hypoglycaemia

• n.

• ((古)低血糖、低血糖症

関

hypoglycaemic、hypoglycemia、hypoglycemic

WordNet

1. abnormally low blood sugar usually resulting from excessive insulin or a poor diet (同)hypoglycaemia
2. of or relating to hypoglycemia; "hypoglycemic agents" (同)hypoglycaemic

PrepTutorEJDIC

1. 低血糖症,血糖減少症

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/06/01 22:09:30」(JST)

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For information about the condition commonly known as Hypoglycemia, but which does not involve low blood glucose, see idiopathic postprandial syndrome.

Hypoglycemia
Classification and external resources
Glucose meter
ICD-10	E16.0-E16.2
ICD-9	250.8, 251.0, 251.1, 251.2, 270.3, 775.6, 962.3
DiseasesDB	6431
MedlinePlus	000386
eMedicine	emerg/272 med/1123 med/1939 ped/1117
MeSH	D007003

Paramedics in Southern California attend a diabetic man who lost effective control of his vehicle due to low blood sugar (hypoglycemia) and drove it over the curb.

Hypoglycemia (also spelled hypoglycaemia or hypoglycæmia, not to be confused with hyperglycemia) is an abnormally diminished content of glucose in the blood. The term literally means "low sugar blood" (Gr. ὑπογλυκαιμία, from hypo-, glykys, haima). It can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose to the brain, resulting in impairment of function (neuroglycopenia). Effects can range from mild dysphoria to more serious issues such as seizures, unconsciousness, and (rarely) permanent brain damage or death.

The most common forms of hypoglycemia occur as a complication of treatment of diabetes mellitus with insulin or oral medications. Hypoglycemia is less common in non-diabetic persons, but can occur at any age. Among the causes are excessive insulin produced in the body (hyperinsulinemia), inborn error of metabolism, medications and poisons, alcohol, hormone deficiencies, prolonged starvation, alterations of metabolism associated with infection, and organ failure.

Hypoglycemia is treated by restoring the blood glucose level to normal by the ingestion or administration of dextrose or carbohydrate foods. In more severe circumstances, it is treated by injection or infusion of glucagon. Recurrent hypoglycemia may be prevented by reversing or removing the underlying cause, by increasing the frequency of meals, with medications like diazoxide, octreotide, or glucocorticoids, or by surgical removal of much of the pancreas.

The level of blood glucose low enough to define hypoglycemia may be different for different people, in different circumstances, and for different purposes, and occasionally has been a matter of controversy. Most healthy adults maintain fasting glucose levels above 4.0 mmol/L (72 mg/dl), and develop symptoms of hypoglycemia when the glucose falls below 4 mmol/L. It can sometimes be difficult to determine whether a person's symptoms are due to hypoglycemia. Criteria referred to as Whipple's triad are used to determine a diagnosis of hypoglycemia:

1. Symptoms known to be caused by hypoglycemia
2. Low glucose at the time the symptoms occur
3. Reversal or improvement of symptoms or problems when the glucose is restored to normal

Hypoglycemia (common usage) is also a term in popular culture and alternative medicine for a common, often self-diagnosed, condition characterized by shakiness and altered mood and thinking, but without measured low glucose or risk of severe harm. It is treated by changing eating patterns.

Definition

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

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

The precise level of glucose considered low enough to define hypoglycemia is dependent on (1) the measurement method, (2) the age of the person, (3) presence or absence of effects, and (4) the purpose of the definition. While there is no disagreement as to the normal range of blood sugar, debate continues as to what degree of hypoglycemia warrants medical evaluation or treatment, or can cause harm.

Glucose concentrations are expressed as milligrams per deciliter (mg/dL or mg/100 mL) in the United States, Japan, Spain, France, Belgium, Egypt, Saudi Arabia, Colombia and Israel, while millimoles per liter (mmol/L or mM) are the units used in most of the rest of the world. Glucose concentrations expressed as mg/dL can be converted to mmol/L by dividing by 18.0 g/dmol (the molar mass of glucose). For example, a glucose concentration of 90 mg/dL is 5.0 mmol/L or 5.0 mM.

Method of measurement

Blood glucose levels discussed in this article are venous plasma or serum levels measured by standard, automated glucose oxidase methods used in medical laboratories. For clinical purposes, plasma and serum levels are similar enough to be interchangeable. Arterial plasma or serum levels are slightly higher than venous levels, and capillary levels are typically in between. This difference between arterial and venous levels is small in the fasting state but is amplified and can be greater than 10% in the postprandial state. On the other hand, whole blood glucose levels (e.g., by fingerprick meters) are about 10%-15% lower than venous plasma levels. Furthermore, available fingerstick glucose meters are only warranted to be accurate to within 15% of a simultaneous laboratory value under optimal conditions,^{[citation needed]} and home use in the investigation of hypoglycemia is fraught with misleading low numbers. In other words, a meter glucose reading of 39 mg/dL could be properly obtained from a person whose laboratory serum glucose was 53 mg/dL; even wider variations can occur with "real world" home use.

Two other factors significantly affect glucose measurement: hematocrit and delay after blood drawing. The disparity between venous and whole blood concentrations is greater when the hematocrit is high, as in newborn infants, or adults with polycythemia. High neonatal hematocrits are particularly likely to confound glucose measurement by meter. Second, unless the specimen is drawn into a fluoride tube or processed immediately to separate the serum or plasma from the cells, the measurable glucose will be gradually lowered by in vitro metabolism of the glucose at a rate of approximately 7 mg/dL/hr, or even more in the presence of leukocytosis. The delay that occurs when blood is drawn at a satellite site and transported to a central laboratory hours later for routine processing is a common cause of mildly low glucose levels in general chemistry panels.

Age differences

Children's blood sugar levels are often slightly lower than adults'. Overnight fasting glucose levels are below 70 mg/dL (3.9 mM) in 5% of healthy adults, but up to 5% of children can be below 60 mg/dL (3.3 mM) in the morning fasting state. As the duration of fasting is extended, a higher percentage of infants and children will have mildly low plasma glucose levels, usually without symptoms. The normal range of newborn blood sugars continues to be debated. It has been proposed that newborn brains are able to use alternate fuels when glucose levels are low more readily than adults. Experts continue to debate the significance and risk of such levels, though the trend has been to recommend maintenance of glucose levels above 60–70 mg/dL the first day after birth.

Presence or absence of effects

Research in healthy adults shows that mental efficiency declines slightly but measurably as blood glucose falls below 65 mg/dL (3.6 mM) in many people. Hormonal defense mechanisms (adrenaline and glucagon) are normally activated as it drops below a threshold level (about 55 mg/dL (3.0 mM) for most people), producing the typical hypoglycemic symptoms of shakiness and dysphoria. Obvious impairment may not occur until the glucose falls below 40 mg/dL (2.2 mM), and many healthy people may occasionally have glucose levels below 65 in the morning without apparent effects. Since the brain effects of hypoglycemia, termed neuroglycopenia, determine whether a given low glucose is a "problem" for that person, most doctors use the term hypoglycemia only when a moderately low glucose level is accompanied by symptoms or brain effects.

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

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

Purpose of definition

For all of the reasons explained in the above paragraphs, deciding whether a blood glucose in the borderline range of 45–75 mg/dL (2.5-4.2 mM) represents clinically problematic hypoglycemia is not always simple. This leads people to use different "cutoff levels" of glucose in different contexts and for different purposes. Because of all of the statistical and measurement variations listed above, the Endocrine Society recommends that a diagnosis of hypoglycemia as problem for an individual person be based on the combination of a low glucose level and evidence of adverse effects.

Signs and symptoms

Hypoglycemic symptoms and manifestations can be divided into those produced by the counterregulatory hormones (epinephrine/adrenaline and glucagon) triggered by the falling glucose, and the neuroglycopenic effects produced by the reduced brain sugar.

Adrenergic manifestations

• Shakiness, anxiety, nervousness
• Palpitations, tachycardia
• Sweating, feeling of warmth (although sweat glands have muscarinic receptors, thus "adrenergic manifestations" is not entirely accurate)
• Pallor, coldness, clamminess
• Dilated pupils (mydriasis)
• Feeling of numbness "pins and needles" (paresthesia)

Glucagon manifestations

• Hunger, borborygmus
• Nausea, vomiting, abdominal discomfort
• Headache

Neuroglycopenic manifestations

• Abnormal mentation, impaired judgment
• Nonspecific dysphoria, moodiness, depression, crying, exaggerated concerns
• Negativism, irritability, belligerence, combativeness, rage
• Personality change, emotional lability
• Fatigue, weakness, apathy, lethargy, daydreaming, sleep
• Confusion, amnesia, lightheadedness or dizziness, delirium
• Staring, "glassy" look, blurred vision, double vision
• Flashes of light in the field of vision
• Automatic behavior, also known as automatism
• Difficulty speaking, slurred speech
• Ataxia, incoordination, sometimes mistaken for "drunkenness"
• Focal or general motor deficit, paralysis, hemiparesis
• Paresthesia, headache
• Stupor, coma, abnormal breathing
• Generalized or focal seizures

Not all of the above manifestations occur in every case of hypoglycemia. There is no consistent order to the appearance of the symptoms, if symptoms even occur. Specific manifestations may also vary by age, by severity of the hypoglycemia and the speed of the decline. In young children, vomiting can sometimes accompany morning hypoglycemia with ketosis. 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. The symptoms of a single person may be similar from episode to episode, but are not necessarily so and may be influenced by the speed at which glucose levels are dropping, as well as previous incidents.

In newborns, hypoglycemia can produce irritability, jitters, myoclonic jerks, cyanosis, respiratory distress, apneic episodes, sweating, hypothermia, somnolence, hypotonia, refusal to feed, and seizures or "spells." Hypoglycemia can resemble asphyxia, hypocalcemia, sepsis, or heart failure.

In both young and old patients, the brain may habituate to low glucose levels, with a reduction of noticeable symptoms despite neuroglycopenic 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.

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

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

Causes

The circumstances of hypoglycemia provide most of the clues to diagnosis. Circumstances include the age of the patient, time of day, time since last meal, previous episodes, nutritional status, physical and mental development, drugs or toxins (especially insulin or other diabetes drugs), diseases of other organ systems, family history, and response to treatment. When hypoglycemia occurs repeatedly, a record or "diary" of the spells over several months, noting the circumstances of each spell (time of day, relation to last meal, nature of last meal, response to carbohydrate, and so forth) may be useful in recognizing the nature and cause of the hypoglycemia.

An especially important aspect is whether the patient is seriously ill with another problem. Severe disease of nearly all major organ systems can cause hypoglycemia as a secondary problem. Hospitalized patients, especially in intensive care units or those prevented from eating, can suffer hypoglycemia from a variety of circumstances related to the care of their primary disease. Hypoglycemia in these circumstances is often multifactorial or even iatrogenic. Once identified, these types of hypoglycemia are readily reversed and prevented, and the underlying disease becomes the primary problem.

It may take longer to recover from severe hypoglycemia with unconsciousness or seizure even after restoration of normal blood glucose. When a person has not been unconscious, failure of carbohydrate to reverse the symptoms in 10–15 minutes increases the likelihood that hypoglycemia was not the cause of the symptoms. When severe hypoglycemia has persisted in a hospitalized patient, the amount of glucose required to maintain satisfactory blood glucose levels becomes an important clue to the underlying etiology. Glucose requirements above 10 mg/kg/minute in infants, or 6 mg/kg/minute in children and adults are strong evidence for hyperinsulinism. In this context this is referred to as the glucose infusion rate (GIR). Finally, the blood glucose response to glucagon given when the glucose is low can also help distinguish among various types of hypoglycemia. A rise of blood glucose by more than 30 mg/dl (1.70 mmol/l) suggests insulin excess as the probable cause of the hypoglycemia.

In less obvious cases, a "critical sample" may provide the diagnosis. In the majority of children and adults with recurrent, unexplained hypoglycemia, the diagnosis may be determined by obtaining a sample of blood during hypoglycemia. If this critical sample is obtained at the time of hypoglycemia, before it is reversed, it can provide information that would otherwise require a hospital admission and unpleasant starvation testing. Perhaps the most common inadequacy of emergency department care in cases of unexplained hypoglycemia is the failure to obtain at least a basic sample before giving glucose to reverse it.

Part of the value of the critical sample may simply be the proof that the symptoms are indeed due to hypoglycemia. More often, measurement of certain hormones and metabolites at the time of hypoglycemia indicates which organs and body systems are responding appropriately and which are functioning abnormally. For example, when the blood glucose is low, hormones which raise the glucose should be rising and insulin secretion should be completely suppressed.

The following is a brief list of hormones and metabolites which may be measured in a critical sample. Not all tests are checked on every patient. A "basic version" would include insulin, cortisol, and electrolytes, with C-peptide and drug screen for adults and growth hormone in children. The value of additional specific tests depends on the most likely diagnoses for an individual patient, based on the circumstances described above. Many of these levels change within minutes, especially if glucose is given, and there is no value in measuring them after the hypoglycemia is reversed. Others, especially those lower in the list, remain abnormal even after hypoglycemia is reversed, and can be usefully measured even if a critical specimen is missed.

Newborn infants

Hypoglycemia is a common problem in critically ill or extremely low birthweight infants. If not due to maternal hyperglycemia, in most cases it is multifactorial, transient and easily supported. In a minority of cases hypoglycemia turns out to be due to significant hyperinsulinism, hypopituitarism or an inborn error of metabolism and presents more of a management challenge.

• Transient neonatal hypoglycemia
  • Prematurity, intrauterine growth retardation, perinatal asphyxia
  • Maternal hyperglycemia due to diabetes or iatrogenic glucose administration
  • Sepsis
  • Prolonged fasting (e.g., due to inadequate breast milk or condition interfering with feeding)
• Congenital hypopituitarism
• Congenital hyperinsulinism, several types, both transient and persistent
• Inborn errors of carbohydrate metabolism such as glycogen storage disease

Young children

Single episodes of hypoglycemia may occur due to gastroenteritis or fasting, but recurrent episodes nearly always indicate either an inborn error of metabolism, congenital hypopituitarism, or congenital hyperinsulinism. A list of common causes:

• Prolonged fasting
  • Diarrheal illness in young children, especially rotavirus gastroenteritis
• Idiopathic ketotic hypoglycemia
• Isolated growth hormone deficiency, hypopituitarism
• Insulin excess
  • Hyperinsulinism due to several congenital disorders of insulin secretion
  • Insulin injected for type 1 diabetes
  • Hyperinsulin Hyperammonia syndrome (HIHA) due to Glutamate dehydrogenase 1 gene. Can cause mental retardation and epilepsy in severe cases.
• Gastric dumping syndrome (after gastrointestinal surgery)
• Other congenital metabolic diseases; some of the common include
  • Maple syrup urine disease and other organic acidurias
  • Type 1 glycogen storage disease
  • Type III glycogen storage disease. Can cause less severe hypoglycemia than type I
  • Phosphoenolpyruvate carboxykinase deficiency, causes metabolic acidosis and severe hypoglycemia.
  • Disorders of fatty acid oxidation
  • Medium chain acylCoA dehydrogenase deficiency (MCAD)
  • Familial Leucine sensitive hypoglycemia
• Accidental ingestions
  • Sulfonylureas, propranolol and others
  • Ethanol (mouthwash, alcoholic beverages)

Young adults

By far, the most common cause of severe hypoglycemia in this age range is insulin injected for type 1 diabetes. Circumstances should provide clues fairly quickly for the new diseases causing severe hypoglycemia. All of the congenital metabolic defects, congenital forms of hyperinsulinism, and congenital hypopituitarism are likely to have already been diagnosed or are unlikely to start causing new hypoglycemia at this age. Body mass is large enough to make starvation hypoglycemia and idiopathic ketotic hypoglycemia quite uncommon. Recurrent mild hypoglycemia may fit a reactive hypoglycemia pattern, but this is also the peak age for idiopathic postprandial syndrome, and recurrent "spells" in this age group can be traced to orthostatic hypotension or hyperventilation as often as demonstrable hypoglycemia.

• Insulin-induced hypoglycemia
  • Insulin injected for type 1 diabetes
  • Factitious insulin injection (Munchausen syndrome)
  • Insulin-secreting pancreatic tumor
  • Reactive hypoglycemia and idiopathic postprandial syndrome
• Addison's disease
• Sepsis

Older adults

The incidence of hypoglycemia due to complex drug interactions, especially involving oral hypoglycemic agents and insulin for diabetes, rises with age. Though much rarer, the incidence of insulin-producing tumors also rises with advancing age. Most tumors causing hypoglycemia by mechanisms other than insulin excess occur in adults.

• Insulin-induced hypoglycemia
  • Insulin injected for diabetes
  • Factitious insulin injection (Munchausen syndrome)
  • Excessive effects of oral Anti-diabetic medication, beta-blockers, or drug interactions
  • Insulin-secreting neuroendocrine tumor (insulinoma) of the pancreas
  • Alcohol induced hypoglycemia often linked with ketoacidosis (depletion of NAD+ leads to a block of gluconeogenesis)
  • Alimentary (rapid jejunal emptying with exaggerated insulin response)
    • After gastrectomy dumping syndrome or bowel bypass surgery or resection
  • Reactive hypoglycemia and idiopathic postprandial syndrome
• Tumor hypoglycemia, Doege-Potter syndrome
• Acquired adrenal insufficiency
• Acquired hypopituitarism
• Immunopathologic hypoglycemia

Causes by Organ System

Cardiovascular	No underlying causes
Chemical / poisoning	1,1-Dichloroethene, Ackee fruit, Jamaican vomiting sickness, Systemic monochloroacetate poisoning
Dermatologic	No underlying causes
Drug Side Effect	Acetohexamide, Amprenavir, Chloramphenicol, Chlorpromazine, Chlorpropamide, Cibenzoline, Clove, Ethanol, Ethionamide, Fluorodeoxyglucose, Gatifloxacin, Ginseng, Glibenclamide, Gliclazide, Glimepiride, Glipizide, Gliquidone, Glisolamide, Glisoxepide, Insulin, Insulin like growth factor, Lanreotide, Levomepromazine, Mitiglinide, Nateglinide, Pazopanib, Pentamidine, Perazine, Pipothiazine, Pramlintide, Quinine, Repaglinide, Ritonavir, Saquinavir, Somatostatin, Sulfamethoxazole, Temafloxacin, Tolazamide, Tolbutamide, Trimethoprim
Ear Nose Throat	No underlying causes
Endocrine	Addison's disease, Adrenal cortex insufficiency, Adrenal insufficiency, Beginning stages of diabetes, Glucagon deficiency, Hypopituitarism, Hypothyroidism, Multiple endocrine neoplasia, Myxedema coma, Timme syndrome
Environmental	No underlying causes
Gastroenterologic	Acute fatty liver of pregnancy, Acute liver failure, Cirrhosis, Diabetic gastroparesis, Diarrhea, Dumping syndrome, Functioning pancreatic endocrine tumor, Gastric dumping syndrome, Hepatic congestion, Hepatic failure, Idiopathic postprandial syndrome, Insulinoma, Liver cancer, Malabsorption, Maldigestion, Reactive hypoglycemia, Severe hepatitis
Genetic	2-methylbutyryl-coenzyme A dehydrogenase deficiency, 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency, 3-Methylcrotonyl-CoA carboxylase deficiency, ACAD9 deficiency, Alpers Syndrome, Carbohydrate-deficient glycoprotein syndrome type 1b, Carnitine palmitoyltransferase 1 deficiency, Carnitine-acylcarnitine translocase deficiency, Cleft lip palate pituitary deficiency, Dicarboxylicaminoaciduria, Dihydrolipoamide dehydrogenase deficiency, Donohue syndrome, Dopamine beta-hydroxylase deficiency, Familial glucocorticoid deficiency, Familial hyperinsulinemic hypoglycemia type 3, Familial hyperinsulinemic hypoglycemia type 5, Familial hyperinsulinemic hypoglycemia type 7, Fructose-1, 6-diphosphatase deficiency, Fructose-1-phosphate aldolase deficiency, Galactose-1-phosphate uridyltransferase deficiency, Glucose 6 phosphate dehydrogenase deficiency, Glutaric acidemia type 2, Glycogenosis type 1a, Glycogenosis type 1b, Glycogenosis type 3, Glycogenosis type 6, Glycogenosis type 9a, Glycogenosis type 9b, Glycogenosis type 9c, Glycogenosis type V, Growth hormone deficiency (congenital), Hereditary ACTH resistance, HMG-CoA lyase deficiency, Hydroxymethylglutaryl-CoA lyase deficiency, Hyperinsulinism-hyperammonemia syndrome, Laron dwarfism, Leucine-induced hypoglycaemia, Liver glycogen synthase deficiency, Long chain hydroxyacyl-CoA dehydrogenase deficiency, Malonyl-CoA decarboxylase deficiency, Maple syrup urine disease, Medium chain acyl-CoA dehydrogenase deficiency, Methylmalonic acidemia, Mitochondrial DNA depletion syndrome, hepatocerebral form, Mitochondrial trifunctional protein deficiency, Navajo neurohepatopathy, Nephroblastomatosis-fetal ascites-macrosomia-wilms tumor, Nesidioblastosis, Plasma membrane carnitine transporter deficiency, Propionyl-CoA carboxylase deficiency PCCA type, Short chain acyl-CoA dehydrogenase deficiency, Short stature-pituitary and cerebellar defects-small sella turcica, Triple A syndrome, Tyrosinaemia type 1, Very long-chain acyl-CoA dehydrogenase deficiency, Wiedemann-Beckwith syndrome, X-linked congenital adrenal hypoplasia
Hematologic	Hemolytic disease of the newborn
Iatrogenic	Gastrojejunostomy, Postgastrectomy syndrome, Pyloroplasty, Reye syndrome
Infectious Disease	Acute meningitis, Malaria (malignant tertian), Sepsis, Visceral leishmaniasis
Musculoskeletal / Ortho	No underlying causes
Neurologic	Autonomic dystonia, Autonomic neuropathy, Elevated vagal tone
Nutritional / Metabolic	Coenzyme Q cytochrome c reductase deficiency, Deficiency in enzymes of fat oxidation, Fructose intolerance, Galactosemia, Glycogen debranching deficiency, Hypoketonemic hypoglycemia, Ketotic hypoglycemia of infancy, Mcquarrie type infantile idiopathic hypoglycemia, Organic acidemia, Phosphoenolpyruvate carboxykinase (PEPCK) deficiency, Urea cycle disorder, Glucagon deficiency, ACAD9 deficiency, Dicarboxylicaminoaciduria, Fructose-1, 6-diphosphatase deficiency, Fructose-1-phosphate aldolase deficiency, Glucose 6 phosphate dehydrogenase deficiency, Glutaric acidemia type 2, Glycogenosis type 1a, Glycogenosis type 1b, Glycogenosis type 3, Glycogenosis type 6, Glycogenosis type 9a, Glycogenosis type 9b, Glycogenosis type 9c, Glycogenosis type V, HMG-CoA lyase deficiency, Hydroxymethylglutaryl-CoA lyase deficiency, Long chain hydroxyacyl-CoA dehydrogenase deficiency, Malonyl-CoA decarboxylase deficiency, Maple syrup urine disease, Medium chain acyl-CoA dehydrogenase deficiency, Methylmalonic acidemia, Nesidioblastosis, Propionyl-CoA carboxylase deficiency PCCA type, Short chain acyl-CoA dehydrogenase deficiency, Tyrosinaemia type 1, Very long-chain acyl-CoA dehydrogenase deficiency
Obstetric/Gynecologic	Diabetic mother, Gestational diabetes, Intrauterine growth retardation, Pregnancy, Premature labour and/or delivery, Sheehan syndrome
Oncologic	Adrenal cancer, Doege-Potter syndrome, IGF producing tumors, Tumors, Functioning pancreatic endocrine tumor, Insulinoma, Liver cancer, Mesothelioma
Opthalmologic	No underlying causes
Overdose / Toxicity	Acetohexamide, Amprenavir, Chloramphenicol, Chlorpromazine, Chlorpropamide, Cibenzoline, Clove, Ethanol, Ethionamide, Fluorodeoxyglucose, Gatifloxacin, Ginseng, Glibenclamide, Gliclazide, Glimepiride, Glipizide, Gliquidone, Glisolamide, Glisoxepide, Insulin, Lanreotide, Levomepromazine, Mitiglinide, Nateglinide, Pazopanib, Pentamidine, Perazine, Pipothiazine, Pramlintide, Quinine, Repaglinide, Ritonavir, Saquinavir, Somatostatin, Sulfamethoxazole, Temafloxacin, Tolazamide, Tolbutamide, Trimethoprim
Psychiatric	Anorexia nervosa, Bullimia nervosa, Munchausen syndrome
Pulmonary	Mesothelioma
Renal / Electrolyte	Benign glucosuria, Renal Failure, Renal hypoglycemia, Uremia
Rheum / Immune / Allergy	Autoimmune adrenalitis, Hemolytic disease of the newborn, Immunopathologic hypoglycemia, Insulin receptor antibodies
Sexual	No underlying causes
Trauma	Burns
Urologic	No underlying causes
Dental	No underlying causes
Miscellaneous	Alcoholism, Binge drinking, Cachexia, Delayed separation blood sample, Drip arm sample, Fasting, Heavy exercise, Hypothermia, Idiopathic hypoglycemia, Septic shock, Starvation (acute)

Causes in Alphabetical Order

1,1-Dichloroethene 2-methylbutyryl-coenzyme A dehydrogenase deficiency 3-alpha-hydroxyacyl-CoA dehydrogenase deficiency 3-Methylcrotonyl-CoA carboxylase deficiency ACAD9 deficiency Acetohexamide Ackee fruit Acute fatty liver of pregnancy Acute liver failure Acute meningitis Addison's disease Adrenal cancer Adrenal cortex insufficiency Adrenal insufficiency Alcoholism Alpers Syndrome Amprenavir Anorexia nervosa Autoimmune adrenalitis Autonomic dystonia Autonomic neuropathy Beginning stages of diabetes Benign glucosuria Binge drinking Bullimia nervosa Burns Cachexia Carbohydrate-deficient glycoprotein syndrome type 1b Carnitine palmitoyltransferase 1 deficiency Carnitine-acylcarnitine translocase deficiency Chloramphenicol Chlorpromazine Chlorpropamide Cibenzoline Cirrhosis Cleft lip palate pituitary deficiency Clove Coenzyme Q cytochrome c reductase deficiency Deficiency in enzymes of fat oxidation Delayed separation blood sample Diabetic gastroparesis Diabetic mother Diarrhea Dicarboxylicaminoaciduria Dihydrolipoamide dehydrogenase deficiency Doege-Potter syndrome Donohue syndrome Dopamine beta-hydroxylase deficiency Drip arm sample Dumping syndrome Elevated vagal tone Ethanol Ethionamide Familial glucocorticoid deficiency Familial hyperinsulinemic hypoglycemia type 3 Familial hyperinsulinemic hypoglycemia type 5 Familial hyperinsulinemic hypoglycemia type 7 Fasting Fluorodeoxyglucose Fructose intolerance Fructose-1, 6-diphosphatase deficiency Fructose-1-phosphate aldolase deficiency Functioning pancreatic endocrine tumor Galactose-1-phosphate uridyltransferase deficiency Galactosemia Gastric dumping syndrome Gastrojejunostomy Gatifloxacin Gestational diabetes Ginseng Glibenclamide Gliclazide Glimepiride Glipizide Gliquidone Glisolamide Glisoxepide Glucagon deficiency Glucose 6 phosphate dehydrogenase deficiency Glutaric acidemia type 2 Glycogen debranching deficiency Glycogenosis type 1a Glycogenosis type 1b Glycogenosis type 3 Glycogenosis type 6 Glycogenosis type 9a Glycogenosis type 9b Glycogenosis type 9c Glycogenosis type V Growth hormone deficiency (congenital) Heavy exercise Hemolytic disease of the newborn

Hepatic congestion Hepatic failure Hereditary ACTH resistance HMG-CoA lyase deficiency Hydroxymethylglutaryl-CoA lyase deficiency Hyperinsulinism-hyperammonemia syndrome Hypoketonemic hypoglycemia Hypopituitarism Hypothermia Hypothyroidism Idiopathic hypoglycemia Idiopathic postprandial syndrome IGF producing tumors Immunopathologic hypoglycemia Insulin Insulin like growth factor Insulin receptor antibodies Insulinoma Intrauterine growth retardation Jamaican vomiting sickness Ketotic hypoglycemia of infancy Lanreotide Laron dwarfism Leucine-induced hypoglycaemia Levomepromazine Liver cancer Liver glycogen synthase deficiency Long chain hydroxyacyl-CoA dehydrogenase deficiency Malabsorption Malaria (malignant tertian) Maldigestion Malonyl-CoA decarboxylase deficiency Maple syrup urine disease Mcquarrie type infantile idiopathic hypoglycemia Medium chain acyl-CoA dehydrogenase deficiency Mesothelioma Methylmalonic acidemia Mitiglinide Mitochondrial DNA depletion syndrome, hepatocerebral form Mitochondrial trifunctional protein deficiency Multiple endocrine neoplasia Munchausen syndrome Myxedema coma Nateglinide Navajo neurohepatopathy Nephroblastomatosis-fetal ascites-macrosomia-wilms tumor Nesidioblastosis Organic acidemia Pazopanib Pentamidine Perazine Phosphoenolpyruvate carboxykinase (PEPCK) deficiency Pipothiazine Plasma membrane carnitine transporter deficiency Postgastrectomy syndrome Pramlintide Pregnancy Premature labour and/or delivery Propionyl-CoA carboxylase deficiency PCCA type Pyloroplasty Quinine Reactive hypoglycemia Renal Failure Renal hypoglycemia Repaglinide Reye syndrome Ritonavir Saquinavir Sepsis Septic shock Severe hepatitis Sheehan syndrome Short chain acyl-CoA dehydrogenase deficiency Short stature-pituitary and cerebellar defects-small sella turcica Somatostatin Starvation (acute) Sulfamethoxazole Systemic monochloroacetate poisoning Temafloxacin Timme syndrome Tolazamide Tolbutamide Trimethoprim Triple A syndrome Tumors Tyrosinaemia type 1 Urea cycle disorder Uremia Very long-chain acyl-CoA dehydrogenase deficiency Visceral leishmaniasis Wiedemann-Beckwith syndrome X-linked congenital adrenal hypoplasia

Pathophysiology of hypoglycemia

Like most animal tissues, brain metabolism depends primarily on glucose for fuel in most circumstances. A limited amount of glucose can be derived from glycogen stored in astrocytes, but it is consumed within minutes. For most practical purposes, the brain is dependent on a continual supply of glucose diffusing from the blood into the interstitial tissue within the central nervous system and into the neurons themselves.

Therefore, if the amount of glucose supplied by the blood falls, the brain is one of the first organs affected. In most people, subtle reduction of mental efficiency can be observed when the glucose falls below 65 mg/dl (3.6 mM). Impairment of action and judgment usually becomes obvious below 40 mg/dl (2.2 mM). Seizures may occur as the glucose falls further. As blood glucose levels fall below 10 mg/dl (0.55 mM), most neurons become electrically silent and nonfunctional, resulting in coma. These brain effects are collectively referred to as neuroglycopenia.

The importance of an adequate supply of glucose to the brain is apparent from the number of nervous, hormonal and metabolic responses to a falling glucose level. Most of these are defensive or adaptive, tending to raise the blood sugar via glycogenolysis and gluconeogenesis or provide alternative fuels. If the blood sugar level falls too low the liver converts a storage of glycogen into glucose and releases it into the bloodstream, to prevent the person going into a diabetic coma, for a short period of time.

Brief or mild hypoglycemia produces no lasting effects on the brain, though it can temporarily alter brain responses to additional hypoglycemia. Prolonged, severe hypoglycemia can produce lasting damage of a wide range. This can include impairment of cognitive function, motor control, or even consciousness. The likelihood of permanent brain damage from any given instance of severe hypoglycemia is difficult to estimate, and depends on a multitude of factors such as age, recent blood and brain glucose experience, concurrent problems such as hypoxia, and availability of alternative fuels. It has been frequently found that those Type 1 diabetics found "dead in bed" in the morning after suspected severe hypoglycemia had some underlying coronary pathology that led to an induced fatal heart attack. Recently, several of these individuals found "dead in bed" were wearing Continuous Glucose Monitors, which provided a history of glucose levels prior to the fatal event. It has been found in several cases, that the fatal event was preceded by at least two hours of blood glucose levels under 40 mg/dl, possibly lower as the continuous glucose monitors are not accurate at levels below 40 mg/dl. The individuals failed to respond to the audible alarms produced by the continuous glucose monitor which may have been "alarming" for many hours prior to the fatal event. The vast majority of symptomatic hypoglycemic episodes result in no detectable permanent harm.

Diagnosis

When suspected hypoglycemia recurs and a critical specimen has not been obtained, the diagnostic evaluation may take several paths. However good nutrition and prompt intake is essential.

When general health is good, the symptoms are not severe, and the person can fast normally through the night, experimentation with diet (extra snacks with fat or protein, reduced sugar) may be enough to solve the problem. If it is uncertain whether "spells" are indeed due to hypoglycemia, some physicians will recommend use of a home glucose meter to test at the time of the spells to confirm that glucoses are low. This approach may be most useful when spells are fairly frequent or the patient is confident that he or she can provoke a spell. The principal drawback of this approach is the high rate of false positive or equivocal levels due to the imprecision of the currently available meters: both physician and patient need an accurate understanding of what a meter can and cannot do to avoid frustrating and inconclusive results.

In cases of recurrent hypoglycemia with severe symptoms, the best method of excluding dangerous conditions is often a diagnostic fast. This is usually conducted in the hospital, and the duration depends on the age of the patient and response to the fast. A healthy adult can usually maintain a glucose level above 50 mg/dl (2.8 mM) for 72 hours, a child for 36 hours, and an infant for 24 hours. The purpose of the fast is to determine whether the person can maintain his or her blood glucose as long as normal, and can respond to fasting with the appropriate metabolic changes. At the end of the fast the insulin should be nearly undetectable and ketosis should be fully established. The patient's blood glucose levels are monitored and a critical specimen is obtained if the glucose falls. Despite its unpleasantness and expense, a diagnostic fast may be the only effective way to confirm or refute a number of serious forms of hypoglycemia, especially those involving excessive insulin.

A traditional method for investigating suspected hypoglycemia is the oral glucose tolerance test, especially when prolonged to 3, 4, or 5 hours. Although quite popular in the United States in the 1960s, repeated research studies have demonstrated that many healthy people will have glucose levels below 70 or 60 during a prolonged test, and that many types of significant hypoglycemia may go undetected with it. This combination of poor sensitivity and specificity has resulted in its abandonment for this purpose by physicians experienced in disorders of glucose metabolism.

Prevention

The most effective means of preventing further episodes of hypoglycemia depends on the cause.

The risk of further episodes of diabetic hypoglycemia can often (but not always) be reduced by lowering the dose of insulin or other medications, or by more meticulous attention to blood sugar balance during unusual hours, higher levels of exercise, or decreasing alcohol intake.

Many of the inborn errors of metabolism require avoidance or shortening of fasting intervals, or extra carbohydrates. For the more severe disorders, such as type 1 glycogen storage disease, this may be supplied in the form of cornstarch every few hours or by continuous gastric infusion.

Several treatments are used for hyperinsulinemic hypoglycemia, depending on the exact form and severity. Some forms of congenital hyperinsulinism respond to diazoxide or octreotide. Surgical removal of the overactive part of the pancreas is curative with minimal risk when hyperinsulinism is focal or due to a benign insulin-producing tumor of the pancreas. When congenital hyperinsulinism is diffuse and refractory to medications, near-total pancreatectomy may be the treatment of last resort, but in this condition is less consistently effective and fraught with more complications.

Hypoglycemia due to hormone deficiencies such as hypopituitarism or adrenal insufficiency usually ceases when the appropriate hormone is replaced.

Hypoglycemia due to dumping syndrome and other post-surgical conditions is best dealt with by altering diet. Including fat and protein with carbohydrates may slow digestion and reduce early insulin secretion. Some forms of this respond to treatment with a glucosidase inhibitor, which slows starch digestion.

Reactive hypoglycemia with demonstrably low blood glucose levels is most often a predictable nuisance which can be avoided by consuming fat and protein with carbohydrates, by adding morning or afternoon snacks, and reducing alcohol intake.

Idiopathic postprandial syndrome without demonstrably low glucose levels at the time of symptoms can be more of a management challenge. Many people find improvement by changing eating patterns (smaller meals, avoiding excessive sugar, mixed meals rather than carbohydrates by themselves), reducing intake of stimulants such as caffeine, or by making lifestyle changes to reduce stress. See the following section of this article.

Treatment

Treatment of some forms of hypoglycemia, such as in diabetes, involves immediately raising the blood sugar to normal through the ingestion of carbohydrates, determining the cause, and taking measures to hopefully prevent future episodes. However, this treatment is not optimal in other forms such as reactive hypoglycemia, where rapid carbohydrate ingestion may lead to a further hypoglycemic episode.

Blood glucose can be raised to normal within minutes by taking (or receiving) 10-20 grams of carbohydrate. It can be taken as food or drink if the person is conscious and able to swallow. This amount of carbohydrate is contained in about 3–4 ounces (100–120 ml) of orange, apple, or grape juice although fruit juices contain a higher proportion of fructose which is more slowly metabolized than pure dextrose, alternatively, about 4–5 ounces (120-150 ml) of regular (non-diet) soda may also work, as will about one slice of bread, about 4 crackers, or about 1 serving of most starchy foods. Starch is quickly digested to glucose (unless the person is taking acarbose), but adding fat or protein retards digestion. Symptoms should begin to improve within 5 minutes, though full recovery may take 10–20 minutes. Overfeeding does not speed recovery and if the person has diabetes will simply produce hyperglycemia afterwards. A mnemonic used by the American Diabetes Association and others is the "rule of 15" – consuming 15 grams of carbohydrate followed by a 15 minute wait, repeated if glucose remains low (variable by individual, sometimes 70 mg/dl).

If a person is suffering such severe effects of hypoglycemia that they cannot (due to combativeness) or should not (due to seizures or unconsciousness) be given anything by mouth, medical personnel such as paramedics, or in-hospital personnel can establish IV access and give intravenous dextrose, concentrations varying depending on age (infants are given 2 ml/kg dextrose 10%, children are given dextrose 25%, and adults are given dextrose 50%). Care must be taken in giving these solutions because they can cause skin necrosis if the IV is infiltrated, sclerosis of veins, and many other fluid and electrolyte disturbances if administered incorrectly. If IV access cannot be established, the patient can be given 1 to 2 milligrams of glucagon in an intramuscular injection. More treatment information can be found in the article diabetic hypoglycemia. If a person is suffering less severe effects, and is conscious with the ability to swallow, medical personal such as EMT-B's may administer gelatinous oral glucose.

One situation where starch may be less effective than glucose or sucrose is when a person is taking acarbose. Since acarbose and other alpha-glucosidase inhibitors prevents starch and other sugars from being broken down into monosaccharides that can be absorbed by the body, patients taking these medications should consume monosaccharide-containing foods such as glucose tablets, honey, or juice to reverse hypoglycemia.

See also

• Diabetic Hypoglycemia (journal)
• Idiopathic hypoglycemia
• Spontaneous hypoglycemia

References

External links

• The National Diabetes Information Clearinghouse
• Hypoglycemia at the Mayo Clinic
• American Diabetes Association

UpToDate Contents

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• 1. 糖尿病でない成人における低血糖症：診断的アプローチ hypoglycemia in adults without diabetes mellitus diagnostic approach
• 2. 成人における低血糖：臨床症状、定義、および原因 hypoglycemia in adults clinical manifestations definition and causes
• 3. 乳児および小児における低血糖に対するアプローチ approach to hypoglycemia in infants and children
• 4. 糖尿病の治療における低血糖のマネージメント management of hypoglycemia during treatment of diabetes mellitus
• 5. Causes of hypoglycemia in infants and children

English Journal

• Why do they die? Comparison of selected aspects of organ injury and dysfunction in mice surviving and dying in acute abdominal sepsis.

• Drechsler S1, Weixelbaumer KM, Weidinger A, Raeven P, Khadem A, Redl H, van Griensven M, Bahrami S, Remick D, Kozlov A, Osuchowski MF.
• Intensive care medicine experimental.Intensive Care Med Exp.2015 Dec;3(1):48. doi: 10.1186/s40635-015-0048-z. Epub 2015 Apr 7.
• BACKGROUND: The mechanisms of sepsis mortality remain undefined. While there is some evidence of organ damage, it is not clear whether this damage alone is sufficient to cause death. Therefore, we aimed to examine contribution of organ injury/dysfunction to early deaths in the mouse abdominal sepsis
• PMID 26215812

• Influence of acute glycaemic level on measures of myocardial infarction in non-diabetic pigs.

• Diemar SS1,2, Sejling AS1,3, Iversen KK4, Engstrøm T5, Honge JL6, Tønder N1, Vejlstrup N4, Idorn M7, Ekström K1,2, Pedersen-Bjergaard U1,2, Thorsteinsson B1,2, Dalsgaard M4.
• Scandinavian cardiovascular journal : SCJ.Scand Cardiovasc J.2015 Dec;49(6):376-82. doi: 10.3109/14017431.2015.1085079. Epub 2015 Sep 10.
• Abstract> Objective. Patients with diabetes are at increased risk of experiencing myocardial infarction. The influence of the prevailing plasma glucose level on infarction and mortality after acute ischaemia is however unknown. The aim was to study the effect of the acute plasma glucose level on
• PMID 26359322

• A compound heterozygous mutation of ABCC8 gene causing a diazoxide-unresponsive congenital hyperinsulinism with an atypical form: Not a focal lesion in the pancreas reported by (18)F-DOPA-PET/CT scan.

• Zhang W1, Liu L2, Wen Z3, Cheng J1, Li C1, Li X1, Niu H4, Wang F4, Sheng H1, Liu H5.
• Gene.Gene.2015 Nov 10;572(2):222-6. doi: 10.1016/j.gene.2015.07.012. Epub 2015 Jul 8.
• Congenital hyperinsulinism (CHI) is a severe heterogeneous disorder due to dysregulation of insulin secretion from the pancreatic β-cells leading to severe hypoglycemia in infancy. 18-fluoro-l-3,4-dihydroxyphenylalanine positron emission tomography ((18)F‑DOPA‑PET)/CT is a useful tool in distin
• PMID 26162674

Japanese Journal

• 超持効型インスリンによる新たなインスリン療法の可能性

• 加来 浩平
• 内分泌・糖尿病・代謝内科 33(4), 384-388, 2011-10
• NAID 40019080748

• The Glu23Lys polymorphism in KCNJ11 and impaired hypoglycaemia awareness in patients with type 1 diabetes

• Holstein Andreas,Plaschke Armin,Stumvoll Michael [他],KOVACS Peter
• Journal of human genetics 50(10), 530-533, 2005-10-01
• NAID 10016758650

• Differential responds of prolactin secretion to hyperglycaemia and hypoglycaemia in healthy women and in women with polycystic ovary syndrome(Reproduction 1)

• Tauchert S.,Schroder A. K.,Ortmann O.,Diedrich K.,Weiss J. M.
• 日本産科婦人科學會雜誌 57(2), 815, 2005-02-01
• NAID 110004038325

Related Links

• Hypoglycemia - Wikipedia, the free encyclopedia

a b Koh TH, Eyre JA, Aynsley-Green A (1988). "Neonatal hypoglycaemia--the controversy regarding definition". Arch. Dis. ... PMID 3677983. ^ Gama R, Anderson NR, Marks V (2000). "'Glucose meter hypoglycaemia': often a non- disease".

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★リンクテーブル★

リンク元	「hypoglycemic」「hypoglycaemic」

「hypoglycemic」

　　[★]

• adj.

• 低血糖の、血糖降下の、低血糖性の

• n.

• 血糖降下薬、血糖降下剤

関

glucose-lowering、glucose-lowering agent、hypoglycaemia、hypoglycaemic、hypoglycemia、hypoglycemic agent、hypoglycemic drug、hypoglycemics

　

「hypoglycaemic」

　　[★]

• adj.

• 低血糖性の、低血糖の

関

hypoglycaemia、hypoglycemia、hypoglycemic