Hypoglycemia (hypoglycæmia in the UK) is a medical term referring to a pathologic state produced by a lower than normal amount of sugar (glucose) in the blood. The term hypoglycemia literally means "low blood sugar". Hypoglycemia can produce a variety of symptoms and effects but the principal problems arise from an inadequate supply of glucose as fuel to the brain, resulting in impairment of function (neuroglycopenia). Derangements of function can range from vaguely "feeling bad" to coma, and (rarely) permanent brain damage or death. Hypoglycemia can arise from many causes, and can occur at any age. The most common forms of moderate and severe hypoglycemia occur as a complication of treatment of diabetes mellitus with insulin or oral medications.
Endocrinologists (specialists in disorders of blood glucose metabolism) typically consider the following criteria (referred to as Whipple's triad) as proving that an individual's symptoms can be attributed to hypoglycemia:
However, not everyone has accepted these suggested diagnostic criteria, and even the level of glucose low enough to define hypoglycemia has been a source of controversy in several contexts. For many purposes, plasma glucose levels below 70 mg/dl or 3.9 mmol/L are considered hypoglycemic, but these issues are elaborated in more detail below.
Two other factors significantly affect glucose measurement. The disparity between venous and whole blood concentrations is greater when the hematocrit is high, as in newborns. High neonatal hematocrits are particularly likely to confound meter glucose measurement. 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.
The normal range of newborn blood sugars continues to be debated. Surveys and experience have revealed blood sugars often below 40 mg/dl (2.2 mM), rarely below 30 mg/dl (1.7 mM), in apparently healthy full-term infants on the first day of life. 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 after the first day of life. In ill, undersized, or premature newborns, low blood sugars are even more common, but there is a consensus that sugars should be maintained at least above 50 mg/dl (2.8 mM) in such circumstances. Some experts advocate 70 mg/dl as a therapeutic target, especially in circumstances such as hyperinsulinism where alternate fuels may be less available.
Even this criterion is complicated by the facts that hypoglycemic symptoms are vague and can be produced by other conditions, that people with persistently or recurrently low glucose levels can lose their threshold symptoms so that severe neuroglycopenic impairment can occur without much warning, and that many of our 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. Although home glucose meter readings are sometimes misleading, the probability that a low reading accompanied by symptoms represents real hypoglycemia is higher in a person who takes insulin. Second, the hypoglycemia has a greater chance of progressing to more serious impairment if not treated, compared to most other forms of hypoglycemia that occur in adults. Third, because glucose levels are above normal most of the time in people with diabetes, hypoglycemic symptoms may occur at higher thresholds than in people who are normoglycemic most of the time. For all of these reasons, people with diabetes usually use higher meter glucose thresholds to determine hypoglycemia.
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 judgement 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, 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. Most of these are defensive or adaptive, tending to raise the blood sugar via glycogenolysis and gluconeogenesis or provide alternative fuels.
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. The vast majority of symptomatic hypoglycemic episodes result in no detectable permanent harm.
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 severity of the hypoglycemia. In young children vomiting often accompanies 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 do tend to be similar from episode to episode.
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.
Nearly always, hypoglycemia severe enough to cause seizures or unconsciousness can be reversed without obvious harm to the brain. Cases of death or permanent neurologic 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.
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.
Apart from determining nutritional status and identifying whether there is likely to be an underlying disease more serious than hypoglycemia, the physical examination of the patient is only occasionally helpful. Macrosomia in infancy usually indicates hyperinsulinism. A few syndromes and metabolic diseases may be recognizable by clues such as hepatomegaly or micropenis.
Response to treatment, especially the amount of carbohydrate needed to reverse or prevent recurrence of hypoglycemia, may provide important clues as well. When 15-30 grams of sugar or starch are given by mouth, a low blood glucose will usually rise by 18-36 mg/dl (1-2 mmol/l) within 5-10 minutes, relieving hypoglycemic symptoms within 10 minutes. This oral treatment is only practical if the person is conscious. A person who is unconscious may be treated with a Glucagon kit, available by prescription and recommended for people using insulin. 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 (1.7 mmol/l) suggests insulin excess as the probable cause of the hypoglycemia.
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. Although interpretation in difficult cases is beyond the scope of this article, for most of the tests, the primary significance is briefly noted.
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.
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, glucose can be given by intravenous infusion or the glucose can be rapidly raised by an injection of glucagon. Further details of glucagon use are provided in the article on diabetic hypoglycemia.
The risk of further episodes of diabetic hypoglycemia can often 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 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.
This condition therefore overlaps with the definition and forms of hypoglycemia described in the remainder of this article but is not entirely congruent. When low glucose levels can be measured, this condition is what is usually described by physicians as idiopathic reactive hypoglycemia. When glucose levels are not low enough to distinguish the patient's glucose from normal levels, this type of "hypoglycemia" does not carry the same risks of coma or brain damage as measurable hypoglycemia that meets the Whipple criteria. A variety of terms have been used in the medical literature: functional hypoglycemia, idiopathic postprandial syndrome, pseudohypoglycemia, nonhypoglycemia, and "hypoglycemia". The terms range from favorable to pejorative and reflect the range of attitudes of physicians as much as the nature of the condition.
Advising people on management of this condition is a significant "sub-industry" of alternative medicine. More information about this form of "hypoglycemia", with far more elaborate dietary recommendations, is available on the internet and in health food stores. Most of these websites and books describe a conflated mixture of reactive hypoglycemia and idiopathic postprandial syndrome but do not recognize a distinction. The value of these recommendations is unproven.
Medical emergencies | Metabolic disorders
Hypoglykämie | Hipoglucemia | Hipoglikemio | Hypoglycémie | Ipoglicemia | היפוגליקמיה | Hypoglykemie | Hypoglykemi | Hipoglikemia | Hipoglicémia
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"Hypoglycemia".
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