Ravindra Kumar Garg MD (Dr. Garg of King George's Medical University in Lucknow, India, has no relevant financial relationships to disclose.)
Douglas J Lanska MD FAAN MS MSPH, editor. (

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health, the Medical College of Wisconsin, and IM Sechenov First Moscow State Medical University has no relevant financial relationships to disclose.

Originally released January 19, 1999; last updated March 10, 2019; expires March 10, 2022


The human brain primarily uses glucose as its source of energy. In certain situations, plasma glucose may fall to a dangerous level. When plasma glucose falls, hormonal and sympathoadrenal mechanisms get activated to restore glucose levels to normal. The counterregulatory mechanisms involve reduction of insulin secretion, increasing glucagon secretion, adrenergic activation, and increased growth hormone and cortisol secretion. Repeated hypoglycemia can lead to impaired awareness, increasing the risk of severe hypoglycemia up to 6-fold. Recurrent episodes of hypoglycemia impair sympathoadrenal counterregulatory responses to a subsequent episode of hypoglycemia. The mainstay of treatment of impaired awareness of hypoglycemia is the avoidance of hypoglycemia. Hypoglycemia-induced autonomic dysfunction increases the risk of another hypoglycemic episode. Hypoglycemia often goes undiagnosed, and in the advanced stage it is frequently not treated. In patients with diabetes mellitus who lose awareness of being hypoglycemic, involvement of corticolimbic brain and centers serving higher executive functions as well as the hypothalamus has been demonstrated. Manifestations of hypoglycemia are seizures, coma, persistent vegetative state, and even death. Hypoglycemia has a very significant impact on the pathogenesis of dementia and cognitive dysfunction among patients with diabetes mellitus. Cognitive decline can be explained by both the direct effects of altered glucose metabolism in the brain and diabetes-related cardiovascular disease. Transplantation of islets or whole pancreas may be required in those with recurrent disabling hypoglycemia. In this article, the author has described the definition, physiology, pathophysiology, clinical features, imaging abnormalities, and management of hypoglycemia.

Key points


• Hypoglycemia is defined as a fall of serum glucose level below 50 mg/dL, which results in clinical manifestations.


• Manifestations of hypoglycemia are seizures, coma, persistent vegetative state, and even death.


• Hypoglycemia is the most important complication of insulin therapy for type 1 diabetes. Hypoglycemia is less frequent in type 2 diabetes.


• Intravenous glucose as a bolus of 50% solution should be given, and continuous infusion of 5% or 10% glucose solution should be provided until a patient can start taking orally.

Historical note and terminology

Although the importance of the liver in maintaining fasting blood glucose concentration was suggested as early as 1876 by Claude Bernard (Zimmerman 1983), the full spectrum of symptomatic hypoglycemia–systemic, neurologic, and psychiatric–was described only after the discovery of insulin in 1921 (Fletcher and Campbell 1922; Wolf et al 1933). Hypoglycemic encephalopathy, comprising of delirium, coma, seizures, and a "stroke-like illness" was described in the 1960s.

In most hospitals, a lower limit of normal plasma glucose is 70 mg/dL. Although a value below 70 mg/dL may meet a laboratory definition of hypoglycemia, symptomatic hypoglycemia occurs at lower plasma glucose levels. A clinically helpful definition of hypoglycemia has been a plasma glucose level of 40 to 50 mg/dL or less by most authors. Below this level, symptoms and signs of hypoglycemia may occur, although usual symptomatic hypoglycemia often occurs even at a lower level. A low laboratory value may be misleading because a normal female may have a value as low as 20 mg/dL during a fast without any symptoms (Merimee and Tyson 1974). This rather large overlap between normal and symptomatic hypoglycemic values suggests that additional aggravating factors may be necessary in evoking clinical signs and symptoms. These include rapidity of glucose lowering, concomitant other diseases or metabolic derangement, and concurrent medications. Despite these reservations, the presence of appropriate symptoms accompanied by a "low" plasma glucose level and prompt reversal of symptoms and signs with glucose administration constitute a helpful diagnostic entity known as Whipple triad (Whipple 1938).

The content you are trying to view is available only to logged in, current MedLink Neurology subscribers.

If you are a subscriber, please log in.

If you are a former subscriber or have registered before, please log in first and then click select a Service Plan or contact Subscriber Services. Site license users, click the Site License Acces link on the Homepage at an authorized computer.

If you have never registered before, click Learn More about MedLink Neurology  or view available Service Plans.