late post-absorptive or fasting state) tend to fall, insulin secretion is suppressed to such an extent that true hypoglycemia can almost always be prevented.
This inability is known as the clinical syndrome of impaired awareness of hypoglycemia and increases the risk of particularly severe hypoglycemia, defined as those events requiring assistance from another person .Both the attenuated adrenaline response and impaired awareness of hypoglycemia are usually the result of (recurrent) antecedent hypoglycemia rather than of autonomic neuropathy, for which the term ‘hypoglycemia-associated autonomic failure’ (HAAF) has been introduced .Finally, although 4–10 % of all deaths in patients with type 1 diabetes have been attributed to hypoglycemia, most of these deaths are thought to be either accidental (e.g. arrhythmia) rather than the direct consequence of brain death , seem more susceptible to harm from hypoglycemia.Children with type 1 diabetes performed worse on cognitive tests when they had a history of severe hypoglycemia below the age of 5 years, compared to patients without such a history and non-diabetic controls .This review will focus on the effect of hypoglycemia on brain (glucose) metabolism, with a particular emphasis on recent findings from functional and metabolic neuroimaging studies.
Basic mechanisms of brain energy metabolism and neuroimaging techniques will be discussed briefly.
These impairments first include the inability to decrease insulin and to increase glucagon in response to hypoglycemia.
The latter is not a structural defect, but specific for hypoglycemia and probably secondary to loss of control by non-functioning beta-cells .
In patients with longer diabetes duration and more frequent exposure to hypoglycemia, adrenaline responses to hypoglycemia become attenuated, in part due to a shift of these responses to lower glucose values .
Disappearance of these symptoms interferes with the ability to timely and accurately perceive, interpret and respond to falling plasma glucose levels.
In humans, the brain represents only about 2 % of total body weight, yet it accounts for approximately 20 % of the body’s oxygen use and 25 % of the body’s use of glucose. In young adults, the ‘resting’ brain consumes approximately 110 g of glucose per day, i.e.