Neuroglycopenia

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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 consciousness, damage to the brain, and eventual death. [1] [2] [3]

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Signs and symptoms

[4] [5] [6]

Not all of the above manifestations occur in every case of hypoglycemia. There is no consistent order to the appearance of the symptoms. Specific manifestations vary by age and by the severity of the hypoglycemia. In older children and adults, moderately severe hypoglycemia can resemble mania, mental illness, drug intoxication, or drunkenness. In the elderly, hypoglycemia can produce focal stroke-like effects or a hard-to-define malaise.[ medical citation needed ] The symptoms of a single person do tend to be similar from episode to episode.

In the large majority of cases, hypoglycemia severe enough to cause seizures or unconsciousness can be reversed without obvious harm to the brain. Cases of death or permanent neurological damage occurring with a single episode have usually involved prolonged, untreated unconsciousness, interference with breathing, severe concurrent disease, or some other type of vulnerability. Nevertheless, brain damage or death has occasionally resulted from severe hypoglycemia.

Metabolic responses

Most neurons have the ability to use other fuels besides glucose (e.g. lactic acid, ketones). Knowledge of the "switchover" process is incomplete.[ further explanation needed ] The most severe neuroglycopenic symptoms occur with hypoglycemia caused by excess insulin because insulin reduces the availability of other fuels by suppressing ketogenesis and gluconeogenesis.

A few types of specialized neurons, especially in the hypothalamus, act as glucose sensors, responding to changing levels of glucose by increasing or decreasing their firing rates. They can elicit a variety of hormonal, autonomic, and behavioral responses to neuroglycopenia. The hormonal and autonomic responses include release of counterregulatory hormones. There is some evidence that the autonomic nervous system can alter liver glucose metabolism independently of the counterregulatory hormones.

Adjustment of efficiency of transfer of glucose from blood across the blood–brain barrier into the central nervous system represents a third form of compensation which occurs more gradually. Levels of glucose within the central nervous system are normally lower than the blood, regulated by an incompletely understood transfer process. Chronic hypoglycemia or hyperglycemia seems to result in an increase or decrease in efficiency of transfer to maintain CNS levels of glucose within an optimal range.

In both young and old individuals, the brain may habituate to low glucose levels with a reduction of noticeable symptoms, sometimes despite neuroglycopenic impairment. In insulin-dependent diabetic patients this phenomenon is termed hypoglycemia unawareness and is a significant clinical problem when improved glycemic control is attempted. Another aspect of this phenomenon occurs in type I glycogenosis, when chronic hypoglycemia before diagnosis may be better tolerated than acute hypoglycemia after treatment is underway.

Neuroglycopenia without hypoglycemia

A rare metabolic disease of the blood-brain glucose transport system has been described in which severe neuroglycopenic effects occurred despite normal blood glucose levels. Low levels of glucose were discovered in the cerebrospinal fluid (CSF), a condition referred to as hypoglycorrhachia [or hypoglycorrhacia].

Hypoglycorrhachia is associated with Glucose transporter type 1 GLUT1 deficiency syndrome (De Vivo disease). [7]

Perhaps a much more common example of the same phenomenon occurs in the people with poorly controlled type 1 diabetes who develop symptoms of hypoglycemia at levels of blood glucose which are normal for most people.

Related Research Articles

<span class="mw-page-title-main">Hypoglycemia</span> Health condition

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.

<span class="mw-page-title-main">Hyperglycemia</span> Too much blood sugar, usually because of diabetes

Hyperglycemia is a condition in which an excessive amount of glucose 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.

<span class="mw-page-title-main">Diabetic coma</span> Medical condition

Diabetic coma is a life-threatening but reversible form of coma found in people with diabetes mellitus.

<span class="mw-page-title-main">Ketogenesis</span> Chemical synthesis of ketone bodies

Ketogenesis is the biochemical process through which organisms produce ketone bodies by breaking down fatty acids and ketogenic amino acids. The process supplies energy to certain organs, particularly the brain, heart and skeletal muscle, under specific scenarios including fasting, caloric restriction, sleep, or others.

Polyphagia or hyperphagia is an abnormally strong, incessant sensation of hunger or desire to eat often leading to overeating. In contrast to an increase in appetite following exercise, polyphagia does not subside after eating and often leads to rapid intake of excessive quantities of food. Polyphagia is not a disorder by itself; rather, it is a symptom indicating an underlying medical condition. It is frequently a result of abnormal blood glucose levels, and, along with polydipsia and polyuria, it is one of the "3 Ps" commonly associated with uncontrolled diabetes mellitus.

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.

<span class="mw-page-title-main">Hyperinsulinism</span> Medical condition

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).

Ketotic hypoglycemia refers to any circumstance in which low blood glucose is accompanied by ketosis, the presence of ketone bodies in the blood or urine. This state can be either physiologic or pathologic; physiologic ketotic hypoglycemia is a common cause of hypoglycemia in children, often in response to stressors such as infection or fasting. Pathologic ketotic hypoglycemia is typically caused by metabolic defects, such as glycogen storage disorders.

<span class="mw-page-title-main">Glycogen storage disease type I</span> Medical condition

Glycogen storage disease type I is an inherited disease that prevents the liver from properly breaking down stored glycogen, which is necessary to maintain adequate blood sugar levels. GSD I is divided into two main types, GSD Ia and GSD Ib, which differ in cause, presentation, and treatment. There are also possibly rarer subtypes, the translocases for inorganic phosphate or glucose ; however, a recent study suggests that the biochemical assays used to differentiate GSD Ic and GSD Id from GSD Ib are not reliable, and are therefore GSD Ib.

<span class="mw-page-title-main">Diabetic hypoglycemia</span> Medical condition

Diabetic hypoglycemia is a low blood glucose level occurring in a person with diabetes mellitus. It is one of the most common types of hypoglycemia seen in emergency departments and hospitals. According to the National Electronic Injury Surveillance System-All Injury Program (NEISS-AIP), and based on a sample examined between 2004 and 2005, an estimated 55,819 cases involved insulin, and severe hypoglycemia is likely the single most common event.

<span class="mw-page-title-main">Reactive hypoglycemia</span> Medical condition

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.

<span class="mw-page-title-main">Type 1 diabetes</span> Form of diabetes mellitus

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. Before treatment this results in high blood sugar levels in the body. 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.

<span class="mw-page-title-main">Diabetes and pregnancy</span> Effects of pre-existing diabetes upon pregnancy

For pregnant women with diabetes, some particular challenges exist for both mother and fetus. If the pregnant woman has diabetes as a pre-existing disorder, it can cause early labor, birth defects, and larger than average infants. Therefore, experts advise diabetics to maintain blood sugar level close to normal range about 3 months before planning for pregnancy.

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.

Chronic Somogyi rebound is a contested explanation of phenomena of elevated blood sugars experienced by diabetics in the morning. Also called the Somogyi effect and posthypoglycemic hyperglycemia, it is a rebounding high blood sugar that is a response to low blood sugar. When managing the blood glucose level with insulin injections, this effect is counter-intuitive to people who experience high blood sugar in the morning as a result of an overabundance of insulin at night.

The dawn phenomenon, sometimes called the dawn effect, is an observed increase in blood sugar (glucose) levels that takes place in the early-morning, often between 2 a.m. and 8 a.m. First described by Schmidt in 1981 as an increase of blood glucose or insulin demand occurring at dawn, this naturally occurring phenomenon is frequently seen among the general population and is clinically relevant for patients with diabetes as it can affect their medical management. In contrast to Chronic Somogyi rebound, the dawn phenomenon is not associated with nocturnal hypoglycemia.

Complications of diabetes are secondary diseases that are a result of elevated blood glucose levels that occur in diabetic patients. These complications can be divided into two types: acute and chronic. Acute complications are complications that develop rapidly and can be exemplified as diabetic ketoacidosis (DKA), hyperglycemic hyperosmolar state (HHS), lactic acidosis (LA), and hypoglycemia. Chronic complications develop over time and are generally classified in two categories: microvascular and macrovascular. Microvascular complications include neuropathy, nephropathy, and retinopathy; while cardiovascular disease, stroke, and peripheral vascular disease are included in the macrovascular complications.

<span class="mw-page-title-main">Sympathoadrenal system</span>

The sympathoadrenal system is a physiological connection between the sympathetic nervous system and the adrenal medulla and is crucial in an organism's physiological response to outside stimuli. When the body receives sensory information, the sympathetic nervous system sends a signal to preganglionic nerve fibers, which activate the adrenal medulla through acetylcholine. Once activated, norepinephrine and epinephrine are released directly into the blood by postganglionic nerve fibers where they act as the bodily mechanism for "fight-or-flight" responses. Because of this, the sympathoadrenal system plays a large role in maintaining glucose levels, sodium levels, blood pressure, and various other metabolic pathways that couple with bodily responses to the environment. During numerous diseased states, such as hypoglycemia or even stress, the body's metabolic processes are skewed. The sympathoadrenal system works to return the body to homeostasis through the activation or inactivation of the adrenal gland. However, more severe disorders of the sympathoadrenal system such as Pheochromocytoma can affect the body's ability to maintain a homeostatic state. In these cases, curative agents such as adrenergic agonists and antagonists are used to modify epinephrine and norepinephrine levels released by the adrenal medulla.

Neonatal hypoglycemia occurs when the neonate's blood glucose level is less than the newborn's body requirements for factors such as cellular energy and metabolism. 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 thereafter. In the UK, however, lower and more variable thresholds are used. The neonate's gestational age, birth weight, metabolic needs, and wellness state of the newborn has a substantial impact on the neonates blood glucose level. There are known risk factors that can be both maternal and neonatal. This is a treatable condition. 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.

References

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