Hyperinsulinism | |
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Insulin | |
Specialty | Endocrinology |
Hyperinsulinism refers to an above normal level of insulin in the blood of a person or animal. Normal insulin secretion and blood levels are closely related to the level of glucose in the blood, so that a given level of insulin can be normal for one blood glucose level but low or high for another. Hyperinsulinism can be associated with several types of medical problems, which can be roughly divided into two broad and largely non-overlapping categories: those tending toward reduced sensitivity to insulin and high blood glucose levels (hyperglycemia), and those tending toward excessive insulin secretion and low glucose levels (hypoglycemia).[ citation needed ]
Hyperinsulinism due to reduced insulin sensitivity is usually asymptomatic. [1] In contrast, hyperinsulinemic hypoglycemia can produce any of the entire range of hypoglycemic symptoms, from shakiness and weakness, to seizures or coma. [2]
Although many factors influence insulin secretion, the most important control is the amount of glucose moving from the blood into the beta cells of the pancreas. In healthy people, even small rises in blood glucose result in increased insulin secretion. As long as the pancreatic beta cells are able to sense the glucose level and produce insulin, the amount of insulin secreted is usually the amount required to maintain a fasting blood glucose between 70 and 100 mg/dL (3.9–5.6 mmol/L) and a non-fasting glucose level below 140 mg/dL (<7.8 mmol/L).[ citation needed ]
When liver cells and other cells that remove glucose from the blood become less sensitive (more resistant) to the insulin, the pancreas increases secretion and the level of insulin in the blood rises. This increased secretion can compensate for reduced sensitivity for many years, with maintenance of normal glucose levels. However, if insulin resistance worsens or insulin secretion ability declines, the glucose levels will begin to rise. Persistent elevation of glucose levels is termed diabetes mellitus.[ citation needed ]
Typical fasting insulin levels found in this type of hyperinsulinism are above 20 μU/mL. When resistance is severe, levels can exceed 100 μU/mL.[ citation needed ]
In addition to being a risk factor for type 2 diabetes, hyperinsulinism due to insulin resistance may increase blood pressure and contribute to hypertension by direct action on vascular endothelial cells (the cells lining blood vessels). Hyperinsulinism has also been implicated as a contributing factor in the excessive production of androgens in polycystic ovary syndrome.[ citation needed ]
The principal treatments of hyperinsulinism due to insulin resistance are measures that improve insulin sensitivity, such as weight loss, physical exercise, and drugs such as thiazolidinediones or metformin.[ citation needed ]
Hyperinsulinism may also refer to forms of hypoglycemia caused by excessive insulin secretion. In normal children and adults, insulin secretion should be minimal when blood glucose levels fall below 70 mg/dL (3.9 mM). There are many forms of hyperinsulinemic hypoglycemia caused by various types of insulin excess. Some of those that occur in infants and young children are termed congenital hyperinsulinism. In adults, severe hyperinsulinemic hypoglycemia is often due to an insulinoma, an insulin-secreting tumor of the pancreas.[ citation needed ]
Insulin levels above 3 μU/mL are inappropriate when the glucose level is below 50 mg/dL (2.8 mM), and may indicate hyperinsulinism as the cause of the hypoglycemia. The treatment of this form of hyperinsulinism depends on the cause and the severity of the hyperinsulinism, and may include surgical removal of the source of insulin, or a drug such as diazoxide or octreotide that reduces insulin secretion.[ citation needed ]
That spontaneous hyperinsulinism might be a cause of symptomatic hypoglycemia was first proposed by Seale Harris, MD, 1924, in Journal of the American Medical Association. [3] [4] Dr. Seale Harris first diagnosed hyperinsulinism in 1924 [5] and also is credited with the recognition of spontaneous hypoglycemia. [6]
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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). Whipple's triad 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, tiredness, clumsiness, trouble talking, confusion, fast heart rate, sweating, shakiness, nervousness, hunger, loss of consciousness, seizures, or death. Symptoms typically come on quickly.
Insulin resistance (IR) is a pathological condition in which cells in insulin-sensitive tissues in the body fail to respond normally to the hormone insulin or downregulate insulin receptors in response to hyperinsulinemia.
The glucose tolerance test is a medical test in which glucose is given and blood samples taken afterward to determine how quickly it is cleared from the blood. The test is usually used to test for diabetes, insulin resistance, impaired beta cell function, and sometimes reactive hypoglycemia and acromegaly, or rarer disorders of carbohydrate metabolism. In the most commonly performed version of the test, an oral glucose tolerance test (OGTT), a standard dose of glucose is ingested by mouth and blood levels are checked two hours later. Many variations of the GTT have been devised over the years for various purposes, with different standard doses of glucose, different routes of administration, different intervals and durations of sampling, and various substances measured in addition to blood glucose.
Hyperglycemia or Hyperglycaemia is a condition in which an excessive amount of glucose (glucotoxicity) circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even higher values such as 13.9–16.7 mmol/L (~250–300 mg/dL). A subject with a consistent fasting blood glucose range between ~5.6 and ~7 mmol/L is considered slightly hyperglycemic, and above 7 mmol/L is generally held to have diabetes. For diabetics, glucose levels that are considered to be too hyperglycemic can vary from person to person, mainly due to the person's renal threshold of glucose and overall glucose tolerance. On average, however, chronic levels above 10–12 mmol/L (180–216 mg/dL) can produce noticeable organ damage over time.
The blood sugar level, blood sugar concentration, blood glucose level, or glycemia is the measure of glucose concentrated in the blood. The body tightly regulates blood glucose levels as a part of metabolic homeostasis.
Glucokinase is an enzyme that facilitates phosphorylation of glucose to glucose-6-phosphate. Glucokinase occurs in cells in the liver and pancreas of humans and most other vertebrates. In each of these organs it plays an important role in the regulation of carbohydrate metabolism by acting as a glucose sensor, triggering shifts in metabolism or cell function in response to rising or falling levels of glucose, such as occur after a meal or when fasting. Mutations of the gene for this enzyme can cause unusual forms of diabetes or hypoglycemia.
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 minority metastasize. Insulinomas are one of the functional pancreatic neuroendocrine tumour (PNET) group. In the Medical Subject Headings classification, insulinoma is the only subtype of "islet cell adenoma".
Hyperinsulinemic hypoglycemia describes the condition and effects of low blood glucose caused by excessive insulin. Hypoglycemia due to excess insulin is the most common type of serious hypoglycemia. It can be due to endogenous or injected insulin.
Nesidioblastosis is a controversial medical term for hyperinsulinemic hypoglycemia attributed to excessive insulin production by pancreatic beta cells that have an abnormal microscopic appearance. The term was coined in the first half of the 20th century. The abnormal microscopic features of the tissue included the presence of islet cell enlargement, pancreatic islet cell dysplasia, beta cells budding from ductal epithelium, and islets in close proximity to ducts.
Congenital hyperinsulinism (HI or CHI) is a rare condition causing severe hypoglycemia in newborns due to the overproduction of insulin. There are various causes of HI, some of which are known to be the result of a genetic mutation. Sometimes HI occurs on its own (isolated) and more rarely associated with other medical conditions.
Hyperinsulinemia is a condition in which there are excess levels of insulin circulating in the blood relative to the level of glucose. While it is often mistaken for diabetes or hyperglycaemia, hyperinsulinemia can result from a variety of metabolic diseases and conditions, as well as non-nutritive sugars in the diet. While hyperinsulinemia is often seen in people with early stage type 2 diabetes mellitus, it is not the cause of the condition and is only one symptom of the disease. Type 1 diabetes only occurs when pancreatic beta-cell function is impaired. Hyperinsulinemia can be seen in a variety of conditions including diabetes mellitus type 2, in neonates and in drug-induced hyperinsulinemia. It can also occur in congenital hyperinsulinism, including nesidioblastosis.
Reactive hypoglycemia, postprandial hypoglycemia, or sugar crash is a term describing recurrent episodes of symptomatic hypoglycemia occurring within four hours after a high carbohydrate meal in people with and without diabetes. The term is not necessarily a diagnosis since it requires an evaluation to determine the cause of the hypoglycemia.
Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar for energy and it helps regulate glucose levels in the bloodstream. It results in high blood sugar levels in the body prior to treatment. The common symptoms of this elevated blood sugar are frequent urination, increased thirst, increased hunger, weight loss, and other serious complications. Additional symptoms may include blurry vision, tiredness, and slow wound healing. Symptoms typically develop over a short period of time, often a matter of weeks if not months.
The term diabetes includes several different metabolic disorders that all, if left untreated, result in abnormally high concentrations of a sugar called glucose in the blood. Diabetes mellitus type 1 results when the pancreas no longer produces significant amounts of the hormone insulin, usually owing to the autoimmune destruction of the insulin-producing beta cells of the pancreas. Diabetes mellitus type 2, in contrast, is now thought to result from autoimmune attacks on the pancreas and/or insulin resistance. The pancreas of a person with type 2 diabetes may be producing normal or even abnormally large amounts of insulin. Other forms of diabetes mellitus, such as the various forms of maturity-onset diabetes of the young, may represent some combination of insufficient insulin production and insulin resistance. Some degree of insulin resistance may also be present in a person with type 1 diabetes.
Blood sugar regulation is the process by which the levels of blood sugar, the common name for glucose dissolved in blood plasma, are maintained by the body within a narrow range.
An insulin tolerance test (ITT) is a medical diagnostic procedure during which insulin is injected into a patient's vein, after which blood glucose is measured at regular intervals. This procedure is performed to assess pituitary function, adrenal function, insulin sensitivity, and sometimes for other purposes. An ITT is usually ordered and interpreted by an endocrinologist.
Seale Harris was an American physician and researcher born in Cedartown, Georgia. He was nicknamed "the Benjamin Franklin of Medicine" by contemporaries for his leadership and writing on a wide range of medical and political topics. Dr. Harris' most celebrated accomplishments were his 1924 hypothesis of hyperinsulinism as a cause of spontaneous hypoglycemia.
Glucose clamp technique is a method for quantifying insulin secretion and resistance. It is used to measure either how well an individual metabolizes glucose or how sensitive an individual is to insulin.
Neonatal hypoglycemia, also called low blood sugar in newborn babies, occurs when an infant's blood glucose level is less than what is considered normal. There is inconsistency internationally for diagnostic thresholds. In the US, hypoglycemia is when the blood glucose level is below 30 mg/dL within the first 24 hours of life and below 45 mg/dL after, but international standards differ. Age, birth weight, metabolic needs, and wellness state of the newborn has a substantial impact on their blood glucose level. This is a treatable condition, but its treatment depends on the cause of the hypoglycemia. Though it is treatable, it can be fatal if gone undetected. Hypoglycemia is the most common metabolic problem in newborns.
Quote from the original article: «Conclusions:
1. Hyperinsulinism is a condition, perhaps a disease entity, with definite symptoms; i.e. those described as being due to hypoglycemia.
2. It seems probable that one of the causes of hyperinsulinism is the excessive ingestion of glucose-forming foods [...]»