Mechanisms of hypoglycemia-associated autonomic failure in diabetes

The key feature of HAAF in diabetes is attenuated sympathoadrenal responses to hypoglycemia, most often caused by recent hypoglycemia. In the context of the lack of a decrease in insulin and of an increase in glucagon - both plausibly attributed to beta-cell failure - attenuation of the epinephrine response causes defective glucose counterregulation. Attenuation of the sympathetic neural response largely causes hypoglycemia unawareness. The precise mechanisms of the attenuated sympathoadrenal responses are not known, but there are provocative clues, ranging from evidence that available drugs might lower the burden of iatrogenic hypoglycemia and that lactate can affect brain metabolism to the notion of alterations in a cerebral network in the pathogenesis of HAAF.