Hypoglycemia

What is Hypoglycemia?

Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood" (Gr. ''hypo-'', ''glykys'', ''haima'').

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). Effects can range from vaguely "feeling bad" to seizures, unconsciousness, and (rarely) permanent brain damage or death.

The most common forms of moderate and severe 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, from many causes. Among the causes are excessive insulin produced in the body, inborn errors of carbohydrate, fat, amino acid or organic acid metabolism, medications and poisons, alcohol, hormone deficiencies, certain tumors, prolonged starvation, and alterations of metabolism associated with infection or failures of various organ systems.

Hypoglycemia is treated rapidly by restoring the blood glucose level to normal by the ingestion or administration of dextrose or carbohydrate foods quickly digestible to glucose. In some circumstances it is treated by injection or infusion of glucagon. Prolonged or 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 even 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 70 mg/dL (3.9 mmol/L), and develop symptoms of hypoglycemia when the glucose falls below 55 mg/dL (3 mmol/L).

It can sometimes be difficult to determine whether a person's symptoms are due to hypoglycemia. Endocrinologists (physicians with expertise in disorders of glucose metabolism) typically consider the criteria referred to as Whipple's triad as conclusive evidence that an individual's symptoms can be attributed to hypoglycemia instead of to some other cause:

  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 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.

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Defining Hypoglycemia

No single glucose value alone serves to define the medical condition termed hypoglycemia for all people and purposes. Throughout the 24 hour cycles of eating, digestion, and fasting, blood plasma glucose levels of healthy people past infancy are generally maintained between 72 and 144 mg/dL (4-8 mmol/L) throughout a 24 hour period. Although 60 or 70 mg/dL (3.3 or 3.9 mmol/L) is commonly cited as the lower limit of normal glucose, different values (typically below 40, 50, 60, or 70 mg/dL) have been defined as low for different populations, clinical purposes, or circumstances. In other words, many healthy people can occasionally have glucose levels in the hypoglycemic range without symptoms or disease.

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, Egypt, and Columbia, 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. 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, 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. 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. 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.

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Hypoglycemia Causes

There are several ways to classify hypoglycemia. The following is a list of the more common causes and factors which may contribute to hypoglycemia grouped by age, followed by some causes that are relatively age-independent. See causes of hypoglycemia for a more complete list grouped by etiology.

Hypoglycemia in 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

Hypoglycemia in 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, "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-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

Hypoglycemia in 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 diabetes drugs, beta-blockers, or drug interactions
    • Insulin-secreting pancreatic tumor
    • 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

This article is licensed under the Creative Commons Attribution-ShareAlike License. It uses material from the Wikipedia article on "Hypoglycemia" All material adapted used from Wikipedia is available under the terms of the Creative Commons Attribution-ShareAlike License. Wikipedia® itself is a registered trademark of the Wikimedia Foundation, Inc.