[The phenomenon of hypoglycemia unawareness--definition, frequency, pathogenesis and clinical forms]

Failure to recognize autonomic warning symptoms or failure for them to occur before the development of neuroglycopenia is defined as hypoglycemia unawareness. Incidence of this phenomenon among patients with insulin-dependent diabetes mellitus is frequent. Using a standardized insulin infusion test it has been found that one out of four patients (26%) with insulin-dependent diabetes mellitus has present hypoglycemia unawareness. Various mechanisms and predisposing factors have been implicated in the pathogenesis of the phenomenon of hypoglycemia unawareness. This defect is probably at the central nervous system level and could be due to: 1. lack of appropriate recognition by the central nervous system of a decreasing glycemia (altered hypothalamic glucostat function or altered blood-brain glucose transport); 2. diminished release of neurotransmitters; 3. diminished target tissue responses on appropriate neurotransmitters secretion. Theory of pathogenesis of hypoglycemia unawareness must be able to explain and define its association with duration of diabetes, strict glycemic control, autonomic neuropathy and repetitive episodes of hypoglycemia. The present hypothesis of hypoglycemia unawareness is that the repetitive frequent hypoglycemia leads to generalized central nervous system adaptation by means of increased transport of glucose through the blood-brain barrier which results in diminished counterregulatory hormone responses and symptoms. A dangerous vicious circle develops whereby hypoglycemia induces unawareness, which in itself increases the risk for development of new hypoglycemia. This state is at least partially reversible. The presence of hypoglycemia unawareness should influence the physician's decision before using intensive insulin therapy regimen in diabetic patients. (Tab. 2, Fig. 1, Ref. 39.)