Hypoglycemia pathophysiology
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Pathophysiology
RESPONSE TO HYPOGLYCEMIA IN DIABETES
Insulin[1-3,6].
the ability to suppress insulin release, cannot occur in patients with absolute beta-cell failure those with type 1 diabetes and long-standing type 2 diabetes.
inhibition of hepatic glucose production continues. Thus, the main defense against hypoglycemia is increased release of counterregulatory hormones (glucagon and epinephrine).
Glucagon
This may be the result of beta-cell failure and subsequent loss of the hypoglycemia-induced decline in intraislet insulin that normally signals increased glucagon secretion during hypoglycemia [3,9,10].
Epinephrine
epinephrine response to hypoglycemia also becomes attenuated in many patients, at least in part because of recent antecedent hypoglycemia [1,2,7,11]. An attenuated epinephrine response causes defective glucose counterregulation, which is associated with a 25-fold or greater increased risk of severe hypoglycemia [12,13].
An attenuated sympathoadrenal (largely sympathetic neural) response causes hypoglycemia unawareness[14].
by shifting the glycemic threshold for the sympathoadrenal response to subsequent hypoglycemia to a lower plasma glucose concentration. 4
Brain metabolism depends primarily on glucose for fuel in most circumstances. A limited amount of glucose can be derived from glycogen stored in astrocytes, but it is consumed within minutes. For most practical purposes, the brain is dependent on a continual supply of glucose diffusing from the blood into the interstitial tissue within the central nervous system and into the neurons themselves.
If the amount of glucose supplied by the blood falls, the brain is one of the first organs affected. In most people, subtle reduction of mental efficiency can be observed when the glucose falls below 65 mg/dl.
Impairment of action and judgement,Seizures may occur as the glucose falls further, resulting in coma. These brain effects are collectively referred to as neuroglycopenia.
The importance of an adequate supply of glucose to the brain is apparent from the number of nervous, hormonal and metabolic responses to a falling glucose. Most of these are defensive or adaptive, tending to raise the blood sugar via glycogenolysis and gluconeogenesis or provide alternative fuels.
This can include impairment of cognitive function, motor control, or even consciousness.