How does hypoglycemia (low blood sugar) lead to confusion?

From the Guidelines

Hypoglycemia leads to confusion because the brain depends heavily on glucose as its primary energy source, and when blood sugar levels drop, the brain becomes deprived of the fuel it needs to function properly, affecting cognitive function and leading to impaired neural communication. According to the most recent and highest quality study, hypoglycemia is a major limiting factor in the glycemic management of type 1 and type 2 diabetes, and its occurrence and risk should be reviewed at every encounter 1. The study defines level 1 hypoglycemia as a measurable glucose concentration <70 mg/dL (3.9 mmol/L) but ≥54 mg/dL (3.0 mmol/L), and level 2 hypoglycemia as a blood glucose concentration <54 mg/dL (3.0 mmol/L), which is the threshold at which neuroglycopenic symptoms begin to occur and requires immediate action to resolve the hypoglycemic event.

Some key points to consider when managing hypoglycemia include:

• Glucose (approximately 15–20 g) is the preferred treatment for the conscious individual with blood glucose <70 mg/dL (3.9 mmol/L) 1
• Glucagon should be prescribed for all individuals at increased risk of level 2 or 3 hypoglycemia, so that it is available should it be needed 1
• Hypoglycemia unawareness or one or more episodes of level 3 hypoglycemia should trigger hypoglycemia avoidance education and reevaluation and adjustment of the treatment plan to decrease hypoglycemia 1
• Ongoing assessment of cognitive function is suggested with increased vigilance for hypoglycemia by the clinician, patient, and caregivers if impaired or declining cognition is found 1

Rapid recognition and treatment of hypoglycemia with fast-acting carbohydrates is essential to prevent confusion and other severe symptoms, and for diabetic patients experiencing frequent hypoglycemic episodes causing confusion, medication adjustments may be necessary, and carrying glucose sources at all times is recommended. The American Diabetes Association standards of medical care in diabetes also emphasize the importance of self-monitoring of blood glucose and continuous glucose monitoring (CGM) to monitor glucose levels and prevent hypoglycemia 1.

From the FDA Drug Label

Very low blood sugar can cause confusion, seizures, passing out (loss of consciousness) and death Hypoglycemia can lead to confusion as a result of very low blood sugar levels, which can also cause other severe symptoms such as seizures, passing out (loss of consciousness), and even death 2.

From the Research

Hypoglycemia and Cognitive Function

• Hypoglycemia can lead to confusion due to the brain's dependence on a continuous supply of glucose, and deprivation of which rapidly causes malfunction 3.
• The cerebral cortex is the most sensitive region to neuroglycopenia, and a fall in blood glucose can provoke a hierarchy of responses, including secretion of counter-regulatory hormones and development of warning symptoms 3.
• Symptoms of hypoglycemia can be classified as autonomic and neuroglycopenic, with the latter being related to altered cognitive functioning, including impaired judgment and decreased memory capacity 3, 4.

Neurological Effects of Hypoglycemia

• Acute hypoglycemia can produce electroencephalographic (EEG) changes and neurophysiological abnormalities, including increased latency and/or reduced amplitude of sensory evoked potentials 3.
• Cognitive function does not recover fully until 40-90 min after blood glucose is restored to normal, and recurrent severe hypoglycemia may have long-term sequelae in the form of cumulative cognitive impairment 3.
• Hypoglycemia can also provoke changes in mood, increase anxiety, and may induce depression and fear of further hypoglycemia, which can modify behavior and influence quality of glycaemic control 3.

Brain Energetics and Hypoglycemia

• The brain's unique bioenergetic properties, particularly the metabolic coupling of neuronal and astrocyte metabolism, play a crucial role in the pathophysiology of hypoglycemia 5.
• Non-glucose substrates, including pyruvate, glycogen, ketone bodies, glutamate, glutamine, and aspartate, can be metabolized by neurons in the absence of glucose and contribute to prolong neuronal function and delay ATP depletion during hypoglycemia 4.