Counterregulatory mechanisms to insulin-induced hypoglycemia in humans: relevance to the problem of intensive treatment of IDDM.

Hypoglycemia unawareness is a condition of decreased/absent perception of specific symptoms which normally inform the subject that plasma glucose is decreasing to dangerous levels resulting in neuroglycopenia. This syndrome is frequent in IDDM. In the absence of warning symptoms, IDDM patients cannot take any measure (e.g. eating) to prevent severe neuroglycopenia (unconsciousness). Because hypoglycemia unawareness is associated with impaired glucose counterregulation, especially reduced adrenaline responses, hypoglycemia unawareness is a risky condition for severe hypoglycemia. A number of studies in animals and humans indicate that hypoglycemia unawareness is largely, if not fully, secondary to recurrent or chronic hypoglycemia. Meticulous prevention of hypoglycemia in IDDM largely recovers the symptoms of hypoglycemia and the responses of adrenaline. It is important that diabetologists and IDDM patients are familiar with the syndrome of hypoglycemia unawareness and learn how to prevent/treat it in programs of intensive therapy. Intensive therapy aiming strictly at normoglycemia may increase the frequency of hypoglycemia and hypoglycemia unawareness. On the other hand, if intensive therapy is combined with a program of prevention of hypoglycemia, the percentage of HbA1c can be maintained long-term below 7.0% (i.e. below values risky for onset/progression of complications), and at the same time the frequency of hypoglycemia is very low. Under these conditions, IDDM patients maintain the awareness of warning symptoms and adrenaline response to hypoglycemia, a vital back-up system for the safety of intensive therapy of IDDM.