic and mitral valves on the left side of heart and the pulmonic and tricuspid valves on the right side of heart). These ...
* Postprandial syndrome
* Hyperthyroidism
Hyperthyroidism is the condition that occurs due to excessive production of thyroid hormones by the thyroid gland. Thyrotoxicosis is the condition that occurs due to excessive thyroid hormone of any cause and therefore includes hyperthyroidism ...
* Pheochromocytoma
Pheochromocytoma (PHEO or PCC) is a rare tumor of the adrenal medulla composed of chromaffin cells, also known as pheochromocytes. When a tumor composed of the same cells as a pheochromocytoma develops outside the adrenal gland, it is referred t ...
* Post-gastric bypass hypoglycemia
* Generalized anxiety disorder
Generalized anxiety disorder (GAD) is a mental and behavioral disorder, specifically an anxiety disorder characterized by excessive, uncontrollable and often irrational worry about events or activities. Worry often interferes with daily function ...
* Surreptitious insulin use
* Lab or blood draw error (lack of antiglycolytic agent in collection tube or during processing)
Signs and symptoms
Hypoglycemic symptoms are divided into two main categories. The first category is symptoms caused by low glucose in the brain, called neuroglycopenic
Neuroglycopenia is a shortage of glucose (glycopenia) in the brain, usually due to hypoglycemia. Glycopenia affects the function of neurons, and alters brain function and behavior. Prolonged or recurrent neuroglycopenia can result in loss of consc ...
symptoms. The second category of symptoms is caused by the body's reaction to low glucose in the brain, called adrenergic
Adrenergic means "working on adrenaline (epinephrine) or noradrenaline (norepinephrine)" (or on their receptors). When not further qualified, it is usually used in the sense of enhancing or mimicking the effects of epinephrine and norepinephrine in ...
symptoms.
Everyone experiences different symptoms of hypoglycemia, so someone with hypoglycemia may not have all of the symptoms listed above. Symptoms also tend to have quick onset. It is important to quickly obtain a blood glucose measurement in someone presenting with symptoms of hypoglycemia to properly identify the hypoglycemic episode.
Pathophysiology
Glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
is the main source of energy for the brain, and a number of mechanisms are in place to prevent hypoglycemia and protect energy supply to the brain. The body can adjust insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
production and release, adjust glucose production by the liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
, and adjust glucose use by the body. The body naturally produces the hormone insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, in an organ called the pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
. Insulin helps to regulate the amount of glucose in the body, especially after meals. Glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
is another hormone involved in regulating blood glucose levels, and can be thought of as the opposite of insulin. Glucagon helps to increase blood glucose levels, especially in states of hunger.
When blood sugar levels fall to the low-normal range, the first line of defense against hypoglycemia is decreasing insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
release by the pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
. This drop in insulin allows the liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
to increase glycogenolysis
Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.
Mechanism
The ...
. Glycogenolysis
Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.
Mechanism
The ...
is the process of glycogen
Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body.
Glycogen functions as one o ...
breakdown that results in the production of glucose. Glycogen
Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body.
Glycogen functions as one o ...
can be thought of as the inactive, storage form of glucose. Decreased insulin also allows for increased gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
in the liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s. Gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
is the process of glucose production from non-carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
sources, supplied from muscles and fat.
Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia. The pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
is signaled to release glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
, a hormone
A hormone (from the Greek participle , "setting in motion") is a class of signaling molecules in multicellular organisms that are sent to distant organs by complex biological processes to regulate physiology and behavior. Hormones are required ...
that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supply gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
. If increased glucagon does not raise blood sugar levels to normal, the adrenal glands release epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
. Epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
works to also increase gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
and glycogenolysis
Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.
Mechanism
The ...
, while also decreasing the use of glucose by organs, protecting the brain's glucose supply.
After hypoglycemia has been prolonged, cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
and growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
are released to continue gluconeogenesis
Gluconeogenesis (GNG) is a metabolic pathway that results in the generation of glucose from certain non-carbohydrate carbon substrates. It is a ubiquitous process, present in plants, animals, fungi, bacteria, and other microorganisms. In vertebrat ...
and glycogenolysis
Glycogenolysis is the breakdown of glycogen (n) to glucose-1-phosphate and glycogen (n-1). Glycogen branches are catabolized by the sequential removal of glucose monomers via phosphorolysis, by the enzyme glycogen phosphorylase.
Mechanism
The ...
, while also preventing the use of glucose by other organs. The effects of cortisol and growth hormone are far less effective than epinephrine. In a state of hypoglycemia, the brain also signals a sense of hunger and drives the person to eat, in an attempt to increase glucose.
Causes
Hypoglycemia is most common in those with diabetes treated by insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, glinides
Meglitinides or glinides are a class of drugs used to treat type 2 diabetes.
Drugs
Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997.
Other drugs in this class include nateglinide (Starlix) and mitiglin ...
, and sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
s. Hypoglycemia is rare in those without diabetes, because there are many regulatory mechanisms in place to appropriately balance glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
, insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, and glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
. Please refer to ''Pathophysiology'' section (above) for more information on glucose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
, insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, and glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
.
Diabetics
Medications
The most common cause of hypoglycemia in diabetics is medications used to treat diabetes such as insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
s, and biguanide
Biguanide () is the organic compound with the formula HN(C(NH)NH2)2. It is a colorless solid that dissolves in water to give highly basic solution. These solutions slowly hydrolyse to ammonia and urea.
Synthesis
Biguanide can be obtained from ...
s. This is often due to excessive doses or poorly timed doses. Sometimes diabetics may take insulin in anticipation of a meal or snack, and missing or forgetting that meal will lead to hypoglycemia. This is due to increased insulin without the presence of glucose from the planned meal.
Hypoglycemic unawareness
Recurrent episodes of hypoglycemia can lead to ''hypoglycemic unawareness'', or the decreased ability to recognize hypoglycemia. As diabetics experience more episodes of hypoglycemia, the blood glucose level which triggers symptoms of hypoglycemia decreases. In other words, people ''without'' hypoglycemic unawareness experience symptoms of hypoglycemia at a blood glucose of about 55 mg/dL (3.0 mmol/L). Those ''with'' hypoglycemic unawareness experience the symptoms of hypoglycemia at far lower levels of blood glucose. This is dangerous for a number of reasons. The hypoglycemic person not only gains awareness of hypoglycemia at very low blood glucose levels, but they also require high levels of carbohydrates or glucagon to recover their blood glucose to normal levels. These individuals are also at far greater risk of severe hypoglycemia.
While the exact cause of hypoglycemic unawarenss is still under research, it is thought that these individuals progressively begin to develop fewer adrenergic-type symptoms, resulting in the loss of neuroglycopenic-type symptoms. ''Neuroglycopenic symptoms'' are caused by low glucose in the brain, and can result in tiredness, confusion, difficulty with speech, seizures, and loss of consciousness. ''Adrenergic symptoms'' are caused by the body's reaction to low glucose in the brain, and can result in fast heart rate, sweating, nervousness, and hunger. See section above on ''Signs and Symptoms'' for further explanation of neuroglycopenic symptoms and adrenergic symptoms.
In terms of epidemiology, hypoglycemic unawarenss occurs in 20-40% of type 1 diabetics.
Other causes
Other causes of hypoglycemia in diabetics include the following:
* Fasting, whether it be a planned fast or overnight fast, as there is a long period of time without glucose intake
* Exercising more than usual as it leads to more use of glucose, especially by the muscles
* Drinking alcohol, especially when combined with diabetic medications, as alcohol inhibits glucose production
* Kidney disease
Kidney disease, or renal disease, technically referred to as nephropathy, is damage to or disease of a kidney. Nephritis is an inflammatory kidney disease and has several types according to the location of the inflammation. Inflammation can ...
, as insulin cannot be cleared out of circulation well
Non-diabetics
Serious illness
Serious illness may result in low blood sugar. Severe disease of many organ systems can cause hypoglycemia as a secondary problem. Hypoglycemia is especially common in those in the intensive care unit
220px, Intensive care unit
An intensive care unit (ICU), also known as an intensive therapy unit or intensive treatment unit (ITU) or critical care unit (CCU), is a special department of a hospital or health care facility that provides intensiv ...
or those in whom food and drink is withheld as a part of their treatment plan.
Sepsis
Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...
, a common cause of hypoglycemia in serious illness, can lead to hypoglycemia through many ways. In a state of sepsis, the body uses large amounts of glucose for energy. Glucose use is further increased by cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
production. Cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s are a protein produced by the body in a state of stress, particularly when fighting an infection
An infection is the invasion of tissues by pathogens, their multiplication, and the reaction of host tissues to the infectious agent and the toxins they produce. An infectious disease, also known as a transmissible disease or communicable dise ...
. Cytokine
Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...
s may inhibit glucose production, further decreasing the body's energy stores. Finally, the liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
and kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s are sites of glucose production, and in a state of sepsis those organs may not receive enough oxygen, leading to decreased glucose production due to organ damage.
Other causes of serious illness that may cause hypoglycemia include liver failure and kidney failure. The liver
The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...
is the main site of glucose production in the body, and any liver failure or damage will lead to decreased glucose production. While the kidney
The kidneys are two reddish-brown bean-shaped organs found in vertebrates. They are located on the left and right in the retroperitoneal space, and in adult humans are about in length. They receive blood from the paired renal arteries; blood ...
s are also sites of glucose production, their failure of glucose production is not significant enough to cause hypoglycemia . Instead, the kidneys are responsible for removing insulin from the body, and when this function is impaired in kidney failure, the insulin stays in circulation longer, leading to hypoglycemia.
Drugs
A number of medications have been identified which may cause hypoglycemia, through a variety of ways. Moderate quality evidence implicates the non-steroidal anti-inflammatory drug indomethacin
Indometacin, also known as indomethacin, is a nonsteroidal anti-inflammatory drug (NSAID) commonly used as a prescription drug, prescription medication to reduce fever, pain, joint stiffness, stiffness, and swelling (medical), swelling from infl ...
and the anti-malarial quinine
Quinine is a medication used to treat malaria and babesiosis. This includes the treatment of malaria due to ''Plasmodium falciparum'' that is resistant to chloroquine when artesunate is not available. While sometimes used for nocturnal leg cr ...
. Low quality evidence implicates lithium
Lithium (from el, λίθος, lithos, lit=stone) is a chemical element with the symbol Li and atomic number 3. It is a soft, silvery-white alkali metal. Under standard conditions, it is the least dense metal and the least dense solid el ...
, used for bipolar disorder
Bipolar disorder, previously known as manic depression, is a mental disorder characterized by periods of depression and periods of abnormally elevated mood that last from days to weeks each. If the elevated mood is severe or associated with ...
. Finally, very low quality evidence implicates a number of hypertension
Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high bl ...
medications including angiotensin converting enzyme inhibitors
Angiotensin-converting-enzyme inhibitors (ACE inhibitors) are a class of medication used primarily for the treatment of high blood pressure and heart failure. They work by causing relaxation of blood vessels as well as a decrease in blood volum ...
(also called ACE-inhibitors), angiotensin receptor blockers
Angiotensin II receptor blockers (ARBs), formally angiotensin II receptor type 1 (AT1) antagonists, also known as angiotensin receptor blockers, angiotensin II receptor antagonists, or AT1 receptor antagonists, are a group of pharmaceuticals tha ...
(also called ARBs), and β-adrenergic blockers (also called beta blockers). Other medications with very low quality evidence include the antibiotics levofloxacin
Levofloxacin, sold under the brand name Levaquin among others, is an antibiotic medication. It is used to treat a number of bacterial infections including acute bacterial sinusitis, pneumonia, H. pylori (in combination with other medications), ...
and trimethoprim-sulfamethoxazole
Trimethoprim/sulfamethoxazole, sold under the brand name Bactrim among others, is a fixed-dose combination antibiotic medication used to treat a variety of bacterial infections. It consists of one part trimethoprim to five parts sulfamethoxazo ...
, progesterone blocker mifepristone
Mifepristone, also known as RU-486, is a medication typically used in combination with misoprostol to bring about a medical abortion during pregnancy and manage early miscarriage. This combination is 97% effective during the first 63 days of p ...
, anti-arrhythmic disopyramide
Disopyramide (INN, trade names Norpace and Rythmodan) is an antiarrhythmic medication used in the treatment of ventricular tachycardia. It is a sodium channel blocker and therefore classified as a Class 1a anti-arrhythmic agent. Disopyramide has ...
, anti-coagulant heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the treatm ...
, and chemotherapeutic mercaptopurine
Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL), acute promyelocytic leukemia (APL), Crohn's di ...
.
If a person without diabetes accidentally takes medications that are traditionally used to treat diabetes, this may also cause hypoglycemia. These medications include insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, glinides
Meglitinides or glinides are a class of drugs used to treat type 2 diabetes.
Drugs
Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997.
Other drugs in this class include nateglinide (Starlix) and mitiglin ...
, and sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
s. This may occur through medical errors in a healthcare setting or through pharmacy errors, also called iatrogenic
Iatrogenesis is the causation of a disease, a harmful complication, or other ill effect by any medical activity, including diagnosis, intervention, error, or negligence. "Iatrogenic", ''Merriam-Webster.com'', Merriam-Webster, Inc., accessed 2 ...
hypoglycemia.
Surreptitious insulin use
When individuals take insulin without needing it, to purposefully induce hypoglycemia, this is referred to as ''surreptitious insulin use'' or ''factitious hypoglycemia''. Some people may use insulin to induce weight loss, whereas for others this may be due to malingering
Malingering is the fabrication, feigning, or exaggeration of physical or psychological symptoms designed to achieve a desired outcome, such as relief from duty or work.
Malingering is not a medical diagnosis, but may be recorded as a "focus of c ...
or factitious disorder
A factitious disorder is a condition in which a person, ''without'' a malingering motive, acts as if they have an illness by deliberately producing, feigning, or exaggerating symptoms, purely to attain (for themselves or for another) a patient's ...
, which is a psychiatric disorder. Demographics affected by factitious hypoglycemia include women aged 30–40, particularly those with diabetes, relatives with diabetes, healthcare workers, or those with history of a psychiatric disorder. The classic way to identify surreptitious insulin use is through blood work revealing high insulin levels with low C-peptide
The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum lev ...
and proinsulin
Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. In humans, proinsulin is encoded by the ''INS'' gene. The islets of Langerhans only secrete between 1% and 3 ...
.
Alcohol misuse
The production of glucose is blocked by alcohol. In those who misuse alcohol, hypoglycemia may be brought on by a several-day alcohol binge associated with little to no food intake. The cause of hypoglycemia is multifactorial, where glycogen
Glycogen is a multibranched polysaccharide of glucose that serves as a form of energy storage in animals, fungi, and bacteria. The polysaccharide structure represents the main storage form of glucose in the body.
Glycogen functions as one o ...
becomes depleted in a state of starvation
Starvation is a severe deficiency in caloric energy intake, below the level needed to maintain an organism's life. It is the most extreme form of malnutrition. In humans, prolonged starvation can cause permanent organ damage and eventually, dea ...
. Glycogen stores are then unable to be repleted due to the lack of food intake, all compounded the inhibition of glucose production by alcohol.
Hormone deficiency
Children with primary adrenal failure, also called Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
, may experience hypoglycemia after long periods of fasting
Fasting is the abstention from eating and sometimes drinking. From a purely physiological context, "fasting" may refer to the metabolic status of a person who has not eaten overnight (see " Breakfast"), or to the metabolic state achieved after ...
. Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
is associated with chronically low levels of the stress hormone cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
, which leads to decreased glucose production.
Hypopituitarism
Hypopituitarism is the decreased (''hypo'') secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is know ...
, leading to decreased growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
, is another cause of hypoglycemia in children, particularly with long periods of fasting or increased exercise.
Inborn errors of metabolism
Briefly, inborn errors of metabolism
Inborn errors of metabolism form a large class of genetic diseases involving congenital disorders of enzyme activities. The majority are due to defects of single genes that code for enzymes that facilitate conversion of various substances ( substra ...
are a group rare of genetic disorder
A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...
s that are associated with the improper breakdown or storage of protein
Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respo ...
s, carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
s, or fatty acid
In chemistry, particularly in biochemistry, a fatty acid is a carboxylic acid with an aliphatic chain, which is either saturated or unsaturated. Most naturally occurring fatty acids have an unbranched chain of an even number of carbon atoms, fr ...
s. Inborn errors of metabolism may cause infant hypoglycemia, and much less commonly adult hypoglycemia. Disorders that are related to the breakdown of glycogen, called ''glycogen storage diseases'', may cause hypoglycemia. Normally, breakdown of glycogen leads to increased glucose levels, particularly in a fasting state. In glycogen storage disease
A glycogen storage disease (GSD, also glycogenosis and dextrinosis) is a metabolic disorder caused by an enzyme deficiency affecting glycogen synthesis, glycogen breakdown, or glucose breakdown, typically in muscles and/or liver cells.
GSD has ...
s however, glycogen cannot be properly broken-down, leading to inappropriately decreased glucose levels in a fasting state, and thus hypoglycemia. The glycogen storage diseases associated with hypoglycemia include type 0, type I, type III, and type IV
Type may refer to:
Science and technology Computing
* Typing, producing text via a keyboard, typewriter, etc.
* Data type, collection of values used for computations.
* File type
* TYPE (DOS command), a command to display contents of a file.
* Typ ...
, as well as Fanconi syndrome
Fanconi syndrome or Fanconi's syndrome (, ) is a syndrome of inadequate reabsorption in the proximal renal tubules of the kidney. The syndrome can be caused by various underlying congenital or acquired diseases, by toxicity (for example, from toxi ...
.
Insulinomas
A primary B-cell tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
, such as an insulinoma
An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a min ...
, is associated with hypoglycemia. This is a tumor located in the pancreas
The pancreas is an organ of the digestive system and endocrine system of vertebrates. In humans, it is located in the abdomen behind the stomach and functions as a gland. The pancreas is a mixed or heterocrine gland, i.e. it has both an end ...
. An insulinoma produces insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, which in turn decreases glucose levels, causing hypoglycemia. Normal regulatory mechanisms are not in place, which prevent insulin levels from falling during states of low blood glucose. During an episode of hypoglycemia, plasma insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, C-peptide
The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum lev ...
, and proinsulin
Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. In humans, proinsulin is encoded by the ''INS'' gene. The islets of Langerhans only secrete between 1% and 3 ...
will be inappropriately high.
Non-B cell tumors
Hypoglycemia may occur in people with non-B cell tumors
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
such as hepatoma
Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer in adults and is currently the most common cause of death in people with cirrhosis. HCC is the third leading cause of cancer-related deaths worldwide.
It occurs in t ...
s, adrenocorticoid carcinomas, and carcinoid
A carcinoid (also carcinoid tumor) is a slow-growing type of neuroendocrine tumor originating in the cells of the neuroendocrine system. In some cases, metastasis may occur. Carcinoid tumors of the midgut (jejunum, ileum, appendix, and cecum) ...
tumors. These tumors lead to a state of increased insulin, specifically increased insulin-like growth factor II, which decreases glucose levels.
Post-gastric bypass postprandial hypoglycemia
The Roux-en-Y gastric bypass
Gastric bypass surgery refers to a technique in which the stomach is divided into a small upper pouch and a much larger lower "remnant" pouch and then the small intestine is rearranged to connect to both. Surgeons have developed several diff ...
, is a weight-loss surgery performed on the stomach, and has been associated with hypoglycemia, called ''post-gastric bypass postprandial hypoglycemia.'' Although the entire mechanism of hypoglycemia following this surgery is not fully understood, it is thought that meals cause very high levels of glucagon-like peptide-1
Glucagon-like peptide-1 (GLP-1) is a 30- or 31-amino-acid-long peptide hormone deriving from the tissue-specific posttranslational processing of the proglucagon peptide. It is produced and secreted by intestinal enteroendocrine L-cells and certa ...
(also called GLP-1), a hormone that increases insulin, causing glucose levels to drop.
Autoimmune hypoglycemia
Antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
can be formed against insulin, leading to autoimmune
In immunology, autoimmunity is the system of immune responses of an organism against its own healthy cells, tissues and other normal body constituents. Any disease resulting from this type of immune response is termed an "autoimmune disease". P ...
hypoglycemia. Antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
are immune cells produced by the body, that normally attack bacteria
Bacteria (; singular: bacterium) are ubiquitous, mostly free-living organisms often consisting of one biological cell. They constitute a large domain of prokaryotic microorganisms. Typically a few micrometres in length, bacteria were among ...
and virus
A virus is a submicroscopic infectious agent that replicates only inside the living cells of an organism. Viruses infect all life forms, from animals and plants to microorganisms, including bacteria and archaea.
Since Dmitri Ivanovsky's 1 ...
es, but sometimes can attack normal human cells, leading to an autoimmune disorder
An autoimmune disease is a condition arising from an abnormal immune response to a functioning body part. At least 80 types of autoimmune diseases have been identified, with some evidence suggesting that there may be more than 100 types. Nearly a ...
. In autoimmune hypoglycemia, there are two possible mechanisms. In one instance, antibodies bind to insulin following its release associated with a meal, resulting in insulin being non-functional. At a later time, the antibodies fall off insulin, causing insulin to be functional again leading late hypoglycemia after a meal, called ''late postprandial hypoglycemia''. Another mechanism causing hypoglycemia is due to antibodies formed against insulin receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
, called ''insulin receptor antibodies''. The antibodies attach to insulin receptors and prevent insulin breakdown, or degradation, leading to inappropriately high insulin levels and low glucose levels.
Neonatal hypoglycemia
Low blood sugar may occur in healthy neonates
An infant or baby is the very young offspring of human beings. ''Infant'' (from the Latin word ''infans'', meaning 'unable to speak' or 'speechless') is a formal or specialised synonym for the common term ''baby''. The terms may also be used to ...
aged less than 48 hours who have not eaten for a few hours. During the 48 hour neonatal period, the neonate adjusts glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
and epinephrine
Adrenaline, also known as epinephrine, is a hormone and medication which is involved in regulating visceral functions (e.g., respiration). It appears as a white microcrystalline granule. Adrenaline is normally produced by the adrenal glands and ...
levels following birth, which may trigger transient hypoglycemia. In children who are aged greater than 48 hours, serum glucose on average ranges from 70 to 100 mg/dL (3.9-5.5 mmol/L), similar to adults, with hypoglycemia being far less common.
Diagnostic approach
The most reliable method of identifying hypoglycemia is through identifying Whipple's triad
Whipple's triad is a collection of three signs (called Whipple's criteria) that suggests that a patient's symptoms result from hypoglycaemia that may indicate insulinoma. The essential conditions are symptoms of hypoglycaemia, low blood plasma g ...
. The components of Whipple's triad
Whipple's triad is a collection of three signs (called Whipple's criteria) that suggests that a patient's symptoms result from hypoglycaemia that may indicate insulinoma. The essential conditions are symptoms of hypoglycaemia, low blood plasma g ...
are a blood sugar level below 70 mg/dL (3.9 mmol/L), symptoms related to low blood sugar, and improvement of symptoms when blood sugar is restored to normal. Identifying Whipple's triad
Whipple's triad is a collection of three signs (called Whipple's criteria) that suggests that a patient's symptoms result from hypoglycaemia that may indicate insulinoma. The essential conditions are symptoms of hypoglycaemia, low blood plasma g ...
in a patient helps to avoid unnecessary diagnostic testing
A medical test is a medical procedure performed to detect, diagnose, or monitor diseases, disease processes, susceptibility, or to determine a course of treatment. Medical tests such as, physical and visual exams, diagnostic imaging, genetic te ...
and decreases healthcare costs.
In those with a history of diabetes treated with insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, glinides
Meglitinides or glinides are a class of drugs used to treat type 2 diabetes.
Drugs
Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997.
Other drugs in this class include nateglinide (Starlix) and mitiglin ...
, or sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
, who demonstrate Whipple's triad, it is reasonable to assume the cause of hypoglycemia is due to insulin, glinides, or sulfonylurea use. In those without a history of diabetes with hypoglycemia, further diagnostic testing is necessary to identify the cause. Testing, during an episode of hypoglycemia, should include the following:
* Plasma glucose
Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the bl ...
level, not point-of-care
Clinical point of care (POC) is the point in time when clinicians deliver healthcare products and services to patients at the time of care.
Clinical documentation
Clinical documentation is a record of the critical thinking and judgment of a health ...
measurement
* Insulin level
* C-peptide
The connecting peptide, or C-peptide, is a short 31-amino-acid polypeptide that connects insulin, insulin's A-chain to its B-chain in the proinsulin molecule. In the context of diabetes or hypoglycemia, a measurement of C-peptide blood serum lev ...
level
* Proinsulin
Proinsulin is the prohormone precursor to insulin made in the beta cells of the islets of Langerhans, specialized regions of the pancreas. In humans, proinsulin is encoded by the ''INS'' gene. The islets of Langerhans only secrete between 1% and 3 ...
level
* Beta-hydroxybutyrate
β-Hydroxybutyric acid, also known as 3-hydroxybutyric acid or BHB, is an organic compound and a beta hydroxy acid with the chemical formula CH3CH(OH)CH2CO2H; its conjugate base is β-hydroxybutyrate, also known as 3-hydroxybutyrate. β-Hydroxyb ...
level
* Oral hypoglycemic agent screen
* Response of blood glucose level to glucagon
* Insulin antibodies
An antibody (Ab), also known as an immunoglobulin (Ig), is a large, Y-shaped protein used by the immune system to identify and neutralize foreign objects such as pathogenic bacteria and viruses. The antibody recognizes a unique molecule of the ...
If necessary, a diagnostic hypoglycemic episode can be produced in an inpatient or outpatient setting. This is called a diagnostic fast, in which a patient undergoes an observed fast to cause a hypoglyemic episode, allowing for appropriate blood work to be drawn. In some, the hypoglycemic episode may be reproduced simply after a mixed meal, whereas in others a fast may last up to 72 hours.
In those with a suspected insulinoma
An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a min ...
, imaging is the most reliable diagnostic technique, including ultrasound
Ultrasound is sound waves with frequency, frequencies higher than the upper audible limit of human hearing range, hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hea ...
, computed tomography
A computed tomography scan (CT scan; formerly called computed axial tomography scan or CAT scan) is a medical imaging technique used to obtain detailed internal images of the body. The personnel that perform CT scans are called radiographers ...
imaging (also called CT imaging), and magnetic resonsance imaging (also called MRI).
Treatment
After hypoglycemia in a person is identified, rapid treatment is necessary and can be life-saving. The main goal of treatment is to raise blood glucose back to normal levels, which is done through various ways of administering glucose, depending on the severity of the hypoglycemia, what is on-hand to treat, and who is administering the treatment. A general rule used by the American Diabetes Association
The American Diabetes Association (ADA) is a United States-based nonprofit that seeks to educate the public about diabetes and to help those affected by it through funding research to manage, cure and prevent diabetes (including type 1 diabetes, ...
is the "15-15 Rule," which suggests consuming or administering 15 grams of a carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
, followed by a 15-minute wait and re-measurement of blood glucose level to assess if blood glucose has returned to normal levels.
Self-treatment
If an individual recognizes the symptoms of hypoglycemia coming on, blood sugar should promptly be measured, and a sugary food or drink should be consumed. The person must be conscious
Consciousness, at its simplest, is sentience and awareness of internal and external existence. However, the lack of definitions has led to millennia of analyses, explanations and debates by philosophers, theologians, linguisticians, and scien ...
and able to swallow. The goal is to consume 10-20 grams of a carbohydrate to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L).
Examples of products to consume are:
* Glucose tabs or gel (refer to instructions on packet)
* Juice containing sugar like apple, grape, or cranberry juice, 4 ounces or 1/2 cup
* Soda or a soft-drink, 4 ounces or 1/2 cup (not diet soda)
* Candy
* Table sugar or honey, 1 tablespoon
Improvement in blood sugar levels and symptoms are expected to occur in 15–20 minutes, at which point blood sugar should be measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), consume another 10-20 grams of a carbohydrate and remeasure blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels. The greatest improvements in blood glucose will be seen if the carbohydrate chewed or drunk, and then swallowed. This results in the greatest '' bioavaliablity'' of glucose, meaning the greatest amount of glucose enters the body producing the best possible improvements in blood glucose levels. The second best way to consume a carbohydrate it to allow it to dissolve under the tongue, also referred to as ''sublingual administration
Sublingual (abbreviated SL), from the Latin for "under the tongue", refers to the pharmacological route of administration by which substances diffuse into the blood through tissues under the tongue.
The sublingual glands receive their primar ...
.'' For example, a hard candy can be dissolved under the tongue, however the best improvements in blood glucose will occur if the hard candy is chewed and crushed, then swallowed.
After correcting blood glucose levels, people may consume a full meal within one hour in order to replenish glycogen stores.
Education
Family, friends, and co-workers of a person with diabetes may provide life-saving treatment in the case of a hypoglycemic episode It is important for these people to receive training on how to recognize hypoglycemia, what foods to help the hypoglycemic eat, how to administer injectable or intra-nasal glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
, and how use a glucose meter
A glucose meter, also referred to as a "glucometer", is a medical device for determining the approximate concentration of glucose in the blood. It can also be a strip of glucose paper dipped into a substance and measured to the glucose chart. ...
.
Treatment by family, friends, or co-workers
Family, friends, and co-workers of those with hypoglycemia are often first to identify hypoglycemic episodes, and may offer help. Upon recognizing the signs and symptoms of hypoglycemia in a diabetic, a blood sugar level should first be measured using a glucose meter
A glucose meter, also referred to as a "glucometer", is a medical device for determining the approximate concentration of glucose in the blood. It can also be a strip of glucose paper dipped into a substance and measured to the glucose chart. ...
. If blood glucose is below 70 mg/dL (3.9 mmol/L), treatment will depend on whether the person is conscious and can swallow safely. If the person is conscious and able to swallow, the family, friend, or co-worker can help the hypoglycemic consume 10-20 grams of a carbohydrate
In organic chemistry, a carbohydrate () is a biomolecule consisting of carbon (C), hydrogen (H) and oxygen (O) atoms, usually with a hydrogen–oxygen atom ratio of 2:1 (as in water) and thus with the empirical formula (where ''m'' may or ma ...
to raise blood glucose levels to a minimum of 70 mg/dL (3.9 mmol/L). Improvement in blood sugar level and symptoms is expected to occur in 15–20 minutes, at which point blood sugar is measured again. If the repeat blood sugar level is not above 70 mg/dL (3.9 mmol/L), the hypoglycemic should consume another 10-20 grams of a carbohydrate and with remeasurement of blood sugar levels after 15–20 minutes. Repeat until blood glucose levels have returned to normal levels, or call emergency services for further assistance.
If the person is unconscious, a glucagon
Glucagon is a peptide hormone, produced by alpha cells of the pancreas. It raises concentration of glucose and fatty acids in the bloodstream, and is considered to be the main catabolic hormone of the body. It is also used as a Glucagon (medicati ...
kit may be used to treat severe hypoglycemia, which delivers glucagon either by injection into a muscle or through nasal inhalation. In the United States, glucacon kits are available by prescription for diabetic patients to carry in case of an episode of severe hypoglycemia. Emergency services should be called for further assistance.
Treatment by medical professionals
In a healthcare setting, treatment depends on the severity of symptoms and intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
access. If a patient is conscious and able to swallow safely, food or drink may be administered, as well as glucose tabs or gel. In those with intravenous
Intravenous therapy (abbreviated as IV therapy) is a medical technique that administers fluids, medications and nutrients directly into a person's vein. The intravenous route of administration is commonly used for rehydration or to provide nutrie ...
access, 25 grams of 50% dextrose is commonly administered. When there is no intravenous access, intramuscular
Intramuscular injection, often abbreviated IM, is the injection of a substance into a muscle. In medicine, it is one of several methods for parenteral administration of medications. Intramuscular injection may be preferred because muscles have l ...
or intra-nasal glucagon may be administered.
Other treatments
While the treatment of hypoglycemia is typically managed with carbohydrate consumption, glucagon injection, or dextrose
Glucose is a simple sugar with the molecular formula . Glucose is overall the most abundant monosaccharide, a subcategory of carbohydrates. Glucose is mainly made by plants and most algae during photosynthesis from water and carbon dioxide, using ...
administration, there are some other treatments available. Medications like diazoxide
Diazoxide, sold under the brand name Proglycem and others, is a medication used to treat low blood sugar due to a number of specific causes. This includes islet cell tumors that cannot be removed and leucine sensitivity. It can also be used in re ...
and octreotide
Octreotide, sold under the brand name Sandostatin among others, 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. It was ...
decrease insulin levels, increasing blood glucose levels. Dasiglucagon was approved for medical use in the United States in March 2021, to treat severe hypoglycemia. Dasiglucagon (brand name Zegalogue) is unique because it is glucagon in a prefilled syringe or auto-injector pen, as opposed to traditional glucagon kits that require mixing powdered glucagon with a liquid.
The soft drink Lucozade
Lucozade is a British brand of soft drink manufactured and marketed by the Japanese company Suntory. Created as "Glucozade" in the UK in 1927 by a Newcastle-upon-Tyne, Newcastle pharmacist, William Walker Hunter (trading as W. Owen & Son), it ...
has been used for hypoglycemia in the United Kingdom, but it has recently replaced much of its glucose with artificial sweeteners, which do not treat hypoglycemia.
Prevention
Diabetics
The prevention of hypoglycemia depends on the cause. In those with diabetes treated by insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, glinides
Meglitinides or glinides are a class of drugs used to treat type 2 diabetes.
Drugs
Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997.
Other drugs in this class include nateglinide (Starlix) and mitiglin ...
, or sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
, the prevention of hypoglycemia has a large focus on patient education and medication adjustments. The foundation of diabetes education is learning how to recognize the signs and symptoms of hypoglycemia, as well as learning how to act quickly to prevent worsening of an episode. Another cornerstone of prevention is strong self-monitoring of blood glucose, with consistent and frequent measurements. Research has shown that patients with type 1 diabetes who use continuous glucose monitor
A continuous glucose monitor (CGM) is a device used for monitoring blood glucose on a continual basis by insulin-requiring people with diabetes, e.g. people with type I, type II diabetes or other types of diabetes (e.g. gestational diabetes). A ...
ing systems with insulin pump
An insulin pump is a medical device used for the administration of insulin in the treatment of diabetes mellitus, also known as continuous subcutaneous insulin therapy.
The device configuration may vary depending on design. A traditional pump ...
s significantly improve blood glucose control. Insulin pumps help to prevent high glucose spikes, and help prevent inappropriate insulin dosing. Continuous glucose monitor
A continuous glucose monitor (CGM) is a device used for monitoring blood glucose on a continual basis by insulin-requiring people with diabetes, e.g. people with type I, type II diabetes or other types of diabetes (e.g. gestational diabetes). A ...
s can sound alarms when blood glucose is too low or too high, especially helping those with nocturnal hypoglycemia or hypoglycemic unawareness. In terms of medication adjustments, medication doses and timing can be adjusted in order to prevent hypoglycemia, or a medication can be stopped altogether.
Non-diabetics
In those with hypoglycemia who do not have diabetes, there are a number of preventative measures dependent on the cause. Hypoglycemia caused by hormonal dysfunction like lack of cortisol
Cortisol is a steroid hormone, in the glucocorticoid class of hormones. When used as a medication, it is known as hydrocortisone.
It is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal cortex in the adrenal gland ...
in Addison's disease
Addison's disease, also known as primary adrenal insufficiency, is a rare long-term endocrine disorder characterized by inadequate production of the steroid hormones cortisol and aldosterone by the two outer layers of the cells of the adrenal ...
or lack of growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
in hypopituitarism
Hypopituitarism is the decreased (''hypo'') secretion of one or more of the eight hormones normally produced by the pituitary gland at the base of the brain. If there is decreased secretion of one specific pituitary hormone, the condition is know ...
can be prevented with appropriate hormone replacement. The hypoglycemic episodes associated with non-B cell tumors can be decreased following surgical removal of the tumor, as well as following radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Radia ...
or chemotherapy
Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...
to reduce the size of the tumor
A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...
. In some cases, those with non-B cell tumors may have hormone therapy
Hormone therapy or hormonal therapy is the use of hormones in medical treatment. Treatment with hormone antagonists may also be referred to as hormonal therapy or antihormone therapy. The most general classes of hormone therapy are oncologic horm ...
with growth hormone
Growth hormone (GH) or somatotropin, also known as human growth hormone (hGH or HGH) in its human form, is a peptide hormone that stimulates growth, cell reproduction, and cell regeneration in humans and other animals. It is thus important in h ...
, glucocorticoid
Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebr ...
, or octreotide
Octreotide, sold under the brand name Sandostatin among others, 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. It was ...
to also lessen hypoglycemic episodes. Post-gastric bypass hypoglycemia can be prevented by eating smaller, more frequent meals, avoiding sugar-filled foods, as well as medical treatment with an alpha-glucosidase inhibitor Alpha-glucosidase inhibitors (AGIs) are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates (such as starch and table sugar). Carbohydrates are normally converted into simple sugars ( ...
, diazoxide
Diazoxide, sold under the brand name Proglycem and others, is a medication used to treat low blood sugar due to a number of specific causes. This includes islet cell tumors that cannot be removed and leucine sensitivity. It can also be used in re ...
, or octreotide
Octreotide, sold under the brand name Sandostatin among others, 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. It was ...
.
Some causes of hypoglycemia require treatment of the underlying cause to best prevent hypoglycemia. This is the case for insulinoma
An insulinoma is a tumour of the pancreas that is derived from beta cells and secretes insulin. It is a rare form of a neuroendocrine tumour. Most insulinomas are benign in that they grow exclusively at their origin within the pancreas, but a min ...
s which often require surgical removal of the tumor in order for hypoglycemia to remit. In patients who cannot undergo surgery for removal of the insulinoma, diazoxide
Diazoxide, sold under the brand name Proglycem and others, is a medication used to treat low blood sugar due to a number of specific causes. This includes islet cell tumors that cannot be removed and leucine sensitivity. It can also be used in re ...
or octreotide
Octreotide, sold under the brand name Sandostatin among others, 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. It was ...
may be used.
Epidemiology
Hypoglycemia is common in people with type 1 diabetes
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for ...
, and in people with type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
taking insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, glinides
Meglitinides or glinides are a class of drugs used to treat type 2 diabetes.
Drugs
Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997.
Other drugs in this class include nateglinide (Starlix) and mitiglin ...
, or sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
. It is estimated that type 1 diabetics experience two mild, symptomatic episodes of hypoglycemia ''per week.'' Additionally, people with type 1 diabetes have at least one severe hypoglyemic episode ''per year'', requiring treatment assistance. In terms of mortality
Mortality is the state of being mortal, or susceptible to death; the opposite of immortality.
Mortality may also refer to:
* Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...
, hypoglycemia causes death in 6-10% of type 1 diabetics.
In those with type 2 diabetes
Type 2 diabetes, formerly known as adult-onset diabetes, is a form of diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. Common symptoms include increased thirst, frequent urination, ...
, hypoglycemia is less common compared to type 1 diabetics, because medications that treat type 2 diabetes like metformin
Metformin, sold under the brand name Glucophage, among others, is the main first-line medication for the treatment of type 2 diabetes, particularly in people who are overweight. It is also used in the treatment of polycystic ovary syndrome. ...
, glitazones, alpha-glucosidase inhibitor Alpha-glucosidase inhibitors (AGIs) are oral anti-diabetic drugs used for diabetes mellitus type 2 that work by preventing the digestion of carbohydrates (such as starch and table sugar). Carbohydrates are normally converted into simple sugars ( ...
s, glucagon-like peptide 1 agonists, and dipeptidyl peptidase IV inhibitors, do not cause hypoglycemia. Hypoglycemia is common in type 2 diabetics who take insulin
Insulin (, from Latin ''insula'', 'island') is a peptide hormone produced by beta cells of the pancreatic islets encoded in humans by the ''INS'' gene. It is considered to be the main anabolic hormone of the body. It regulates the metabolism o ...
, glinides
Meglitinides or glinides are a class of drugs used to treat type 2 diabetes.
Drugs
Repaglinide (trade name Prandin) gained US Food and Drug Administration approval in 1997.
Other drugs in this class include nateglinide (Starlix) and mitiglin ...
, or sulfonylurea
Sulfonylureas (UK: sulphonylurea) are a class of organic compounds used in medicine and agriculture, for example as antidiabetic drugs widely used in the management of diabetes mellitus type 2. They act by increasing insulin release from the beta ...
. Insulin use remains a key risk factor in developing hypoglycemia, regardless of diabetes type.
History
Hypoglycemia was first discovered by James Collip
James Bertram Collip (November 20, 1892 – June 19, 1965) was a Canadian biochemist who was part of the Toronto group which isolated insulin. He served as the Chair of the Department of Biochemistry at McGill University from 1928–1941 an ...
when he was working with Frederick Banting
Sir Frederick Grant Banting (November 14, 1891 – February 21, 1941) was a Canadian medical scientist, physician, painter, and Nobel laureate noted as the co-discoverer of insulin and its therapeutic potential.
In 1923, Banting and J ...
on purifying insulin in 1922. Collip was asked to develop an assay to measure the activity of insulin. He first injected insulin into a rabbit, and then measured the reduction in blood-glucose levels. Measuring blood glucose was a time-consuming step. Collip observed that if he injected rabbits with a too large a dose of insulin, the rabbits began convulsing, went into a coma, and then died. This observation simplified his assay. He defined one unit of insulin as the amount necessary to induce this convulsing hypoglycemic reaction in a rabbit. Collip later found he could save money, and rabbits, by injecting them with glucose once they were convulsing.
Etymology
The word ''hypoglycemia'' is also spelled ''hypoglycaemia'' or ''hypoglycæmia''. The term means 'low blood sugar' from Greek
Greek may refer to:
Greece
Anything of, from, or related to Greece, a country in Southern Europe:
*Greeks, an ethnic group.
*Greek language, a branch of the Indo-European language family.
**Proto-Greek language, the assumed last common ancestor ...
ὑπογλυκαιμία, from ὑπο- ''hypo-'' 'under' + γλυκύς ''glykys'' 'sweet' + αἷμᾰ ''haima'' 'blood'.
References
External links
Hypoglycemia at the Mayo Clinic
American Diabetes Association
*
{{Blood tests
Disorders of endocrine pancreas
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