The generally accepted normal range for fasting plasma glucose is 70–100 mg/dL, so patients with a fasting plasma glucose concentration less than 60 mg/dL may have a hypoglycemic disorder. Symptomatic hypoglycemia is usually associated with concentrations less than 50 mg/dL. The most common cause is an excessive dose of insulin or other hypoglycemic agents.26In general, the causes of fasting hypoglycemia can be divided into those that involve overutilization of glucose by the body, and those that involve impaired production:

  • Overutilization of glucose
    • Hyperinsulinis
      • Insulinoma
      • Exogenous insulin
      • Sulfonylureas
      • Immune disease with insulin or insulin receptor antibodies
      • Drugs (e.g., quinine, disopyramide, pentamidine)
      • Sepsis
    • Appropriate insulin levels
      • Extrapancreatic tumors
      • Systemic carnitine deficiency
      • Deficiency in enzymes of fat oxidation
      • 3-Hydroxy-3-methylglutaryl-CoA lyase deficiency
      • Cachexia with fat depletion
  • Impaired production of glucose
    • Hormone deficiencies
      • Hypopituitarism
      • Adrenal insufficiency
      • Catecholamine deficiency
      • Glucagon deficiency
    • Enzyme defects
      • Glucose-6-phosphatase
      • Liver phosphorylase
      • Pyruvate carboxylase
      • Phosphoenolpyruvate carboxykinase
      • Fructose-1,6-bisphosphatase
      • Glycogen synthetase
    • Substrate deficiency
      • Ketotic hypoglycemia of infancy
      • Severe malnutrition, muscle wasting
      • Late pregnancy
    • Liver disease
      • Hepatic congestion
      • Severe hepatitis
      • Cirrhosis
      • Uremia
      • Hypothermia
    • Drugs


      • Alcohol
      • Propranolol
      • Salicylates

Clinical presentation

The clinical manifestations of hypoglycemia parallel the rate of decline in serum glucose concentration, more so than the absolute glucose concentration.

Early symptoms may include

  • sweating
  • sensation of warmth
  • fatigue
  • headache
  • anxiety
  • nausea
  • visual disturbances
  • dizziness
  • hunger
  • tremor

Few patients have every symptom.

Later findings are confusion, drowsiness, delirium, seizures, and coma. Seizures are usually generalized, although partial seizures may occur.27 Lateralized weakness, even in the absence of a structural brain lesion, may be seen.


Symptomatic hypoglycemia should be suspected when patients under treatment for diabetes have a change in mental status or new-onset seizures. To confirm the diagnosis, serum glucose concentrations ideally should be measured when patients are symptomatic.28 Further evaluation usually discloses the underlying cause.29 An electroencephalogram (EEG) while patients are symptomatic from hypoglycemia may show background slowing with or without epileptiform features.


Early or mild symptoms resolve with oral sugar. Patients presenting with altered mental status or seizures should be treated with intravenous glucose once blood samples have been drawn.

Diabetic patients with recurrent symptomatic hypoglycemia require modification in their treatment regimen and instruction on the use of oral glucose to prevent the onset or worsening of hypoglycemic symptoms.

Reviewed By: 
Steven C. Schachter, MD
Thursday, April 1, 2004