Hypoglycemia
Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L).[1][3] Whipple's triad is used to properly identify hypoglycemic episodes.[2] 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.[2] Hypoglycemia may result in headache, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death.[1][3][2] Symptoms typically come on quickly.[1]
Not to be confused with the opposite disorder, hyperglycemia.Hypoglycemia
Hypoglycaemia, hypoglycæmia, low blood glucose, low blood sugar
Headache, blurred vision, shakiness, dizziness, weakness, tiredness, sweating, clamminess, fast heart rate, pounding heartbeat, nervousness or anxiety, hunger, nausea, pins and needles sensation, difficulty talking, confusion, unusual behavior, lightheadedness, pale skin color, seizures[1][2][3][4][5]
Rapid[1]
Medications (insulin, glinides and sulfonylureas), sepsis, kidney failure, certain tumors, liver disease[1][6]
Whipple's triad: Symptoms of hypoglycemia, serum blood glucose level <70 mg/dL (3.9 mmol/L), and resolution of symptoms when blood glucose returns to normal[2]
Eating foods high in simple sugars
In type 1 diabetics, mild hypoglycemia occurs twice per week on average, and severe hypoglycemia occurs once per year.[3]
In type 1 diabetics, 6–10% will die of hypoglycemia.[3]
The most common cause of hypoglycemia is medications used to treat diabetes such as insulin, sulfonylureas, and biguanides.[3][2][6] Risk is greater in diabetics who have eaten less than usual, recently exercised, or consumed alcohol.[1][3][2] Other causes of hypoglycemia include severe illness, sepsis, kidney failure, liver disease, hormone deficiency, tumors such as insulinomas or non-B cell tumors, inborn errors of metabolism, and several medications.[1][3][2] Low blood sugar may occur in otherwise healthy newborns who have not eaten for a few hours.[7]
Hypoglycemia is treated by eating a sugary food or drink, for example glucose tablets or gel, apple juice, soft drink, or lollies.[1][3][2] The person must be conscious and able to swallow.[1][3] 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).[3][2] If a person is not able to take food by mouth, glucagon by injection or insufflation may help.[1][3][8] The treatment of hypoglycemia unrelated to diabetes includes treating the underlying problem.[3][2]
Among people with diabetes, prevention starts with learning the signs and symptoms of hypoglycemia.[3][2] Diabetes medications, like insulin, sulfonylureas, and biguanides can also be adjusted or stopped to prevent hypoglycemia.[3][2] Frequent and routine blood glucose testing is recommended.[1][3] Some may find continuous glucose monitors with insulin pumps to be helpful in the management of diabetes and prevention of hypoglycemia.[3]
Other conditions that may present at the same time as hypoglycemia include the following:
Pathophysiology[edit]
Glucose 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.[3][12] The body can adjust insulin production and release, adjust glucose production by the liver, and adjust glucose use by the body.[3][12] The body naturally produces the hormone insulin, in an organ called the pancreas.[3] Insulin helps to regulate the amount of glucose in the body, especially after meals.[3] Glucagon is another hormone involved in regulating blood glucose levels, and can be thought of as the opposite of insulin.[3] Glucagon helps to increase blood glucose levels, especially in states of hunger.[3]
When blood sugar levels fall to the low-normal range, the first line of defense against hypoglycemia is decreasing insulin release by the pancreas.[3][12] This drop in insulin allows the liver to increase glycogenolysis.[3][12] Glycogenolysis is the process of glycogen breakdown that results in the production of glucose.[3][12] Glycogen can be thought of as the inactive, storage form of glucose.[3] Decreased insulin also allows for increased gluconeogenesis in the liver and kidneys.[3][12] Gluconeogenesis is the process of glucose production from non-carbohydrate sources, supplied from muscles and fat.[3][12]
Once blood glucose levels fall out of the normal range, additional protective mechanisms work to prevent hypoglycemia.[3][12] The pancreas is signaled to release glucagon, a hormone that increases glucose production by the liver and kidneys, and increases muscle and fat breakdown to supply gluconeogenesis.[3][13] If increased glucagon does not raise blood sugar levels to normal, the adrenal glands release epinephrine.[3][12] Epinephrine works to also increase gluconeogenesis and glycogenolysis, while also decreasing the use of glucose by organs, protecting the brain's glucose supply.[3][12]
After hypoglycemia has been prolonged, cortisol and growth hormone are released to continue gluconeogenesis and glycogenolysis, while also preventing the use of glucose by other organs.[3][12] The effects of cortisol and growth hormone are far less effective than epinephrine.[3][12] 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.[3][12]
The most reliable method of identifying hypoglycemia is through identifying Whipple's triad.[3][2] The components of Whipple's triad 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.[3][2] Identifying Whipple's triad in a patient helps to avoid unnecessary diagnostic testing and decreases healthcare costs.[2]
In those with a history of diabetes treated with insulin, glinides, or sulfonylurea, who demonstrate Whipple's triad, it is reasonable to assume the cause of hypoglycemia is due to insulin, glinides, or sulfonylurea use.[2] In those without a history of diabetes with hypoglycemia, further diagnostic testing is necessary to identify the cause.[2] Testing, during an episode of hypoglycemia, should include the following:
If necessary, a diagnostic hypoglycemic episode can be produced in an inpatient or outpatient setting.[3] This is called a diagnostic fast, in which a patient undergoes an observed fast to cause a hypoglycemic episode, allowing for appropriate blood work to be drawn.[3] In some, the hypoglycemic episode may be reproduced simply after a mixed meal, whereas in others a fast may last up to 72 hours.[3][2]
In those with a suspected insulinoma, imaging is the most reliable diagnostic technique, including ultrasound, computed tomography imaging (also called CT imaging), and magnetic resonance imaging (also called MRI).[3][2]
Epidemiology[edit]
Hypoglycemia is common in people with type 1 diabetes, and in people with type 2 diabetes taking insulin, glinides, or sulfonylurea.[1][3] It is estimated that type 1 diabetics experience two mild, symptomatic episodes of hypoglycemia per week.[3] Additionally, people with type 1 diabetes have at least one severe hypoglyemic episode per year, requiring treatment assistance.[3] In terms of mortality, hypoglycemia causes death in 6–10% of type 1 diabetics.[3]
In those with type 2 diabetes, hypoglycemia is less common compared to type 1 diabetics, because medications that treat type 2 diabetes like metformin, glitazones, alpha-glucosidase inhibitors, glucagon-like peptide 1 agonists, and dipeptidyl peptidase IV inhibitors, do not cause hypoglycemia.[1][3] Hypoglycemia is common in type 2 diabetics who take insulin, glinides, or sulfonylurea.[1][3] Insulin use remains a key risk factor in developing hypoglycemia, regardless of diabetes type.[1][3]
History[edit]
Hypoglycemia was first discovered by James Collip when he was working with Frederick Banting on purifying insulin in 1922.[40] Collip was asked to develop an assay to measure the activity of insulin.[40] He first injected insulin into a rabbit, and then measured the reduction in blood-glucose levels.[40] Measuring blood glucose was a time-consuming step.[40] 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.[40] This observation simplified his assay.[40] He defined one unit of insulin as the amount necessary to induce this convulsing hypoglycemic reaction in a rabbit.[40] Collip later found he could save money, and rabbits, by injecting them with glucose once they were convulsing.[40]
Etymology[edit]
The word hypoglycemia is also spelled hypoglycaemia or hypoglycæmia. The term means 'low blood sugar' from Greek ὑπογλυκαιμία, from ὑπο- hypo- 'under' + γλυκύς glykys 'sweet' + αἷμᾰ haima 'blood'.