Hypoglycemia (hypoglycaemia in the UK and Canada) 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) 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:
Symptoms known to be caused by hypoglycemia
Low glucose at the time the symptoms occur
Reversal or improvement of symptoms or problems when the glucose is restored to normal
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.
Measurement method: Different methods can yield different values
Glucose levels discussed in this article are venous plasma or serum levels measured by standard 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 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. In other words, a meter glucose reading of 39 mg/dl could be properly obtained from a person whose serum glucose was 55 mg/dl.
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.
Presence or absence of effects: are symptoms more important than the number?
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 activated as it drops below a threshold level (about 55 mg/dl for most people), producing the typical symptoms of shakiness and dysphoria. On the other hand, obvious impairment does not often occur until the glucose falls below 40 mg/dl, and up to 10% of the population may occasionally have glucose levels below 65 in the morning without apparent effects. Brain effects of hypoglycemia, termed neuroglycopenia, determine whether a given low glucose is a "problem" for that person, and hence some people tend to use the term hypoglycemia only when a moderately low glucose is accompanied by symptoms.
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.
Signs and symptoms of hypoglycemia
Hypoglycemic symptoms and manifestations can be divided into those produced by the counter-regulatory hormones (adrenaline and glucagon) triggered by the falling glucose, and the neuroglycopenic effects produced by the reduced brain sugar.
Abnormal mentation, impaired judgment
Nonspecific dysphoria, anxiety, moodiness, depression, crying, fear of dying
Negativism, irritability, belligerence, combativeness, rage
Personality change, emotional lability
Fatigue, weakness, apathy, lethargy, daydreaming, sleep
Confusion, amnesia, dizziness, delirium
Staring, "glassy" look, blurred vision, double vision
Automatic behavior, also known as automatism
Difficulty speaking, slurred speech
Ataxia, incoordination, sometimes mistaken for "drunkenness"
Focal or general motor deficit, paralysis, hemiparesis
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. 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.
Preventing further episodes
The most effective means of preventing further episodes of hypoglycemia depends on the cause.
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.
Hypoglycemia as American folk medicine
Hypoglycemia is also a term of contemporary American folk medicine which refers to a recurrent state of symptoms of altered mood and subjective cognitive efficiency, sometimes accompanied by adrenergic symptoms, but not necessarily by measured low blood glucose. Symptoms are primarily those of altered mood, behavior, and mental efficiency. This condition is usually treated by dietary changes which range from simple to elaborate.
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.
Hypoglycemia in young children
Single episodes of hypoglycemia due to gastroenteritis or fasting, but recurrent episodes nearly always indicate either an inborn error of metabolism, congenital hypopituitarism, or congenital hyperinsulinism
Diarrheal illness in young children, especially rotavirus gastroenteritis
Idiopathic ketotic hypoglycemia
Isolated growth hormone deficiency, hypopituitarism
Hyperinsulinism due to several congenital disorders of insulin secretion
Insulin injected for type 1 diabetes
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
Disorders of fatty acid oxidation
Medium chain acylCoA dehydrogenase deficiency (MCAD)
Sulfonylureas, propranolol and others
Ethanol (mouthwash, "leftover morning-after-the-party drinks")
Hypoglycemia in older children and 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 injected for type 1 diabetes
Factitious insulin injection (Munchausen syndrome)
Insulin-secreting pancreatic tumor
Reactive hypoglycemia and idiopathic postprandial syndrome