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Pathophysiology. metabolism depends primarily on glucose for fuel 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
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Pathophysiology • metabolism depends primarily on glucose for fuel • 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 • brain is one of the first organs affected if the amount of glucose supplied by the blood falls
Pathophysiology • reduction of mental efficiency can be observed when the glucose falls below 65mg/dl (3.6 mM) • impairment of action and judgment usually becomes obvious below 40 mg/dl (2.2 mM) • most neurons become electrically silent and nonfunctional, resulting in coma as blood glucose levels fall below 10 mg/dl (0.55 mM) • seizures may occur as the glucose falls further
Pathophysiology • if the blood sugar level falls too low the liver converts storage of glycogen into glucose and releases it into the bloodstream, to prevent the person going into a diabetic coma, for a short period of time • brief or mild hypoglycemia produces no lasting effects on the brain, though it can temporarily alter brain responses to additional hypoglycemia
Pathophysiology • prolonged, severe hypoglycemia can produce lasting damage of a wide range which includes impairment of cognitive function, motor control, or even consciousness • likelihood of permanent brain damage from any given instance of severe hypoglycemia depends on a multitude of factors such as age, recent blood and brain glucose experience, concurrent problems such as hypoxia, and availability of alternative fuels
Pathophysiology • prevention or correction of hypoglycemia normally involves both decrements in insulin and increments in glucose counterregulatory hormones, particularly glucagon and epinephrine • the secretion of all three of these hormones is altered in T1DM and advanced T2DM.
Pathophysiology • as glucose levels fall (exogenous) insulin levels do not decrease and glucagon levels do not increase. The latter is also the result of insulin deficiency. Thus, the first and second defenses against hypoglycemia are lost • further, the epinephrine response, the third defense, is typically attenuated, i.e., the glycemic threshold for its release is shifted to lower plasma glucose concentrations. The latter is generally the result of recent antecedent hypoglycemia although sleep, and to some extent prior exercise, causes a similar phenomenon
Pathophysiology • the combination of absent glucagon and attenuated epinephrine responses causes defective glucose counterregulation which is associated with a 25-fold or greater increased risk of severe hypoglycemia • the reduced autonomic (adrenomedullary and sympathetic neural) response causes hypoglycemia unawareness – loss of the warning, largely neurogenic, symptoms of developing hypoglycemia – which, because it compromises the behavioral defense (e.g., food ingestion), is also associated with a high frequency of hypoglycemia
The concept of hypoglycemia-associated autonomic failure (HAAF) in T1DM and advanced T2DM posits that recent antecedent hypoglycemia causes both defective glucose counterregulation (by reducing epinephrine responses in the setting of absent insulin and glucagon responses) and hypoglycemia unawareness (by reducing sympathoadrenal and thus neurogenic symptom responses) (see figure 1)
