Human cells require fuel to perform their day-to-day functions. Glucose is the preferred form of cellular fuel, and some cells (e.g., brain cells) have difficulty utilizing any other source.
Glucose is a sugar that is derived from the digestion of carbohydrates. Although other sugars are also byproducts of carbohydrate metabolism, these sugars are usually broken down further or altered to form glucose as the end product.
Hypoglycemia is a condition characterized by lower-than-normal plasma glucose levels. Symptomatic hypoglycemia unrelated to treatment of diabetes is rare, because the body uses multiple counter-regulatory mechanisms to compensate for low blood glucose levels. (The Merck Manual, 18th Edition 2006:1293-1294)
Specific Conditions Associated with Hypoglycemia
- Alcoholism
- Diabetes (treated)
- Sepsis
- Pheochromocytoma
- Insulinoma
- Addison’s disease
- Reactive hypoglycemia (includes gastrectomy or gastric bypass)
- Cancer
- Inborn metabolic defects (e.g., glycogen storage disorders)
- Cirrhosis
- Renal failure
- Factitious hypoglycemia
Causes of Hypoglycemia
Causes of physiologic hypoglycemia can be classified as reactive or fasting, insulin-induced or non-insulin-induced, and drug-induced or non-drug-induced.
- Reactive hypoglycemia occurs when, following a meal, the normal upsurge in insulin is exaggerated. This abnormally high insulin spike drives plasma glucose down to lower-than-normal levels.
- Fasting hypoglycemia occurs when, following a prolonged unfed state, all readily available stores of glucose are exhausted, and plasma glucose falls.
- Insulin-induced hypoglycemia occurs when plasma glucose levels are driven downward by either exogenously-administered insulin (e.g., in diabetes management), by relatively high physiologic levels of insulin, or by insulin-secreting tumors (insulinomas).
- Drug-induced hypoglycemia is the result of medications or medication interactions that either decrease the availability or increase the metabolism of glucose.
- Factitious hypoglycemia—a specific instance of insulin- or drug-induced hypoglycemia—occurs when nondiabetic individuals inadvertently or deliberately take insulin or oral diabetes medications.
Signs and Symptoms of Hypoglycemia
A surge in autonomic nervous system activity in response to low glucose levels is the basis for many symptoms associated with hypoglycemia. As glucose levels fall further and the brain is deprived of critically-needed fuel, signs and symptoms grow more severe:
- Sweating
- Palpitations
- Nausea
- Anxiety
- Tremor
- Hunger pangs
- Abnormal sensations (paresthesias)
- Headache
- Blurred or double vision
- Confusion
- Light-headedness or fainting (syncope)
- Slurred speech
- Seizures
- Coma
In most instances, symptoms occur at or below a plasma glucose level around 60 mg/dL; central nervous system symptoms usually begin at or below 50 mg/dL.
Unfortunately, the symptoms of hypoglycemia are nonspecific; people with abnormally low glucose levels don’t always exhibit symptoms until hypoglycemia is profound, and most people with symptoms that suggest hypoglycemia have normal plasma glucose levels.
Diagnosis of Hypoglycemia
The key to a diagnosis of hypoglycemia is the documented presence of a plasma glucose level <50 mg/dL in association with symptoms, combined with resolution of those symptoms after the administration of glucose. Ideally, blood tests could be performed at the time symptoms occur, but medical facilities aren’t always readily available.
- A 72-hour fast, conducted in a controlled setting, has traditionally been used to diagnose hypoglycemia. Plasma glucose levels are measured at the outset of and periodically during the fast.
- The fast is ended early if a patient develops symptoms in conjunction with a glucose level ≤45 mg/dL; additional blood tests can help to distinguish between the various potential causes.
- The test is terminated at 72 hours if the patient’s glucose remains normal and no symptoms develop. The patient may be exercised in an attempt to unmask hypoglycemia; if no symptoms occur and glucose remains normal, no further testing is needed.
Hypoglycemia may appear to be an enigmatic disorder, but an orderly approach and a few standard tests can narrow the possibilities and lead to a reasonable treatment plan.
