Hypoglycemia is diagnosed when blood glucose levels fall to abnormally low levels. Under normal conditions, and despite wide variations in food intake and energy expenditure, the body maintains a very narrow range of blood glucose levels (Braunwald 2001).
This careful balance is partly regulated by two hormones, insulin and glucagon, which have opposite effects. Both are produced in the pancreas in small clusters of cells called the islets of Langerhans. High blood levels of glucose stimulate the secretion of insulin, which results in cellular uptake of glucose, and subsequent lowering of blood glucose.
Low blood levels of glucose stimulate the secretion of glucagon from the liver. Glucagon stimulates a rise in blood glucose through two processes. First, glycogen (the animal version of starch) in the liver is metabolized into glucose. A normal liver stores relatively small amounts of glucose as glycogen, so glycogen stores can be depleted fairly quickly. Most people's glycogen stores are virtually gone within 24 hours of no caloric intake. When glycogen levels are low, or when energy needs are high, fatty acids and amino acids are converted into glucose in the liver and kidneys through the process of gluconeogenesis. Adrenal glands also play a role in increasing blood glucose. The hormone epinephrine stimulates glycogen breakdown, and cortisol promotes gluconeogenesis.
Hypoglycemia is a result of any disorder that causes abnormal restrictions in the production of glucose by the liver or kidneys, or that causes an abnormal increase in glucose uptake by the cells (Barzilai 1999). Hypoglycemia can be divided broadly into three categories: reactive, drug induced, and fasting.
Reactive hypoglycemia occurs within four hours after eating if glucose levels rise too rapidly because of underlying conditions (eg, increased absorption of glucose from the small intestine). In response, the body over-excretes insulin, which drives the glucose from the blood, resulting in hypoglycemia. It may be caused by the following factors (Kasper 2005):
- Increased sensitivity to counterregulatory hormones (eg, epinephrine)
- Deficiency in glucagon release
- Polycystic ovarian syndrome
- Rare enzyme deficiencies (eg, hereditary fructose intolerance and galactosemia)
Drugs used in the treatment of diabetes (eg, insulin and sulfonylurea) are the most common cause of drug-induced hypoglycemia. These drugs are used to lower blood glucose levels. When used in excess, blood glucose levels drop rapidly and markedly, leading to hypoglycemia (Kasper 2005). Alcohol-induced hypoglycemia can result from alcohol ingestion after fasting long enough to exhaust glycogen stores, making liver glucose output dependent on gluconeogenesis. Hypoglycemia can be induced by blood alcohol levels well below legal driving limits (Barzilai 1999).
Fasting hypoglycemia occurs after strenuous exercise or during an extended period between meals. It is relatively uncommon among healthy people. Fasting hypoglycemia can occur in people who drink heavily, have liver disease, and in children with genetic enzyme abnormalities that disrupt sugar metabolism (Kasper 2005).
Hypoglycemia may also be caused by other factors (Kasper 2005):
- Certain types of tumors secrete insulin-like growth factor, which acts in a manner similar to insulin.
- Autoimmune disorders may cause abnormal insulin secretion.
- Addison's disease, which affects the pituitary and adrenal glands, and chronic illnesses (eg, hepatic, renal, or cardiac failure or sepsis), which cause inadequate glucose to be delivered to the body's cells, may also cause hypoglycemia.