What is the pathophysiology of hypoglycemia (low blood sugar)?

Updated: Jul 23, 2020
  • Author: Osama Hamdy, MD, PhD; Chief Editor: Romesh Khardori, MD, PhD, FACP  more...
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Hypoglycemic symptoms are related to sympathetic activation and brain dysfunction secondary to decreased levels of glucose. Stimulation of the sympathoadrenal nervous system leads to sweating, palpitations, tremulousness, anxiety, and hunger. Reduction in cerebral glucose availability (ie, neuroglycopenia) can manifest as confusion, difficulty with concentration, irritability, hallucinations, focal impairments (eg, hemiplegia), and, eventually, coma and death.

The adrenergic symptoms often precede the neuroglycopenic symptoms and, thus, provide an early warning system for the patient. Studies have shown that the primary stimulus for the release of catecholamines is the absolute level of plasma glucose; the rate of decrease of glucose is less important. Previous blood sugar levels can influence an individual's response to a particular level of blood sugar. However, it is important to note that a patient with repeated hypoglycemia can have almost no symptoms (hypoglycemic unawareness). The threshold at which a patient feels the hypoglycemic symptoms decreases with repeated episodes of hypoglycemia.

A study by Zhong et al indicated that in patients with type 2 diabetes mellitus, a proximal hemoglobin A1c (HbA1c) level above or below the reference level of 7.0% increases the risk of a first incidence of hypoglycemia requiring hospitalization (HH). The investigators found that when the proximal HbA1c level ranges between 4.0% and 6.5%, every 0.5% level increase reduces the first HH risk, while for patients with a proximal HbA1c level of 8.0-11.5%, the risk of first HH rises with each 0.5% increase in HbA1c. The investigators also found that current sulfonylurea users in the study did not exhibit this U-shaped phenomenon but that current insulin users did. [3]

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